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CORK Bibliography: Benzodiazepines

99 citations. 2011 to present

Prepared: June 2012

Albiero A; Brigo F; Faccini M; Casari R; Quaglio G; Storti M et al. Focal nonconvulsive seizures during detoxification for benzodiazepine abuse. Epilepsy & Behavior 23(2): 168-170, 2012. (19 refs.)

Chronic benzodiazepine (BDZ) abuse is currently treated with detoxification using a low-dose flumazenil infusion, a relatively recently developed and promising procedure. Given the possibility reported in the literature of the occurrence of generalized seizures during therapeutic BDZ detoxification, we usually administer preventive antiepileptic drug (AED) therapy. We describe two patients with no previous history of seizures or evidence of intracerebral lesions who, during detoxification for benzodiazepine abuse, developed repetitive focal nonconvulsive seizures instead of generalized seizures, even with appropriate doses of preventive AED therapy. There are no previous reported cases of focal nonconvulsive seizures occurring during this procedure or, more generally, during abrupt BDZ discontinuation. The cases we describe suggest that during detoxification for BDZ abuse, not only generalized, but also focal nonconvulsive seizures may occur. In this context, the focal seizures probably result from a diffuse decrease in the seizure threshold (caused by a generalized excitatory rebound), which may trigger focal seizures arising from cortical regions with higher intrinsic epileptogenicity. Detoxification for benzodiazepine abuse, even if performed with adequate-dosage AED treatment, may not be as safe a procedure as previously considered, because not only convulsive, but also nonconvulsive seizures may occur and go unnoticed. It is therefore strongly advisable to perform this detoxification under close medical supervision and to maintain a low threshold for EEG monitoring in the event of sudden onset of behavioral changes.

Copyright 2012, Elsevier Science

Amato L; Minozzi S; Davoli M. Efficacy and safety of pharmacological interventions for the treatment of the alcohol withdrawal syndrome. (review). Cochrane Database of Systematic Reviews 6(e-article CD008537), 2011. (43 refs.)

Background: Alcohol abuse and dependence represents a very serious health problem worldwide with major social, interpersonal and legal interpolations. Pharmacological treatments presently used are of uncertain effectiveness and there is even more doubt on the comparative effects and value for money. Objectives: To summarize Cochrane reviews that assess the effectiveness and safety of pharmacological interventions in the treatment of alcohol withdrawal. Methods: We searched the Cochrane Database of Systematic Reviews (30 November 2010). Two authors independently screened, extracted data, summarised key characteristics of the included reviews and assessed their quality using AMSTAR; the quality of the evidence was summarised according to the GRADE methodology. Main results: Five reviews, 114 studies, 7333 participants, satisfied criteria for inclusions. The outcomes considered were alcohol withdrawal seizures, adverse events and dropouts. Comparing the five treatments with placebo, benzodiazepines performed better for seizures, three studies, 324 participants, RR 0.16 (95% CI 0.04 to 0.69), moderate quality of evidence. Comparing each of the five treatments versus specific class of drugs, benzodiazepines performed better than antipsychotics for seizures, 4 studies, 633 participants, RR 0.24 (95% CI 0.07 to 0.88) high quality of the evidence. Comparing different benzodiazepines and anticonvulsants among themselves, 28 comparisons, results never reached statistical significance but chlordiazepoxide performed better. The quality of evidence was high for 3% of the results, moderate for 28%, low for 48% and very low for 20%. Authors' conclusions: Among the treatments considered, benzodiazepines showed a protective benefit against seizures, when compared to placebo and a potentially protective benefit for many outcomes when compared with antipsychotics. Nevertheless, no definite conclusions about the effectiveness and safety of benzodiazepines were possible, because of the heterogeneity of the trials both in interventions and in the assessment of outcomes. Data on potential harms are sparse and fragmented. Results do not provide sufficient evidence in favour of anticonvulsants for the treatment of AWS, but anticonvulsants seem to have limited side effects. There is also not enough evidence of effectiveness and safety of baclofen, because only one study consider this treatment and of GHB for which no strong differences were observed in the comparisons with placebo, benzodiazepines and anticonvulsants.

Copyright 2011, Wiley-Blackwell

Arana JM; Blanco C; Meilan JJG; Perez E; Carro J; Gordillo F. The impact of poly drug use on several prospective memory measures in a sample of university students. Revista Latinoamericana de Psicologia 43(2): 229-240, 2011. (50 refs.)

The prolonged consumption of drugs has been associated with neuropsychological and cognitive deficits. The most important deficits are associated with executive functions and memory problems, specifically with prospective memory (PM). This type of memory plays a central role in our daily life. However, there is a lack of studies on the effects of poly drug consumption on prospective memory. In this study we aim to discover to what extent the length and amount of estimated consumption of alcohol, tobacco, cannabis and tranquilizers predicts the scores of self-reported prospective memory, and the scores on two objective tasks designed for this study. Measures included a Spanish version of the UEL Recreational Drug Use Questionnaire and the Prospective Memory Questionnaire, both with objective scores on two experimental tasks. The sample was composed of 164 participants (145 females and 19 males) aged 19-36 (M = 19.85, SD = 2.21). Stepwise regression analysis showed that years of cannabis consumption explained 13% of self-reported long term PM deficits. Years of alcohol consumption explained 18.4% of total variance of self-rated internally-cued PM deficits. Years of alcohol consumption and estimated amount of alcohol together predicted 30.2% of variance of objective event-based PM tasks. The estimated amount of tobacco and tranquilizers consumption predicted 33.7% of the time-based PM task.

Copyright 2011, Foundation for Advancement Psychology

Atanasov VN; Stoykova S; Runiov A; Dimitrova T; Aleksandrova D; Tsakovski S et al. Stability of diazepam in blood samples at different storage conditions and in the presence of alcohol. Forensic Science International 215(1-3): 159-163, 2012. (17 refs.)

Diazepam is one of the mostly used benzodiazepines and it is frequently analyzed in different biological samples, especially blood samples. The diazepam stability in the sample matrices is an important factor regarding reliable data obtaining. The storage is the main factor determining the stability of diazepam in blood samples and it is the object of the study presented. Remaining diazepam amount in spiked whole blood and plasma samples were tested at different storage temperatures, in the absence or presence of sodium fluoride as stabilizer as well as the influence of ethanol on diazepam stability was evaluated. The results of the study indicated that the temperature is the main storage factor affecting diazepam stability. In the fluoride stabilized blood samples the amount of diazepam decreases up to 85% of initial level when stored at -20 degrees C for the period of testing (12 weeks). The presence of low (0.5 g/L) or high (3 g/L) ethanol concentrations influences the stability of diazepam at -20 degrees C. In whole blood samples, the combination of sodium fluoride and ethanol decreases additionally (15-25%) the concentration of the analyte. Freeze-thaw experiments of whole blood samples show about 5-9% decrease in diazepam concentration after the first cycle. The freeze-thaw experiments on plasma samples, containing ethanol and/or fluoride show insignificant decreases of analyte concentration. Further experiments on benzodiazepines stability at different storage conditions or in combination of different factors should be undertaken in forensic toxicology to ensure the data quality, their reliability and reproducibility.

Copyright 2012, Elsevier Science

Austin AE; van den Heuvel C; Byard RW. Causes of community suicides among indigenous South Australians. Journal of Forensic and Legal Medicine 18(7): 299-301, 2011. (18 refs.)

A retrospective review of suicides occurring among Aboriginal people in the community in South Australia over a 5-year period was undertaken from January 2005 to December 2009. Twenty-eight cases were identified, consisting of 21 males (age range 16-44 years, mean 29.9 years) and 7 females (age range 23-45 years, mean 32.0 years). Deaths in all cases were caused by hanging (100%). Toxicological evaluation of blood revealed alcohol (39.3% of cases), cannabinoids (39.3%), benzodiazepines (10.7%), opiates (7.1%), antidepressants (7.1%), amphetamines (3.6%) and volatiles (3.6%). This study has demonstrated that the method of suicide overwhelmingly preferred by indigenous victims in South Australia is hanging. The precise reasons for this preference are uncertain, however, an indigenous person in South Australia presenting as a suicide where a method other than hanging has been used would be exceedingly uncommon, raising the possibility of alternative manners of death.

Copyright 2011, Faculty of Forensic and Legal Medicine.

Babalonis S; Lile JA; Martin CA; Kelly TH. Physiological doses of progesterone potentiate the effects of triazolam in healthy, premenopausal women. Psychopharmacology 215(3): 429- 439, 2011. (50 refs.)

Gender plays a critical role in the effects of drugs and drug abuse liability. Biological factors, including ovarian hormones, may contribute to gender differences in drug abuse. Preclinical and some clinical research suggests that progesterone and its metabolites have activity at the GABA(A) receptor and may enhance the effect of GABAergic compounds (e.g., benzodiazepines). Because women are exposed to varying levels of progesterone from puberty until menopause, and appear more sensitive to the negative consequences of benzodiazepine use, it is important to understand the impact of progesterone on GABAergic drug effects. The purpose of this experiment was to characterize the behavioral effects of progesterone, alone and in combination with the short-acting benzodiazepine, triazolam, to determine if progesterone potentiates the behavioral effects of triazolam. Oral micronized progesterone (0, 100, and 200 mg) and oral triazolam (0.00, 0.12, and 0.25 mg/70 kg) were administered to healthy, premenopausal women (n = 11) under conditions of low circulating sex hormones. The subjective, performance and physiological effects of progesterone, alone and in combination with triazolam, were assessed. Triazolam alone produced prototypical sedative-like effects. Progesterone alone also engendered some sedative effects, although the time course of the effects was more limited than that of triazolam. Progesterone increased and extended the duration of triazolam effects and delayed the onset of triazolam peak effects, most notably at the 0.12 mg/70 kg dose. Progesterone potentiates the behavioral effects of benzodiazepines and may contribute to benzodiazepine use and abuse among women.

Copyright 2011, Springer

Balhara YPS; Jain R; Dhawan A; Mehta M. Assessment of abuse liability of pheniramine among opioid-dependent human subjects. Journal of Substance Use 16(6): 484-495, 2011. (44 refs.)

Background: Pheniramine is being used harmfully in combination with opiates and benzodiazepines through injecting route. However, the abuse liability of pheniramine has not been studied in humans. Aim: The present study is an attempt to analyze the abuse liability of pheniramine in human subjects. Materials and methodology: The study used a double-blind randomly allotted crossover design. The doses of the drugs used were placebo (normal saline) 2 mL, pheniramine maleate 45.5 mg and lorazepam 2 mg. The assessments were made at baseline and then at 15, 120 and 240 min. The subjects were assessed for the sociodemographic profile, drug-use history, physiological parameters (pulse rate, BP, respiratory rate), and Modified Single-Dose Questionnaire (MSDQ)/Morphine-Benzedrine Group Scale (MBG)/Pentobarbital-Chlorpromazine-Alcohol Group Scale (PCAG)/Visual Analog Scale (VAS)/Profile of Mood States (POMS) scale. Analysis: Analysis was carried out using SPSS version 10.0. In-between drug comparisons were done using one-way analysis of variance (ANOVA) (multiple comparisons). Results: MSDQ and PCAG showed comparable results between the two compounds. VAS and POMS scale had significant increase on the scale for both lorazepam and pheniramine. Conclusions: The findings suggest the possible abuse liability of pheniramine. These findings with the clinical observation of pheniramine abuse used in combination with injection buprenorphine and diazepam warrant the need of caution while prescribing the compound to individuals.

Copyright 2011, Informa Healthcare

Bernardy NC; Lund BC; Alexander B; Friedman MJ.]. Copyright 2012, Physicians Postgraduate Press 2012(73): 3, Journal of Clinical Psychiatry. (30 refs.)

Objective: The revised Department of Veterans Affairs (VA) and Department of Defense Clinical Practice Guideline for Management of Post-Traumatic Stress recommends against long-term use of benzodiazepines to manage posttraumatic stress disorder (PTSD). An analysis of recent trends among veterans receiving care for PTSD in the VA noted a decreasing proportion receiving benzodiazepines. The authors examined prescribing patterns for other medications to better understand the general context in which the changes in benzodiazepine prescribing have occurred in the VA. Method: Administrative VA data from fiscal years 1999 through 2009 were used to identify veterans with PTSD using /CD-9 codes extracted from inpatient discharges and outpatient encounters. Prescribing of antidepressants, antipsychotics, and hypnotics was determined for each fiscal year using prescription drug files. Results:The proportion of veterans receiving either of the 2 Clinical Practice Guideline-recommended first-line pharmacotherapy treatments for PTSD, selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, increased from 49.7% in 1999 to 58,9% in 2009. In addition to reduced benzodiazepine prescriptions, the overall frequency of antipsychotic use declined 6.1%, from 20.0% in 1999 to 13.9% in 2009. Nonbenzodiazepine hypnotic prescribing tripled when zolpidem was added to the VA national formulary in 2008. Buspirone prescribing decreased steadily, while prazosin prescribing expanded nearly 7-fold. Conclusions: This work highlights several clinically important trends in prescribing over the past decade among veterans with PTSD that are generally consistent with the revised VA/Department of Defense Clinical Practice Guideline recommendations. However, the findings illustrate the limitations of administrative data and point to a need to supplement this work with a qualitative examination of PTSD prescribing from interviews with providers to better understand the strategies used to make medication management decisions.

Prescribing trends in veterans with Posttraumatic Stress Disorder

Bird SM; Robertson JR. Toxicology of Scotland's drugs-related deaths in 2000-2007: Presence of heroin, methadone, diazepam and alcohol by sex, age-group and era. Addiction Research & Theory 19(2): 170-178, 2011. (29 refs.)

Scotland has a new database on drugs-related deaths (DRDs). We review the prior toxicology and demography of Scotland's DRDs in 2000-2007. Each DRD was cross-classified by the presence/absence of heroin (H); methadone (M); diazepam (D); and alcohol (A). Comparisons were made by era (2000-2002, 2003-2005 and 2006-2007), sex and age-group (under 35 years and 35+ years). Data were for 1007 DRDs in 2000-2002 (180 female); 1011 in 2003-2005 (206 female); and 875 in 2006 and 2007 (149 female). DRDs citing diazepam decreased from around half in 2000-2002 to only 18% by 2006 and 2007 (95% CI: 15-21%). The presence of alcohol decreased also, for males, down from 43% of 827 DRDs in 2000-2002 (95% CI: 40-46%) to 35% of 726 DRDs in 2006 and 2007 (95% CI: 31-38%). The presence of heroin and alcohol were positively associated; of heroin and methadone strongly negatively. Alcohol's co-presence was age related: present in 53% of 598 male heroin-DRDs at 35+ years of age but in only 36% of 974 male heroin-DRDs under 35 years of age. Neither methadone nor heroin was present in a third of all female DRDs (183/535) and a fifth of male DRDs (460/2358). In 101 female and 276 male DRDs, none of H, M, D or A was mentioned. Periodically, the toxicology and demography of a country's DRDs should be analysed together, as here for Scotland, to highlight idiosyncrasies or insights. That alcohol's co-presence at heroin-DRDs was age related adds to several reasons for (ageing) heroin injectors to moderate their alcohol intake.

Copyright 2011, Informa Healthcare

Blencowe T; Pehrsson A; Mykkanen S; Gunnar T; Lillsunde P. Cannabis findings in drivers suspected of driving under the influence of drugs in Finland from 2006 to 2008. Forensic Science International 217(1-3): 107-112, 2012. (43 refs.)

The authors examined driving under the influence of drugs (DUID) cases which were found to be positive in whole blood for cannabis in Finland from 2006 to 2008. Factors studied were the number of cases positive for any combination of Delta(9)-tetrahydrocannabinol (THC) and the metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH). Concurrent use of amphetamines, benzodiazepines and/or alcohol was also recorded, as well as the drivers' age and gender. Altogether 2957 cannabis positive cases were retrieved from the database of the Alcohol and Drug Analytics Unit, National Institute for Health and Welfare. Drug findings were examined in relation to the zero-tolerance policy operated towards DUID in Finland. The number of cannabis positive cases in each year was approximately 1000 and the main demographic of cases was males aged 20-30 years. In the majority of cases (51.6%) the inactive metabolite THC-COOH was the only indication of cannabis use, however, associated use of amphetamines (58.8% of all cases) and/or benzodiazepines (63.9%) in cannabis positive drivers was very common. Detections for amphetamines and/or benzodiazepines were especially common in drivers with THC-COOH only (92.8% of these cases). Combined use of alcohol (25.7%) was also prevalent. Suspect DUID cases generally arise from suspicion on behalf of the police and the zero-tolerance policy offers an expedient means to deal with the challenges presented in DUID, particularly in view of the high incidence of multiple drug use - the legislation is not unduly punitive when enforced in this manner.

Copyright 2012, Elsevier Science

Boeuf-Cazou O; Bongue B; Ansiau D; Marquie JC; Lapeyre-Mestre M. Impact of long-term benzodiazepine use on cognitive functioning in young adults: The VISAT cohort. European Journal of Clinical Pharmacology 67(10): 1045-1052, 2011. (43 refs.)

Results from a number of studies have suggested a relationship between cognitive alteration and benzodiazepine use in the elderly. The aim of this study was to determine the impact of benzodiazepine use on cognitive functions in a young adult population. This study included 1,019 French salaried workers from the VISAT (Aging, Health and Work) cohort whose objective was to determine the long-term impact of working conditions on health and aging. Data were collected during interviews by occupational physicians in 1996, 2001 and 2006. Cognitive function was assessed using five cognitive tests (immediate free recall test, delayed free recall test, recognition test, Digit Symbol Substitution Subtest and visual search speed test). Cognitive scores obtained after a 10-year follow-up were investigated among three categories of benzodiazepine users, namely, non-users, occasional users and long-term users, using analysis of covariance models adjusted for several potential confounders in men and women separately. In the course of the 10 year-follow-up, 3.9% of subjects were defined as occasional users of benzodiazepine and 7.5% as long-term users. The analysis revealed a significant alteration of long-term memory in women whereas there was no significant association in men. Long-term use of benzodiazepine leads to specific impairment in long-term memory only in women.

Copyright 2011, Springer Heidelberg

Brady K. Withdrawal or dependence: A matter of context. (editorial). Addiction 107(5): 910-911, 2012. (1 refs.)

Bramness JG; Skurtveit S; Morland J; Engeland A. An increased risk of motor vehicle accidents after prescription of methadone. Addiction 107(5): 967-972, 2012. (50 refs.)

Aims: To investigate whether exposure to methadone affects the risk of motor vehicle accident with personal injury. Design: Cohort study linking three Norwegian administrative registries using unique person identifiers. Setting: Information was retrieved from the Norwegian Prescription Database on any prescriptions ever received by the individuals for methadone and all prescriptions for benzodiazepines. The Norwegian Road Accident Registry provided information about motor vehicle accidents involving personal injuries on Norwegian roads. The Central Population Registry provided demographic information on all residents in Norway. Participants: All Norwegian adults aged 18-69 years were observed for 2.5 years. Measurements Standardized incidence ratio (SIR) was calculated by comparing the incidence of traffic accidents with personal injuries in patients exposed to methadone with the incidence in those not exposed. Findings: During the 4626 person-years observed in patients exposed to methadone, there were 26 motor vehicle accidents. There were very few accidents among the females who received methadone and they had no increased risk of being involved in motor vehicle accidents (SIR 1.1; 95% CI 0.2-3.1). We observed an increased risk of involvement in accidents among males (SIR 2.4; 95% CI 1.5-3.6). This figure did not change significantly when exposure to benzodiazepines was excluded. Conclusions: Men exposed to methadone appear to have an increased risk of being involved in motor vehicle accidents involving personal injuries. This increased risk could not be explained by exposure of benzodiazepines.

Copyright 2012, Wiley-Blackwell

Capehart BP. Benzodiazepines, posttraumatic stress disorder, and veterans: Good news and why we're not done yet. (editorial). Journal of Clinical Psychiatry 73(3): 307-309, 2012. (15 refs.)

Carpenter CR. Review: Insufficient evidence exists about which drugs are associated with delirium; benzodiazepines may increase risk. (editorial). Annals of Internal Medicine 154(12): e-article JC6-10, 2011. (5 refs.)

Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. The DAWN Report: ED Visits Involving the Muscle Relaxant Carisoprodol. (October 27, 2011). Rockville MD: Substance Abuse and Mental Health Administration, 2011. (5 refs.)

This issue of The DAWN Report focuses on carisoprodol-related ED visits involving misuse or abuse in 2009 and trends between 2004 and 2009.The number of carisoprodol-related ED visits involving misuse or abuse doubled from 15,830 visits in 2004 to 31,763 visits in 2009. The number of carisoprodol-related ED visits involving misuse or abuse by patients aged 50 or older tripled between 2004 and 2009 (from 2,070 to 7,115 visits). The majority of ED visits involving carisoprodol also involved other pharmaceuticals (77 percent); the most common combinations involved narcotic pain relievers (55 percent) and benzodiazepines (47 percent). Of all the carisoprodol visits classified as misuse or abuse, one third (35 percent) of the visits required hospitalization. Carisoprodol (i.e., Soma(r), Soprodal(r), Vanadom(r)) is a pharmaceutical typically prescribed to relieve symptoms of muscle pain or discomfort, but it can cause drowsiness and sedation in excess doses Carisoprodol is converted by the liver to meprobamate, a drug used to treat anxiety, that can result in physical and psychological dependence when used in excess. This conversion may account for some of the effects of carisoprodol and likely contributes to its potential for abuse. When carisoprodol is combined with drugs such as narcotic pain relievers, benzodiazepines (used to treat anxiety and insomnia), or alcohol, its sedation effects can be dangerously enhanced. Some users have combined carisoprodol with certain narcotic pain relievers and benzodiazepines to create an effect similar to that of heroin. The Food and Drug Administration (FDA) recommends using carisoprodol no longer than 2 to 3 weeks to avoid the risk for dependence, withdrawal, and abuse.

Public Domain

Chan YC; Tse ML; Lau FL. Hong Kong Poison Information Centre: Annual Report 2009. Hong Kong Journal of Emergency Medicine 18(4): 221-231, 2011. (9 refs.)

Objective: To report and analyse the poisoning data of Hong Kong Poison Information Centre (HKPIC) in 2009. Methods: In 2009, all poisoning cases received by HKPIC were retrieved from its database (PICMS) for analysis. Results: Totally 4338 poisoned cases were analysed. There were 1955 male patients (45.1%), 2,367 female patients (54.6%) and 16 patients with no gender specified. More than two-third of cases (68.6%) were between 20 and 59 years old. Common causes of exposure were suspected self harm/suicidal attempt, abusive use and unintentional exposure. Paracetamol, ketamine, zopiclone, benzodiazepine and household products were the common poisons exposed. Majority of the patients were managed supportively, with 13.6% and 13.1% treated by decontamination and antidotes respectively. Most cases had uneventful recovery; about 1% of the poison exposure resulted in death and about 5% of the exposure had major outcomes. Conclusions: The 2009 annual report provides updated epidemiological information on poisoning pattern in Hong Kong and emphasized some changes in comparing with our previous reports.

Copyright 2011, Medcom Ltd

Chavant F; Favreliere S; Lafay-Chebassier C; Plazanet C; Perault-Pochat MC. Memory disorders associated with consumption of drugs: Updating through a case/noncase study in the French PharmacoVigilance Database. British Journal of Clinical Pharmacology 72(6): 898-904, 2011. (53 refs.)

AIMS: To investigate putative associations of reports of memory disorders and suspected drugs. METHODS We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were reports of memory loss in the FPVD between January 2000 and December 2009. Noncases were all other reports during the same period. To assess the association between memory impairment and drug intake, we calculated an odds ratio with its 95% confidence interval. RESULTS: Among the 188,284 adverse drug reactions recorded, we identified 519 cases of memory loss. The sex ratio was 0.6 and the median age was 54 years (range 4-93). The maximal number of cases occurred between 40-49 and 50-59 years. Evolution was favourable in 63% of the cases. We found significant odds ratios for benzodiazepines (alprazolam, bromazepam, prazepam, clonazepam etc.), benzodiazepine-like hypnotics (zolpidem and zopiclone), antidepressants (fluoxetine, paroxetine and venlafaxine), analgesics (morphine, nefopam and tramadol), anticonvulsants (topiramate, pregabalin, levetiracetam etc.), antipsychotics (aripiprazole and lithium) and other drugs, such as trihexyphenidyl, ciclosporin and isotretinoin. CONCLUSIONS: Our study confirmed an association between memory disorders and some drugs, such as benzodiazepines and anticonvulsants. However, other drugs, such as benzodiazepine-like hypnotics, newer anticonvulsants, serotonin reuptake inhibitor antidepressants, isotretinoin and ciclosporin were significantly associated with memory disorders, although this was not described or poorly described in the literature. Taking account of the limits of this study in the FPVD (under-reporting, notoriety bias etc.), the case/noncase method allows assessment and detection of associations between exposure to drugs and a specific adverse drug reaction, such as memory disorders, and could thus generate signals and orientate us to further prospective studies to confirm such associations.

Copyright 2011, Wiley-Blackwell

Chen KW; Berger CC; Forde DP; D'Adamo C; Weintraub E; Gandhi D. Benzodiazepine use and misuse among patients in a methadone program. BMC Psychiatry 11(e-article 90), 2011. (27 refs.)

Background: Benzodiazepines (BZD) misuse is a serious public health problem, especially among opiate-dependent patients with anxiety enrolled in methadone program because it puts patients at higher risk of life-threatening multiple drug overdoses. Both elevated anxiety and BZD misuse increase the risk for ex-addicts to relapse. However, there is no recent study to assess how serious the problem is and what factors are associated with BZD misuse. This study estimates the prevalence of BZD misuse in a methadone program, and provides information on the characteristics of BZD users compared to non-users. Methods: An anonymous survey was carried out at a methadone program in Baltimore, MD, and all patients were invited to participate through group meetings and fliers around the clinic on a voluntary basis. Of the 205 returned questionnaires, 194 were complete and entered into final data analysis. Those who completed the questionnaire were offered a $5 gift card as an appreciation. Results: 47% of the respondents had a history of BZD use, and 39.8% used BZD without a prescription. Half of the BZD users (54%) started using BZD after entering the methadone program, and 61% of previous BZD users reported increased or resumed use after entering methadone program. Compared to the non-users, BZD users were more likely to be White, have prescribed medication for mental problems, have preexistent anxiety problems before opiate use, and had anxiety problems before entering methadone program. They reported more mental health problems in the past month, and had higher scores in anxiety state, depression and perceived stress (p < .05). Conclusions: Important information on epidemiology of BZD misuse among methadone-maintenance patients suggests that most methadone programs do not address co-occurring anxiety problems, and methadone treatment may trigger onset or worsening of BZD misuse. Further study is needed to explore how to curb misuse and abuse of BZD in the addiction population, and provide effective treatments targeting simultaneously addiction symptoms, anxiety disorders and BZD misuse.

Copyright 2011, BioMed Central

Chien CC; Huanga HT; Lung FW; Lin CH. Zolpidem withdrawal delirium, seizure, and acute psychosis: Case reports and literature review. (review). Journal of Substance Use 16(4): 330-338, 2011. (39 refs.)

Zolpidem, a non-benzodiazepine hypnotic drug, shows a high affinity for the BZ1 (omega 1) subtypes of the modulatory sites within the GABAA receptor complex, but classical benzodiazepines (diazepam, lorazepam) have a non-specific affinity profile at omega 1 and omega 2 subtypes of the GABAA receptor. Therefore, zolpidem is thought to be safer than benzodiazepines. We present five cases with withdrawal delirium, seizure, acute psychosis and orofacial dyskinesia that developed following cessation of zolpidem. Adverse effects such as withdrawal seizure and withdrawal delirium have been rarely reported in relation to zolpidem. Chemically unrelated to benzodiazepines, zolpidem is thought to have fewer adverse effects, but shares a pharmacokinetic profile with the benzodiazepines. It is advised that the normal criteria for the prescription of benzodiazepines also be used when prescribing non-benzodiazepine sedatives and hypnotics, as they act upon the same receptor, namely, the benzodiazepine-GABA-chloride complex. However, at higher than recommended doses for extended periods of time, the addictive potential of zolpidem may be similar to that of the benzodiazepines. It is possible that zolpidem abandons its selectivity for the BZ1 receptors and demonstrates all the actions of classic benzodiazepines.

Copyright 2011, Informa Healthcare

Cox S; Kuo C; Jamieson DJ; Kourtis AP; McPheeters ML; Meikle SF et al. Poisoning hospitalisations among reproductive-aged women in the USA, 1998-2006. Injury Prevention 17(5): 332-337, 2011. (36 refs.)

Objective: To describe poisoning hospitalisations among reproductive-aged women from 1998 to 2006. Methods 1998-2006 data from the Nationwide Inpatient Sample of the Healthcare Cost and Utilisation Project were used to identify hospitalisations for poisonings among US women aged 15-44 years. Differences in hospitalisation characteristics were compared by intent using chi(2) statistics. Trends in poisoning hospitalisation rates were calculated overall and by subgroup. Results: There were approximately 636,000 poisoning hospitalisations in women aged 15-44 years during 1998-2006. Hospitalisations for intentionally self-inflicted poisonings had a higher proportion of women aged 15-24 years and privately insured women than did unintentional poisonings (p<0.001). Poisoning hospitalisations in rural areas and those that resulted in death were more likely to be of undetermined intent than those for which intent was specified (p<0.001). Co-diagnoses of substance abuse (34.5%) or mental disorders (66.5%) were high. The rate of poisoning hospitalisations overall and unintentional poisoning hospitalisations increased 6% and 22%, respectively, during this period (p<0.001). The most frequently diagnosed poisoning agent was acetaminophen. Poisonings attributable to acetaminophen, opioids, central nervous system stimulants and benzodiazepines increased, while poisonings attributable to antidepressants decreased (p<0.05). Conclusions: The increase in unintentional poisoning hospitalisations among women aged 15-44 years and the changing profile of poisoning agents should inform the healthcare community's poisoning prevention strategies. Poisoning prevention strategies should include a component to address substance abuse and mental health disorders among reproductive-age women.

Copyright 2011, B M J Publishing

Culberson JW; Ticker RL; Burnett J; Marcus MT; Pickens SL; Dyer CB. Prescription medication use among self neglecting elderly. Journal of Addictions Nursing 22(1-2): 63-68, 2011. (22 refs.)

The elderly use approximately one-third of the prescription medication in the United States, often for problems such as chronic pain, insomnia, and anxiety. This study will describe the use of prescription medication, specifically drugs of abuse such as benzodiazepines and opioid analgesics, in a sample of community dwelling elderly referred to Texas Adult Protective Services for self-neglect. We hypothesize that self-neglecting behavior may result in increased use of prescription drugs with known abuse potential. Self-neglecting elders (n = 100) were matched with community controls and interviewed by geriatric nurse-practitioners in their homes. Benzodiazepine use among self neglecting elderly was four-fold that of matched controls, (OR = 4.2, 95%% CI = 0.9-20.4), and the use of opioid analgesics slightly higher among self-neglecting elders, (OR = 1.1, 95%% CI = 0.5-2.4). Self-neglecters were significantly less likely to be taking non-opioid pain medications such as acetaminophen (p < .011) and gabapentin (p < .02). Self-neglecting elders using benzodiazepines were less likely to be female (OR =.81, 95%% CI, 0.2-3.6), live alone (OR =.94, 95%% CI, 0.2-4.0), report pain (OR =0.2, 95%% CI, 0.1-2.0), or depression (OR =.66, 95%% CI, 0.1-3.2). Those using opioid analgesics were less likely to be female, (OR =0.6, 95%% CI, 0.2-1.9), however, more likely to live alone (OR =1.7, 95%% CI, 0.6-1.9), report pain (OR =1.5, 95%% CI, 0.5-4.5), or depression (OR =3.2, 95%% CI, 1.1-4.9). Self-neglecting elders demonstrate a unique pattern of prescription drug use. Further studies are required to determine if self-neglecting behavior in the elderly increases the prescription of benzodiazepine and opiate drugs.

Copyright 2011, Informa Healthcare

Dassanayake T; Michie P; Carter G; Jones A. Effects of benzodiazepines, antidepressants and opioids on driving: A systematic review and meta-analysis of epidemiological and experimental evidence. (review). Drug Safety 34(2): 125-156, 2011. (102 refs.)

Background: Many individuals in the community are prescribed psychoactive drugs with sedative effects. These drugs may affect their daily functions, of which automobile driving is a major component. Objective: To examine the association of three classes of commonly used psychoactive drugs (viz. benzodiazepines and newer non-benzodiazepine hypnotics, antidepressants and opioids) with (i) the risk of traffic accidents (as indexed by epidemiological indicators of risk); and (ii) driving performance (as indexed by experimental measures of driving performance). Methods: A literature search for material published in the English language between January 1966 and January 2010 in PubMed and EMBASE databases was combined with a search for other relevant material referenced in the retrieved articles. Retrieved articles were systematically reviewed, carrying out meta-analyses where possible. Twenty-one epidemiological studies (13 case-control and 8 cohort studies) fulfilled the inclusion criteria by estimating the accident risk associated with drug exposure (ascertained by blood/urine analysis or prescription records). Sixty-nine experimental studies fulfilled the inclusion criteria by testing actual or simulated driving performance after administering a single dose or multiple doses. Results: Two meta-analyses showed that benzodiazepines are associated with a 60% (for case-control studies: pooled odds ratio [OR] 1.59; 95% CI 1.10, 2.31) to 80% (for cohort studies: pooled incidence rate ratio 1.81; 95% CI 1.35, 2.43) increase in the risk of traffic accidents and a 40% (pooled OR 1.41; 95% CI 1.03, 1.94) increase in 'accident responsibility'. Co-ingestion of benzodiazepines and alcohol was associated with a 7.7-fold increase in the accident risk (pooled OR 7.69; 95% CI 4.33, 13.65). Subgroup analysis of case-control studies showed a lower benzodiazepine-associated accident risk in elderly (>65 years of age) drivers (pooled OR 1.13; 95% CI 0.97, 1.31) than in drivers <65 years of age (pooled OR 2.21; 95% CI 1.31, 3.73), a result consistent with age-stratified risk differences reported in cohort studies. Anxiolytics, taken in single or multiple doses during the daytime, impaired driving performance independent of their half-lives. With hypnotics, converging evidence from experimental and epidemiological studies indicates that diazepam, flurazepam, flunitrazepam, nitrazepam and the short half-life non-benzodiazepine hypnotic zopiclone significantly impair driving, at least during the first 2-4 weeks of treatment. The accident risk was higher in the elderly (>65 years of age) who use tricyclic antidepressants (TCAs); however, the evidence for an association of antidepressants with accident risk in younger drivers was equivocal. Sedative but not non-sedative antidepressants were found to cause short-term impairment of several measures of driving performance. Limited epidemiological research reported that opioids may be associated with increased accident risk in the first few weeks of treatment. Conclusions: Benzodiazepine use was associated with a significant increase in the risk of traffic accidents and responsibility of drivers for accidents. The association was more pronounced in the younger drivers. The accident risk was markedly increased by co-ingestion of alcohol. Driving impairment was generally related to plasma half-lives of hypnotics, but with notable exceptions. Anxiolytics, with daytime dosing, impaired driving independent of their half-lives. TCAs appeared to be associated with increased accident risk, at least in the elderly, and caused short-term impairment in driving performance. Opioid users may be at a higher risk of traffic accidents; however, experimental evidence is limited on their effects on driving.

Copyright 2011, Adis International

de Gier NAH; Gorgels WJMJ; Lucassen PLBJ; Voshaar RO; Mulder J; Zitman F. Discontinuation of long-term benzodiazepine use: 10-year follow-up. Family Practice 28(3): 253- 259, 2011. (20 refs.)

Background. Several interventions aiming at discontinuation of long-term benzodiazepine use have been proven effective in the short term. However, data on the persistence of discontinuation are lacking. Objectives. To assess 10-year follow-up status in patients who succeeded in stopping benzodiazepine use after a discontinuation letter from the patient's own GP. To identify determinants of successfull discontinuation on the long term. Methods. Follow-up data of patients who participated in a large prospective, controlled stepped care intervention programme among long-term benzodiazepine users in primary care. Results. At 10-year follow-up, the percentage of benzodiazepine abstinence was 58.8%. Non-abstinent patients used lower doses of benzodiazepine. Being abstinent at 21 months after the intervention predicted abstinence at 10-year follow-up. Conclusions. Ten years after a minimal intervention to decrease long-term benzodiazepine use, the majority of patients who were able to discontinue benzodiazepine use initially, does not use benzodiazepines at 10-year follow-up. Patients who did not succeed in maintaining abstinence from benzodiazepines appear to use lower or average dosages.

Copyright 2011, Oxford University Press

de los Cobos JP; Sinol N; Trujols J; Banuls E; Batlle F; Tejero A. Drug-dependent inpatients reporting continuous absence of spontaneous drug craving for the main substance throughout detoxification treatment. Drug and Alcohol Review 30(4): 403-410, 2011. (43 refs.)

Introduction and Aims. Drug craving is considered to be an essential component of substance dependence. We aimed to characterise drug-dependent inpatients reporting continuous absence of subjective spontaneous drug craving. Design and Methods. This is a 3 year chart-review study designed to compare drug-dependent inpatients who did not report craving everyday (non-cravers) and their counterparts who did (cravers). All participants were recruited consecutively and completed a 14 day detoxification treatment. Craving was defined as a desire to use the main detoxification substance. This substance was chosen by patients, who completed a craving visual analogue scale, the Beck Depression Inventory and the State-Trait Anxiety Inventory daily. The Temperament and Character Inventory and the Addiction Severity Index were also used. Results. Of the 195 patients who completed the detoxification treatment, 45 (23.1%) were non-cravers and 32 (16.4%) were cravers. The main detoxification substances were alcohol, benzodiazepines, cannabis, cocaine, heroin and methadone. Non-cravers named methadone as the main detoxification substance more frequently than cravers, and benzoylecgonine was less frequently present in their urine at treatment entry. A decreased score on the Temperament and Character Inventory dimension of harm avoidance (i.e. trait anxiety) was the only independent predictor of absence of craving (odds ratio = 1.16, 95% confidence interval = 1.03-1.31). During admission, non-cravers had lower Beck Depression Inventory and State-Trait Anxiety Inventory scores than cravers. These differences were not accounted for by pharmacological treatment. Discussion and Conclusions. Drug-dependent inpatients who report absence of craving are characterised by relatively low levels of depression and anxiety throughout detoxification treatment, and relatively low levels of trait anxiety.

Copyright 2011, Wiley-Blackwell

Deckersbach T; Moshier SJ; Tuschen-Caffier B; Otto MW. Memory dysfunction in panic disorder: An investigation of the role of chronic benzodiazepine use. Depression and Anxiety 28(11): 999-1007, 2011. (67 refs.)

Background: Studies of the neurocognitive effects of long-term benzodiazepine use have been confounded by the presence of neurocognitive deficits characterizing the clinical conditions for which these medications are taken. Similarly, studies of the neurocognitive effects of anxiety disorders have been confounded by the inclusion of chronically benzodiazepine-medicated patients. This study was designed to tease apart the potentially confounding effects of long-term benzodiazepine use and panic disorder (PD) on memory and visuoconstructive abilities. Methods: Twenty chronically benzodiazepine-medicated and 20 benzodiazepine-free patients with PD with agoraphobia were compared with a group of 20 normal control participants, group-matched for age, education, and gender on a battery of neuropsychological tests assessing short-term, episodic long-term, and semantic memory, as well as visuoconstructive abilities. Results: Results indicated that benzodiazepine-free panic patients were relatively impaired in nonverbal short-term and nonverbal episodic long-term memory and visuoconstructive abilities, whereas verbal short-term and verbal episodic memory and semantic memory were preserved. Only limited evidence was found for more pronounced impairments in chronically benzodiazepine-medicated PD patients. Conclusions: This study provides evidence that patients with PD are characterized by relative impairments in nonverbal memory and visuoconstructive abilities, independent of benzodiazepine use. Nonetheless, we found evidence that chronic treatment with benzodiazepines is associated with intensification of select relative impairments in this realm. Documentation of these deficits raises questions about the broader etiology of neurocognitive impairment in PD as well as its impact on daily functioning.

Copyright 2011, Wiley-Blackwell

Dermengiu D; Radu D; Aciu F; Broscauceanu A; Sereteanu L; Gorun G et al. Drugs of abuse identified in the National Institute of Legal Medicine Mina Minovici Bucharest 2010. Romanian Journal of Legal Medicine 19(3): 229-232, 2011. (10 refs.)

In the last few years in Romania a modern system of drug detection has been developed in the legal medicine system, increasing the detection rate and the sensitivity of DRD detection. In this short report we will present a general profile of drug abuse in Bucharest in 2010. The study was conducted in 2010 when a total number of 208 toxicology tests were conducted in the National Institute of Legal Medicine, 105 on cadavers and 103 on living persons. As main results, in living the most frequently identified drugs of abuse were THC and opiates whilst in cadavers opiates were the most frequent, followed by benzodiazepines. Conclusions. Opiate consumption has a tendency to decrease compared with 2009. Legal highs seems to shift the pattern of drug consumption in Bucharest and surrounding areas, but a definite results can only be obtained using test results from 2011.

Copyright 2011, Romanian Legal Medicine Society

Drummer OH; Kourtis I; Beyer J; Tayler P; Boorman M; Gerostamoulos D. The prevalence of drugs in injured drivers. Forensic Science International 215(1-3): 14-17, 2012. (24 refs.)

In mid 2009 Victoria introduced compulsory drug testing of blood taken from all injured drivers taken to hospital. Delta(9)-Tetrahydrocannabinol (THC), methylamphetamine (MA) and 3, 4-methylenedioxy-methylamphetamine (MDMA) are prohibited and if drivers are positive to any amount an automatic penalty is enforced. Laboratory screens were conducted on preserved blood using ELISA testing for cannabis metabolite and methylamphetamines and a fully validated LC-MS/MS method for 105 drugs including THC, amphetamines, opioids, benzodiazepines, antidepressants and antipsychotics and a number of other psychoactive substances using a minimum of two transitions per drug. Conventional GC-testing for ethanol was used to screen and quantify the presence of alcohol. 1714 drivers were tested and showed alcohol in 29% (>= 0.01 g/100 mL) and drugs in 35%. The positive rate for the three drugs prohibited by legislation was 12.5%. The prevalence of THC, MA and MDMA was 9.8%, 3.1%, and 0.8%, respectively. The range of THC concentrations in blood was 2-42 ng/mL (median 7) of which 70% had a concentration of 10 ng/mL or higher. The range of concentrations for MA and MDMA was 0.02-0.4 and 0.03-0.3 mg/L (median for both drugs was 0.05 mg/L). Drugs of any type were detected in 35% of cases. The other drugs were largely prescribed drugs such as the antidepressants (9.3%) and benzodiazepines (8.9%). Neither 6-acetylmorphine nor cocaine (or benzoylecgonine) was detected in these cases.

Copyright 2012, Elsevier Science

Finn KM; Greenwald J. Hospitalists and alcohol withdrawal: Yes, give benzodiazepines but is that the whole story? (editorial). Journal of Hospital Medicine 6(8): 435-437, 2011. (32 refs.)

Flaherty AW. Brain illness and creativity: Mechanisms and treatment risks. (review). Canadian Journal of Psychiatry 56(3): 132-143, 2011. (99 refs.)

Brain diseases and their treatment may help or hurt creativity in ways that shape quality of life. Increased creative drive is associated with bipolar disorder, depression, psychosis, temporal lobe epilepsy, frontotemporal dementia, Parkinson disease treatments, and autism. Creativity depends on goal-driven approach motivation from midbrain dopaminergic systems. Fear-driven avoidance motivation is of less aid to creativity. When serotonin and norepinephrine lower motivation and flexible behaviour, they can inhibit creativity. Hemispheric lateralization and frontotemporal connections must interact to create new ideas and conceptual schemes. The right brain and temporal lobe contribute skill in novelty detection, while the left brain and frontal lobe foster approach motivation and more easily generate new patterns of action from the novel perceptions. Genes and phenotypes that increase plasticity and creativity in tolerant environments with relaxed selection pressure may confer risk in rigorous environments. Few papers substantively address this important but fraught topic. Antidepressants (ADs) that inhibit fear-driven motivation, such as selective serotonin reuptake inhibitors, sometimes inhibit goal-oriented motivation as well. ADs that boost goal-directed motivation, such as bupropion, may remediate this effect. Benzodiazepines and alcohol may be counterproductive. Although dopaminergic agonists sometimes stimulate creativity, their doing so may inappropriately disinhibit behaviour. Dopamine antagonists may suppress creative motivation; lithium and anticonvulsant mood stabilizers may do so less. Physical exercise and REM sleep may help creativity. Art therapy and psychotherapy are not well studied. Preserving creative motivation can help creativity and other aspects of well-being in all patients, not just artists or researchers.

Copyright 2011, Canadian Psychiatric Association

Forsyth AJM; Khan F; Mckinlay B. Diazepam, alcohol use and violence among male young offenders: 'The devil's mixture'. Drugs: Education, Prevention and Policy 18(6, special issue): 468-476, 2011. (41 refs.)

Background: Diazepam is a benzodiazepine which has a history of usage among problem drug using groups. It has also been linked to aggression in laboratory settings. This article will examine illicit diazepam use and violence amongst predominantly alcohol-orientated offenders. Methods: A self-complete survey of male Young Offenders (n = 172) recruited during their induction into Scotland's only Young Offender's Institution was carried out during 2007. Qualitative interviews (n = 30) were conducted during 2008 on another sample recruited in the same way. Results: Survey respondents tended to report alcohol, rather than illegal drugs as being related to their offending behaviour. The exception to this pattern was diazepam, which when used in conjunction with alcohol was associated with violence, including weapon use. The 2008 interviews confirmed this and raised further concerns about the way in which diazepam was being mixed with alcohol, in relation to its mode of action, source of supply, dosage and users' beliefs. Conclusion: Although it receives little dedicated research, education or media attention, diazepam was a factor in more (violent) crime among this population than any/all other illegal drugs.

Copyright 2011, Taylor & Francis

Frauger E; Pauly V; Pradel V; Rouby F; Arditti J; Thirion X et al. Evidence of clonazepam abuse liability: Results of the tools developed by the French Centers for Evaluation and Information on Pharmacodependence (CEIP) network. Fundamental & Clinical Pharmacology 25(5): 633-641, 2011. (58 refs.)

Recent observations suggest the existence of clonazepam abuse. To determine its importance in France, a quantitative and systematic synthesis of all clonazepam data of several epidemiological tools of the Centers for Evaluation and Information on Pharmacodependence (CEIP) network has been performed in comparison with data on others benzodiazepines (BZD). Data on clonazepam and other BZD have been analysed from different epidemiological tools: OSIAP survey that identifies drugs obtained by means of falsified prescriptions, Observation of Illegal Drugs and Misuse of Psychotropic Medications (OPPIDUM) survey that describes modalities of use and data from regional French health reimbursement system. In OSIAP survey, the proportion of clonazepam falsified prescriptions among all BZD falsified prescriptions increased. During the 2006 OPPIDUM survey, the analysis of the BZD modalities of use highlights clonazepam abuse liability (for example 23% of illegal acquisition), in second rank after flunitrazepam. Studies based on data from the French health reimbursed system show that 1.5% of subjects with clonazepam dispensing had a deviant behaviour. Among BZD, clonazepam has the second most important doctor-shopping indicator (3%) after flunitrazepam. All these data provide some arguments in favour of clonazepam abuse liability in real life and the necessity to reinforce its monitoring.

Copyright 2011, Wiley-Blackwell

Fulton HG; Barrett SP; MacIsaac C; Stewart SH. The relationship between self-reported substance use and psychiatric symptoms in low-threshold methadone maintenance treatment clients. Harm Reduction Journal 8: article 18, 2011. (46 refs.)

Background: Ongoing psychiatric symptoms and substance use are common difficulties experienced by clients enrolled in methadone maintenance treatment (MMT). However, little research to date has evaluated if specific types of current substance use are related to specific types of current psychiatric symptoms. The present study investigated these relationships with a sample of clients enrolled in a low-threshold MMT program (i.e., clients are not expelled if they continue to use substances). Some clients enrolled in low-threshold programs may never achieve complete abstinence from all substances. Thus, understanding the possibly perpetuating relationships between concurrent substance use and psychiatric symptoms is important. Understanding such relationships may aid in developing possible target areas of treatment to reduce substance use and/or related harms in this population. Methods: Seventy-seven individuals were interviewed regarding methadone usage and current and past substance use. Current psychiatric symptoms were assessed using a modified version of the Psychiatric Diagnostic Screening Questionnaire (PDSQ). Relationships between types of substances used in the past 30 days and the types and number of psychiatric symptoms experienced in the same timeframe were examined. Results: The majority of participants (87.0%) reported using alcohol, illicit substances, non-prescribed prescription opioids, or non-prescribed benzodiazepines in the past 30 days and 77.9% of participants reported currently experiencing psychiatric symptoms at levels that would likely warrant diagnosis. Current non-prescribed benzodiazepine use was a predictor for increased severity (i.e., symptom count) of almost all anxiety and mood disorders assessed. Conversely, number and presence of generalized anxiety symptoms and presence of social phobia symptoms predicted current non-prescribed benzodiazepine and alcohol use, respectively. Conclusions: Individuals enrolled in the present low-threshold MMT program experience a wide variety of psychiatric symptoms and continue to use a variety of substances, including opioids. There was a particularly consistent pattern of associations between non-prescribed benzodiazepine use and a variety of psychiatric symptoms (particularly anxiety) suggesting that addressing concurrent illicit benzodiazepine use and anxiety symptoms in MMT clients warrants further clinical attention and research.

Copyright 2011, BioMed Central

Geoffroy PA; Rolland B; Cottencin O. Catatonia and alcohol withdrawal: A complex and underestimated syndrome. Alcohol and Alcoholism 47(3): 288-290, 2012. (17 refs.)

Aims: Catatonia is a neuropsychiatric syndrome characterized by alterations in motor behavior, vigilance, thought and mood. Catatonia syndrome occurs in many neuropsychiatric and medical conditions, but it is very rarely mentioned as occurring during alcohol withdrawal. We think that this co-occurrence could be underestimated in clinics because alcohol withdrawal symptoms may distract from its identification. Methods: We report the case of a patient presenting with catatonia during the benzodiazepine reduction period of alcohol detoxification. Results: A 65-year-old woman presented with a 15-year history of alcohol dependence and developed catatonic episodes several times during alcohol withdrawal treatment. Misdiagnosis delayed specific treatment. Symptoms of episodes dramatically improved 48 h after treatment with diazepam and revealed an anxiety disorder. Conclusion: This report confirms that catatonia is a non-specific response to psychological, physical and psychosocial stress factors. Recent alcohol withdrawal may sensitize the patient to benzodiazepine withdrawal catatonia, and this phenomenon is probably underestimated. Catatonia Rating Scales can be useful when diagnosis is complicated as in alcohol and benzodiazepine withdrawal. In that situation, misdiagnosis is common and may delay specific treatment.

Copyright 2012, Oxford University Press

Gisev N; Hartikainen S; Chen TF; Korhonen M; Bell JS. Mortality associated with benzodiazepines and benzodiazepine-related drugs among community-dwelling older people in Finland: A population-based retrospective cohort study. Canadian Journal of Psychiatry 56(6): 377-381, 2011. (19 refs.)

Objective: To investigate the association between the use of benzodiazepines (BDZs) and BDZ-related drugs and mortality among community-dwelling people aged 65 years and older in Finland. Method: This was a population-based retrospective cohort study. Records of all reimbursed drugs purchased by all 2224 residents of Leppavirta, Finland, aged 65 years and older in 2000 were extracted from the Finnish National Prescription Register. Diagnostic data were extracted from the Special Reimbursement Register. All-cause mortality was assessed after 9 years using national registers. Cox proportional hazards models were used to compute unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals for mortality among prevalent users of BDZs and BDZ-related drugs in 2000 (n = 325), compared with nonusers of BDZs and BDZ-related drugs between 2000 and 2008 (n = 1520). Results: BDZs and BDZ-related drugs were used by 325 out of the 2224 residents (14.6%) in 2000. The 9-year mortality was 50.2% among BDZ and BDZ-related drug users in 2000 and 36.3% among BDZ and BDZ-related drug nonusers between 2000 and 2008 (HR 1.53; 95% Cl 1.28 to 1.82). After adjusting for baseline age, sex, antipsychotic drug use, and diagnostic confounders, the HR was 1.01 (95% Cl 0.84 to 1.21). Conclusions: Use of BDZs and BDZ-related drugs was associated with an increased mortality hazard in unadjusted analyses. However, after adjusting for age, sex, antipsychotic drug use, and diagnostic confounders, the use of BDZs and BDZ-related drugs was not associated with excess mortality.

Copyright 2011, Canadian Psychiatric Association

Goel N; Beasley D; Rajkumar V; Banerjee S. Perinatal outcome of illicit substance use in pregnancy: Comparative and contemporary socio-clinical profile in the UK. European Journal of Pediatrics 170(2): 199-205, 2011. (23 refs.)

The aim of the study was to determine the contemporary socio-clinical profile and perinatal outcome of illicit substance use in pregnancy in a large UK city and compare with published literature. Cases were identified retrospectively from the 'cause for concern' referrals over 5 years (2003-2007). Data was collected on mother-infant pair from medical notes and laboratory records. Chi-square and Mann-Whitney U tests were used where appropriate for statistical analysis. One hundred sixty-eight women were identified as using illicit substance in pregnancy. Smoking (97.4%), unemployment (85.4%) and single status (42.3%) were frequent. Besides controlled use of methadone, heroin, cannabis and benzodiazepines were the most commonly used drugs. Hepatitis C prevalence was high (29.9%) despite low antenatal screening rates (57.7%). Neonatal morbidity was related to prematurity (22.9%), small for dates (28.6%) and neonatal abstinence syndrome (NAS; 58.9%). By day 5 of life, 95.1% of the babies developing NAS and 96.1% of those requiring pharmacological treatment were symptomatic. Of the infants developing NAS, 31.7% required pharmacological treatment. A total of 82.5% babies went home with their mother, and 21.2% were placed on the Child Protection Register. Only 14.3% were breast feeding at discharge. Illicit substance use in pregnancy continues to be associated with significant maternal and neonatal morbidity, and the socio-clinical profile in this decade appears unchanged in the UK. Hepatitis C prevalence is high, and detection should be improved through targeted antenatal screening. Where facility in the community is unavailable, 5 days of hospital stay is sufficient to safely identify babies at risk of developing NAS. Most babies were discharged home with their mother.

Copyright 2011, Springer

Handal M; Engeland A; Ronning M; Skurtveit S; Furu K. Use of prescribed opioid analgesics and co-medication with benzodiazepines in women before, during, and after pregnancy: A population-based cohort study. European Jurnal of Clinical Pharmacology 67(9): 953-960, 2011. (37 refs.)

The aim of the study was to describe the use of prescribed opioid analgesics for noncancer pain and the degree of possible concurrent co-medication with benzodiazepines to women in Norway before, during, and after pregnancy. This was a population-based cohort study based on linkage of two nationwide registries: the Medical Birth Registry of Norway, and the Norwegian Prescription Database. Prescribed opioid analgesics and benzodiazepines issued to women 3 months prior to, during, and 3 months after pregnancies were identified. The study population consisted of 194,937 singleton pregnancies beginning in March 2004 or later and ending before January 2009. About 6% of the women were dispensed opioid analgesics before, during, or after pregnancy. Almost all these women received weak opioids (99%) with short-acting codeine in combination with paracetamol (acetaminophen) as the most frequently dispensed drug. The dispensing of codeine was reduced from 24/1,000 women before pregnancy to 10/1,000 in the last trimester, increasing to 17/1,000 during the breastfeeding period. Most women were dispensed codeine once, and treatment was of short duration (about 1 week). A small group of women (n = 271) were dispensed opioids in all trimesters. Increasing benzodiazepine use was observed as the number of opioid prescriptions increased. The use of opioid analgesics in pregnant women in Norway was dominated by treatment of short duration of the weak opioid codeine. As pregnancy proceeded, opioid use was reduced. However, the increase in opioid use during the nursing period has the potential for serious adverse effects.

Copyright 2011, Springer

Heather N; Paton J; Ashton H. Predictors of response to brief intervention in general practice against long-term benzodiazepine use. Addiction Research & Theory 19(6): 519-527, 2011. (41 refs.)

Aims: To predict the response of mostly elderly patients to brief intervention against long-term benzodiazepine (BZD) use delivered in general medical practice from variables measured at baseline in a randomised controlled trial. Method: Logistic regression was used to identify predictors of a complete cessation of BZD intake or a 'clinically significant reduction' by a half or more from baseline to 6 months follow-up among 183 patients who received a brief intervention. Candidate predictor variables were: (i) stage of change (ii) level of BZD dependence (iii) whether BZDs were prescribed by the patient's usual general practitioner (GP) or by another medical practitioner; (iv) baseline BZD dosage; (v) type of BZD and (vi) gender. Results: Both cessation and reduction were predicted by who prescribed BZDs, with patients whose medication was prescribed by their usual GP more likely to show a positive response to brief intervention than those whose medication was prescribed by another medical practitioner. Stage of change was a significant predictor of a reduction in BZD use, with patients in the Contemplation stage nearly three times more likely, and those in the Action stage over eight times more likely, to achieve a clinically significant reduction than those in the Precontemplation stage. Conclusions: Patients receiving prescriptions from their usual GP are more likely to cease or reduce BZD intake than those receiving prescriptions from another medical practitioner. In managing patients with long-term use of BZDs, general medical practitioners should consider recording the patient's stage of change and tailoring their intervention on that basis.

Copyright 2011, Informa Healthcare

Hendey GW; Dery RA; Barnes RL; Snowden B; Mentler P. A prospective, randomized, trial of phenobarbital versus benzodiazepines for acute alcohol withdrawal. American Journal of Emergency Medicine 29(4): 382- 385, 2011. (9 refs.)

Objective: The aim of this study was to compare phenobarbital (PB) versus lorazepam (LZ) in the treatment of alcohol withdrawal in the emergency department (ED) and at 48 hours. Methods: Prospectively, randomized, consenting patients were assessed using a modified Clinical Institute Withdrawal Assessment (CIWA) score and given intravenous PB (mean, 509 mg) or LZ (mean, 4.2 mg). At discharge, LZ patients received chlordiazepoxide (Librium), and PB patients received placebo. Results: Of 44 patients, 25 received PB, and 19 LZ. Both PB and LZ reduced CIWA scores from baseline to discharge (15.0-5.4 and 16.8-4.2, P < .0001). There were no differences between PB and LZ in baseline CIWA scores (P = .3), discharge scores (P = .4), ED length of stay (267 versus 256 minutes, P = .8), admissions (12% versus 16%, P = .8), or 48-hour follow-up CIWA scores (5.8 versus 7.2, P = .6). Conclusion: Phenobarbital and LZ were similarly effective in the treatment of mild/moderate alcohol withdrawal in the ED and at 48 hours.

Copyright 2011, W B Saunders

Hill KD; Wee R. Psychotropic drug-induced falls in older people: A review of interventions aimed at reducing the problem. (review). Drugs & Aging 29(1): 15-30, 2012. (112 refs.)

Falls are a common health problem for older people, and psychotropic medications have been identified as an important independent fall risk factor. The objective of this paper was to review the literature relating to the effect of psychotropic medications on falls in older people, with a particular focus on evidence supporting minimization of their use to reduce risk of falls. A literature search identified 18 randomized trials meeting the inclusion criteria for the review of effectiveness of psychotropic medication withdrawal studies, including four with falls outcomes. One of these, which targeted reduced psychotropic medication use in the community, reported a 66% reduction in falls, while the other studies demonstrated some success in reducing psychotropic medication use but with mixed effects on falls. Other randomized trials evaluated various approaches to reducing psychotropic medications generally or specific classes of psychotropic medications (e.g. benzodiazepines), but did not report fall-related outcomes. Overall, these studies reported moderate success in reducing psychotropic medication use, and a number reported no or limited worsening of key outcomes such as sleep quality or behavioural difficulties associated with withdrawal of psychotropic medication use. Reduced prescription of psychotropic medications (e.g. seeking non-pharmacological alternatives to their use in place of prescription in the first place or, for those patients for whom these medications are deemed necessary, regular monitoring and efforts to cease use or wean off use over time) needs to be a strong focus in clinical practice for three reasons. Firstly, psychotropic medications are commonly prescribed for older people, both in the community and especially in the residential care setting, and their effectiveness in a number of clinical groups has been questioned. Secondly, there is strong evidence of an association between substantially increased risk of falls and use of a number of psychotropic medications, including benzodiazepines (particularly, the long-acting agents), antidepressants and antipsychotic drugs. Finally, the largest effect of any randomized trial of falls prevention to date was achieved with a single intervention consisting of weaning psychotropic drug users off their medications.

Copyright 2012, Adis International

Ho AMC; Cheung BKL; Stadlin A. Pain response in heroin users: Personality, abstinence, and modulation by benzodiazepines. Addictive Behaviors 36(12): 1361-1364, 2011. (40 refs.)

We compared cold-pain responses among male current opioid users with and without concurrent benzodiazepine use, long-term ex-users, and healthy controls. Forty-eight current opioid users (14 concurrently using benzodiazepines), 34 ex-users (abstinent for >= 1 y) and 63 controls received cold-pressor tests. Pain threshold (first reporting pain) and pain tolerance (total immersion time) were recorded. Pain thresholds were similar in ex-users and current users: pain tolerance was similar in ex-users and controls. Net pain tolerance (endurance) in ex-users was intermediate between the other two groups. Current users showed higher pain threshold and shorter pain tolerance than controls (p<0.05). Current users not co-using benzodiazepines showed the lowest pain tolerance and net pain tolerance, and differed significantly from controls, ex-users, and current users co-using benzodiazepines (p<0.05). Neuroticism was higher in current users than in the other two groups (p<0.001), extraversion marginally lower (p<0.05); net pain tolerance differences remained significant after controlling for these. Benzodiazepine use modulates pain tolerance in opioid users. Pain responses altered by opioid use may partially recover with abstinence.

Copyright 2011, Elsevier Science

Hou CC; Chen SC; Tan LB; Chu WY; Huang CM; Liu SY et al. Psychoactive substance use and the risk of motor vehicle crash injuries in southern Taiwan. Prevention Science 13(1): 36-42, 2012. (33 refs.)

The purpose of this study was to examine the association between psychoactive drug use and motor vehicle crash (MVC) injuries requiring hospitalization in southern Taiwan. A case-control study was conducted in southern Taiwan from January 2009 to December 2009. The cases included car or van drivers who were involved in MVCs and required hospitalization. Demographic and trauma-related data were collected from questionnaires and hospital and ambulance records. Urine and/or blood samples were collected on admission. The controls consisted of drivers who were randomly recruited while driving on public roads. Study subjects were interviewed and asked to provide urine samples. All blood and urine samples were tested for alcohol and a number of other legal and illegal drugs. Only those subjects who provided urine and/or blood specimens were included in the study. During the study period, 254 case patients and 254 control drivers were enrolled. The analysis showed an odds ratio (OR) of 3.41 (95% confidence intervals (95% CI), 1.76-6.70; p < 0.001) for persons taking benzodiazepines, and an OR of 3.50 (95% CI, 1.81-6.85; p < 0.001) for those taking alcohol (blood alcohol concentrations (BAC) a parts per thousand Euro parts per thousand 0.8 g/l) with regard to hospitalizations due to MVCs. For persons taking combinations of benzodiazepines and alcohol, the OR increased to 5.12 (95% CI: 1.77-15.91, p < 0.001). This study concluded that drug use among motor vehicle drivers increases the risk of MVCs that require hospitalization. From a public health perspective, the high risk ratios are concerning, and preventive measures are warranted.

Copyright 2012, Springer

Ilomaki R; Ilomaki E; Hakko H; Rasanen P. Psychotropic medication history of inpatient adolescent: Is there a rationale for benzodiazepine prescription? Addictive Behaviors 36(1-2): 161-165, 2011. (21 refs.)

We evaluated the pre hospitalization psychotropic medication of adolescents with different psychiatric disorders and examined possible differences in medication history in relation to lifetime psychiatric diagnoses of study subjects. The study sample consisted of 300 girls and 208 boys (age 12-17) admitted to psychiatric inpatient hospital between April 2001 and March 2006. The information on drug therapy history and psychiatric diagnoses were obtained from the Schedule for Affective Disorders and Schizophrenia for School Aged Children Present and Lifetime (K-SADS PL). Adolescents with drug use disorders had elevated rates of pre hospitalization prescribed benzodiazepines (BZDs). Antidepressants and antipsychotics were mainly used by depressed and psychotic adolescents. Previously prescribed BZD medication was associated with 3-fold Increased rates of sedative abuse or dependence Girls had been prescribed antidepressants and BZDs statistically significantly more commonly than boys. The results of our study underline the importance of careful consideration of the use of benzochazepines especially in the outpatient treatment of adolescents.

Copyright 2011, Elsevier Science

Iqbal SP; Ahmer S; Farooq S; Parpio Y; Tharani A; Khan RAM et al. Benzodiazepine use among adults residing in the urban settlements of Karachi, Pakistan: A cross sectional study. Substance Abuse Treatment, Prevention and Policy 6: e-article 19, 2011. (48 refs.)

Background: There are hardly any studies carried out in Pakistan on the usage of benzodiazepines at the level of community. This research was aimed to determine the frequency of benzodiazepine use, along with its associations with socio-demographic and clinical characteristics among community dwelling adults, residing in two urban settlements of Karachi, Pakistan. Methods: We performed a cross sectional study from August 2008 to December 2009, in 2 areas of Karachi, namely Garden and Sultanabad. We followed the systematic sampling strategy to randomly select the households, with an adult of either sex and of age 18 years or more. Data collection was carried out through interview, using a pre-tested questionnaire, with items on socio-demographic position, medical history and benzodiazepine use. Student's t-test and chi(2) test was employed to determine the associations between socio-demographic and clinical characteristics, and their relationship with benzodiazepine use was determined using applied logistic regression. Results: The overall percentage of benzodiazepine consumption was estimated to be 14%. There were significantly more benzodiazepine users in the peri-urban Sultanabad community to the urban community of Garden (p-value = 0.001). The mean age (+/- SD) for users was 51.3 (+/- 15.6) years compared to 37.1 (+/- 14.4) years among non-users. Bromazepam was the most widely used benzodiazepine (29%); followed by diazepam, with a median duration on primary use being 144 weeks (IQR = 48-240). The adjusted logistic regression model revealed that increasing age, location, female sex, unemployment and psychiatric consultation were associated with increased likelihood of benzodiazepine use. Conclusion: We believe the unregulated over-the-counter sales of benzodiazepines and social conditions might be playing a role in this high consumption of benzodiazepines in the community.

Copyright 2011, BioMed Central

Jambet S; Guiu B; Olive-Abergel P; Grandvuillemin A; Yeguiayan JM; Ortega-Deballon P. Psychiatric drug-induced fatal abdominal compartment syndrome. American Journal of Emergency Medicine 30(3): e-article 513.e5, 2012. (5 refs.)

Several drugs used in psychiatry may induce constipation, paralytic ileus, or acute megacolon (Ogilvie's syndrome). We report here 2 cases of patients presenting with fatal abdominal compartment syndrome related to the absorption of antidepressants and benzodiazepines. Two patients (a 27-year-old man and a 57-year-old woman) with a previous psychiatric history and treatment with psychiatric drugs were admitted to the emergency department for coma. Both presented hypothermia; a hard, distended abdomen; and ischemia of the lower limbs. In both cases, the abdominal scan showed massive colonic dilatation without mechanical obstruction; there was even aortic compression and ischemia of the abdominal viscera. Emergency laparotomy with bowel decompression was performed in both cases, but multiple organ failure led to death in both patients. Psychiatric drugs may induce acute severe megacolon with life-threatening abdominal compartment syndrome.

Copyright 2012, WB Saunders

Jones AW; Holmgren A; Ahlner J. Heroin poisoning deaths with 6-acetylmorphine in blood: demographics of the victims, previous drug-related offences, polydrug use, and free morphine concentrations in femoral blood. Forensic Toxicology 30(1): 19-24, 2012. (31 refs.)

This article discusses cases of drug-poisoning death in which 6-acetylmorphine (6-AM) was identified in blood as evidence for recent use of heroin. We report the demographics of the victims, previous drug-related offences, polydrug use, and the concentrations of free morphine in peripheral blood. After solid-phase extraction, morphine, codeine, and 6-AM were determined in blood samples by isotope-dilution gas chromatography-mass spectrometry (GC-MS) using limits of quantitation of 0.005 mg/l for each opiate. The victims of heroin poisoning were mainly men (88%), with a mean age of 35.4 +/- A 8.4 years (+/- SD) and no significant gender difference in age (men 35 +/- A 8.4 years; women 35 +/- A 8.6 years). The median concentration of free morphine in blood (n = 671) was 0.25 mg/l (66% > 0.20 mg/l) and women had a higher concentration (0.30 mg/l) than men (0.24 mg/l) (P < 0.05). No significant difference (P > 0.05) was found for the concentration of free morphine in blood when heroin was the only drug taken (median 0.26 mg/l, n = 53) compared with multidrug deaths (median 0.24 mg/l, n = 618) (P > 0.05). The coingested drugs most commonly identified in heroin-related deaths were ethanol (44%), diazepam (27%), cannabis (20%), and flunitrazepam (19%). We found that 61% of victims had previous drug-related offences ranging from 1 to 48 times. The close agreement between the concentrations of free morphine in blood when heroin was the only drug taken and multidrug deaths suggests that differences in tolerance to opiates is more important in causing death than adverse drug-drug interactions.

Copyright 2012, Springer

Jones KA; Nielsen S; Bruno R; Frei M; Lubman DI. Benzodiazepines: Their role in aggression and why GPS should prescribe with caution. Australian Family Physician 40(11): 862-865, 2011. (27 refs.)

Background: Benzodiazepines are widely prescribed in Australia, despite concerns about their potential for abuse and dependence. Paradoxical reactions, disinhibition and amnesia are all associated with benzodiazepine use, misuse and intoxication. While violent and aggressive behaviour may be a consequence of such disinhibition, there is limited information available regarding the links between benzodiazepine use and violence. Objective This article aims to examine the existing evidence on the relationship between benzodiazepines, violence and aggression. Discussion While current evidence suggests that benzodiazepines rarely induce violence, it is important to note that the available literature is limited in its scope and that benzodiazepine related violence is often severe and of potential concern to frontline workers. Mediating risk factors for benzodiazepine related violence include concurrent alcohol use, benzodiazepine dose, a history of aggression and underlying impulsivity. Comprehensive assessment and alternate nonpharmacological treatment options should be considered before prescribing benzodiazepines within primary care.

Copyright 2011, Royal Australian College General Practitioners

Kahan M; Wilson L; Wenghofer EF; Srivastava A; Resnick A; Janecek E et al. Pharmacists' experiences with dispensing opioids Provincial survey. Canadian Family Physician 57(11): E448-E454, 2011. (10 refs.)

Objective: To explore pharmacists' beliefs, practices, and experiences regarding opioid dispensing. Design Mailed survey. Setting: The province of Ontario. Participants: A total of 1011 pharmacists selected from the Ontario College of Pharmacists' registration list. Main outcome measures Pharmacists' experiences with opioid-related adverse events (intoxication and aberrant drug-related behaviour) and their interactions with physicians. Results A total of 652 pharmacists returned the survey, for a response rate of 64%. Most (86%) reported that they were concerned about several or many of their patients who were taking opioids; 36% reported that at least 1 patient was intoxicated from opioids while visiting their pharmacies within the past year. Reasons for opioid intoxication included the patient taking more than prescribed (84%), the patient using alcohol or sedating drugs along with the opioid (69.9%), or the prescribed dose being too high (34%). Participants' most common concerns in the 3 months before the survey were patients coming in early for prescription refills, suspected double-doctoring, and requests for replacement doses for lost medication (reported frequently by 39%, 12%, and 16% of respondents, respectively). Pharmacists were concerned about physician practices, such as prescribing benzodiazepines along with opioids. Pharmacists reported difficulty in reaching physicians directly by telephone (43%), and indicated that physicians frequently did not return their calls promptly (28%). The strategies rated as most helpful for improving opioid dispensing were a provincial prescription database and opioid prescribing guidelines. Conclusion: Pharmacists commonly observe opioid intoxication and aberrant drug-related behaviour in their patients but have difficulty communicating their concerns to physicians. System-wide strategies are urgently needed to improve the safety of opioid prescribing and to enhance communication between physicians and pharmacists.

Copyright 2011, College of Family Physicians, Canada

Klemenc-Ketis Z; Hladnik Z; Kersnik J. A cross sectional study of sex differences in self-medication practices among university students in Slovenia. Collegium Antropologicum 35(2): 329-334, 2011. (28 refs.)

Self-medication patterns in adults depend on sex. Self-medication among students is very common, but little is known about the influence of sex. The aim of the study was to determine the incidence of self-medication college students and to determine the effect of sex on self-medication patterns. A web based incidence study conducted on a sample of Slovenian university students. The main outcome measures were percentages of male and female students reporting the use of self-medication in the past year A majority of students (92.3%) reported the use of some sort of self-medication in the past year. Most female students (94.1%) and most male students (90.9%) reported the use of self-medication in the past year. The difference was not statistically significant. More female students than male ones (p<0.05) acquired the drugs for self-medication in pharmacies, used OTC drugs, herbal teas, herbs, vitamins and minerals, remedies for muscle mass gain, antibiotics, benzodiazepines, antacids, acetylsalicylic acid, topical corticosteroids, and nasal decongestives only with the advice of physicians or pharmacists, and thought that increasing drug dosage can be dangerous, that in case of side effects physicians' help must be sought, that no drug can be used during pregnancy, and that self-treatment can mask the symptoms and signs of diseases so the physicians can overlook them easily. Sex appears to be important factor in self-medication patterns even in young adults, such as students. The physicians should actively seek the presence of self-medication in this population. Inappropriate or unsafe use should be properly addressed and managed.

Copyright 2011, Collegium Antropologicum

Kriikku P; Wilhelm L; Schwarz O; Rintatalo J. New designer drug of abuse: 3,4-Methylenedioxypyrovalerone (MDPV). Findings from apprehended drivers in Finland. Forensic Science International 210(1-3): 195-200, 2011. (23 refs.)

Starting in 2008 a new designer drug, 3,4-methylenedioxypyrovalerone (MDPV) appeared among users of illegal drugs in Finland. Since then there have been several seizures of MDPV by police and customs and it has been connected to many crimes of different types. In this study the incidence and impact of the use of MDPV in drivers suspected of being under the influence of drugs (DUID) in Finland was assessed. Since autumn 2009, blood samples from drivers suspected of DUID in Finland have been analysed for the presence of MDPV. A new LC-MS/MS method for the determination of MDPV in serum was established. In order to assess the impact of MDPV on driving performance, drug and alcohol findings of positive MDPV cases were compared with data from the clinical examination carried out while the suspect was under arrest. In a period of one year there were 259 positive MDPV cases from apprehended drivers (5.7% of all confirmed DUID cases). In 80% of the cases in which MDPV was found, amphetamine was also present. Benzodiazepines were also frequently found together with MDPV, which was to be expected since in Finland, in our experience, stimulants are very often used together with benzodiazepines. In most cases it remained unclear whether the observed psycho-physical achievement deficiency was induced by MDPV because the concentrations of other drugs, especially other stimulants, were often high. However, in some subjects, MDPV, or MDPV in combination with other substances was the most probable cause of the impairment. The concentrations of MDPV varied from 0.016 mg/L to over 8.000 mg/L. Little is known about the pharmacology of MDPV. However, based on our findings it is clear that MDPV has a serious impact on traffic safety in Finland.

Copyright 2011, Elsevier Science

Kunz D; Bineau S; Maman K; Milea D; Toumi M. Benzodiazepine discontinuation with prolonged-release melatonin: Hints from a German longitudinal prescription database. (review). Expert Opinion on Pharmacotherapy 13(1): 9-16, 2012. (26 refs.)

Objective: Prolonged-release (PR) melatonin is approved in Europe for the treatment of insomnia in patients aged 55 years and above. The objective of the study was to describe its prescription patterns and its impact on hypnotics use in routine clinical practice. Research design and methods: This is a retrospective study analyzing PR melatonin prescription data from a German longitudinal database (IMS (R) Disease Analyzer). All patients initiating PR melatonin over the 10 months after approval (April 2008 - February 2009) were included. Patients were classified according to their use of hypnotic benzodiazepines or benzodiazepine-like drugs (BZD/Z) in the 3-month period before and after PR melatonin initiation. Results: of the 512 eligible patients, 380 (74%) were aged 55 years, 344 (67%) women and 112 (22%) previous BZD/Z users. Most of the latter (79/99, 79.8%) had used BZD/Z for at least 180 days. Approximately one-third (35/112, 31%) discontinued BZD/Z after PR melatonin initiation, and the BZD/Z discontinuation rate was higher in patients receiving two or three PR melatonin prescriptions than in patients receiving only one prescription (10/24 = 42% vs 25/88 = 28%, p = 0.21). of the 400 patients without prior BZD/Z use, 39 (10%) received BZD/Z during the follow-up. Conclusions: Based on the observed 31% discontinuation rate, PR melatonin may help to facilitate BZD/Z discontinuation in older insomniacs.

Copyright 2012, Informa Healthcare

Kurtz SP; Surratt HL; Levi-Minzi MA; Mooss A. Benzodiazepine dependence among multidrug users in the club scene. Drug and Alcohol Dependence 119(1-2): 99-105, 2011. (45 refs.)

Background: Benzodiazepines (BZs) are among the most frequently prescribed drugs with the potential for abuse. Young adults ages 18-29 report the highest rates of BZ misuse in he United States. The majority of club drug users are also in this age group, and BZ misuse is prevalent in the nightclub scene. BZ dependence, however, is not well documented. This paper examines BZ dependence and its correlates among multidrug users in South Florida's nightclub scene. Methods: Data were drawn from structured interviews with men and women (N=521) who reported regular attendance at large dance clubs and recent use of both club drugs and BZs. Results: Prevalence of BZ-related problems were 7.9% for BZ dependence, 22.6% BZ abuse, and 25% BZ abuse and/or dependence. In bivariate logistic regression models, heavy cocaine use (OR 2.27; 95% CI 1.18, 4.38), severe mental distress (OR 2.63; 95% CI 1.33, 5.21), and childhood victimization history (OR 2.43; 95% CI 1.10, 5.38) were associated with BZ dependence. Heavy cocaine use (OR 2.14; 95% CI 1.10, 4.18) and severe mental distress (OR 2.16; 95% CI 1.07, 4.37) survived as predictors in the multivariate model. Discussion: BZ misuse is widespread among multidrug users in the club scene, who also exhibit high levels of other health and social problems. BZ dependence appears to be more prevalent in this sample than in other populations described in the literature. Recommendations for intervention and additional research are described.

Copyright 2011, Elsevier Science

Lader M. Dependence and withdrawal: Comparison of the benzodiazepines and selective serotonin re-uptake inhibitors. (editorial). Addiction 107(5): 909-910, 2012. (11 refs.)

Lalive AL; Rudolph U; Luscher C; Tan KR. Is there a way to curb benzodiazepine addiction? Swiss Medical Weekly 141: w13277, 2011

Benzodiazepines are widely prescribed drugs used to treat anxiety and insomnia, induce muscle relaxation, control epileptic seizures, promote anaesthesia or produce amnesia. Benzodiazepines are also abused for recreational purposes and the number of benzodiazepine abusers is unfortunately increasing. Within weeks of chronic use, tolerance to the pharmacological effects can develop and withdrawal becomes apparent once the drug is no longer available, which are both conditions indicative of benzodiazepine dependence. Diagnosis of addiction (i.e. compulsive use despite negative consequences) may follow in vulnerable individuals. Here, we review the historical and current use of benzodiazepines from their original synthesis, discovery and commercialisation to the recent identification of the molecular mechanism by which benzodiazepines induce addiction. These results have identified the mechanisms underlying the activation of midbrain dopamine neurons by benzodiazepines, and how these drugs can hijack the mesocorticolimbic reward system. Such knowledge calls for future developments of new receptor subtype specific benzodiazepines with a reduced addiction liability.

Copyright 2011, Swiss Medical Publishers

Lendoiro E; Quintela O; de Castro A; Cruz A; Lopez-Rivadulla M; Concheiro M. Target screening and confirmation of 35 licit and illicit drugs and metabolites in hair by LC-MSMS. Forensic Science International 217(1-3): 207-215, 2012. (22 refs.)

A liquid chromatography-tandem mass spectrometry (LC-MSMS) target screening in 50 mg hair was developed and fully validated for 35 analytes (Delta 9-tetrahidrocannabinol (THC), morphine, 6-acetylmorphine, codeine, methadone, fentanyl, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, benzoylecgonine, cocaine, lysergic acid diethylamide, ketamine, scopolamine, alprazolam, bromazepam, clonazepam, diazepam, flunitrazepam, 7-aminoflunitrazepam, lorazepam, lormetazepam, nordiazepam, oxazepam, tetrazepam, triazolam, zolpidem, zopiclone, amitriptyline, citalopram, clomipramine, fluoxetine, paroxetine and venlafaxine). Hair decontamination was performed with dichloromethane, and incubation in 2 mL of acetonitrile at 50 degrees C overnight. Extraction procedure was performed in 2 steps, first liquid-liquid extraction, hexane: ethyl acetate (55: 45, v: v) at pH 9, followed by solid-phase extraction (Strata-X cartridges). Chromatographic separation was performed in AtlantisT3 (2.1 mm x 100 mm, 3 mu m) column, acetonitrile and ammonium formate pH 3 as mobile phase, and 32 min total run time. One transition per analyte was monitored in MRM mode. To confirm a positive result, a second injection monitoring 2 transitions was performed. The method was specific (no endogenous interferences, n = 9); LOD was 0.2-50 pg/mg and LOQ 0.5-100 pg/mg; linearity ranged from 0.5-100 to 2000-20,000 pg/mg; imprecision <15%; analytical recovery 85-115%; extraction efficiency 4.1-85.6%; and process efficiency 2.5-207.7%; 27 analytes showed ion suppression (up to -86.2%), 4 ion enhancement (up to 647.1%), and 4 no matrix effect; compounds showed good stability 24-48 h in autosampler. The method was applied to 17 forensic cases. In conclusion, a sensitive and specific target screening of 35 analytes in 50 mg hair, including drugs of abuse (THC, cocaine, opiates, amphetamines) and medicines (benzodiazepines, antidepressants) was developed and validated, achieving lower cut-offs than Society of Hair Testing recommendations.

Copyright 2012, Elsevier Science

Lerat MC; Cabelguenne D; Lassia J; Meunier F; Zimmer L. Impact of pharmacist and clinician dual intervention on prescribed benzodiazepines in prisoner patients: A retrospective study. Fundamental & Clinical Pharmacology 25(6): 762-767, 2011

High-dose benzodiazepine (BDZs) represents an important risk factor for dependence, particularly in a prison environment. In Lyon's prison, BDZs and/or opioid maintenance treatment are often prescribed to patients with mental disorders. The aim of this retrospective study was to assess the impact of psychiatrist and pharmacist collaboration on reducing the BDZs dose prescribed to prisoner patients. Since 2001, clinicians and pharmacists have been holding monthly meetings to develop prescribing guidelines and discuss those patients receiving high-dose BDZs. All prescribed psychotropic drugs were noted for each included patient in the control (before guidelines) and intervention groups. Criteria used to define each patient profile included age, diagnosis (mental disorder), and concomitant treatment (opioids, antidepressants). To compare each group, the daily dose of prescribed BDZs was used as a quantitative variable and expressed in diazepam equivalent. Four hundred and seventy-three patients were included, 222 in the control group and 251 in the intervention group. The two groups showed no difference in terms of diagnosis. The daily dose of BDZ was higher in the control group when all patients were considered (mean(CONTROL GROUP) =46mg in diazepam equivalent vs. mean(INTERVENTIION GROUP) =34mg) and for each of the following patient categories: 'mental disorder' (48mg vs. 30mg), 'no opioid treatment' (44mg vs. 31mg), 'buprenorphin treatment' (58mg vs. 63mg), 'no antidepressant treatment' (41mg vs. 29mg), and 'antidepressant treatment' (53mg vs. 38mg). The results of this retrospective study show the positive impact of multidisciplinary intervention on reducing the prescribed daily dose of BDZs. This experience confirms the positive impact that pharmacist feedback on prescriptions and the development of treatment guidelines by clinician and pharmacist collaboration have on improving the prescribing practice in a prison environment.

Copyright 2011, Wiley-Blackwell

Leung SY. Benzodiazepines, opioids and driving: An overview of the experimental research. Drug and Alcohol Review 30(3): 281- 286, 2011. (53 refs.)

Issues. Road crashes contribute significantly to the total burden of injury in Australia, with the risk of injury being associated with the presence of drugs and/or alcohol in the driver's blood. Increasingly, some of the most commonly detected drugs include prescription medicines, the most notable of these being benzodiazepines and opioids. However, there is a paucity of experimental research into the effects of prescribed psychoactive drugs on driving behaviours. Approach. This paper provides an overview of experimental studies investigating the effects of prescribed doses of benzodiazepines and opioids on driving ability, and points to future directions for research. Key Findings. There is growing epidemiological evidence linking the therapeutic use of benzodiazepines and opioids to an increased crash risk. However, the current experimental literature remains unclear. Limitations to study methodologies have resulted in inconsistent findings. Implications. Limited experimental evidence exists to inform policy and guidelines regarding fitness-to-drive for patients taking prescribed benzodiazepines and opioids. Conclusion. Further experimental research is required to elucidate the effects of these medications on driving, under varying conditions and in different medical contexts. This will ensure that doctors prescribing benzodiazepines and opioids are well informed, and can appropriately advise patients of the risks associated with driving whilst taking these medications.

Copyright 2011, Wiley-Blackwell

Licata SC; Mashhoon Y; MacLean RR; Lukas SE. Modest abuse-related subjective effects of zolpidem in drug-naive volunteers. Behavioural Pharmacology 22(2): 160-166, 2011. (47 refs.)

Recent case reports suggest that the short-acting benzodiazepine-like hypnotic, zolpidem, may have abuse potential among individuals who have no personal history of abusing drugs or alcohol, particularly at doses higher than those recommended for treating insomnia. This study recruited drug-naive volunteers to assess the subjective effects of multiple doses of zolpidem (0, 5, 10, or 20 mg) administered in a within-subject double-blind design. Participants (n = 11) answered computerized questionnaires (Addiction Research Center Inventory, visual analog scales, and a hypothetical Drug versus Money Choice) to address the hypothesis that a supratherapeutic dose (20 mg) would increase ratings of abuse-related subjective effects, while lower therapeutic doses (5 and 10 mg) would not. Although participants rated some effects as negative at 10 and 20 mg, the highest dose engendered predominantly positive abuse-like effects such as 'High', 'Like', and 'Good Effects'. However, no dose of zolpidem was chosen over money ($0.35-$10) when participants made hypothetical choices between them. Results suggest that although individuals without a drug abuse history are not inclined to choose zolpidem when presented with an alternative reinforcer such as money, it may possess moderate abuse potential that limits its clinical utility.

Copyright 2011, Lippincott, Williams & Wilkins

Lin SC; Chen CC; Chen YH; Chung KS; Lin CH. Benzodiazepine prescription among patients with severe mental illness and co-occurring alcohol abuse/dependence in Taiwan. Human Psychopharmacology: Clinical and Experimental 26(3): 201-207, 2011. (40 refs.)

Objective. Because benzodiazepines (BZDs) may be abused, prescribing them is debatable. The purpose of this study was to investigate the prescription of BZDs to explore the current status of BZD use at discharge and at 4 months after discharge. Methods. From 1 January 2006 to 31 December 2006, prescribed doses for BZDs at discharge and at 4 months after discharge were recorded for all discharged inpatients with schizophrenia, bipolar I disorder, and major depressive disorder. Two-way analysis of variance was used to analyze the effects of severe mental illness and co-occurring alcohol abuse/dependence on BZD doses at discharge and at 4 months after discharge. Results. Patients with severe mental illness prescribed with significantly higher rates and higher doses of BZDs at discharge and at 4 months after discharge are more likely to have major depressive disorder and to have co-occurring alcohol abuse/dependence problems. No significant interactions were found between severe mental illness and co-occurring alcohol abuse/dependence. Conclusions. These findings suggest that caution should be applied in prescribing BZDs to patients with severe mental illness, particularly those with major depressive disorder and co-occurring alcohol abuse/dependence. Future studies require being conducted in many different mental health-care systems in Taiwan to generalize the findings.

Copyright 2011, Wiley-Blackwell

Lund BC; Bernardy NC; Alexander B; Friedman MJ. Declining benzodiazepine use in veterans with Posttraumatic Stress Disorder. Journal of Clinical Psychiatry 73(3): 292-296, 2012. (24 refs.)

Objective: Clinical practice guidelines issued by the US Department of Veterans Affairs (VA) and the Department of Defense caution against benzodiazepine use among veterans with posttraumatic stress disorder (PTSD) because of insufficient evidence for efficacy and emerging safety concerns. We examined recent trends in benzodiazepine prescribing among veterans with PTSD in terms of frequency of use, duration of use, and dose. Method: Administrative VA data from fiscal years 1999 through 2009 were used to identify veterans with PTSD according to ICD-9 codes extracted from inpatient discharges and outpatient encounters. Benzodiazepine use among these individuals was determined for each fiscal year by using prescription drug files. Modal daily doses were examined by using standard daily dosage units. Results: The number of veterans receiving care for PTSD in the VA increased from 170,685 in 1999 to 498,081 in 2009. The proportion of individuals receiving a benzodiazepine decreased during this time period from 36.7% to 30.6%. In addition, the proportion of long-term users (>90 days) decreased from 69.2% to 64.1%, and daily dose decreased from 2.1 to 1.8 standard daily dosage units. Conclusions: Decreasing benzodiazepine use among veterans with PTSD is encouraging. However, the frequency of use remains above 30%, and focused interventions may be required to achieve further reductions. Given the growing number of veterans being diagnosed and treated for PTSD, minimizing benzodiazepine exposure will remain a vital policy issue for the VA.

Copyright 2012, Physicians Postgraduate Press

Luzardo OP; Almeida M; Zumbado M; Boada LD. Occurrence of contamination by controlled substances in Euro banknotes from the Spanish archipelago of the Canary Islands. Journal of Forensic Sciences 56(6): 1588-1593, 2011. (18 refs.)

The social problems of drug abuse are a matter of increasing global problem. Nowadays, international agencies need fresh methods to monitor trends of the use of illicit drugs. In this sense, small amounts of drugs are transferred to banknotes and they could be detected and quantified. An analytical procedure based upon extraction with organic solvent, liquid chromatography separation, and mass spectrometric detection allowed the identification of 21 drugs and metabolites in 120 used Euro banknotes collected in the Canary Islands (Spain). Most of the banknotes analyzed showed detectable drug residues (92.5%). Cocaine was the most frequently detected drug, present in approximately 90% of the samples. In addition, 75%, 35%, and 15% of the banknotes showed residues of amphetamine derivatives, opiates, and benzodiazepines, respectively. An average of three drug residues per banknote was detected. In summary, the presence of drug residues in banknotes could be useful as tracer for drug prevalence.

Copyright 2011, Wiley-Blackwell

Manthey L; van Veen T; Giltay EJ; Stoop JE; Neven AK; Penninx BWJH et al. Correlates of (inappropriate) benzodiazepine use: the Netherlands Study of Depression and Anxiety (NESDA). British Journal of Clinical Pharmacology 71(2): 263-272, 2011. (59 refs.)

AIM: Results on determinants of benzodiazepine (BZD) use in general and inappropriate use were inconsistent and mostly univariate. The relative importance of sociodemographic, psychological and physical determinants has never been investigated in a comprehensive, multivariate model. METHODS: We included 429 BZD users and 2423 non-users from the Netherlands Study of Depression and Anxiety (NESDA) in order to investigate sociodemographic, psychological and physical determinants of BZD use and inappropriate use by logistic and linear regression analyses. RESULTS: BZDs were used by a considerable proportion of the 2852 NESDA participants (15.0%). BZD use was independently associated with older age, singleness, unemployment, treatment in secondary care, higher medical consumption (more severe) anxiety, depression (OR [95% CI] = 1.95 [1.29, 2.93]), comorbidity, insomnia, SSRI (OR [95% CI] = 2.05 [1.55, 2.70]), TCA and other antidepressant (OR [95% CI] = 2.44 [1.64, 3.62]) use. Overall, BZD use was rarely in accordance with all guidelines, mainly because most users (82.5%) exceeded the recommended duration of safe use. Inappropriate use was independently associated with older age (beta = 0.130) and chronic illnesses (beta = 0.120). Higher scores on agreeableness were associated with less inappropriate use. CONCLUSIONS: Mentally or physically vulnerable subjects were most likely to use BZDs. The most vulnerable (i.e. the old and physically ill) BZD users were at highest risk of inappropriate BZD use. Without further evidence of the effectiveness of BZDs in long-term use, caution in initiating BZD prescriptions is recommended, particularly when patients are chronically ill and old, as those are most likely to display inappropriate use.

Copyright 2011, Wiley-Blackwell

McAuley A; Best D. A quantitative exploration of risk factors associated with drug-related deaths involving heroin, alcohol or methadone in the west of Scotland. Addiction Research & Theory 20(2): 153-161, 2012. (42 refs.)

A number of risk factors have been identified that increase the potential for overdose events to occur, however in-depth studies exploring multiple Drug-Related Death (DRD) risk factors simultaneously are less prevalent and mainly conducted among non-fatal OD populations. Using retrospective data from two Scottish NHS Board areas, this study looked at three main types of DRD in more depth, namely those involving heroin, alcohol or methadone, exploring the associations between personal and population DRD risk factors and attempting to predict their impact. Of a total of 291 DRDs across the two areas between 2006 and 2007; almost two-thirds (65%; n = 190) involved heroin, one-third (34%; n = 100) involved methadone and over a quarter (28%; n = 80) involved alcohol. The direct involvement of benzodiazepines was much less prominent (4%; n = 11). Age and geographical area were both significant predictors of DRDs involving both heroin and alcohol. Heroin-related DRDs were significantly more likely to affect males than females and prison release within the last 14 days a significant predictor. Gender and heroin involvement were both significant predictors of Methadone-related DRDs with females more likely to be affected than males and heroin less likely to be co-involved. These findings support previous research into DRD and overdose risk factors by revealing co-presences and predictors of DRD-subtypes. They suggest new areas where overdose prevention messages should be targeted; such as an increasing risk of alcohol involvement in DRD with age and an increased risk of Methadone-related DRD for females.

Copyright 2012, Informa HealthCare

Meuleners LB; Duke J; Lee AH; Palamara P; Hildebrand J; Ng JQ. Psychoactive medications and crash involvement requiring hospitalization for older drivers: A population-based study. Journal of the American Geriatrics Society 59(9): 1575-1580, 2011. (46 refs.)

Objectives: To determine the association between psychoactive medications and crash risk in drivers aged 60 and older. Design: Retrospective population-based case-crossover study. Setting: A database study that linked the Western Australian Hospital Morbidity Data System and the Pharmaceutical Benefits Scheme. Participants: Six hundred sixteen individuals aged 60 and older who were hospitalized as the result of a motor vehicle crash between 2002 and 2008 in Western Australia. Measurements: Hospitalization after a motor vehicle crash. Results: Greater risk for a hospitalization crash was found for older drivers prescribed benzodiazepines (odds ratio (OR) = 5.3, 95% confidence interval (CI) = 3.6-7.8, P < .001), antidepressants (OR = 1.8, 95% CI = 1.0-3.3, P = .04), and opioid analgesics (OR = 1.5, 95% CI = 1.0-2.3, P = .05). Crash risk was significantly greater in men prescribed a benzodiazepine (OR = 6.2, 95% CI = 3.2-12.2, P < .001) or an antidepressant (OR = 2.7, 95% CI = 1.1-6.9, P = .03). Women prescribed benzodiazepines (OR = 4.9, 95% CI = 3.1-7.8, P < .001) or opioid analgesics (OR = 1.8, 95% CI = 1.1-3.0, P = .03) also had a significantly greater crash risk. Subgroup analyses further suggested that drivers with (OR = 4.0, 95% CI = 2.9-8.1, P < .001) and without (OR = 6.0, 95% CI = 3.8-9.5, P < .001) a chronic condition who were prescribed benzodiazepines were at greater crash risk. Drivers with a chronic condition taking antidepressants (OR = 3.4, 95% CI = 1.3-8.5, P = .01) also had a greater crash risk. CONCLUSION: Psychoactive medication usage was associated with greater risk of a motor vehicle crash requiring hospitalization in older drivers.

Copyright 2011, Wiley-Blackwell

Mohler H. The rise of a new GABA pharmacology. Neuropharmacology 60(7-8, special issue): 1042- 1049, 2011. (110 refs.)

Key developments in GABA pharmacology over the last 30 years are reviewed with special reference to the advances pioneered by Erminio Costa. His passion for innovative science, and his quest for novel therapies for psychiatric disorders are particularly apparent in his fundamental contributions to the field of GABA research, with a focus on anxiety disorders and schizophrenia. He was a cofounder of the GABAergic mechanism of action of benzodiazepines. He envisaged partial agonists as novel anxiolytics. He identified DBI (diazepam binding inhibitor) as endogenous agonist of neurosteroidogenesis with multiple CNS effects and he pointed to the developmental origin of GABAergic dysfunctions in schizophrenia through his discovery of a reelin deficit, all this in collaboration with Sandro Guidotti. Today, the GABA pharmacology comprises selective hypnotics, non-sedative anxiolytics, memory enhancers and powerful analgesics. This article is part of a Special Issue entitled 'Trends in Neuropharmacology: In Memory of Erminio Costa'.

Copyright 2011, Elsevier Science

Musshoff F; Kirschbaum KM; Graumann K; Herzfeld C; Sachs H; Madea B. Evaluation of two immunoassay procedures for drug testing in hair samples. Forensic Science International 215(1-3): 60-63, 2012. (20 refs.)

A preliminary initial enzyme-linked immunosorbent assay (LUCIO (R)-Direct ELISA kit) and a preliminary DRI (R) enzyme immunoassay were evaluated for drug detection in head hair with respect to lowered cutoff values recommended in Germany for the control of abstinence in cases of re-granting of drivers' licences. Following drug classes were included: cannabinoids, opiates, cocaine like substances, amphetamine, methamphetamine (and methylenedioxyamphetamines), methadone, and benzodiazepines. 759 analyses were performed using LUCIO (R)-Direct ELISA kits and 936 analyses using DRI (R) enzyme immunoassay tests. Sample size for each drug group and immunoassay test reached from 74 to 178. The LUCIO (R)-Direct ELISA kit revealed a sensitivity of 91% for amphetamine up to 98% for methadone (methamphetamine 92%, cocaine 94%, opiates 94%, benzodiazepines 96%) and values of specificity of 72% for methadone up to 89% for amphetamine and benzodiazepines. The test was not useful for a preliminary screening for tetrahydrocannabinol (sensitivity of 65%) in consideration of a suggested cutoff of 0.02 ng/mg. The DRI (R) enzyme immunoassay test was only useful for morphine and cocaine testing at low recommended new cutoff values (0.1 ng/mg) revealing sensitivities of 94% and 99%, respectively.

Copyright 2012, Elsevier Science

Nielsen M; Hansen EH; Gotzsche PC. What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors. (review). Addiction 107(5): 900-908, 2012. (54 refs.)

Aims: To explore the rationale for claiming that benzodiazepines cause dependence while selective serotonin re-uptake inhibitors (SSRIs) do not. Methods: We analysed the definitions of dependence and withdrawal reactions as they had appeared over time in the Diagnostic Statistical Manual of Mental Diseases (DSM) and the International Classification of Diseases (ICD). We also compared the discontinuation symptoms described for the two drug groups in a systematic review. Results: The definition of substance dependence has changed over time in both the DSM and ICD. In the most recent classifications several criteria, including behavioural, physiological and cognitive manifestations, must be fulfilled. This change was published with the revision of the DSM-III revision in 1987 (DSM-IIIR), after the recognition of benzodiazepine dependence and just before the SSRIs were marketed in 1987-88. We found that discontinuation symptoms were described with similar terms for benzodiazepines and SSRIs and were very similar for 37 of 42 identified symptoms described as withdrawal reactions. Conclusions: Withdrawal reactions to selective serotonin re-uptake inhibitors appear to be similar to those for benzodiazepines; referring to these reactions as part of a dependence syndrome in the case of benzodiazepines, but not selective serotonin re-uptake inhibitors, does not seem rational.

Copyright 2012, Wiley-Blackwell

O'Connor K; Belanger L; Aardema F; Perodeau G; Harel F. The predictive utility of health preoccupations and outcome expectancies prior to benzodiazepine withdrawal. Journal of Substance Use 17(2): 122-133, 2012. (43 refs.)

Aim: The aim of this study was to examine the predictive utility of measuring health preoccupations and outcome expectancies prior to tapered benzodiazepine (BZD) withdrawal. Method: In an initial exploratory study, 44 adult participants (18-65) with a principal diagnosis of either anxiety or insomnia or both and wishing to discontinue BZD use were administered a Benzodiazepine Withdrawal Outcome Expectancy Scale (B-WOES) pre- and post-tapered withdrawal. Results: Two factors emerged from the health preoccupation section of the B-WOES: personal well-being and somatic concerns. A third subscale was derived from the section of the B-WOES measuring outcome expectancies if BZD were discontinued: an enhanced positive experience factor. A replication on a second independent sample of 38 adult participants (18-65) confirmed the three-factor structure. Conclusion: In the pooled data, the first two preoccupation subscales emerged as significant predictors of outcome following a tapered withdrawal program, so health preoccupations as well as outcome expectancies prior to discontinuation may impact on the discontinuation process.

Copyright 2012, Informa Healthcare

Orriols L; Philip P; Moore N; Castot A; Gadegbeku B; Delorme B et al. Benzodiazepine-like hypnotics and the associated risk of road traffic accidents. Clinical Pharmacology & Therapeutics 89(4): 595-601, 2011. (20 refs.)

The aim of the study was to investigate the association between the use of benzodiazepine or benzodiazepine-like hypnotics and the risk of road traffic accidents. Data from three French national databases were matched: the health-care insurance database, police reports, and the police database of injury-related traffic accidents. A total of 72,685 drivers involved in injury-related road traffic accidents in France, from 2005 to 2008, were included in the study. The risk of being responsible for a traffic accident was higher in users of benzodiazepine hypnotics (odds ratio (OR) = 1.39 (1.08-1.79)) and in the 155 drivers to whom a dosage of more than one pill of zolpidem a day had been dispensed during the 5 months before the collision (OR=2.46 (1.70-3.56)). No association was found between the use of zopiclone and risk of traffic accidents. Although this study did not find any association between the use of zolpidem as recommended and causation of traffic accidents, the potential risk related to possible abuse of the drug and risky driving behaviors should be further investigated. The results related to benzodiazepine hypnotics are consistent with those of previous studies.

Copyright 2011, Nature Publishing

Ostini R; Jackson C; Hegney D; Tett SE. How is medication prescribing ceased? A systematic review. (review). Medical Care 49(1): 24-36, 2011. (60 refs.)

Background: Medication prescribing is a complex process where the focus tends to be on starting new medication, changing a drug regimen, and continuing a drug regimen. On occasion, a prudent approach to prescribing may necessitate ending an ongoing course of medication, either because it should not have been started in the first place; because its continued use would cause harm; or because the medication is no longer effective. Objective: To identify effective strategies for stopping pre-existing prescribing in situations where continued prescribing may no longer be clinically warranted. Research design: Systematic searches for English-language reports of experimental and quasi-experimental research were conducted in PubMed (1951-November 2009), EMBASE (1966 -September 2008), and International Pharmaceutical Abstract b (1970 -September 2008). A manual search for relevant review articles and a keyword search of a local database produced by a previous systematic search for prescribing influence and intervention research were also conducted. Study selection and data extraction: Following initial title screening for relevance 2 reviewers, using formal assessment and data extraction tools, independently assessed abstracts for relevance and full studies for quality before extracting data from studies selected for inclusion. Results: Of 1306 articles reviewed, 12 were assessed to be of relevant, high-quality research. A variety of drugs were examined in the included studies with benzodiazepines the most common. Studies included in the review tested 9 different types of interventions. Effective interventions included patient-mediated interventions, manual reminders to prescribers, educational materials given to patients, a face-to-face intervention with prescribers, and a case of regulatory intervention. Partially effective interventions included audit and feedback, electronic reminders, educational materials alone sent to prescribers, and distance communication combined with educational materials sent to prescribers. Conclusions: It appears possible to stop the prescribing of a variety of medications with a range of interventions. A common theme in effective interventions is the involvement of patients in the stopping process. However, prescribing at the level of individual patients was rarely reported, with data often aggregated to number of doses or number of drugs per unit population, attributing any reduction to cessation. Such studies are not measuring the actual required outcome (stopping prescribing), and this may reflect the broader ambiguity about when or why it might be important to end a prescription. Much more research is required into the process of stopping pre-existing prescribing, paying particular attention to improving the outcomes that are measured.

Copyright 2011, Lippincott, Willams & Wilkins

Parr JM; Kavanagh DJ; Young RM; Mitchell G. Acceptability of cognitive-behaviour therapy via the Internet for cessation of benzodiazepine use. Drug and Alcohol Review 30(3): 306- 314, 2011. (42 refs.)

Introduction and Aims: Long-term use of benzodiazepines remains common, and conveys significant risk. Providing psychological intervention in association with gradual dose reduction increases cessation rates above dose reduction alone, but appropriate psychological support is difficult to obtain. This study was undertaken to assess the outcomes of an uncontrolled case series of an Internet-based cognitive-behaviour therapy for benzodiazepine cessation. Design: and Methods: Users of benzodiazepines for > 3 months who wanted to reduce or cease benzodiazepines participated in the trial. They completed online assessments and accessed 13 newsletters on managing withdrawal symptoms and developing alternate ways to cope with life events. Therapist assistance was provided by email. Follow up was at 3 and 6 months and feedback was obtained via comments and emails. Results: Program ratings and emailed comments of the program were positive. Thirty-two people registered for the program and 14 (44%) completed a 6 month follow up. Of these, eight (57%) reduced weekly intake by at least half, including five (36%) who ceased use. Shorter duration of use and birth outside Australia predicted greater percentage reductions at 3 months, while being living with a partner and being in paid employment predicted reductions at 6 months. Discussion and Conclusions: While results were encouraging, controlled research is required to confirm the efficacy of the program, and engagement of both users and prescribers needs further attention.

Copyright 2011, Wiley-Blackwell

Pauly V; Frauger E; Pradel V; Nordmann S; Pourcel L; Natali F et al. Monitoring of benzodiazepine diversion using a multi-indicator approach. International Clinical Psychopharmacology 26(5): 268-277, 2011. (60 refs.)

Fourteen benzodiazepine (BZD) or BZD-like medications were analyzed with three data sources aiming to assess prescription drug abuse for the year 2008. After a descriptive analysis, a principal component analysis was carried out to explore correlations between seven indicators obtained by different methods using these three different data sources and to compute a composite score of diversion for these drugs. For all the indicators, flunitrazepam appears first with much higher values than the other drugs, whereas clonazepam appears in the second or third place. These methods produce globally correlated indicators and the composite score obtained from principal component analysis ranks the drugs with the highest diversion as follows: flunitrazepam, clonazepam, oxazepam, diazepam, and bromazepam. This study shows that these methods yield consistent results. Their integration into a single multi-indicator approach gives health authorities a global view of different behaviors regarding diversion of a given drug.

Copyright 2011, Lippincott, Williams & Wilkins

Peron EP; Gray SL; Hanlon JT. Medication use and functional status decline in older adults: A narrative review. (review). American Journal of Geriatric Pharmacotherapy 9(6): 378-391, 2011. (97 refs.)

Background: Functional status is the cornerstone of geriatric care and serves as an indicator of general well-being. A decline in function can increase health care use, worsen quality of life, threaten independence, and increase the risk of mortality. One of several risk factors for decline in functional status is medication use. Objective: Our aim was to critically review published articles that have examined the relationship between medication use and functional status decline in the elderly. Methods: The MEDLINE and EMBASE databases were searched for English-language articles published from January 1986 to June 2011. Search terms included aged, humans, drug utilization, polypharmacy, inappropriate prescribing, anticholinergics, psychotropics, antihypertensives, drug burden index, functional status, function change or decline, activities of daily living, gait, mobility limitation, and disability. A manual search of the reference lists of the identified articles and the authors' article files, book chapters, and recent reviews was conducted to retrieve additional publications. Only articles that used rigorous observational or interventional designs were included. Cross-sectional studies and case series were excluded from this review. Results: Nineteen studies met the inclusion criteria. Five studies addressed the impact of suboptimal prescribing on function, 3 of which found an increased risk of worse function in community-dwelling subjects receiving polypharmacy. Three of the 4 studies that assessed benzodiazepine use and functional status decline found a statistically significant association. One cohort study identified no relationship between antidepressant use and functional status, whereas a randomized trial found that amitriptyline, but not desipramine or paroxetine, impaired certain measures of gait. Two studies found that increasing anticholinergic burden was associated with worse functional status. In a study of hospitalized rehabilitation patients, users of hypnotics/anxiolytics (e.g., phenobarbital, zolpidem) had lower relative functional Independence Measure motor gains than nonusers. Use of multiple central nervous system (CNS) drugs (using different definitions) was linked to greater declines in self-reported mobility and Short Physical Performance Battery (SPPB) scores in 2 community-based studies. Another study of nursing home patients did not report a significant decrease in SPPB scores in those taking multiple CNS drugs. Finally, 2 studies found mixed effects between antihypertensive use and functional status in the elderly. Conclusions: Benzodiazepines and anticholinergics have been consistently associated with impairments in functional status in the elderly. The relationships between suboptimal prescribing, antidepressants, and antihypertensives and functional status decline were mixed. Further research using established measures and methods is needed to better describe the impact of medication use on functional status in older adults.

Copyright 2011, Elsevier Science

Preville M; Vasiliadis HM; Bosse C; Dionne PA; Voyer P; Brassard J. Pattern of psychotropic drug use among older adults having a depression or an anxiety disorder: Results from the longitudinal ESA Study. Canadian Journal of Psychiatry 56(6): 348-357, 2011. (48 refs.)

Objective: To document the use of psychotropic drugs in Quebec older adult population with a depressive or anxiety disorder. Method: Data from the Enquete sur la Sante des Nines (ESA) study conducted between 2005 and 2008 using a representative sample (n = 1869) of community-dwelling adults aged 65 years and older were used to examine the use of psychotropic drugs in the Quebec older adult population. Results: Our results indicate that only 46.9% of the older adults with a diagnosis of depression or anxiety during the 24-month period studied according to the Regie de l'assurance maladie du Quebec (RAMQ) register used antidepressants (AD) for 400 days (12.9 months) on average during this period. Also, 59% of the RAMQ's mental health disorder patients used a mean daily dose of 5 mg of a diazepam equivalent for 338 days (10.9 months) on average during the same period. However, 10.0% of the older adults without any symptoms (ESA) at T1 and at T2 and any RAMQ depression and anxiety diagnosis between T0 and T2 were AD users during the 24-month period studied. They represent 26.2% of the AD users and consumed them for 494 days (15.9 months) on average during the 24-month period studied. Finally, the number of days of AD and benzodiazepine use was not associated with partial or total remission. Conclusions: This result questions the population effectiveness of these drugs in this population.

Copyright 2011, Canadian Psychiatric Association

Rapoport MJ; Zagorski B; Seitz D; Herrmann N; Molnar F; Redelmeier DA. At-fault motor vehicle crash risk in elderly patients treated with antidepressants. American Journal of Geriatric Psychiatry 19(12): 998-1006, 2011. (44 refs.)

Objective: To assess whether antidepressant treatment is associated with a temporary increase in the risk of a motor vehicle crash among older adults. Design: Population-based case-only time-to-event analysis. Setting and Subjects: Data from transportation and healthcare databases for adults age 65 and older in Ontario, Canada, between January 1, 2000, and October 31, 2007. Consecutive adults who had a motor vehicle crash anytime following their 66th birthday. Measurements: The primary exposure variable was treatment with antidepressant medication, and the primary outcome measure was a motor vehicle crash. Results: A total of 159,678 individuals had a crash during the study, of whom 7,393 (5%) received an antidepressant in the month prior to the crash. The hazard ratio (HR) of crash associated with second-generation antidepressants was 1.10 (95% confidence interval [CI]: 1.07-1.13, chi(2) = 41.77, df = 1, p < 0.0001), adjusted for gender, license suspensions, and other medications, but the risk for first-generation antidepressants was not significant. The increased risk was restricted to those who were also concurrently prescribed a benzodiazepine (adjusted HR: 1.23, 95% CI: 1.17-1.28, chi(2) = 85.28, df = 1, p < 0.0001) or a strong anticholinergic medication (adjusted HR: 1.63, 95% CI: 1.57-1.69, chi(2) = 627.31, df = 1, p < 0.0001), and was confined to crashes where the patient was at fault. The increased risk was apparent for the first 3-4 months following initiation of an antidepressant and returned to baseline thereafter. Conclusions: Prescriptions for second-generation antidepressants in older adults are associated with a modest increased risk of motor vehicle crashes, when combined with other medications that can impair cognition.

Copyright 2011, Lippincott, Williams & Wilkins

Riboldi L; Bordini L; Ferrario MM. Fitness for work in health care workers: State of the art and possible operational recommendations for its formulation and management in relationship to alcohol and drug addiction. Medicina del Lavoro 103(3): 203-211, 2012. (32 refs.)

Both chronic and acute alcohol or drug consumption have severe health consequences, alter the subject's cognitive functions and work performance and increase the risk of work-related accidents, for the worker and for third parties (e. g., co-workers and other people subject to negative impact of worker's actions). Limited scientific evidence has suggested that some working conditions present in the health care sector (e. g., high levels of responsibility, competitiveness, burnout, shiftwork, work-related stress) may favour alcohol and drug abuse. The aim of the present report is to describe the problem of alcohol and drug consumption among health care professionals and to evaluate the problem of related fitness for work. The magnitude of this problem remains unclear; recent estimates have reported alcohol abuse and addiction problems in 1-14% and psychotropic, illicit and non-illicit, substance abuse in 6-15% of health care workers. The prevalence of tranquilizer and sedative/hypnotic drug use is high, particularly among physicians. However, it remains unclear whether the incidence of workplace accidents and injuries is higher among drug abusers, and whether the statutory introduction of prevention programmes has led to actual control of this problem in the workplace. Italian legislation identifies the occupational physician as a key figure to prevent psychotropic substance abuse in some work activities, but some difficulties in its application remain. Legislators should issue simple norms that clearly define the responsibilities and skills of each actor involved in safeguarding workplace health and safety, as well as clearly outlining workplace monitoring procedures.

Copyright 2012, Mattioli 1885

Rich BA; Webster LR. A review of forensic implications of opioid prescribing with examples from malpractice cases involving opioid-related overdose. (review). Pain Medicine 12(2 apecial issue): S59-S65, 2011. (17 refs.)

Objective. To provide a forensic overview and trace common threads among malpractice lawsuits involving patients who overdosed while consuming therapeutic opioids. Methods. One of us (LRW) reviewed 35 medical records of patients with chronic pain who overdosed, 20 of them fatally, while consuming therapeutic opioids, leading to lawsuits against physicians for malpractice. The reviews were requested by plaintiff and defense attorneys from across the United States from 2005 to 2009 to ascertain which drug(s) were primarily responsible for each death and whether the death was due to physician error, patient nonadherence, or some other reason. Complaints against pharmaceutical companies were excluded. Cases were examined for common trends, and comment is offered. Results. Methadone was responsible for the most deaths at 10 (50%), and hydrocodone was second at four deaths (20%) The most common risk factors found in the medical records of decedents included prescriber error in initiating, converting or titrating doses, patient nonadherence to medical instruction, presence of comorbid mental disorders, toxicological presence of benzodiazepines, middle age, and unrelieved pain. This article focuses on examples of physician errors and how they can be prevented. Conclusions. Common trends emerge from medical records of opioid decedents. Patient actions contribute, but physician error, particularly regarding prescribing methadone for pain, is apparent as well. A focused effort to determine the types and causes of common physician errors and how they might be avoided may lead to safer, more effective clinical interventions in the management of pain.

Copyright 2011, Wiley-Blackwell

Ries R; Wolitzky-Taylor KB; Operskalski JT; Craske MG; Roy-Byrne P. Treatment of co-morbid substance use and anxiety disorders A case study. (editorial). Journal of Addiction Medicine 5(4): 248-253, 2011. (18 refs.)

This case study of combined anxiety with both alcohol and benzodiazepine dependence illustrates key issues in presentation, differential diagnosis and management. The case is discussed from a biopsychosocial perspective with each of the discussants focusing on their particular area of experience and expertise, then the treatment package is presented in an integrated fashion. Of particular interest is how social anxiety disorder may become a significant barrier to engagement and retention, and thus outcome in persons presenting for addiction treatment, and how a treatment plan for such patients can be built.

Copyright 2011, Lippincott, Williams & Wilkins

Rigg KK; Kurtz SP; Surratt HL. Patterns of prescription medication diversion among drug dealers. Drugs: Education, Prevention and Policy 19(2): 145-155, 2012. (41 refs.)

This research examined the following questions: (1) how do drug dealers acquire their inventories of prescription medications? and (2) which types of prescription medications do dealers most commonly sell? Data are drawn from a National Institute on Drug Abuse-funded research study that examined prescription drug diversion and abuse in South Florida. In-depth semi-structured interviews (n = 50) were conducted with an ethnically diverse sample of prescription drug dealers from a variety of milieus to assess patterns of diversion. Audiotapes of the interviews were transcribed, coded, and thematically analysed using the NVivo 8 software program. Dealers relied on a wide array of diversion methods including visiting multiple pain clinics, working with pharmacy employees to steal medications from pharmacies, and purchasing medications from indigent patients. The type of medication most commonly sold by dealers was prescription opioid analgesics, and to a lesser extent benzodiazepines such as alprazolam. These findings inform public health policy makers, criminal justice officials, the pharmaceutical industry and government regulatory agencies in their efforts to reduce the availability of diverted prescription drugs in the illicit market. Specifically, these data support the need for state-wide prescription drug monitoring programs and increased training for healthcare workers who have access to controlled medications.

Copyright 2012, Informa Healthcare

Rikala M; Korhonen MJ; Sulkava R; Hartikainen S. Psychotropic drug use in community-dwelling elderly people: Characteristics of persistent and incident users. European Journal of Clinical Pharmacology 67(7): 731-739, 2011. (42 refs.)

The aim of this prospective cohort study was to analyze psychotropic drug use in community-dwelling elderly people over a 3-year period and characterize those individuals most susceptible to persistent and incident use. Data on demographics, health status, cognition, functional capacity and drug use were gathered by interviews at baseline (2004) and in three follow-ups (2005-2007) in a population-based sample of 700 community-dwelling people aged 75 years and older. Characteristics associated with persistent and incident use were identified using Cox proportional-hazards regression. At baseline, 38% (n = 269) of the participants used psychotropic drugs. Of these, 60% (n = 162) reported use in all three follow-ups, whereas 22% (n = 59) discontinued use. Among the baseline users of antipsychotics (n = 40), antidepressants (n = 83) and benzodiazepines (n = 219), respectively, 43, 51 and 55% reported use in all three follow-ups. The characteristics associated with persistent use of psychotropic drugs included concomitant use of psychotropic drugs, regular use of psychotropic drugs, increasing age and good self-rated health. Among the baseline nonusers of psychotropic drugs (n = 431), 20% (n = 88) initiated use during the follow-up. Incident use of psychotropic drugs was associated with increasing Geriatric Depression Scale scores, a Mini-Mental State Examination score 24 and less, 6 or more visits to physician, moderate/poor self-rated health and moderate/poor life satisfaction. Psychotropic drugs, benzodiazepines in particular, are frequently used for extended periods in community-dwelling people aged 75 years. Individuals with multiple psychotropic drugs and a regular pattern of use are most susceptible to persistent use. Characteristics associated with incident use include depressive symptoms, cognitive decline and poor general health.

Copyright 2011, Springer

Rossat A; Fantino B; Bongue B; Colvez A; Nitenberg C; Annweiler C et al. Association between benzodiazepines and recurrent falls: A cross-sectional elderly population-based study. Journal of Nutrition, Health & Aging 15(1): 72-77, 2011. (31 refs.)

Background: While the association between benzodiazepines (BZD) and single fall is long-known, the association between BZD and recurrent falls has been few studied. Objective: The aims of this study were 1) to examine whether BZD were associated with recurrent falls while taking into account the effect of potential confounders, and 2) to determine whether there was an interaction in terms of risk of falls between BZD and balance impairment in a community-dwelling population-based adults aged 65 and older. Study design: Cross-sectional. Setting: Three health centers in North-East of France. Population: 7643 community-dwelling volunteers aged 65 and older. Outcome measures: The use of BZD, the Mini Mental State Examination (MMSE) score, the Clock Drawing Test (CDT), the One Leg Balance (OLB) test, the Five Times Sit-To-Stand test (FTSS), and a history of falls were recorded. Subjects were separated into 4 groups based on the number of falls: 0, 1, 2 and >= 3 falls. Results: Among the 1456 (19.2%) fallers, 994 (13.0%) were single fallers and 462 (6.1%) were recurrent fallers (i.e., > 2 falls). The number of falls increased significantly with age (Incident Rate Ratio (IRR) = 1.04, P < 0.001), female gender (IRR = 2.24, P < 0.001), the use of benzodiazepine (IRR = 1.65 P < 0.001) and especially while subjects used bromazepam (IRR = 1.44, P = 0.006), clobazam (IRR = 3.01, P = 0.014) and prazepam (IRR = 2.29, P < 0.001). A low MMSE score (IRR = 0.96, P < 0.001), an impaired CDT (IRR = 0.91, P < 0.001), and a bad performance at OLB and FTSS (respectively IRR = 1.85, P < 0.001 and IRR = 1.26, P < 0.001) were related to the recurrence of falls. After adjustment only the advance in age (IRR = 1.02, P < 0.001), female gender (IRR = 2.15, P < 0.001), clobazam (IRR = 2.54, P = 0.04), prazepam (IRR = 1.63, P = 0.03) and OLB (IRR = 1.55, P < 0.001) were still significantly related to the number of falls. Conclusion: The current study shows that the age, the female gender, the use of clobazam or prazepam and a low score at OLB are related to the recurrence of falls.

Copyright 2011, Springer

Rouve N; Bagheri H; Telmon N; Pathak A; Franchitto N; Schmitt L et al. Prescribed drugs and violence: A case/noncase study in the French PharmacoVigilance Database. European Journal of Clinical Pharmacology 67(11): 1189-1198, 2011. (35 refs.)

Aim Our aim was to identify prescribed drugs associated with violent behaviours using the French PharmacoVigilance Database (FPVD). Methods All reports of adverse drug reactions (ADR) recorded in the FPVD between 1January 1985 and 31July 2008 and including the terms aggressiveness or violence were selected. We compared proportion of exposure to different drugs between cases (reports with violence) and noncases (other reports in the database). Results Among 537 cases, 56 were included (48 men, mean age 46 years). Misuse was observed in ten cases (18%). In 25 cases (44.6%), a previous psychiatric history was documented. Main drugs involved were nervous system (63.6%) followed by respiratory (7.8%), alimentary tract and metabolism (7.8%), dermatological (5.2%) and anti-infective (5.2%) agents. Case/noncase analysis found an association with dopaminergic agonists (pergolide, pramipexole, bromocriptine, piribedil), benzodiazepines (alprazolam, bromazepam) and serotoninergic antidepressants (taken as a whole), but not antipsychotics or antiepileptics. Association was also found with varenicline, isotretinoin, interferon alpha-2b, rimonabant, benfluorex, topiramate and antiviral drugs (ribavirin, efavirenz). Conclusion: Dopaminergic agonists, benzodiazepines and serotoninergic antidepressants are the main pharmacological classes able to induce aggressive behaviour. This study also emphasises the putative role of other drugs less known to be involved in such ADR.

Copyright 2011, Springer

Rubio G; Bobes J; Cervera G; Teran A; Perez M; Lopez-Gomez V et al. Effects of pregabalin on subjective sleep disturbance symptoms during withdrawal from long-term benzodiazepine use. European Addiction Research 17(5): 262-270, 2011. (35 refs.)

Aim: To evaluate the effectiveness of pregabalin as a tapering therapy on the subjective sleep quality of patients who underwent a benzodiazepine withdrawal program in routine medical practice. Methods: Secondary analysis of a 12-week prospective, open noncontrolled study carried out in patients who met DSM-IV-TR criteria for benzodiazepine dependence. Sleep was evaluated with the Medical Outcomes Study Sleep Scale (MOS Sleep Scale). Results: 282 patients were included in the analysis. Mean (+/- SD) pregabalin dose was 315 +/- 166 mg/day at the end of the trial. We observed a significant and clinically relevant improvement in sleep outcomes at the endpoint, with a total score reduction from 55.8 +/- 18.9 to 25.1 +/- 18.0 at week 12 (i.e. a 55% reduction). Similar findings were apparent using the six dimensions of the MOS Sleep Scale. Moderate correlations were observed between the MOS Sleep summary index and sleep domains, and there were improvements in anxiety symptoms and disease severity. Conclusions: These findings suggest that pregabalin may improve subjective sleep quality in patients who underwent a benzodiazepine withdrawal program. This effect appears to be partly independent of improvements in symptoms of anxiety or withdrawal. However, controlled studies are needed to establish the magnitude of the effect of pregabalin.

Copyright 2011, Karger

Saha TD; Compton WM; Chou SP; Smith S; Ruan WJ; Huang B et al. Analyses related to the development of DSM-5 criteria for substance use related disorders 1. Toward amphetamine, cocaine and prescription drug use disorder continua using item response theory. Drug and Alcohol Dependence 122(1-2): 38-46, 2012. (40 refs.)

Background: Prior research has demonstrated the dimensionality of alcohol, nicotine and cannabis use disorders criteria. The purpose of this study was to examine the unidimensionality of DSM-IV cocaine, amphetamine and prescription drug abuse and dependence criteria and to determine the impact of elimination of the legal problems criterion on the information value of the aggregate criteria. Methods: Factor analyses and Item Response Theory (IRT) analyses were used to explore the unidimensionality and psychometric properties of the illicit drug use criteria using a large representative sample of the U.S. population. Results: All illicit drug abuse and dependence criteria formed unidimensional latent traits. For amphetamines, cocaine, sedatives, tranquilizers and opioids, IRT models fit better for models without legal problems criterion than models with legal problems criterion and there were no differences in the information value of the IRT models with and without the legal problems criterion, supporting the elimination of that criterion. Conclusion: Consistent with findings for alcohol, nicotine and cannabis, amphetamine, cocaine, sedative, tranquilizer and opioid abuse and dependence criteria reflect underlying unitary dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the American Psychiatric Association's DSM-5 Substance and Related Disorders Workgroup.

Copyright 2012, Elsevier Science

Salonika M; Salminen M; Vahlberg T; Aarnio P; Kivela SL. Withdrawal of psychotropic drugs decreases the risk of falls requiring treatment. Archives of Gerontology and Geriatrics 54(1): 160-167, 2012. (34 refs.)

This non-randomized, controlled trial assessed the effects of ceasing fall-risk-increasing drugs (FRIDs) (psychotropics or opiates or potent anticholinergics) on the risk of falls requiring medical treatment as a sub-analysis of a randomized, controlled multifactorial fall prevention. The population in this 12-month study consisted of 528 community-dwelling subjects aged 65 years or older with a history of at least one fall. The subjects were divided retrospectively into three groups according to the use of any FRID, any psychotropic drug, and benzodiazepine or related drug (BZD/BZDRD). The subjects in the intervention group (IG) ceasing the drug use were compared with the subjects in IG and the control group (CG) not ceasing the use of the corresponding type of drugs during the intervention period. Falls were recorded from medical records. For the year after the 12-month intervention the relative risk ratio (with 95% confidence intervals = CI) for controls in CG compared with the withdrawal group in IG was 8.26 (1.07-63.73) among the users of psychotropics and 8.11 (1.03-63.60) among the users of BZDs/BZDRDs. Withdrawal of psychotropics, especially BZDs/BZDRDs may have played an important role by lowering the risk of falls requiring medical treatment during the year after the 12-month multifactorial intervention.

Copyright 2012, Elsevier Science

Samms WC; Jiang YJ; Dixon MD; Houck SS; Mozayani A. Analysis of alprazolam by DART-TOF mass spectrometry in counterfeit and routine drug identification cases. Journal of Forensic Sciences 56(4): 993-998, 2011. (14 refs.)

The high prevalence of alprazolam abuse translates to an increased workload for crime laboratories in characterizing seized tablets. These tablets may originate as diverted pharmaceuticals or counterfeited mimics, so efficient analytical techniques should provide confirmatory data while minimizing destruction of evidence. We offer the first report of a validated forensic method for confirming alprazolam tablets by direct analysis in real time-time of flight (DART-TOF) mass spectrometric analysis. This technique provides rapid identification of target analytes with minimal sample preparation, allowing direct analysis in the atmospheric sample gap. Selectivity is achieved through high resolution and mass accuracy, unique ion fragments, and chlorine isotopic ratios. This method utilizes fragmentation in two separate voltage functions to observe the alprazolam pseudo molecular ion at 309.09070 using 40 V and major ion fragments of 281.07197 and 205.07657 at 120 V. These parameters allow our laboratory to confirm alprazolam tablets efficiently, without compromising quality forensic standards.

Copyright 2011, Wiley-Blackwell

Sanyal C; Asbridge M; Kisely S; Sketris I; Andreou P. The utilization of antidepressants and benzodiazepines among people with major depression in Canada. Canadian Journal of Psychiatry 56(11): 667-676, 2011. (53 refs.)

Objective: Although clinical guidelines recommend monotherapy with antidepressants (ADs) for major depression, polypharmacy with benzodiazepines (BDZs) remains an issue. Risks associated with such treatments include tolerance and dependence, among others. We assessed the prevalence and determinants of AD and BDZ utilization among Canadians who experienced a major depressive episode (MDE) in the previous 12 months, and determined the association of seeing a psychiatrist on the utilization of ADs and BDZs. Method: Data were drawn from the 2002 Canadian Community Health Survey: Health and Well-Being, a nationally representative sample of Canadians aged 15 years and older. Descriptive statistics quantified utilization, while logistic regression identified factors associated with utilization, such as sociodemographic characteristics or type of physician seen. Sampling weights and bootstrap variance estimations were used for all analysis. Results: The overall prevalence of AD and BDZ utilization was 49.3% of respondents who experienced an MDE in the past 12 months and reported AD use. Key determinants of utilization were younger age and unemployment in the past week (OR 2.6; P < 0.001). Being seen by a psychiatrist increased utilization (OR 2.5; P < 0.001), possibly because psychiatrists were seeing patients with severe depression. Conclusion: A large proportion of people with past-year MDEs utilized ADs and BDZs. It is unclear how much of this is appropriate given that evidence-based clinical guidelines recommend monotherapy with ADs in the treatment of major depression.

Copyright 2011, Canadian Psychiatric Association

Smith GW; Farrell M; Bunting BP; Houston JE; Shevlin M. Patterns of polydrug use in Great Britain: Findings from a national household population survey. Drug and Alcohol Dependence 113(2-3): 222-228, 2011. (55 refs.)

Background: Polydrug use potentially increases the likelihood of harm. As little is known about polydrug use patterns in the general population, it is difficult to determine patterns associated with highest likelihood. Methods: Latent class analysis was performed on nine illicit substance groups indicating past year use of cannabis, cocaine, amphetamines, ecstasy, LSD, mushrooms, amyl nitrate, tranquillisers and heroin or crack. Analyses were based on data from a large multi-stage probability sample of the population of Great Britain (n=8538) collected in 2000. Multinomial logistic regression was performed highlighting associations between classes, and demographic and mental health variables. Results: A three class solution best described patterns of polydrug use; wide range, moderate range, and no polydrug use. For males and young people, there was a significantly increased chance of being in the wide and moderate range polydrug use groups compared to the no polydrug use class. Hazardous drinking was more likely in the wide and moderate polydrug classes with odds ratios of 9.99 and 2.38 (respectively) compared to the no polydrug use class. Current smokers were more likely to be wide and moderate range polydrug users compared to the no polydrug use class with odds ratios of 4.53 and 5.85 respectively. A range of mental health variables were also related to class membership. Conclusions: Polydrug use in Great Britain can be expressed as three distinct classes. Hazardous alcohol use and tobacco use were strongly associated with illicit polydrug use, polydrug use appeared to be significantly associated with mental health, particularly lifetime suicide attempts.

Copyright 2011, Elsevier Science

Sorodoc V; Jaba IM; Lionte C; Mungiu OC; Sorodoc L. Epidemiology of acute drug poisoning in a tertiary center from Iasi County, Romania. Human & Experimental Toxicology 30(12): 1896-1903, 2011. (40 refs.)

The aim of this retrospective epidemiological study was to investigate the demographical, etiological and clinical characteristics of acute drug poisonings in Iasi County, Romania. All patients were referred and admitted in the Toxicology Clinic of "Sf. loan" Emergency Clinic Hospital Iasi, Romania. Between 2003 and 2009, 811 cases of acute drug poisonings were recorded, counting for 28.43% from the total number of poisonings. The majority of these poisonings resulted in mild (51.94%) and medium (28.35%) clinical forms, while 19.71% were coma situations. In all, 63.51% of patients originated from urban areas, 39.94% were unemployed and the patients were predominantly women (66.46%). A high percentage (97.27%) were suicide attempts, using only one type of drug (65.88%) and the 21-30 years group (29.8%) records the highest incidence, for both women and men. The most frequently involved drugs were benzodiazepines 13.69%, anticonvulsive drugs 8.63%, barbiturates 8.51% and cardiovascular drugs 5.92%. Drugs combinations were recorded in 32.92% of cases and 1.2% were combinations between drugs and other substances. Mortality was the outcome in 0.3% of the total registered number of acute drug poisonings. This study underlines that in order to provide a proper management of these situations, a Regional Poison Information Center is absolutely necessary.

Copyright 2011, Sage Publications

Spanemberg L; Nogueira EL; da Silva CTB; Dargel AA; Menezes FS; Neto AC. High prevalence and prescription of benzodiazepines for elderly: Data from psychiatric consultation to patients from an emergency room of a general hospital. General Hospital Psychiatry 33(1): 45-50, 2011. (33 refs.)

Objectives: The aim of this study is to compare the use and prescription of psychotropic drugs, with emphasis on benzodiazepines, in elderly and non-elderly patients who are assisted at the emergency room by a psychiatric consultation of a university teaching hospital. Method: This is a cross-sectional study. We analyzed all records of psychiatric consultation in an emergency room of a general hospital from March 2009 until March 2010. Sociodemographic and clinical variables were compared between the group of elderly and non-elderly in two cutoff points (>= 60 and >= 65 years), with emphasis on the use and prescription of benzodiazepines. Results: Five hundred seventy-five records were found with 71 elderly and 504 nonelderly for the first cutoff point and 51 elderly and 524 nonelderly in the second. Differences between groups were found in all sociodemographic variables (gender, marital status, education, current occupational status). Elderly patients treated at emergency rooms used more psychotropic drugs, particularly antidepressants and benzodiazepines, than non-elderly. About 25% of the patients received benzodiazepine treatment in the emergency setting, and there was no statistical difference between age groups. Conclusion: There is a wide prevalence of benzodiazepine use among elderly patients in a psychiatric emergency service. Despite the recommendations for its judicious use, benzodiazepines were the most commonly used drug by psychiatrists on duty, regardless of patient's age. These results call for caution in prescribing these drugs and require alternatives to the treatment of psychiatric disorders in the elderly.

Copyright 2011, Elsevier Science

Specka M; Bonnet U; Heilmann M; Schifano F; Scherbaum N. Longitudinal patterns of benzodiazepine consumption in a German cohort of methadone maintenance treatment patients. Human Psychopharmacology: Clinical and Experimental 26(6): 404-411, 2011. (40 refs.)

Objective Cross-sectional studies show that considerable proportions of opiate dependents in methadone maintenance treatment (MMT) consume benzodiazepines (BZD). The longitudinal patterns of BZD use over time were described here. Methods After admission to MMT, patients from two outpatient MMT clinics (n=345) were observed for up to 2years whilst in treatment. The use of BZD, cannabis, opiates and cocaine was assessed by urine sampling carried out twice a month. Results: For the whole sample, the mean BZD-positive urine specimen rate was 0.36 during the first 3months. Rates slightly decreased during the first year and remained stable afterwards (last observation carried forward). For study completers (n=152), the rate decreased over time, from 0.31 (first 3-month period) to 0.19 (last period; p < 0.001). According to a longitudinal cluster analysis, 26% of all patients showed a pattern of constantly high BZD-positivity rates, mostly in combination with other substances. Inpatient detoxifications from BZD (carried out in 18% of cases) did not have a sustained effect on levels of BZD use. Conclusions: BZD consumption in MMT is often part of a polydrug consumption pattern and is associated with poorer treatment retention. It is necessary to further investigate the reasons for BZD use in MMT patients and to develop effective interventions to reduce levels of BZD consumption.

Copyright 2011, Wiley-Blackwell

Temple JR; Freeman DH. Dating violence and substance use among ethnically diverse adolescents. Journal of Interpersonal Violence 26(4): 701-718, 2011. (61 refs.)

Teen dating violence is a serious public health concern with numerous and long-lasting consequences. Although alcohol and drug use have been associated with dating violence, little is known about the role of specific substances, especially the use of club drugs and the nonmedical use of prescription drugs. Thus, the authors examined the association between dating violence victimization and the use of a variety of licit and illicit substances among 1,565 ethnically diverse and economically disadvantaged high school students in southeast Texas. Past year dating violence victimization was reported by 14.1% of boys and 11.3% of girls. Compared to their nonabused counterparts, youth who experienced dating violence were more likely to smoke cigarettes, drink alcohol, binge drink alcohol, sniff glue to get high, use marijuana, use ecstasy, use Vicodin, and use Xanax. However, with the exception of alcohol and cigarettes, all substances were reduced to nonsignificance in multivariate analyses. No differences were found in the rate of dating violence between African American, White, and Hispanic adolescents.

Copyright 2011, Sage Publications

Todorovic MS; Mitrovic S; Aleksandric B; Mladjenovic N; Matejic S. Association of pulmonary histopathological findings with toxicological findings in forensic autopsies of illicit drug users. Vojnosanitetski Pregled 68(8): 639-642, 2011. (11 refs.)

Background/Aim. Drug abuse remains a significant social problem in many countries. The aim of the study was to estimate association between pulmonary histopathological changes and results of toxicological analyses in forensic autopsies of illicit drug users. Methods. This investigation was performed in the Institute of Forensic Medicine, Belgrade, and in the Clinical Center, Department of Forensic Medicine, Kragujevac, from 2000 to 2004, and included 63 medicolegal autopsies of heroin or other drug consumers who suddenly died. Autopsies, postmortem toxicological examination of drugs and serological analyses of anti-HIV/HBV/HCV antibodies were performed. Results. The deceased persons were mostly male, 46/63 (73.01%), ranged in age from 19 to 49 years (mean 31 years) and all were whites. Postmortem toxicological examination was performed on all of the deceased persons and drugs in the fatal range were identified in only eight of them (12.7%), in the toxic range in ten (15.87%), and in minimal concentrations in 35 (55.56%) of the deceased persons. Drugs identified in the fatal, toxic or minimal range included heroin-morphine (38/53), cocaine (4/53), tramadol (3/53), and lorazepam (1/53). In the 7 remaining subjects, ethanol in combination with heroin was found in 4 cases, and diazepam in combination with heroin in 3 cases. Dominant pathomorphological changes were findings in the lung tissue. Most common histological changes observed in drug users were pulmonary edema - 55/63 (87.3%), acute alveolar hemorrhages - 49/63 (77.78%), hemosiderin-laden macrophages (siderophages) - 52/63 (82,54%), and emphysematous changes - 51/63 (80,95%). Conclusion. Pulmonary edema is the frequent non-specific autopsy finding which is associated with virtually all routes of drug administration. The histopathological study is necessary to determinate a cause of death when a deceased person has the history of dependence or abouse of psychoactive drugs with negative toxicological results.

Copyright 2011, Military Medical Academy

Vaidya R; Sood R; Karlin N; Jatoi A. Benzodiazepine use in breast cancer survivors: Findings from a consecutive series of 1,000 patients. Oncology 81(1): 9-11, 2011. (8 refs.)

Objective: This study reports the percentage of breast cancer survivors receiving ongoing benzodiazepines and the circumstances surrounding their usage. Methods: The medical records of 1,000 consecutive breast cancer survivors who were no longer receiving adjuvant chemotherapy were reviewed. Results: Among those patients, 7.9% (95% confidence interval 6.2-9.6; higher than the 3% rate in the general population) were receiving benzodiazepines. Lorazepam was most commonly prescribed. Sixty-eight patients were cancer free at their last visit, and 51 had not been taking benzodiazepines prior to their cancer diagnosis. Anxiety was the single most frequent reason for initiating and continuing benzodiazepines. Conclusion: Anxiety appears to be a common explanation for relatively high rates of benzodiazepine use in breast cancer survivors. This finding merits further study.

Copyright 2011, Karger

Vogel M; Dursteler-MacFarland KM; Walter M; Strasser J; Fehr S; Prieto L et al. Prolonged use of benzodiazepines is associated with childhood trauma in opioid-maintained patients. Drug and Alcohol Dependence 119(1-2): 93-98, 2011. (43 refs.)

Background: Benzodiazepine (BZD) misuse in opioid-maintained patients is widespread and has been related to poorer treatment success. Associated factors, in particular, traumatic childhood experiences, have not been investigated extensively. Methods: Cross-sectional survey including the childhood trauma questionnaire (CTQ) and clinical data among 193 patients prescribed oral opioids or injectable diacetylmorphine for opioid dependence. Results: BZD use was prevalent (61%) and the burden of childhood traumatic experiences was high with 67% reporting at least one trauma subscore of moderate-to-severe level. In univariate analysis, CTQ-subcategories "emotional abuse" (p < 0.05), "emotional neglect" (p < 0.01) and "physical neglect" (p < 0.001) were significantly associated with prolonged BZD use. In multivariate analysis, prolonged BZD use was associated with categorized overall CTQ-scores (OR 1.5), FICV-seropositivity (OR 4.0), psychiatric family history (OR 2.3), and opioid dose (mg methadone equivalents, OR 1.010). Conclusions: Childhood traumatic experiences may be associated with prolonged BZD use in opioid-maintained patients and could pose an important starting-point for prevention.

Copyright 2011, Elsevier Science

Voyer P; Preville M; Martin LS; Roussel ME; Beland SG; Berbiche D. Factors associated with self-rated benzodiazepine addiction among community-dwelling seniors. Journal of Addictions Nursing 22(1-2): 46-56, 2011. (57 refs.)

Long-term use of benzodiazepines carries considerable personal consequences such as memory loss and functional impairment. In addition, use over time may bring about dependence and habituation thus leading older persons to believe they cannotdiscontinue the drug and to experience withdrawal symptoms should its use suddenly cease. The frequency of such negative consequences remains unclear. The purpose of this study is to determine the prevalence of self-rated addiction among older persons and its associated factors. Face-to-face computer-assisted interviews were conducted in the homes of 2,785 persons aged 65 years and over, randomly selected from across the Province of Quebec, Canada. Of the 707 users of benzodiazepines, 43%% considered themselves addicted. They were more likely to be 75 years or over, to suffer from panic disorder, to believe that health professionals are ready and available to discuss emotional problems with them, and to be less than satisfied with their social relationships. This study showed that a large proportion of benzodiazepine users rated themselves as addicted. These findings indicate that it is important for nurses to screen older adults living in the community to identify those who continue to use benzodiazepine beyond the recommended therapeutic time frame, perceive themselves to be dependent, and could potentially benefit from participation in a withdrawal program.

Copyright 2011, Informa Healthcare

Wilkins C; Sweetsur P; Griffiths R. Recent trends in pharmaceutical drug use among frequent injecting drug users, frequent methamphetamine users and frequent ecstasy users in New Zealand, 2006-2009. Drug and Alcohol Review 30(3): 255- 263, 2011. (22 refs.)

Aims. To examine the rates of pharmaceutical drug use, and level of prescription use and injection of pharmaceutical drugs, by frequent injecting drug users (IDU), frequent methamphetamine users and frequent ecstasy users in New Zealand for 2006-2009. Design: and method. The paper draws on findings from the 2006, 2007, 2008 and 2009 Illicit Drug Monitoring System (IDMS). The IDMS interviews three groups of frequent illegal drug users (i.e. IDU, methamphetamine users and ecstasy users) from the three main cities of New Zealand using purposive sampling and 'snowballing'. Results. Pharmaceutical morphine rather than heroin was the principal opioid used by the IDU. Few of the IDU or frequent methamphetamine users had prescriptions to use morphine. A lower proportion of the IDU had a prescription to use morphine in 2009 compared to 2008. The injection of methadone by IDU and methamphetamine users was common. A higher proportion of the IDU had injected methadone in 2009 compared to previous years. A higher proportion of the IDU had used oxycodone in 2009 compared to 2008 and prescription use of oxycodone by IDU was very low. All three groups of frequent drug users were involved in the extra-medical use of methylphenidate and benzodiazepines. Discussion and conclusion. Extra-medical use of pharmaceuticals occurred among all three groups of frequent illegal drug users to varying degrees. Differences between the three groups in the level and type of extra-medical pharmaceutical drug use suggest that different control strategies may be effective for each group.

Copyright 2011, Wiley-Blackwell

Wu CS; Lin YJ; Liu SK. Benzodiazepine use among patients with schizophrenia in Taiwan: A nationwide population-based survey. Psychiatric Services 62(8): 908-914, 2011. (28 refs.)

Objective: This study aimed to describe the pattern of benzodiazepine use in a representative sample of patients with schizophrenia in Taiwan. Methods: Data from the National Health Insurance Research Database in Taiwan were used to examine the prevalence and indices of benzodiazepine use in 2005. Demographic and clinical characteristics associated with long-term benzodiazepine use (more than 180 days of cumulated prescription in one year) were further explored by multivariate logistic regression analysis. Results: Among the 3,690 patients with schizophrenia, the one-year prevalence rate of benzodiazepine use was 79.2% (N=2,923). Among those who used benzodiazepines, 1,840 (62.9%) were long-term users. Use of benzodiazepines was associated with having a comorbid psychiatric disorder, use of concomitant psychotropic agents, and antipsychotic polypharmacy. Among benzodiazepine users, older age, longer duration of illness, and use of concomitant psychotropic agents were associated with significantly higher odds of being a long-term user. Conclusions: The study showed that benzodiazepine use was highly prevalent among patients with schizophrenia in Taiwan and that a substantial proportion of users (62.9%) were long-term users. Because long-term use was associated with longer duration of illness and with use of concomitant psychotropic medications, long-term users may be at higher risk of neurocognitive side effects caused by benzodiazepines and interactions with other psychotropic medications. Therefore, this group should be closely monitored for drug-drug interactions and the benefits and risks of benzodiazepine use.

Copyright 2011, American Psychiatric Association

Yeh HH; Chen CY; Fang SY; Chang IS; Wu ECH; Lin KM. Five-year trajectories of long-term benzodiazepine use by adolescents: Patient, provider, and medication factors. Psychiatric Services 62(8): 900-907, 2011. (41 refs.)

Objectives: This study sought to understand the stability of and change in benzodiazepine use among incident long-term benzodiazepine users over a five-year period and to investigate predictors of variation in use patterns from adolescence into adulthood. Methods: Long-term use was defined as receipt of benzodiazepine prescriptions for 31 or more cumulative days in a calendar year. Data for 1999-2005 were obtained from the National Health Insurance Research Database in Taiwan. Two age groups of incident long-term users in 2000 were identified-1,758 aged 12-15 and 5,265 aged 16-19-and their benzodiazepine prescription records from 2001 to 2005 were retrieved. Group-based trajectory analyses and polytomous logistic regression were performed to evaluate differential risk of benzodiazepine use over time. Results: From 3% to 5% of the incident benzodiazepine users were long-term users. Four distinct groups of users emerged from the five years of study data: occasional, decelerating, accelerating, and chronic users. Overall, one-quarter were accelerating or chronic users. A history of psychosis or epilepsy, prescription by providers from multiple specialties, and receipt of benzodiazepines with a long half-life or mixed indications significantly increased one's risk of becoming a chronic or accelerating user (range of adjusted odds ratios from 2 to 6). Conclusions: Patient characteristics and attributes of service providers and pharmacological agents played significant roles in benzodiazepine use patterns. Prescribers can reduce the risk of long-term use by assessing whether pediatric patients have received benzodiazepines from multiple doctors for various medical conditions.

Copyright 2011, American Psychiatric Association