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CORK Bibliography: Benzodiazepines

48 citations. July 2006 to present

Prepared: June 2007

Acheson A; Richards JB; Reynolds B; de Wit H. Diazepam impairs behavioral inhibition but not delay discounting or risk taking in healthy adults. Experimental and Clinical Psychopharmacology 14(2): 190-198, 2006. (49 refs.)

There are reports that diazepam can increase, decrease, or have no effect on measures of impulsive behavior, which may be related, in part, to differences among the tasks used to measure impulsivity. This study examined the effects of a relatively high dose of diazepam (20 mg) on 5 measures of impulsive behavior in healthy adult men and women. Volunteers (N = 18) participated in a 2-session double-blind randomized design in which they received 20 mg diazepam or placebo. One hour after ingesting the capsule, participants completed mood questionnaires and several impulsivity tasks to measure subtypes of impulsive behavior, including behavioral inhibition, delay and probability discounting, and risk taking. Diazepam impaired behavioral inhibition but had no effect on measures of discounting or risk taking. These results are discussed in the context of other recent findings suggesting that different behavioral indices of impulsivity are dissociable and governed by separate underlying mechanisms.

Bartu A; Sharp J; Ludlow J; Doherty DA. Postnatal home visiting for illicit drug-using mothers and their infants: A randomised controlled trial. Australian & New Zealand Journal of Obstetrics & Gynaecology 46(5): 419-426, 2006. (15 refs.)

Background: Postnatal home-visiting programs for illicit drug-using mothers have reported some success in reducing harms in some areas but there is a lack of data on their impact on breastfeeding and immunisation rates. Aims: To investigate the effect on breastfeeding, immunisation and parental drug use. The hypothesis was that the outcomes of the home-visiting group (HVG) would be superior to the control group (CG). Method: One hundred and fifty-two illicit drug-using women were recruited at 35-40 weeks gestation from King Edward Memorial Hospitalital, Perth, Western Australia and randomised after delivery to the HVG or the CG. The HVG had eight home visits; the CG had telephone contact at two months and a home visit at six months. The HVG received education and support for parenting, breastfeeding and child development. This was not provided by the research midwives for the CG. Results: The main drugs were heroin, amphetamines, cannabis and benzodiazepines. Immunisation rates were similar for each group. Median duration of breastfeeding for the HVG was eight weeks (95% CI, 3.8-12.2); for the CG ten weeks (95% CI, 7.3-12.7). Drug use was reduced during pregnancy but increased by six months post-partum in both groups. The retention rates were: HVG 93%; CG 86%. Conclusion: The hypothesis for this study was not supported. Long-term studies are urgently required to assess the effects of parental drug use on infant and child development.

Bonsack C; Camus D; Kaufmann N; Aubert AC; Besson J; Baumann P et al. Prevalence of substance use in a Swiss psychiatric hospital: Interview reports and urine screening. Addictive Behaviors 31(7): 1252-1258, 2006. (21 refs.)

Background: Co-morbid substance misuse is common in psychiatric disorders, has potentially severe adverse consequences and may be frequently undetected. Aims: To measure the prevalence of substance use among patients admitted to a Swiss psychiatric hospital and to examine the potential utility of routine urine drug screening in this setting. Method: 266 inpatients were included. 238 patients completed the interview and 240 underwent a urine drug screening. Results: Lifetime prevalence of substance use among psychiatric patients was very high for alcohol (98%; 95% CI: 96-100), benzodiazepines (86%; 95% CI: 82-91) and cannabis (53%; 95% CI: 47-60), but also for Òhard drugsÓ like cocaine (25% ; 95% CI: 19-30) or opiates (20%; 95% CI: 15-25). Regular current use of alcohol (32%; 95% CI: 26-38) or cannabis (17%; 95% CI: 12-22) was the most frequent. Substance use was associated with male sex, younger age, unmarried status and nicotine smoking. Urine screening confirms reports from patients on recent use, and remained positive for cannabis during hospitalisation, but not for cocaine nor for opiates. Conclusion: Substance use is frequent among psychiatric patients. Systematic interviewing of patients about their substance use remains essential, and is usually confirmed by urine screening. Urine screening can be useful to provide specific answers about recent use.

Boumba VA; Ziavrou KS; Vougiouklakis T. Hair as a biological indicator of drug use, drug abuse or chronic exposure to environmental toxicants. (review). International Journal of Toxicology 25(3): 143-163, 2006. (165 refs.)

In recent years hair has become a fundamental biological specimen, alternative to the usual samples blood and urine, for drug testing in the fields of forensic toxicology, clinical toxicology and clinical chemistry. Moreover, hair-testing is now extensively used in workplace testing, as well as, on legal cases, historical research etc. This article reviews methodological and practical issues related to the application of hair as a biological indicator of drug use/abuse or of chronic exposure to environmental toxicants. Hair structure and the mechanisms of drug incorporation into it are commented. The usual preparation and extraction methods as well as the analytical techniques of hair samples are presented and commented on. The outcomes of hair analysis have been reviewed for the following categories: drugs of abuse ( opiates, cocaine and related, amphetamines, cannabinoids), benzodiazepines, prescribed drugs, pesticides and organic pollutants, doping agents and other drugs or substances. Finally, the specific purpose of the hair testing is discussed along with the interpretation of hair analysis results regarding the limitations of the applied procedures.

Bruno R. Tasmanian Drug Trends 2005: Findings from the Illicit Drug Reporting System (IDRS). NDARC Technical Report No. 245. Sydney: National Drug and Alcohol Research Centre (Australia), 2006. (66 refs.)

In 1999, the Tasmanian component of a national Illicit Drug Reporting System was initiated. It involves interviews with injecting drug users, interviews with key experts, and use of health and law enforcement data. The drugs included in the survey are heroin, methamphetamine, cocaine, cannabis, opioids, benzodiazepines, and 'other drugs' (ecstasy, prescription stimulants, inhalants, hallucinogens, and alkaloid poppies). For each of these drugs there is information about price, availability, patterns or use, the harm associated with use, trends in patterns of use. This is followed by a general discussion of drug related harms -- overdose, blood-borne infections, injection related health problems, driving risk behaviors, mental health problems, substance-related aggression, crime, and pharmacy burglaries. A concluding section sets forth the policy implication. Data is presented in 60 tables and 48 figures

Centers for Disease Control and Prevention; Kaplan J; Paulozzi L. Alcohol and drug use in fatal vehicle crashes -- West Virginia. MMWR. Morbidity and Mortality Weekly Report 55(48): 1293-1296, 2006. (10 refs.)

In 2005, approximately 39% of all traffic fatalities in the United States were alcohol related. Evidence of driver impairment from use of drugs other than alcohol is less definitive. In 2005, an estimated 4.3% of persons in the United States reported driving under the influence of a drug used recreationally during the preceding year, and an unknown percentage drove while impaired by drugs being used for medical reasons. To measure the prevalence of alcohol and drug use among persons killed in motor-vehicle crashes in West Virginia (where test results were available for >80% of fatalities), CDC analyzed 2004 and 2005 data reported by the West Virginia Office of the Chief Medical Examiner (OCME) to the Fatality Analysis Reporting System. This report summarizes the results of that analysis, which determined that the prevalence of drug use (25.8%) was similar to the prevalence of a blood alcohol concentration (BAC) >0.08 g/dL (27.7%) among persons killed in motor-vehicle crashes. These results suggest that drug use contributes substantially to driver impairment in West Virginia. In 2004 and 2005, a total of 784 motor-vehicle fatalities resulted from crashes on public roads in West Virginia. Of these, 663 (84.6%) had alcohol test results, 660 (84.2%) had drug test results, and 658 (83.9%) had both. Alcohol was detected in 32.5% of decedents tested for both alcohol and drugs. Illegal BACs (>0.08 g/dL) were detected in 27.7% of decedents, and BACs ranging from 0.01 to 0.07 g/dL were detected in 4.9%. The prevalence of detectable blood alcohol was higher in males and highest among persons aged 16--34 years. Drivers were more likely to have detectable blood alcohol levels than passengers. Detectable levels of at least one drug were reported for 170 (25.8%) decedents. The prevalence of detectable drug levels was higher in males and highest among persons aged 35--54 years. Drivers were more likely to have detectable drug levels than passengers. Among women and persons aged >55 years, drugs were more prevalent than alcohol. Nearly half (47.3%) of all decedents had alcohol or drugs in their bodies; 11.1% had both. Among decedents with detectable blood alcohol levels, 34.1% tested positive for drugs. Among decedents with no detectable blood alcohol levels, 21.8% tested positive for drugs. Opioid analgesics and depressants were each found in 7.3% of tested decedents. The three most common opioid analgesics were hydrocodone, oxycodone, and methadone. The depressants reported were sedatives and muscle relaxants, of which benzodiazepines accounted for 83.3%. The most common benzodiazepines were diazepam and alprazolam. Methamphetamines were involved in four of the five amphetamine reports. Overall, 7.6% of decedents and 9.0% of drivers had two or more of the five different types of drugs in their bodies.

Public Domain

Chan GM; Stajic M; Marker EK; Hoffman RS; Nelson LS. Testing positive for methadone and either a tricyclic antidepressant or a benzodiazepine is associated with an accidental overdose death: Analysis of medical examiner data. Academic Emergency Medicine 13(5): 543-547, 2006. (23 refs.)

Objectives: Patients in emergency departments who use methadone frequently use tricyclic antidepressants (TCAs) and/or benzodiazepines (BZDs). This is a potentially dangerous drug combination. The authors hypothesized that the presence of methadone and a TCA, a BZD, or both is associated with an "accidental" overdose (AOD) death more often than a death from any other cause. Methods: A retrospective chart review or New York City Office of Chief Medical Examiner data for 2003 was performed. Decedents who tested positive for methadone that were classified as an AOD death, as determined by the medical examiner, were compared with deaths from all other causes for the presence of a TCA, a BZD, or both. A logistical regression was performed to develop a multivariate model identifying additional variables associated with a methadone-positive AOD death. A p-value of <0.05 was considered significant, and 95% confidence intervals (CIs) were calculated. Results: In 2003, there were 5,817 medical examiner cases, of which 500 (8.6%) were methadone positive. Of the methadone-positive cases, 493 were available for analysis; 95 (19.3%) were TCA positive and 158 (32.0%) were BZD positive. The odds of having an AOD death in methadone-positive decedents testing TCA positive, BZD positive, or both were 2.11 (95%, CI = 1.32 to 3.37; (p < 0.01) for TCAs, 1.66 (95% Cl = 1.12 to 2.45; p < 0.02) for BZDs, and 4.34 (95% CI = 1.97 to 9.56; p < 0.001) for both. The multivariate logistic regression of analytes revealed the following covariates associated with an AOD death as well: amitriptyline, cocaine, morphine, or opiates. Conclusions: Among the methadone-positive cases, testing positive for a TCA, a BZD, or both was associated with an AOD death.

Cubala WJ; Landowski J. Seizure following sudden zolpidem withdrawal. (review). Progress in Neuro-Psychopharmacology & Biological Psychiatry 31(2): 539-540, 2007. (9 refs.)

Zolpidem is a short acting hypnotic drug belonging to imidazopyridine family. It produces its hypnotic effects via the GABA-A benzodiazepine receptor complex, and binds preferentially to those receptors containing the alpha-1 subunit. In comparison with benzodiazepines this mechanism is thought to reduce liability to induce dependence. Several case reports of zolpidem abuse and dependence have been published along with a small number of cases demonstrating seizures after sudden zolpidem withdrawal. We describe a case of a 29-year-old Caucasian woman who developed a generalized seizure following sudden zolpidem withdrawal subsequent to drug dependence to 160 mg of zolpidem. The clinical effects of zolpidem seem to be comparable to those of benzodiazepines and abuse, dependence and withdrawal seizures belong to the spectrum of its adverse drug reactions.

Darke S; Williamson A; Ross J; Teesson M. Reductions in heroin use are not associated with increases in other drug use: 2-year findings from the Australian Treatment Outcome Study. Drug and Alcohol Dependence 84(2): 201-205, 2006. (27 refs.)

Aims: To determine whether reductions in frequency of heroin use were associated with reductions in the use of other drugs over a 24-month period. Design: Longitudinal cohort, with follow-up at 3, 12 and 24 months. Participants: Six hundred and fifteen heroin users recruited for the Australian Treatment Outcome Study. Setting: New South Wales, Australia. Findings: The proportion reporting weekly heroin use declined significantly at 3, 12 and 24 months. Reductions in heroin use were associated with longer periods in both residential rehabilitation (RR) and maintenance treatment (MT). Less frequent use of other opioids, cocaine, amphetamine, cannabis and benzodiazepines were noted over follow-up, with alcohol use remaining stable. Across follow-up, lower frequency heroin use was associated with reduced likelihood of frequent use of other opioids, cocaine, amphetamine and benzodiazepines. Alcohol and cannabis use were unrelated to heroin use. Longer periods spent in RR were associated with declines in the use of all other drug classes, with MT associated with declines in other opioid and alcohol use. Conclusions: There was no evidence for drug substitution in the face of reduced heroin use in this cohort of treatment seekers. The fear that a successful reduction in heroin use amongst treatment seekers will precipitate an increase in the use of other drugs appears ill-founded.

Denis C; Fatseas M; Lavie E; Auriacombe M. Pharmacological interventions for benzodiazepine mono-dependence management in outpatient settings. (review). Cochrane Database of Systematic Reviews 3(CD005194), 2006. (53 refs.)

Background: The improved safety profile of benzodiazepines compared to barbiturates has contributed to a high rate of prescription since the seventies. Although benzodiazepines are highly effective for some disorders, they are potentially addictive drugs and they can provide reinforcement in some individuals. Objectives To evaluate the effectiveness of pharmacological interventions for benzodiazepine mono-dependence. Search strategy We searched the Cochrane Drugs and Alcohol Group' Register of Trials (October 2004), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (January 1966 to October 2004), EMBASE (January 1988 to October 2004), PsycInfo (1985 to October 2004), CINAHL (1982 to October 2004), Pascal, Toxibase, reference lists of articles. Selection criteria Randomized trials of benzodiazepines dependence management regardless of type, dose (daily and total) and duration of benzodiazepine treatment. Data collection and analysis: Reviewers independently assessed trials for inclusion, rated their methodological quality and extracted data. Main results Eight trials involving 458 participants were included. The studies included could not be analysed cumulatively because of heterogeneity of inteventions and participants' characteristics. Results support the policy of gradual rather than abrupt withdrawal of benzodiazepine. Progressive withdrawal (over 10 weeks) appeared preferable if compared to abrupt since the number of drop-outs was less important and the procedure judged more favourable by the participants. Short half-life benzodiazepine, associated with higher drop-out rates, did not have higher withdrawal symptoms scores. Switching from short half-life benzodiazepine to long half-life benzodiazepine before gradual taper withdrawal did not receive much support from this review. The role of propanolol in benzodiazepine withdrawal was unclear; adding tricyclic antidepressant (dothiepin) decreased the intensity of withdrawal symptoms but did not increase the rate of benzodiazepine abstinence at the end of the trial. Buspirone and Progesterone failed to suppress any benzodiazepine symptoms. Carbamazepine might have promise as an adjunctive medication for benzodiazepine withdrawal, particularly in patients receiving benzodiazepines in daily dosages of 20 mg/d or more of diazepam (or equivalents). Authors' conclusions: The results of this systematic review point to the potential value of carbamazepine as an effective intervention for benzodiazepine gradual taper discontinuation. Carbamazepine has shown rather modest benefit in reducing withdrawal severity, although it did significantly improve drug-free outcome. Larger controlled studies are needed to confirm these benefits, to assess adverse effects and to identify when its clinical use might be most indicated. Other suggested treatment approaches to benzodiazepine discontinuation management should be explored (antidepressants, benzodiazepine receptors modulator).

Dickson S; Park A; Nolan S; Kenworthy S; Nicholson C; Midgley J et al. The recovery of illicit drugs from oral fluid sampling devices. Forensic Science International 165(1): 78-84, 2007. (11 refs.)

Testing for drugs in oral fluid is a convenient procedure for determining recent drug use. A number of issues are still to be resolved and this paper investigates the effects of storage systems on drug stability and recovery using three different collection devices supplied by Cozart, Immunalysis and Microgenics (third party). Drugs were analysed using a range of immunoassay systems followed by MS confirmation and quantitation. The reproducibility of the weight of specimen collected was excellent (CV < 10%) for the three collection devices tested. Of the three systems studied, only the Cozart product gave acceptable recovery of THC from drug-spiked oral fluid. A combination of Cozart, Immunalysis and Diagnostix immunoassays with the Cozart collection system gave the most sensitive and discriminating screening assays for the drugs studied, namely THC, benzodiazepines, methamphetamine and morphine. Storage at either 5 degrees C or room temperature had no significant effect on drug recoveries.

Egger SS; Bachmann A; Hubmann N; Schlienger RG; Krahenbuhl S. Prevalence of potentially inappropriate medication use in elderly patients - Comparison between general medical and geriatric wards. Drugs & Aging 23(10): 823-837, 2006. (54 refs.)

Background and objective: Inappropriate drug use is one of the risk factors for adverse drug reactions in the elderly. We hypothesised that, in elderly patients, geriatricians are more aware of potentially inappropriate medications (PIMs) and may replace or stop PIMs more frequently compared with internists. We therefore evaluated and compared the prevalence of PIMs as well as anticholinergic drug use throughout hospital stay in elderly patients admitted to a medical or geriatric C, ward. Methods: In this retrospective cross-sectional study, 800 patients aged >= 65 years admitted to a general medical or geriatric ward of a 700-bed teaching hospital in Switzerland during 2004 were included. PIMs were identified using the Beers criteria published in 2003. The prevalence of anticholinergic drug use was assessed based on drug lists published in the literature. Results: The prevalence of use of PIMs that should generally be avoided was similar in medical and geriatric inpatients both at admission (16.0% vs 20.8%, respectively; p = 0.08) and at discharge (13.3% vs 15.9%, respectively; p = 0.31). In contrast to medical patients, the reduction in the prevalence of use of PIMs between admission and discharge in geriatric patients reached statistical significance (p < 0.05). Overall, the three most prevalent inappropriate drugs/drug classes were amiodarone, long-acting benzodiazepines and anticholinergic antispasmodics. At admission, the prevalence of use of PIMs related to a specific diagnosis was not significantly different between patients hospitalised to a medical or a geriatric ward (14.0% vs 17.5%, respectively; p = 0.17), as compared with the significant difference evident at hospital discharge (11.7% vs 23.7%, respectively; p < 0.001). This was largely because of a higher prescription rate of platelet aggregation inhibitors in combination with low-molecular-weight heparins and benzodiazepines in patients with a history of falls and syncope. The proportions of patients taking anticholinergic drugs in medical and geriatric patients at admission (13.0% vs 17.5%, respectively; p = 0.08) and discharge (12.2% vs 16.5%, respectively p = 0.10) were similar. Conclusion: Inappropriate drug use as defined by the Beers criteria was common in both medical and geriatric inpatients. Compared with internists, geriatricians appear to be more aware of PIMs that should generally be avoided, but less aware of PIMs related to a specific diagnosis, and of the need to avoid anticholinergic drug use. However, the results of this study should be interpreted with caution because some of the drugs identified as potentially inappropriate may in fact be beneficial when the patient's clinical condition is taken into consideration.

Gilchrist G; Atkinson J; Gruer L. Illicit tranquilliser use and dependence among female opiate users. Drug and Alcohol Review 25(5): 459-461, 2006. (21 refs.)

This study determined the predictors of 12-month dependence on illicit tranquillisers among female opiate users attending three services in Glasgow, Scotland, UK. Twelve-month drug dependence was measured using the Diagnostic Interview Schedule. The Revised Clinical Interview Schedule (CIS-R) measured current neurotic symptoms. 60% (159/266) had used illicit tranquillisers in the past 30 days, and 50% (132/266) met criteria for 12-month dependence on illicit tranquillisers. Polydrug use, injecting drug use, childhood and adulthood abuse, adverse life experiences and current and previous mental health problems were associated with 12-month dependence on illicit tranquillisers. Using multiple logistic regression, polydrug use in last 30 days (OR 3.2, 95% CI 1.5-7.0), history of deliberate self-harm (OR 2.5, 95% CI 1.4-4.4), history of injecting drug use (OR 2.5, 1.2-5.2) and likely to need treatment for current neurotic symptoms (CIS-R >= 18) (OR 2.4, 95% CI 1.3-4.4) predicted 12-month dependence on illicit tranquillisers. Drug users in general and female drug users in particular who are using illicit tranquillisers are also particularly likely to have psychiatric symptoms requiring treatment. Mental health problems should be assessed and monitored among this client group and counselling and psychosocial support should be provided when indicated.

Hallstrom C, ed. Benzodiazepine Dependence. Oxford: Oxford University Press, 2005. (Chapter refs.)

This edited volume examines the range of issues related to benzodizapines. It examines biological, pharmacological, psychological, and epidemiological perspectives. Attention is paid to the elderly, the use of the drugs in general practice, the place of benzodiazepines in the wider field of psychological treatments, and even to the role of the pharmaceutical industry in the current controversy about harm resulting from the drugs. There is a review of abuse of benzodiazepines in special populations: by illicit drug users and among women. Alternative pharmacological and psychological treatments to benzodiazepines are considered in detail, but there is almost no consideration of the economic implications of either. What is not addressed are the larger social questions raised by benzodiazeine use, and a current major law suit underway in the United Kingdom.

Handel DA; Raja A; Lindsell CJ. The use of sleep aids among Emergency Medicine residents: A web based survey. BMC Health Services Research 6(e136), 2006. (28 refs.)

Background: Sleepiness is a significant problem among residents due to chronic sleep deprivation. Recent studies have highlighted medical errors due to resident sleep deprivation. We hypothesized residents routinely use pharmacologic sleep aids to manage their sleep deprivation and reduce sleepiness. Methods: A web-based survey of US allopathic Emergency Medicine ( EM) residents was conducted during September 2004. All EM residency program directors were asked to invite their residents to participate. E-mail with reminders was used to solicit participation. Direct questions about use of alcohol and medications to facilitate sleep, and questions requesting details of sleep aids were included. Results: Of 3,971 EM residents, 602 (16%) replied to the survey. Respondents were 71% male, 78% white, and mean (SD) age was 30 ( 4) years, which is similar to the entire EM resident population reported by the ACGME. There were 32% 1st year, 32% 2nd year, 28% 3rd year, and 8% 4th year residents. The Epworth Sleepiness Scale (ESS) showed 38% of residents were excessively sleepy ( ESS 11 - 16) and 7% were severely sleepy (ESS> 16). 46% ( 95 CI 42% - 50%) regularly used alcohol, antihistamines, sleep adjuncts, benzodiazepines, or muscle relaxants to help them fall or stay asleep. Study limitations include low response and self-report. Conclusion: Even with a low response rate, sleep aid use among EM residents may be common. How this affects performance, well-being, and health remains unknown.

Hay G; Gannon M. Capture-recapture estimates of the local and national prevalence of problem drug use in Scotland. International Journal of Drug Policy 17(3): 203-210, 2006. (26 refs.)

Estimates of the prevalence of problem drug use, defined within this study as the illicit use of opiates or benzodiazepines, have been provided for all 32 local government areas in Scotland. A national prevalence estimate has been derived as the sum of the local estimates. Data on individual drug users were collated from the police, social work departments, general practitioners, drug treatment services. These data were augmented by the Scottish Drug Misuse Database. In total 22,795 individuals were identified as opiate or benzodiazepine users. This figure corresponds to 0.8% of the population aged 15 to 54. In terms of the national prevalence of problem drug use, it was estimated that there were 55,800 individuals illicitly using opiates and benzodiazepines in Scotland in the year 2000 (95% CI: 43,591-77,697%). That figure corresponds to 2.0% (95% CI: 1.5-2.7%) of the population aged 15 to 54. The local prevalence rates, derived from capture-recapture estimates, ranged from 0.8 to 3.8%. This study has demonstrated that it is possible to use the capture-recapture method in urban and rural areas and, by systematically applying this method at the local level, a national prevalence estimate can be obtained.

Henderson M; MacGregor E; Sykes N; Hotopf M. The use of benzodiazepines in palliative care. Palliative Medicine 20(4): 407-412, 2006. (24 refs.)

Background: Benzodiazepines are widely used in palliative care, but few studies have attempted to study their use. Aim: To determine the frequency and nature of benzodiazepine prescribing in a palliative care setting. Method: The notes of a consecutive series of 100 patients who had died or been discharged from the hospice were studied. Demographic, illness and prescription data were noted. The indication for the administration of benzodiazepines, their effectiveness and any adverse effects were recorded. Results: Notes were found on 93 patients. Some 54 (58%) were prescribed benzodiazepines either by the hospice or their General Practitioner. Younger patients and those on opioids or anti-psychotics were more likely to be prescribed benzodiazepines. Most administration of benzodiazepines occurred within the last three weeks of life in response to symptoms of anxiety or less specific distress. Conclusions: A relatively high proportion of patients was prescribed benzodiazepines. The role of benzodiazepines at different stages of palliative care merits further study.

Herzberg D. "The pill you love can turn on you": Feminism, tranquilizers, and the Valium panic of the 1970s. American Quarterly 58(1): 79-103, 2006. (69 refs.)

This essay analyzes the cultural politics of a late-1970s Valium addiction scare in the context of other episodes of American drug hysteria. Since the days of "Demon Rum," antidrug campaigns in the U.S. typically associated drugs with marginal populations such as immigrants, nonwhites, or the urban poor. The "drug menace" helped dramatize the threat posed by such "dangerous classes" to "our" society, while mobilizing state police power to control it. The Valium panic was a different matter, involving a quintessentially middle-class drug prescribed legally by reputable physicians for their respectable patients, and popularly recognized as an entrenched part of life in the comfortable classes, especially for women. Its emergence signaled important but little-examined changes in American drug politics, and raised the prospect of a new kind of antidrug warrior. Central to creating the Valium addiction scare were certain white, middle-class segments of the diverse "second-wave" feminist movement, who redeployed the powerful cultural tools of the drug war for their own agendas. They revised classic drug-scare narratives to sensationalize Valium addiction as a central symbol of sexism, and held up liberation from the "mother's little helper" as an archetypal story of self-emancipation through feminism. This was a remarkable campaign, earning new audiences for feminist political messages and challenging the punitive logic of the 20th century's "war against drugs." It was also, however, limited in important ways by the class and race dynamics of American drug politics. The stories about Valium addiction they constructed for popular consumption traded on assumptions of white, middle-class women's essential innocence in a way that excluded-and even reified-the "dangerous classes" as a different sort of drug user. And yet, their success in reworking the anti-drug tradition for their own ends challenges us to imagine exactly that: a "war against drugs" rebuilt as a civil rights campaign, challenging rather than reinforcing cultural stereotypes.

Huang BJ; Dawson DA; Stinson FS; Hasin DS; Ruan WJ; Saha TD et al. Prevalence, correlates, and comorbidity of nonmedical prescription drug use and drug use disorders in the United States: Results of the National Epidemiology Survey on Alcohol and Related Conditions. Journal of Clinical Psychiatry 67(7): 1062-1073, 2006. (58 refs.)

Objective: To present national data on the prevalence, correlates, and comorbidity of nonmedical prescription drug use and drug use disorders for sedatives, tranquilizers, opioids, and amphetamines. Method: Data were derived from the National Epidemiologyogic Survey on Alcohol and Related Conditions (NESARC), a face-to-face nationally representative survey of 43,093 adults conducted during 2001 and 2002. Results: Lifetime prevalences of nonmedical use of sedatives, tranquilizers, opioids, and amphetamines were 4.1%, 3.4%, 4.7%, and 4.7%, respectively. Corresponding rates of abuse and/or dependence on these substances were 1.1%, 1.0%, 1.4%, and 2.0%. The odds of nonmedical prescription drug use and drug use disorders were generally greater among men, Native Americans, young and middle-aged, those who were widowed/separated/divorced or never married, and those residing in the West. Abuse/dependence liability was greatest for amphetamines, and nonmedical prescription drug use disorders were highly comorbid with other Axis I and II disorders. The majority of individuals with nonmedical prescription drug use disorders never received treatment. Conclusions: Nonmedical prescription drug use and disorders are pervasive in the U.S. population and highly comorbid with other psychiatric disorders. Native Americans had significantly greater rates of nonmedical prescription drug use and drug use disorders, highlighting the need for culturally-sensitive prevention and intervention programs. Unprecedented comorbidity between nonmedical prescription drug use disorders and between nonmedical prescription drug use disorders and illicit drug use disorders suggests that the typical individual abusing or dependent on these drugs obtained them illegally, rather than through a physician. Amphetamines had the greatest abuse/dependence liability, and recent increases in the potency of illegally manufactured amphetamines may portend an epidemic in the youngest NESARC cohort.

Kinner S; Fischer J; Lloyd B. Queensland Drug Trends 2005: Findings from the Illicit Drug Reporting System (IDRS). NDARC Technical Report No. 254. Sydney: National Drug and Alcohol Research Centre (Australia), 2006. (17 refs.)

This report presents the results of an ongoing survey of drug use in Queensland. Data is provided on the injecting drug users, their demographic characteristics, their patterns of drug use. Particular attention is directed to heroin, but also data are provided on methamphetamine, cocaine, marijuana, diverted prescription drugs -- methadone, buprenorphine, morphine, other opiates, and benzodiazepines. The report then considers associated harms, as well as considering the implications of the changes in heroin availability and resulting changes in other drug use. Data is presented in 37 tables and 69 figures.

Kliewer W; Murrelle L. Risk and protective factors for adolescent substance use: Findings from a study in selected Central American countries. Journal of Adolescent Health 40(5): 448-455, 2007. (25 refs.)

Purpose: To identify the prevalence of substance use and problems with use, and risk and protective factors at different levels of the adolescent's ecology associated with substance use among adolescents in selected Central American countries. Methods: Results of a survey of 17,215 students from Panama, Costa Rica, and Guatemala conducted in 2000-2001 served as the basis for the analyses. Lifetime use of alcohol, tobacco, marijuana, and five other drugs (inhalants, tranquilizers, cocaine, crack, and ecstasy), and problems with drugs and alcohol were the outcome variables. Risk factors included dysregulation, family problems with drugs/alcohol, negative family interactions, school disengagement, peer deviance, and exposure to community violence. Protective factors included a personal belief in God, positive family interactions, parent religiosity, and positive student-teacher interaction. Both hierarchical linear regression and logistic regression analyses were used to model main and interaction effects of risk and protective factors. Results: There was a linear association between number of risk and protective factors and substance use, however, risk factors were more strongly associated with substance use than were protective factors. There were significant risk-by-protective-factor interactions for alcohol and marijuana use, and for problems with drugs and alcohol. Risk interacted most consistently with a personal belief in God, but also with parent religiosity and with student-teacher communication. Conclusions: It is important to consider risk and protective factors at different levels of an adolescent's ecology. Prevention and intervention efforts should focus on interactions adolescents have in different microsystems (e.g., with parents, teachers, and peers).

Krupitsky EM; Rudenko AA; Burakov AM; Slavina TY; Grinenko AA; Pittman B et al. Antiglutamatergic strategies for ethanol detoxification: Comparison with placebo and diazepam. Alcoholism: Clinical and Experimental Research 31(4): 604-611, 2007. (52 refs.)

Background: Benzodiazepines are the standard pharmacotherapies for ethanol detoxification, but concerns about their abuse potential and negative effects upon the transition to alcohol abstinence drive the search for new treatments. Glutamatergic activation and glutamate receptor up-regulation contribute to ethanol dependence and withdrawal. This study compared 3 antiglutamatergic strategies for ethanol detoxification with placebo and to the benzodiazepine, diazepam: the glutamate release inhibitor, lamotrigine; the N-methyl-D-aspartate glutamate receptor antagonist, memantine; and the AMPA/kainite receptor inhibitor, topiramate. Methods: This placebo-controlled randomized single-blinded psychopharmacology trial studied male alcohol-dependent inpatients (n=127) with clinically significant alcohol withdrawal symptoms. Subjects were assigned to 1 of 5 treatments for 7 days: placebo, diazepam 10 mg TID, lamotrigine 25 mg QID, memantine 10 mg TID, or topiramate 25 mg QID. Additional diazepam was administered when the assigned medication failed to suppress withdrawal symptoms adequately. Results: All active medications significantly reduced observer-rated and self-rated withdrawal severity, dysphoric mood, and supplementary diazepam administration compared with placebo. The active medications did not differ from diazepam. Conclusions: This study provides the first systematic clinical evidence supporting the efficacy of a number of antiglutamatergic approaches for treating alcohol withdrawal symptoms. These data support the hypothesis that glutamatergic activation contributes to human alcohol withdrawal. Definitive studies of each of these medications are now needed to further evaluate their effectiveness in treating alcohol withdrawal.

Lane SD; Yechiam E; Busemeyer JR. Application of a computational decision model to examine acute drug effects on human risk taking. Experimental and Clinical Psychopharmacology 14(2): 254-264, 2006. (60 refs.)

In 3 previous experiments, high doses of alcohol, marijuana, and alprazolam acutely increased risky decision making by adult humans in a 2-choice (risky vs. nonrisky) laboratory task. In this study, a computational modeling analysis known as the expectancy valence model (J. R. Buserneyer & J. C. Stout, 2002) was applied to individual-participant data from these studies, for the highest administered dose of all 3 drugs and corresponding placebo doses, to determine changes in decision-making processes that may be uniquely engendered by each drug. The model includes 3 parameters: responsiveness to rewards and losses (valence or motivation); the rate of updating expectancies about the value of risky alternatives (learning/memory); and the consistency with which trial-by-trial choices match expected outcomes (sensitivity). Parameter estimates revealed 3 key outcomes: Alcohol increased responsiveness to risky rewards and decreased responsiveness to risky losses (motivation) but did not alter expectancy updating (learning/memory); both marijuana and alprazolam produced increases in risk taking that were related to learning/memory but not motivation; and alcohol and marijuana (but not alprazolam) produced more random response patterns that were less consistently related to expected outcomes on the 2 choices. No significant main effects of gender or dose by gender interactions were obtained, but 2 dose by gender interactions approached significance. These outcomes underscore the utility of using a computational modeling approach to deconstruct decision-making processes and thus better understand drug effects on risky decision making in humans.

Lemmer B. The sleep-wake cycle and sleeping pills. Physiology & Behavior 90(2-3): 285-293, 2007. (69 refs.)

Sleeping pills are drugs which are used world-wide to combat sleep disturbances, and to prevent symptoms due to maladjustment to shiftwork or jet-lag. Today, benzodiazepines and the so-called "non-benzodiazepines", such as zolpidem, which both act on benzodiazepine receptors, are drugs of first choice and they are substitutes for barbiturates. Their use as sleeping pills in insomniacs is established after appropriate medical diagnosis. Symptoms from shiftwork or jet-lag are due to an internal desynchronisation of biological rhythms, and there is ample evidence that benzodiazepines are not effective in preventing these symptoms. Cabin crews in particular should never take sleeping pills, in order not to impair cognitive functions or to reduce the reactivity needed to fly an aircraft safely. The biological clock(s) cannot be reset instantaneously by any drug.

Lindblad CI; Hanlon JT; Gross CR; Sloane RJ; Pieper CF; Hajjar ER; Multidisciplinary Consensus Panel. Clinically important drug-disease interactions and their prevalence in older adults. Clinical Therapeutics 28(8): 1133-1143, 2006. (64 refs.)

Background: Older adults may have decreased homeostatic reserve, have multiple chronic diseases, and take multiple medications. Therefore, they are at risk for adverse outcomes after receiving a drug that exacerbates a chronic disease. Objectives: The aims of this study were to compile a list of clinically important drug-disease interactions in older adults, obtain the consensus of a multidisciplinary panel of geriatric health care professionals on these interactions, and determine the prevalence of these interactions in a sample of outpatients. Methods: This analysis included a 2-round modified Delphi survey and cross-sectional study. Possible drug-disease interactions in patients aged >= 65 years were identified through a search of the English-language literature indexed on MEDLINE and International Pharmaceutical Abstracts (1966-July 2004) using terms that included drug-disease interaction, medication errors, and inappropriate prescribing. Nine health care professionals with expertise in geriatrics (2 geriatricians, 7 geriatric clinical pharmacist specialists) were selected based on specialty training and continuing clinical work in geriatrics, academic appointments, and geographic location. The panel rated the importance of the potential drug-disease interactions using a 5-point Likert scale (from 1 = definitely not serious to 5 = definitely serious). Consensus on a drug-disease interaction was defined as a lower bound of the 95% CI >= 4.0. The prevalence of drug-disease interactions was determined by applying the consensus criteria to a convenience sample of frail older veterans at hospital discharge who were enrolled in a health services intervention trial. Results: The panel reached consensus on 28 individual drug-disease interactions involving 14 diseases or conditions. Overall, 205 (15.3%) of the 1340 veterans in the sample had >= 1 drug-disease interaction. The 2 most common drug-disease interactions were use of first-generation calcium channel blockers in patients with congestive heart failure and use of aspirin in patients with peptic ulcer disease (both, 3.7%) Conclusions: A survey of multidisciplinary geriatric health care professionals resulted in a concise consensus list of clinically important drug-disease interactions in older adults. Further research is needed to examine the impact of these drug-disease interactions on health outcomes and their applicability as national measures for the prevention of drug-related problems. [Note: drugs of note include benzodiazepines, anti-anxiety agents, and sedative/hypnotics.]

Martins SDO; Soares MA; van Mil JWF; Cabrita J. Inappropriate drug use by Portuguese elderly outpatients: Effect of the Beers criteria update. Pharmacy World & Science 28(5): 296-301, 2006. (29 refs.)

Objective: To characterize the use of medicines and to evaluate the inappropriateness of drugs in elderly outpatient population. Setting: Twelve community pharmacies in different districts of Lisbon - Portugal. Method Observational cross-sectional survey, in a sample of 213 elderly outpatients (age >= 65-years-old) presenting a prescription with two or more drugs, for their own use. Main outcome measures Drug use pattern and prevalence of potentially inappropriate medication. Results We have studied 213 outpatients, who were taking a total of 1,543 drugs, with an average of 7.23 per patient. The drugs were distributed mainly in the following 3 ATC (Anatomical Therapeutic Chemical Classification) classes: C (cardiovascular system), N (nervous system) and A (alimentary tract). Using the 1997 Beers Explicit criteria, 75 occurrences of inappropriate medicines were detected in 59 patients (27.7%), while with the 2003 Beers Explicit criteria we detected 114 cases of inappropriate medication in 82 patients (38.5%). The occurrence of inappropriate medicines was significantly associated with the consumption of a high number of drugs. According to the ATC Classification, more than one half of the cases of inappropriateness were related with long acting benzodiazepines and with ticlopidine. The 2003 version detected a significantly higher prevalence of inappropriate drug use having potentially adverse outcomes of high severity. Conclusions: The application of the updated Beers criteria lead to higher rates of potentially inappropriate medication, and especially those responsible for more severe adverse outcomes. The results suggest that there is a need for interventions to improve instructions for safe drug use in the elderly patients and to decrease the number of medications whenever it is possible. This study suggests a high prevalence of potentially inappropriate drug use by the elderly patients of Lisbon region, Portugal.

McCabe SE; West BT; Wechsler H. Trends and college-level characteristics associated with the non-medical use of prescription drugs among US college students from 1993 to 2001. Addiction 102(3): 455-465, 2007. (37 refs.)

Aims The present study examines the prevalence trends and college-level characteristics associated with the nonmedical use of prescription drugs (i.e. amphetamines, opioids, sedatives, tranquilizers) and illicit drug use among US college students between 1993 and 2001. Design Data were collected from self-administered mail surveys, sent to independent cross-sectional samples of college students from a nationally representative sample of 119 colleges in 4 years between 1993 and 2001. Setting Nationally representative 4-year US colleges and universities in 1993, 1997, 1999 and 2001. Participants Representative samples of 15 282, 14 428, 13 953 and 10 904 randomly selected college students at these colleges in 1993, 1997, 1999 and 2001, respectively. Findings: The results indicate that life-time and 12-month prevalence rates of non-medical use of prescription drugs increased between 1993 and 2001. Specific college-level characteristics were found to be correlated positively (marijuana use) and negatively (historically black college status and commuter status) with nonmedical use of prescription drugs, consistently across the four cross-sectional samples. Significant between-college variation in terms of trajectories in the prevalence of NMPD over time was found in hierarchical linear models, and selected college-level characteristics were not found to explain all of the variation in the trajectories, suggesting the need for further investigation of what determines between-college variance in the prevalence trends. Conclusions: The findings of the present study suggest that continued monitoring of nonmedical use of prescription drugs and illicit drug use among college students is needed and collegiate substance prevention programs should include efforts to reduce these drug use behaviors.

Michopoulos I; Douzenis A; Christodoulou C; Lykouras L. Topiramate use in alprazolam addiction. World Journal of Biological Psychiatry 7(4): 265-267, 2006. (20 refs.)

Alprazolam is successful in reducing anxiety but has a high addictive/misuse potential. Topiramate is a novel anticonvulsant which has been used as a mood stabilizer. Other anticonvulsants, such as carbamazepine and valproate, have been used in alcohol and benzodiazepine withdrawal. Topiramate has recently been used in alcohol, cocaine and opiates withdrawal. there has been also one report of topiramate use in midazolam withdrawal. In our case of a patient with reccurent major depressive disorder, subthreshold anxiety disorder and addiction to alprazolam, topiramate appears to be efficient and safe in alprazolam withdrawal.

Monga N; Rehm J; Fischer B; Brissette S; Bruneau J; El-Guebaly N et al. Using latent class analysis (LCA) to analyze patterns of drug use in a population of illegal opioid users. Drug and Alcohol Dependence 88(1): 1-8, 2007. (62 refs.)

Background: The objective of this paper is to empirically determine a categorization of illegal opioid users in Canada in order to describe and analyze drug use patterns within this population. Methods: Drug use patterns of 679 eligible illegal opioid users outside treatment from the OPICAN study, a pan-Canadian cohort (recruited March to December, 2002) involving the cities of Toronto, Montreal, Vancouver, Edmonton and Quebec City, were empirically examined using latent class analysis. These latent classes were then further analyzed for associations using chi-square and t-test statistics. Findings: The opioid and other drug user sample surveyed were categorized into three latent classes. Class I (N=256) was characterized by the use of Tylenol 3 and benzodiazepines along with high levels of depression and self-reported pain. Class 2 (N=68) was described by the non-injection use of both heroin and crack while having a high level of homelessness. Class 3 (N=344) was shown to consist of injection drug users of heroin and cocaine exhibiting the highest levels of HIV and Hepatitis C infections amongst the classes. Conclusions: Using latent class analysis we found distinct patterns of drug use amongst illegal opioid users differing in terms of type of drugs co-used, social context, and co-morbid pathologies. These data may be useful as the empirical basis for the planning of specific prevention and treatment interventions.

Morin AK. Possible intranasal quetiapine misuse. American Journal of Health-System Pharmacy 64(7): 723-725, 2007. (16 refs.)

Purpose. A possible case of intranasal quetiapine misuse in a patient with schizoaffective disorder and substance abuse is presented. Summary. A 28-year-old Caucasian female with schizoaffective disorder (bipolar type), comorbid polysubstance abuse, tobacco dependence, and personality disorder was admitted to an inpatient psychiatric facility following a hit-and-run conviction. Medications on admission included quetiapine, benztropine, haloperidol, lorazepam, diphenhydramine, and trazodone. As-needed medication orders included benztropine and lorazepam. The patient was hospitalized in order to undergo rehabilitation and psychiatric stabilization. During the first four weeks of the patient's hospital stay, the nursing staff suspected her of "cheeking" or "palming" her quetiapine dose on several occasions. During this time she was also suspected of using cocaine and alcohol while away from the hospital. The patient demonstrated symptoms that are consistent with cocaine withdrawal, but the patient denied the use of cocaine. Aspirin tablets, quetiapine tablets, and white powder were found in her room. The patient stated that the white powder was aspirin. It was suspected that it also contained quetiapine, which the patient later admitted to crushing and snorting for its "calming" effects. Quetiapine was discontinued. There have been reports in the literature of oral and intranasal quetiapine abuse among prison inmates. Conclusion. Possible intranasal quetiapine misuse was detected in a patient with schizoaffective disorder and a history of substance abuse. While antipsychotic medications are not typically thought of as drugs with an abuse potential, reports of the use and diversion of intranasal quetiapine among prison inmates, i.v. quetiapine abuse, and this case report indicate otherwise.

Mulvihill AO; Cackett PD; George ND; Fleck BW. Nystagmus secondary to drug exposure in utero. British Journal of Ophthalmology 91(5): 613-615, 2007. (11 refs.)

Aim: To report the occurrence of nystagmus in children exposed to opiates and/or benzodiazepines during pregnancy, and to describe the associated ocular and systemic findings. Methods: Clinical examination and casenote review of 14 children with nystagmus whose mothers had misused opiates and/or benzodiazepines during pregnancy. Results: Twelve children were exposed to opiates during pregnancy, of whom nine had also been exposed to benzodiazepines. Two children were exposed to benzodiazepines alone. In the primary position, the nystagmus was a fine horizontal pendular type in 10 (71.4%) children and was a fine horizontal jerk nystagmus in the other 4 (28.6%) children. The onset of the nystagmus probably occurred in the first 6 months of life in all cases. The mean binocular best-corrected logarithm of the minimum angle of resolution visual acuity was 0.59 (20/80). Electroretinogram and visual evoked potential examinations were found to be normal in the three children tested. Nine (64.3%) children had developmental delay and at least 7 (50%) had delayed visual maturation. Six children had microcephaly and two had bilateral optic nerve hypoplasia. None of the children had a specific neurological diagnosis or seizure disorder. Conclusion: This study strongly supports a teratogenic association between exposure to controlled drugs in utero and infantile nystagmus. Furthermore, the nystagmus and associated clinical features seem to be particularly associated with combined use of opiates and benzodiazepines. Exposure to opiates and/or benzodiazepines during pregnancy should be considered in the differential diagnosis of infantile nystagmus.

Neira-Leon M; Barrio G; Brugal MT; de la Fuente L; Ballesta R; Bravo MJ; Project Itinere Grp. Do young heroin users in Madrid, Barcelona and Seville have sufficient knowledge of the risk factors for unintentional oploid overdose? Journal of Urban Health 83(3): 477-496, 2006. (51 refs.)

To identify the self-perceived reasons for unintentional opioid overdose of young heroin users in three Spanish cities and their agreement with objective risk factors for overdose. Computer-Assisted Personal Interviews (CAPI) were held with 991 street-recruited current heroin users aged 18-30. The general reasons for overdose and the reasons for the last overdose suffered were explored with open-ended (OEQs) and precoded questions (PCQs). Limited knowledge of overdose risk factors was defined as mention of fewer than two objective risk factors for unintentional overdose in the OEQ. Univariate, bivariate, and logistic regression methods were used. 77.8% (Seville), 64.9% (Madrid) and 57.2% (Barcelona) of participants have limited knowledge of overdose risk factors. Residence in Seville and not having attended courses or meetings on overdoses were significantly associated with limited knowledge, after adjusting for other factors. The most frequently identified general reasons in OEQ or PCQ were using heroin in large amounts (66.8%), together with tranquilizers (62.0%), adulterated (60.7%), or purer than usual (57.6%). Most reasons were selected more frequently in PCQ than in OEQ, especially rapid injection of the entire dose and using heroin shortly after using tranquilizers or alcohol, by injection, or after a period of abstinence. The results were similar for overdoses suffered by participants. Most young heroin users do not have sufficient knowledge of overdose risk factors, especially the use of heroin by injection, after a period of abstinence, or together with alcohol or methadone. Specific informational or educational programs adapted to the local context are critically needed.

Newman J; Moon C. Northern Territory Drug Trends 2005: Findings from the Illicit Drug Reporting System (IDRS). NDARC Technical Report No. 243. Sydney: National Drug and Alcohol Research Centre (Australia), 2006. (26 refs.)

In 1999, a national Illicit Drug Reporting System was initiated. It involves interviews with injecting drug users, interviews with key experts, and use of health and law enforcement data. This report draws upon the data for the Northern Territory. The drugs included in the survey are heroin, methamphetamine, cocaine, cannabis, opioids, benzodiazepines, and 'other drugs' (ecstasy, prescription stimulants, inhalants, hallucinogens, and alkaloid poppies). For each of these drugs there is information about price, availability, patterns or use, the harm associated with use, trends in patterns of use. This is followed by a general discussion of drug related harms -- overdose, blood-borne infections, injection related health problems, driving risk behaviors, mental health problems, substance-related aggression, crime, and pharmacy burglaries. A concluding section sets forth the policy implication. Data is presented in 47 tables and 34 figures

Nielsen S; Dietze P; Lee N; Dunlop A; Taylor D. Concurrent buprenorphine and benzodiazepines use and self-reported opioid toxicity in opioid substitution treatment. Addiction 102(4): 616-622, 2007. (33 refs.)

Aims To examine concurrent buprenorphine and benzodiazepine consumption and to compare opioid toxicity symptoms induced by methadone and buprenorphine, examining factors associated with the reporting of these symptoms. Design Self-report cross-sectional survey. Setting Five needle syringe programmes and five opioid substitution treatment services in Melbourne, Australia. Participants A total of 250 people who had experience with methadone or buprenorphine. Eligibility criteria were current or previous methadone or buprenorphine use. Measurements Structured questionnaire covering: demographic characteristics; current treatment and drug use; concurrent use of buprenorphine and benzodiazepines, including route of administration and source of medications; and opioid toxicity symptoms reported in association with methadone and buprenorphine consumption. Findings Of those reporting buprenorphine use, two-thirds reported concurrent benzodiazepine use, with a median dose reported of 30 mg diazepam equivalents. A greater number of opioid toxicity symptoms were reported in relation to methadone consumption compared with buprenorphine. Those reporting opioid toxicity with buprenorphine were more likely to report intravenous use compared with those reporting opioid toxicity with methadone. Conclusions The risk of opioid toxicity appeared greater with methadone compared with buprenorphine, despite high levels of benzodiazepine consumption and injection being reported in relation to buprenorphine use. The prevalence of buprenorphine injection and the normalization of methadone-induced sedation are two findings that merit further investigation. Establishing recommendations as to the safest and most effective way to manage benzodiazepine-using people in opioid substitution treatment is necessary for the optimization of treatment for opioid dependence in polydrug-using individuals.

Pavlic M; Libiseller K; Hermann M; Hengster P; Margreiter R; Wurm M. Small human hepatocytes in rotary culture for treatment of alcohol addicts? A pilot study. Alcoholism: Clinical and Experimental Research 31(5): 729-736, 2007. (33 refs.)

Background: Current approaches to support alcohol addict and/or benzodiazepine-treated patients with liver failure include culturing human cells to take over basic metabolic functions for a certain time. Methods: Small human hepatocytes (SH) were grown in a rotary cell culture system, and their potential to metabolize alcohol and the benzodiazepines oxazepam and diazepam was evaluated. Control experiments were performed with SV40-immortalized HEP cells and cell respective drug-free media. Results: Our results show that SH in rotary culture are able to metabolize ethanol in reasonable amounts compared with evaporation controls (p < 0.01). Moreover, SH are also able to metabolize oxazepam and diazepam which proves their ability to perform conjugation and the presence of functional cytochrome P450 enzymes. Basic metabolic activities such as glucose consumption, albumin and urea production are not significantly influenced by the drugs used, which is a precondition for clinical use of these cells. Significantly increased lactate dehydrogenase release indicates enhanced cell death in cultures of SH incubated with either ethanol (p < 0.05) or diazepam (p < 0.005), but stable viability at or above 90% suggests that cell proliferation is able to keep up with drug-induced cell death. Conclusion: Our preliminary study provides evidence that SH are basically suited to support alcohol-abusing and/or benzodiazepine-treated patients undergoing liver failure.

Perret G; Abudureheman A; Perret-Catipovic M; Flomenbaum M; La Harpe R. Suicides in the young people of Geneva, Switzerland, from 1993 to 2002. Journal of Forensic Sciences 51(5): 1169-1173, 2006. (25 refs.)

Suicides in Geneva in those less than 25 years old, from 1993 to 2002, were reviewed. Scenes investigations, autopsy findings, toxicology results, and psychiatric history (when available) were examined. There were 65 cases. The average annual suicide rate was 11/100,000. Seventy-seven percent were male, and 23% were female. The youngest was 12 years old and most of the victims were 18 years old and over (89%). For men, the use of firearms was the most common method (38%), followed by fall from height (16%) and drowning (10%). For women, fall from height was the most frequent (40%), followed by firearms and medication overdoses (20% each), hanging (13%), and drowning (7%). Toxicological analysis was performed in 41% of the cases and showed that alcohol was present in 26% and other drugs in 67% of these cases. The most common drugs present were benzodiazepines, cannabis, and cocaine.

Pollini RA; McCall L; Mehta SH; Vlahov D; Strathdee SA. Non-fatal overdose and subsequent drug treatment among injection drug users. Drug and Alcohol Dependence 83(2): 104-110, 2006. (40 refs.)

Overdose is a leading cause of death among illicit drug users. Nine hundred twenty-four injection drug users (IDUs) in Baltimore, Maryland, were interviewed to characterize overdose events and determine the circumstances under which they lead to drug treatment. Overall, 366 (39.7%) reported at least one non-fatal drug overdose. Most (96.2%) used heroin on the day of their last overdose and almost half (42.6%) used heroin and alcohol but few (4.1%) used tranquilizers or benzodiazepines. Five percent were in drug treatment when the overdose occurred and 7.1% had been incarcerated 2 weeks prior. One in four IDUs (26.2%) sought drug treatment within 30 days after their last overdose of whom 75% enrolled. Speaking with someone about drug treatment after the overdose was associated with treatment seeking (AOR 5.22; 95% CI: 3.12, 8.71). Family members were the most commonly cited source of treatment information (53.7%) but only those who spoke with spouses, crisis counselors and hospital staff were more likely to seek treatment. Not being ready for treatment (69.6%) and not viewing drug use as a problem (30.7%) were the most common reasons for not seeking treatment and being placed on a waiting list was the most common reason for not subsequently enrolling in treatment (66.7%). Of the IDUs treated by emergency medical technicians, ER staff or hospital staff, only 17.3%, 26.2% and 43.2% reported getting drug treatment information from those sources, respectively. Interventions that provide drug treatment information and enhance motivation for treatment in the medical setting and policies that reduce barriers to treatment entry among motivated drug users are recommended.

Quigley P; Usher C; Bennett K; Feely J. Socioeconomic influences on benzodiazepine consumption in an Irish region. European Addiction Research 12(3): 145-150, 2006. (22 refs.)

Misuse of prescription sedatives is a significant problem for addiction treatment services. The aim of this study was to examine the prescribing of diazepam in disadvantaged Irish communities, and to identify factors which may predict diazepam consumption in that population. We examined prescribing trends for those aged 16-69 years in 2002 in a region of the state-funded General Medical Services Scheme. Material deprivation was based on the 2002 Small Area Health Research Unit (SAHRU) deprivation index. The average defined daily dose (DDD) was calculated and logistic regression analysis was used to predict diazepam use by age, gender and deprivation index. Results showed that patients living in the most-deprived areas were more likely to receive diazepam than patients living in the least-deprived areas (OR = 1.21, 95% CI 1.15-1.27). Female patients living in the most-deprived areas were also more likely to receive diazepam than those living in the least-deprived areas (OR = 1.36, 95% CI 1.18-1.57). It is concluded that there is a pattern of higher diazepam prescribing in areas of greatest deprivation, where prescription sedatives play a complex role within troubled families.

Shields LBE; Hunsaker DM; Hunsaker JC; Ward MK. Toxicologic findings in suicide: A 10-year retrospective review of Kentucky medical examiner cases. American Journal of Forensic Medicine and Pathology 27(2): 106-112, 2006. (50 refs.)

Toxicologic analysis is an integral component in the investigation of suicide and requires correlation with a detailed scene inspection, with an extensive exploration into the decedent's medical and social background to uncover suicidal ideation or intent and a postmortem examination of the body. In this review, the authors analyzed 2864 cases classified as suicide upon autopsy and toxicologic examinations between 1993 and 2002 in the Kentucky Division of Medical Examiner's Services. Blood and urine were collected in 95.0% and 72.3% of cases, respectively. A total of 32.5% of the victims had negative blood toxicologic results, and 52.7% of urine toxicology screens yielded no drugs. Analysis of the data indicated that 3 times as many women had taken antidepressants and more than twice as many had consumed opioids. Drug toxicity ("overdose") ranked as the third (9.9%) leading cause of suicide after firearm injury (67.5%) and hanging (13.7%). Women succumbed to drug toxicity more than men (27.5% versus 5.9%). Of the overdose deaths, 66.5% had a negative blood alcohol concentration (BAC), while antidepressants, opioids, and benzodiazepines were detected in blood in 54.4%, 37.4%, and 29.2% of the subjects, respectively. The collection of these data serves the goals of public health and clinicians in devising strategies for suicide prevention.

Sieghart W. GABA(A) receptors as targets for different classes of drugs. (review). Drugs of the Future 31(8): 685-694, 2006. (84 refs.)

GABA(A) receptors are the major inhibitory transmitter receptors in the brain and are the site of action of many clinically important drugs that modulate anxiety excitability of the brain, feeding and drinking behaviour, circadian rhythms, cognition, vigilance, learning and memory. Evidence has accumulated for the existence of a multiplicity of GABA(A) receptor subtypes with distinct regional cellular and subcellular distribution in the brain. Each of these receptors has a distinct structure and thus also exhibits distinct pharmacological properties. Drugs selectively interacting with these receptor subtypes should therefore exert highly selective actions. This conclusion was recently supported by evidence indicating that different receptor subtypes mediate different actions of drugs. This review discusses recent progress in the development of GABA(A) receptor subtype-selective drugs, as well as recent structural information indicating that these receptors contain a multiplicity of possible binding pockets that could become targets for the development of novel drugs with subtype-specific actions. Targeting drugs to GABA(A) receptor subtypes holds promise for the treatment of various diseases with a reduced incidence of side effects. In addition, therapeutic applications beyond those of classical benzodiazepines may emerge for drugs specifically enhancing or reducing the activity of minor GABA(A) receptor subtypes located only at certain neurons.

Steentoft A; Teige B; Holmgren R; Vuori E; Kristinsson J; Hansen AC et al. Fatal poisoning in Nordic drug addicts in 2002. Forensic Science International 160(2-3): 148-156, 2006. (12 refs.)

The present study from 2002 includes medicolegally examined fatal poisonings among drug addicts in the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. A common definition "drug addict" is applied by the participating countries. The number of deaths, age, sex, place of death, main intoxicant and other drugs present in the blood are recorded in order to obtain national data, as well as comparable Nordic data and data comparable to earlier studies from 1997 and 1991. The Icelandic results are commented on separately due to the low number of cases. The most fatal overdoses are seen in Norway, in both the death rate (number per 100,000 inhabitants = 8.44) and in absolute number (n = 232). The comparable figures for the other four countries are Denmark 5.43 (n = 175), Iceland 3.6 (n = 6), Finland 2.93 (n = 94) and Sweden 2.56 (n = 136). In earlier studies from 1991 and 1997, the highest death rate is seen in Denmark, with Norway as number two. Denmark is the only country where the death rate decreases from 1997 to 2002. A relatively large increase in deaths in the younger age groups(< 30 years) is noted from 1997 to 2002, except in Denmark, where only a small increase in overdose deaths in very young people (15-19 years) is observed. Females account for 12-20% of the overdoses (three out of six deaths in Iceland). Relatively fewer deaths are recorded in the capital areas in 2002 than in 1997 and 199 1, suggesting more geographically widespread drug use in the Nordic countries. Heroin/morphine is the single most frequently encountered main intoxicant, varying from 10% of the cases in Finland to 72% of the cases in Norway. Finland differs from the other countries in that a high percentage of the fatal overdoses in Finland are not caused by an illicit drug; buprenorphine, overdoses are seen, and relatively few deaths resulting from heroin are seen. Methadone is the main intoxicant in 41% of the Danish overdose cases, 15% of the Norwegian cases, 4% of the Swedish cases and none of the Finnish overdose cases, an observation probably linked to different national prescription rules for methadone. The analytical screening reveals extended polydrug use. Frequently seen substances, in addition to the main intoxicant are amphetamine, tetrahydrocannabinol (THC), benzodiazepines and ethanol.

Stinson FS; Grant BF; Dawson DA; Ruan WJ; Huang BJ; Saha T. Comorbidity between DSM-IV alcohol and specific drug use disorders in the United States - Results from the National Epidemiologic Survey on Alcohol and Related Conditions (Reprinted from Drug and Alcohol Dependence, vol 80, pg 105-116, 2005). Alcohol Research & Health 29(2): 94-106, 2006. (46 refs.)

Background: To date, there have been no published data on 12-month comorbidity of DSM-IV alcohol and drug use disorders in the general U.S. population. The purposes of the present study were to examine the prevalence and comorbidity of alcohol and specific drug use disorders, and to identify sociodemographic and psychopathologic correlates and treatment-seeking among three groups of respondents: (1) those with alcohol use disorders only; (2) those with drug use disorders only; (3) those with comorbid alcohol and drug use disorders. Methods: information on 12-month alcohol and specific drug use disorders in the United States was derived from lace-to-face interviews in the National Institute on Alcohol Abuse and Alcoholism's (National Institute on Alcohol Abuse and Alcoholism) 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (in = 43,093). Results: Prevalences were 7.35 percent for alcohol use disorders only, 0.90 percent for drug use disorders only, and 1.10 percent for comorbid alcohol and drug use disorders. Sociodemographic and psychopathologic correlates of these three groups were quite different, with the drug use disorder and comorbid groups significantly more likely to he young, male, never married, and of lower socioeconomic status than the alcohol use disorder only group. Associations between current alcohol use disorders and 25 specific drug use disorders were generally positive and statistically significant. The 12-month prevalence of treatment-seeking significantly increased, from 6.06 percent for those with an alcohol use disorder only to 15.63 percent for those with a drug use disorder only, and to 21.76 percent for those with comorbid alcohol and drug use disorders. Conclusions: This study provides detailed data on the homotypic comorbidity of alcohol use disorders and 25 different drug use disorders and confirms the high levels of association seen in previous studies based on lifetime measures. Implications of this study are discussed in terms of integrating alcohol and drug treatment services and relining prevention and intervention efforts.

Public Domain

Vansickel AR; Hays LR; Rush CR. Discriminative-stimulus effects of triazolam in women and men. American Journal of Drug and Alcohol Abuse 32(3): 329-349, 2006. (45 refs.)

Benzodiazepines are among the most commonly prescribed therapeutics. Women seem to be more likely than men to be prescribed a benzodiazepine and to use benzodiazepines for nonmedical reasons; they also appear to be at higher risk for benzodiazepine dependence. The aim of the present investigation was to assess the acute behavioral effects of a benzodiazepine in women and men. To accomplish this, 13 volunteers (6 women, 7 men) first learned to discriminate 0.375-mg triazolam, a triazolobenzodiazepine hypnotic. After acquiring the discrimination, (i.e., > 80% correct responding on 4 consecutive sessions) a range of doses of triazolam (0, 0.0625, 0.125, 0.25, and 0.375 mg) were tested in each participant. Triazolam dose dependently increased drug-appropriate responding and subject ratings of sedation and impaired performance (i.e., significant effect of dose). The women and men did not differ significantly on any measure. The results of the present experiment suggest that women and men are not differentially sensitive to the behavioral effects of triazolam.

Voshaar RCO; Gorgels WJ; Mol AJ; van Balkom AJ; Mulder J; de Lisdonk EH et al. Predictors of long-term benzodiazepine abstinence in participants of a randomized controlled benzodiazepine withdrawal program. Canadian Journal of Psychiatry 51(7): 445-452, 2006. (39 refs.)

Objective: To identify predictors of resumed benzodiazepine use after participation in a benzodiazepine discontinuation trial. Method: We performed multiple Cox regression analyses to predict the long-term outcome of a 3-condition, randomized, controlled benzodiazepine discontinuation trial in general practice. Results: Of 180 patients, we completed follow-up for 170 (94%). Of these, 50 (29%) achieved long-term success, defined as no use of benzodiazepines during follow-up. Independent predictors of success were as follows: offering a taper-off program with group therapy (hazard ratio [HR] 2.4; 95% confidence interval [CI], 1.5 to 3.9) or without group therapy (HR 2.9; 95%CI, 1.8 to 4.8); a lower daily benzodiazepine dosage at the start of tapering off (HR 1.5; 95%CI, 1.2 to 1.9); a substantial dosage reduction by patients themselves just before the start of tapering off (HR 2.1; 95%CI, 1.4 to 3.3); less severe benzodiazepine dependence, as measured by the Benzodiazepine Dependence Self-Report Questionnaire Lack of Compliance subscale (HR 2.4; 95%CI, 1.1 to 5.2); and no use of alcohol (HR 1.7; 95%CI, 1.2 to 2.5). Patients who used over 10 mg of diazepam equivalent, who had a score of 3 or more on the Lack of Compliance subscale, or who drank more than 2 units of alcohol daily failed to achieve long-term abstinence. Conclusions: Benzodiazepine dependence severity affects long-term taper outcome independent of treatment modality, benzodiazepine dosage, psychopathology, and personality characteristics. An identifiable subgroup needs referral to specialized care.

Weekley J; Simmonds L; Ali R. South Australian Drug Trends 2005: Findings from the Illicit Drug Reporting System (IDRS). NDARC Technical Report No. 250. Sydney: National Drug and Alcohol Research Centre (Australia), 2006. (30 refs.)

This report outlines the results of a nation-wide governmental survey of drug trends in Southern Australia. It deals with heroin, methamphetamine, cocaine, cannabis, opioids, and other drugs including ecstasy, benzodiazepines, and antidepressants. For each of these drugs there is a data is provided on price, availability,potency, use patterns, and drug-related harms to the individual and the larger community.

Williamson S; Jackson L; Skeoch C; Azzim G; Anderson R. Determination of the prevalence of drug misuse by meconium analysis. Archives of Disease in Childhood. Fetal and Neonatal Edition 91(4): F291-F292, 2006. (7 refs.)

In a pilot study to determine the local prevalence of maternal drug misuse, meconium from 400 infants was analysed for metabolites of eight controlled drugs. Cannabinoids were found in 13.25%, cocaine in 2.75%, and amphetamine in 1.75%. The prevalence of opiate and benzodiazepine misuse was masked by the presence of prescribed drugs so was undeterminable.

Wu LT; Schlenger WE; Galvin DM. Concurrent use of methamphetamine, MDMA, LSD, ketamine, GHB, and flunitrazepam among American youths. Drug and Alcohol Dependence 84(1): 102-113, 2006. (101 refs.)

Background: The magnitude and the characteristics of the use of methamphetamine, MDMA (Ecstasy), LSD (d-lysergic acid diethylamide), ketamine, GHB (gamma-hydroxybutyrate), and flunitrazepam (Rohypnol) were examined in a probability sample of the U.S. civilian population that included multiethnic urban, suburban, and rural youths aged 16-23 (N = 19,084). Methods: Data were drawn from the National Survey on Drug Use and Health (NSDUH). Logistic regression analyses were conducted to identify the characteristics associated with the use of each of these drugs and of multiple drugs. Results: Approximately 20% of youths aged 16-23 reported having ever used one or more of these drugs. Less than 1% of club drug users used club drugs only, and 82% of them had ever used three or more drug classes. Females were more likely than males to report using multiple club drugs. Recent users of methamphetamine were most likely to be females and adolescents aged 16 or 17. Recent users of MDMA tended to be young adults aged 18-21 and residents of metropolitan areas. Most recent users of LSD were adolescents aged 16-19 and those in low-income families. Ketamine users were primarily employed youths. Staying in school and getting married were associated with decreased odds of club drug use. Club drug use was highly associated with the presence of criminal behaviors and recent alcohol abuse or dependence. Conclusions: Adolescents are more likely than young adults to use multiple drugs. The clustering of multidrug use and alcohol use disorder is a cause of concern.

Zack M; Poulos CX; Woodford TM. Diazepam dose: Dependently increases or decreases implicit priming of alcohol associations in problem drinkers. Alcohol and Alcoholism 41(6): 604-610, 2006. (28 refs.)

Aims: Words denoting negative affect (NEG) have been found to prime alcohol-related words (ALC) on semantic priming tasks, and this effect is tied to severity of addiction. Previous research suggested that high doses of benzodiazepines may dampen NEG-ALC priming. The present study tested this possibility and the role of motivation for alcohol in this process. Methods: A placebo-controlled, double blind, between-within, counterbalanced design was employed. Two groups of male problem drinkers (n = 6/group) received a high (15-mg) or low (5-mg) dose of diazepam versus placebo on two identical test sessions. A lexical decision task assessed priming. Results: Under placebo, significant NEG -> ALC priming emerged in each group. High-dose diazepam selectively reversed this effect, while low-dose selectively enhanced it. Correlations between NEG -> ALC priming and desire for alcohol provided further support that semantic priming of ALC concepts reflects a motivational process. The bi-directional effects found here parallel the effects of high- versus low-dose benzodiazepines on alcohol self-administration in animals. Conclusions: High-dose diazepam reduces prime-induced activation of ALC concepts in problem drinkers. Low-dose diazepam facilitates this process, and cross-priming of motivation for alcohol appears to explain this effect. Neurochemical modulation of the alcohol memory network may contribute to the motivational effects of benzodiazepines in problem drinkers.