CORK Bibliography: Benzodiazepines
57 citations. January 2010 to present
Prepared: June 2011
Anthierens S; Pasteels I; Habraken H; Steinberg P; Declercq T; Christiaens T. Barriers to nonpharmacologic treatments for stress, anxiety, and insomnia Family physicians' attitudes toward benzodiazepine prescribing. Canadian Family Physician 56(11): E398-E406, 2010. (59 refs.)OBJECTIVE: To explore the attitudes of FPs toward benzodiazepine (BZD) prescribing and the perceived barriers to nonpharmacologic approaches to managing stress, anxiety, and insomnia. DESIGN: A questionnaire including 32 statements about treatment of insomnia, stress, and anxiety. SETTING: Local quality groups for FPs in Belgium. PARTICIPANTS: A total of 948 Belgian FPs. MAIN OUTCOME MEASURES: Barriers to using nonpharmacologic approaches in family practice. RESULTS: We identified 3 different groups of FPs according to their attitudes about BZD prescribing. A first relatively big group of FPs (39%) were not really concerned about the risks of BZD prescribing. Those in the second group (17%) were aware of the problems associated with BZDs, but did not perceive it to be their role to use nonpharmacologic approaches in family practice. Those in the third group (44%) were concerned about BZD prescribing and found it to be a "bad solution," but were faced with various barriers to applying nonpharmacologic approaches. Surprisingly, we found that nearly 97% of FPs thought that most people were eligible for nonpharmacologic approaches, but experienced implementation barriers at the level of the patient, the level of the FP, and the level of the health care system. CONCLUSION: Using different education and behavioural-change strategies for different FP groups seems important. A large group of FPs does not find prescribing BZDs to be problematic. Sensitizing and alerting FPs to this issue remains very important. Copyright 2010, College of Family Physicians of Canada
Barrons R; Roberts N. The role of carbamazepine and oxcarbazepine in alcohol withdrawal syndrome. Journal of Clinical Pharmacy and Therapeutics 35(2): 153-167, 2010. (27 refs.)Objective: The goal of this review is to evaluate the efficacy and safety of carbamazepine and oxcarbazepine in treatment of alcohol withdrawal syndrome (AWS) and determine the role in therapy of both agents. Methods: Relevant literature was identified through a search of MEDLINE (1966-June 2008), PubMed (1966-June 2008); Cochrane database was performed to identify English-language publications. Search terms included carbamazepine, oxcarbazepine, AWS, alcoholism, substance syndrome withdrawal. Results: In seven studies, including 612 patients, carbamazepine demonstrated significant reduction in alcohol withdrawal scores. However, in comparative trials with a benzodiazepine agent, carbamazepine's ability to prevent alcohol withdrawal seizures (OR = 0 center dot 93; 95% CI = 0 center dot 06-14 center dot 97, P = NS) and delirium tremens (DTs; OR = 1 center dot 25; 95% CI = 0 center dot 28-5 center dot 64, P = NS) was uncertain as a result of insufficient patient enrolment. In three trials, carbamazepine failed to reduce alcohol withdrawal symptoms possibly as a result of delayed administration, inadequate dosage or inadequate sample size. At daily doses of 800 mg either fixed or tapered over 5-9 days, carbamazepine was well tolerated, and safely administered when blood alcohol concentration dropped below 0 center dot 15%. The role of oxcarbazepine in AWS is undefined because of inconsistent findings in two trials. Conclusion: Carbamazepine has demonstrated safety, tolerability and efficacy in treatment of moderate to severe symptoms of alcohol withdrawal in the inpatient setting. However, trials of carbamazepine provide inconclusive evidence for prevention of alcohol withdrawal seizures and DTs in comparison with benzodiazepines. Benzodiazepines remain the primary treatment of moderate to severe AWS. Copyright 2010, Wiley-Blackwell
Brahm NC; Yeager LL; Fox MD; Farmer KC; Palmer TA. Commonly prescribed medications and potential false-positive urine drug screens. (editorial). American Journal of Health-System Pharmacy 67(16): 1344-1350, 2010. (41 refs.)Purpose. The implications of potential false-positive urine drug screen (UDS) results for patients receiving commonly prescribed medications were evaluated. Summary. A comprehensive literature review was conducted to identify false-positive UDSs associated with all clinic formulary medications, as well as common nonprescription medications. The references of each report describing a medication whose use was associated with false-positive UDS results were also reviewed. If a class effect was suspected, additional agents in the category were searched. A total of 25 reports of false-positive UDS results were identified. Categories of medications included antihistamines, antidepressants, antibiotics, analgesics, antipsychotics, and nonprescription agents. Reports of false-positive results were found for the following formulary and nonprescription medications: brompheniramine, bupropion, chlorpromazine, clomipramine, dextromethorphan, diphenhydramine, doxylamine, ibuprofen, naproxen, promethazine, quetiapine, quinolones (ofloxacin and gatifloxacin), ranitidine, sertraline, thioridazine, trazodone, venlafaxine, verapamil, and a nonprescription nasal inhaler. False-positive results for amphetamine and methamphetamine were the most commonly reported. False-positive results for methadone, opioids, phencyclidine, barbiturates, cannabinoids, and benzodiazepines were also reported in patients taking commonly used medications. The most commonly used tests to screen urine for drugs of abuse are immunoassays, even though false-positive results for drugs of abuse have been reported with a number of these rapid-screening products. Results from such tests should be confirmed using additional analytical methods, including gas chromatography-mass spectrometry. Conclusion. A number of routinely prescribed medications have been associated with triggering false-positive UDS results. Verification of the test results with a different screening test or additional analytical tests should be performed to avoid adverse consequences for the patients. Copyright 2010, American Society of Health-System Pharmacists
Cai R; Crane E; Poneleit K; Paulozzi L. Emergency department visits involving nonmedical use of selected prescription drugs --- United States, 2004--2008. MMWR. Morbidity and Mortality Weekly Review 59(23): 705-709, 2010. (10 refs.)Rates of overdose deaths involving prescription drugs increased rapidly in the United States during 1999--2006. However, such mortality data do not portray the morbidity associated with prescription drug overdoses. The CDC and the Substance Abuse and Mental Health Services Administration (SAMHSA) reviewed the most recent 5 years of available data (2004--2008) on ED visits involving the nonmedical use of prescription drugs from SAMHSA's Drug Abuse Warning Network (DAWN). This report describes the results of that review, which showed that the estimated number of ED visits for nonmedical use of opioid analgesics increased 111% during 2004--2008 (from 144,600 to 305,900 visits) and increased 29% during 2007--2008. The highest numbers of ED visits were recorded for oxycodone, hydrocodone, and methadone, all of which showed statistically significant increases during the 5-year period. By 2008 these visits matched the number of ED visits involving illicit drugs. ED visits involving such pharmaceuticals accounted for all of the growth in overall drug misuse/abuse rates during 2004--2008. Notably, results from 2008 indicate that in addition to the large increase in visits compared with 2004, peak visit rates for both opioids and benzodiazepines appear to have shifted into the 21--24 and 25--29 years age groups and away from the 30--34 and 35--44 years age groups. As late as 2006, the peak mortality rate for fatal drug overdoses involving opioid analgesics had been in the 35--54 years age group. The 5-year increase in ED visit rates reflects, in part, substantial increases in the prescribing of these classes of drugs. The increase also might reflect an increase in the rate of nonmedical use of prescription drugs per 1,000 prescriptions, as has been observed for selected opioids. In the 2008 National Survey of Drug Use and Health (NSDUH), 4.6% of persons aged �18 years reported past-year nonmedical use of prescription pain relievers, and 2.1% reported nonmedical use of tranquilizers, a category that includes benzodiazepines. In contrast to the results of this study, NSDUH results have shown no increase in self-reported rates of nonmedical use of selected pharmaceuticals since 2004. Increasing ED visit rates in the context of stable self-reported nonmedical use rates might indicate that persons seen in EDs are different from typical respondents to NSDUH; a shift toward riskier types of pain relievers and benzodiazepines, riskier modes of use, more frequent or heavier use; and/or an increased tendency to seek emergency care because of greater awareness of the serious consequences of nonmedical use of such drugs. However, changes in health-seeking behavior would not affect changes in drug-related deaths, and DAWN ED visit trends are consistent with medical examiner data from six states also tracked by DAWN (Maine, Maryland, New Hampshire, New Mexico, Utah, and Vermont). In these states, the number of nonsuicidal deaths related to benzodiazepines increased 64.2%, and the number related to opioid analgesics other than methadone increased 47.4% during 2004--2007. Public Domain
Cunningham CM; Hanley GE; Morgan S. Patterns in the use of benzodiazepines in British Columbia: Examining the impact of increasing research and guideline cautions against long-term use. Health Policy 97(2-3): 122-129, 2010. (35 refs.)Objective: We examined changes in patterns of benzodiazepine use in British Columbia over a period of increasing evidence of harms associated with long-term use. Methods: Using linked administrative databases for the years 1996 and 2006, we performed logistic regression to examine how socio-economic and health factors affect the likelihood of benzodiazepine use and long-term use, and to test for changes in rates of use and long-term use over time. Results: In 2006, 8.4% of British Columbians used benzodiazepines, 3.5% long-term. Use was positively related with being female, lower income, older, and of poorer health status. Long-term use was positively associated with being in the lowest income quintile, of poorest health, and over the age of 65. While the rate of long-term use decreased from 1996 to 2006 for those over age 70, it increased in middle-aged populations. Conclusions: Our results suggest, despite increased awareness of and cautions regarding risks associated with long-term use of benzodiazepines, rates of potentially inappropriate use have changed very little over a decade. Given that early use of benzodiazepines is positively associated with later long-term use, policies targeting populations younger than conventionally studied (i.e. those under age 65) may be needed to decrease rates of long-term use. Copyright 2010, Elsevier Sciences
Dar FJ; Khan AH; Siddiqui I; Ghani F. Pattern of drugs of abuse identified in chemical samples. Journal of the College of Physicians and Surgeons Pakistan 20(9): 608-611, 2010. (23 refs.)Objective: To determine the pattern of drugs of abuse in urine and blood samples processed at referral laboratory in Pakistan so that information on the type of drugs used can be identified and used for ready reference for future strategy. Study Design: Observational study. Place and Duration of Study: Clinical Laboratory of The Aga Khan University Hospital, Karachi, from July 2006 to March 2008. Methodology: Retrospective review of records were done for the common drugs that are used for screening at the Clinical Laboratory include alcohol, amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates. Alcohol was tested in blood and others were identified using urine. Percentages of tests screened positive and negative for individual drugs were computed by using SPSS 16.0. The ratio between male and female users was also established. Results: A total of 17,714 tests were performed for drugs. The mean age of the patients whose samples were processed was 30 +/- 14.84 years. Majority used benzodiazepines 520/1317 (39.5%) among the samples tested for drug of abuse, followed by cannabinoids 423/5450 (7.8%), alcohol 75/1302 (5.8%), barbiturates 32/1148 (2.8%), opiates 137/5640 (2.4%), cocaine 5/1655 (0.3%) and amphetamine 3/1202 (0.2%). In all, males 15411 (87%) were tested more frequently as compared to females 2303 (13%). Conclusion: Males were more frequently tested for drug abuse; however, drug abuse is increasingly seen among females. Benzodiazepines are the most frequently used. The same pattern of drugs abuse existed in different gender and age group. There is a need to explore the pattern and type of drug abuse on national scale. Copyright 2010, College of Physicians & Surgeons Pakistan
Darke S; Duflou J; Torok M. A reduction in blood morphine concentrations amongst heroin overdose fatalities associated with a sustained reduction in street heroin purity. Forensic Science International 198(1-3): 118-120, 2010. (16 refs.)To determine the effects of a sudden and sustained reduction in heroin purity on the toxicology of heroin overdose, 959 consecutive heroin overdose cases autopsied at the NSW Department of Forensic Medicine (1/1/1998-31/12/2006) were analysed. There was a significant reduction in blood morphine concentration across the study period (beta = -0.07), declining from a median of 0.50 mg/L in the years 1998-2000 prior to 0.40 mg/L in the period 2001-2006. There was no significant change in the proportion of alcohol positive cases, but the proportion of benzodiazepine positive cases increased across time (OR 1.11), as did methadone positive cases (OR 1.12). The decline in blood morphine concentrations remained significant after controlling for these factors (beta = -0.07). In determining toxic and lethal morphine concentrations, the fact that the toxicology of overdose is responsive to changes in the opioid street market needs to be borne in mind. Copyright 2010, Elsevier Science
Darke S; Duflou J; Torok M. The comparative toxicology and major organ pathology of fatal methadone and heroin toxicity cases. Drug and Alcohol Dependence 106(1): 1-6, 2010. (23 refs.)In order to determine the comparative toxicology and systemic disease of cases of death due to methadone and heroin toxicity, 1193 coronial cases of opioid overdose that occurred in New South Wales, Australia between I January 1998 and 31 December 2007 were inspected. These comprised 193 cases in which cause of death involved methadone toxicity (METH) and 1000 cases in which cause of death involved heroin toxicity in the absence of methadone (HER). METH cases were significantly more likely to have benzodiazepines (63.7% vs. 32.2%), and less likely to have alcohol (23.6% vs. 42.7%) detected. METH cases were significantly more likely to be diagnosed with pre-existing systemic pathology (94.3% vs. 79.9%), and Multiple organ system pathology (68.8% vs. 41.4%). Specifically, METH cases were more likely to have cardiac (58.9% vs. 34.5%), pulmonary (53.6% vs. 30.9%), hepatic (80.7% vs. 62.8%) and renal (25.0% vs. 9.5%) disease. Given the notable differences in toxicology and disease patterns, great caution appears warranted in prescribing benzodiazepines to methadone users, and regular physical examinations of methadone treatment patients would appear clinically warranted. Copyright 2010, Elsevier Science
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 Millas W; Ganzer F; Kuhn S; Haasen C. Oxazepam versus clomethiazol in alcohol withdrawal treatment. European Addiction Research 16(4): 179-184, 2010. (22 refs.)The pharmacological management of the alcohol withdrawal syndrome associated with alcohol dependence is heterogeneous; however, according to the guidelines, clomethiazol is the standard medication in Germany. Benzodiazepines offer another safe possibility of treating alcohol withdrawal. In a retrospective study, alcohol-dependent patients treated either with oxazepam (n = 141) or clomethiazol (n = 357) were assessed with respect to the course of treatment and withdrawal symptoms. The results showed that under oxazepam treatment, there were fewer days with severe alcohol withdrawal symptoms and less severe adverse events, but patients receiving clomethiazol treatment had a more severe course of alcohol dependence. Oxazepam is a safe, efficient and cheap drug for the treatment of alcohol withdrawal symptoms, but controlled studies are needed to compare its effectiveness with that of clomethiazol. Copyright 2010, Karger
Desrosiers NA; Watterson JH. The effects of burial on drug detection in skeletal tissues. Drug Testing and Analysis 2(7-8): 346-356, 2010. (24 refs.)Skeletal tissues have recently been investigated for use in post-mortem toxicology. Variables affecting drug concentration in these tissues, however, are still poorly characterized. In this work, the relative effects of burial on the response of enzyme-linked immunosorbent assay (ELISA) and gas chromatography-mass spectrometry (GC-MS) assays were examined. Rats were acutely exposed to ketamine or diazepam, euthanized and buried outdoors. After one month, the remains were exhumed and skeletal tissue drug levels were compared those of non-buried rats. A climate-controlled burial was also undertaken using defleshed bones to approximate an extended decomposition. Long bones (femora, tibiae) were isolated and separated into tissue type (diaphyseal bone, epiphyseal bone, and marrow), and according to treatment (i.e. buried or non-buried). Following methanolic extraction (bone) or simple homogenization (marrow), samples were analyzed with ELISA. Samples were then pooled according to treatment, extracted by solid phase extraction (SPE) and confirmed with GC-MS. Under the conditions examined, the effects of burial appear to be drug and tissue dependent. Ketamine-exposed tissues demonstrated the greatest differences, especially in bone marrow. In diazepam-exposed tissues, burial did not seem to greatly affect drug response and some gave greater assay response compared to the non-buried set. Overall, the data suggest that fresh tissue samples may not be representative of decomposed samples in terms of skeletal tissue drug levels. Copyright 2010, John Wiley & Sons Ltd.
Donoghue J; Lader M. Usage of benzodiazepines: A review. (review). International Journal of Psychiatry in Clinical Practice 14(2): 78-87, 2010. (58 refs.)Purpose. The use of benzodiazepines remains a source of controversy. Some prescribers believe that they are beneficial and espouse their use; others regard their risk: benefit ratio as too adverse for any but occasional use. This review considers these viewpoints based on the appropriate literature. Survey. The recent English-language literature relating to this topic was surveyed. The publications proved too heterogeneous for a formal meta-analysis, so a descriptive review is provided. Overview. Surveys of benzodiazepine use provide data mainly from the UK, Europe and North America. Prescribing patterns varied widely but long-term usage is common and sometimes the norm. Conclusions. Long-term prescription of benzodiazepines still takes place despite general warnings from the medical and other professions and drug regulatory bodies that long-term use is unjustified both from the lack of a systemic database establishing such efficacy and a large literature documenting the risks of long-term usage, such as dependence. The young and the old are particularly at risk. Continued monitoring is essential, but the regulatory authorities may need to take a more active role in curbing such undesirable practice. Copyright 2010, Taylor & Francis
Eiroa-Orosa FJ; Haasen C; Verthein U; Dilg C; Schafer I; Reimer J. Benzodiazepine use among patients in heroin-assisted vs methadone maintenance treatment: Findings of the German randomized controlled trial. Drug and Alcohol Dependence 112(3): 226-233, 2010. (32 refs.)Benzodiazepine (BZD) use has been found to be associated with poorer psychosocial adjustment higher levels of polydrug use and more risk-taking behaviors among opioid dependent patients. The aim of this paper is to analyze the correlation between BZD use BZD prescription and treatment outcome among participants in the German trial on heroin-assisted treatment. 1015 patients who participated in the study comparing heroin-assisted and methadone maintenance treatment (HAT & MMT) for 12 months were included in the analysis. Analyses were carried out to assess the association of treatment outcome with baseline BZD use with ongoing BZD use and with different patterns of BZD prescription. Baseline BZD use correlated with lower retention rates but not with poorer outcome Ongoing BZD use correlated with poorer outcomes Significantly better outcomes were found in the course of phobic anxiety symptomatology for those with regular prescription of BZD. The percentage of BZD positive urine tests decreased more in HAT than in MMT. Poorer outcome for benzodiazepine users may be mediated by a higher severity of addiction. Cautious prescribing of benzodiazepines may be beneficial due to the reduction of overall illicit use. Copyright 2010, Elsevier Science
El-Guebaly N; Sareen J; Stein MB. Are there guidelines for the responsible prescription of benzodiazepines? (editorial). Canadian Journal of Psychiatry 55(11): 709-714, 2010. (27 refs.)
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
Havens JR; Walker R; Leukefeld CG. Benzodiazepine use among rural prescription opioids users in a community-based study. Journal of Addiction Medicine 4(3): 137-139, 2010. (16 refs.)Objectives: The purpose of this study was to examine both medical and nonmedical use of benzodiazepines among a community-based cohort of prescription opioid users. Methods: A total of 221 prescription opioid users from 2 rural Appalachian counties were recruited to participate in an interviewer-administered survey assessing sociodemographic characteristics, medical (source was valid prescription) and nonmedical (source other than prescription, such as dealer, friend, or family member) prescription drug use, illicit substance use, psychiatric disorders, and pain. Results: Almost all of the participants (92.8%) reported lifetime benzodiazepine use and two thirds were current users. Only 29.3% of the current users had a legitimate prescription for a benzodiazepine. Current users were significantly more likely than nonusers to report nonmedical use of a variety of prescription opioids and other illicit drugs. The major source of benzodiazepines was a dealer. Conclusions: A high rate of nonmedical benzodiazepine use was observed in this sample of prescription opioid users. Physicians should, therefore, be aware of the potential for nonmedical use of benzodiazepines. Implications for treatment and future research are discussed. Copyright 2010, American Society of Addiction Medicine
Hutton J; Dent A; Buykx P; Burgess S; Flander L; Dietze P. The characteristics of acute non-fatal medication-related events attended by ambulance services in the Melbourne Metropolitan Area 1998-2002. Drug and Alcohol Review 29(1): 53-58, 2010. (32 refs.)Introduction and Aims. To describe the characteristics of non-fatal medication-related ambulance attendances in Melbourne. Design and Methods. A retrospective analysis of 16 705 patient care records completed by ambulance paramedics in Melbourne where medications had a causal role in the attendance. Results. A single medication only was implicated in 11 765 cases (70% of the total). Of these, 85% involved one of six types of medication: benzodiazepines (52%), paracetamol (15%), selective serotonin re-uptake inhibitors (6.5%), combination paracetamol and opioids (4%), phenothiazines (3.4%) and tricyclic antidepressants (TCA) (3.7%). Cases involving benzodiazepines were significantly (P < 0.001) older (Average = 37 years) than those involving paracetamol (Average = 30 years). Thirty-four per cent of cases involved concurrent alcohol use, and this varied according to drug type (paracetamol 26%, benzodiazepines 40%, selective serotonin re-uptake inhibitors 35%, paracetamol and opioids 35%). An abnormal Glasgow Coma Scale score was found in 19% of cases, again varying according to drug type (paracetamol 10%, TCA 39%, benzodiazepines 21%, paracetamol and opioids 17%, phenothiazines 15%). Ten per cent of cases were not transported to hospital ranging from 3% for TCA to 13% for benzodiazepines. Discussion and Conclusions. The majority of non-fatal medication events attended by ambulance paramedics involve one of six substances. Benzodiazepines were most commonly implicated and, as management may require only simple supportive treatment, significant numbers are not transported to hospital. The unique clinical population is identified in this study and the ongoing medical and psychiatric treatment of these patients not transported to hospital in the study period needs to be considered. Copyright 2010, Australian Medical and Professional Society on Alcohol and Other Drugs
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
Kalapatapu RK; Sullivan MA. Prescription use disorders in older adults. (review). American Journal on Addictions 19(6): 515-522, 2010. (105 refs.)The number of older adults needing substance abuse treatment is projected to rise significantly in the next few decades. This paper will focus on the epidemic of prescription use disorders in older adults. Particular vulnerabilities of older adults to addiction will be considered. Specifically, the prevalence and patterns of use of opioids, stimulants, and benzodiazepines will be explored, including the effects of these substances on morbidity and mortality. Treatment intervention strategies will be briefly discussed, and areas for future research are suggested. Copyright 2010, Wiley-Blackwell
Karjalainen KK; Lintonen TP; Impinen AO; Lillsunde PM; Ostamo AI. Poly-drug findings in drugged driving cases during 1977-2007. Journal of Substance Use 15(2): 143-156, 2010. (52 refs.)Background: Driving under the influence of drugs (DUID) is an increasing public health and traffic safety related problem. We examined the poly-drug findings and their trends among all apprehended DUID offenders in Finland. Methods: A register data from 1977 to 2007 was analysed. The data included a total of 31,963 suspected DUID cases with a positive finding for an illicit/licit drug impairing driving performance. Blood and/or urine specimens were analysed in one central laboratory. Results: Poly-drug findings were common among suspected DUID cases during the entire study period. Seventy-seven per cent of the specimens had a finding from two or more substance groups. Benzodiazepines with alcohol (20% of poly-drug cases) and amphetamines with benzodiazepines (18%) were the most frequently found combinations. Benzodiazepines were present in the five most frequent combinations. The proportion of cases including drugs only increased more rapidly than the proportion of cases including a combination of drugs and alcohol during the last three decades. The level of aggravated drink-driving limit in Finland (BAC>1.2 parts per thousand) was exceeded in 44% of the cases including alcohol. Conclusion: In addition to amphetamines, benzodiazepines formed a major concern among suspected DUID cases. The large proportion of poly-drug findings may indicate extensive substance abuse among DUID offenders. Copyright 2010, Informa Healthcare
Ladouceur R. Benzodiazepines: Good or bad medicine? (editorial). Canadian Family Physician 56(11): 1097-1097, 2010. (7 refs.)
Landreat MG; Vigneau CV; Hardouin JB; Bronnec MG; Marais M; Venisse JL et al. Can we say that seniors are addicted to benzodiazepines? Substance Use & Misuse 45(12): 1988-1999, 2010. (14 refs.)Introduction: The elderly are the biggest consumers of Benzodiazepines (BZD) and/or BZD equivalents. However, the risks of developing addiction in this age group are often underestimated. Method: This study describes the nature and extent of addiction in the elderly using DSM IV items. Results: We noted a high prevalence of addiction in our population and identified a two-factor profile in subjects of 65 years of age and older addicted to BZD/equivalents. Conclusion: This profile led us to reconsider anew the definition of addiction, the approach to addiction in this age group, and the way to prescribe treatment by BZD/equivalents in this population. Copyright 2010, Taylor & Francis
Liebrenz M; Boesch L; Stohler R; Caflisch C. Agonist substitution: A treatment alternative for high-dose benzodiazepine-dependent patients? Addiction 105(11): 1870-1874, 2010. (43 refs.)There is vast evidence for the superiority of agonist treatments (methadone, buprenorphine) over a withdrawal approach in opioid-dependent populations. Little research, however, has been conducted on the same approach for the treatment of high-dose benzodiazepine (BZD) dependence. Even large-scale reviews and meta-analyses discussing treatment strategies for benzodiazepine-dependent patients focus solely upon approaches that aim at achieving abstinence, namely on complete BZD withdrawal. While the types of interventions differ (e. g. gradual benzodiazepine taper with a long or a short half-life benzodiazepine, switching to non-benzodiazepine anxiolytics or prescribing adjunctive medications such as antidepressants or anticonvulsants on an inor outpatient basis), the common aim of treatment still is total abstinence from benzodiazepines. However, the majority of patients suffering from high-dose BZD dependence do not succeed with long-term abstinence, irrespective of the procedure, and clinicians have been using BZD 'substitution' treatment in such cases for decades. Therefore, we suggest the evaluation of a substitution approach in this group, consisting of maintenance treatment with a slow-onset, long-acting BZD. Advantages of such a procedure may be improved health, less craving, fewer withdrawal complications, reduced anxiety, increased treatment retention, improvements in social functioning and less illegal activity. Cognitive impairments, the most problematic side effects of substitution treatment with benzodiazepines, could possibly be minimized by using an optimal agonist. Copyright 2010, Society for the Study of Addiction to Alcohol and Other Drugs
Lintzeris N; Nielsen S. Benzodiazepines, methadone and buprenorphine: Interactions and clinical management. (review). American Journal on Addictions 19(1): 59-72, 2010. (122 refs.)Benzodiazepines (BZDs) are widely used by heroin users not in treatment, and by patients in methadone and buprenorphine (BPN) treatment. This review examines the epidemiology of BZD use by opioid users, and the range of harms that are associated with BZD use in this group, including the association of BZD use with opioid-related mortality. Preclinical and clinical data regarding pharmacokinetic and pharmacodynamic interactions between methadone, buprenorphine, and BZDs are reviewed. An overview of treatment approaches for managing BZD use in this population is presented, including strategies for minimizing abuse and addressing BZD dependence. Copyright 2010, American Academy of Psychiatrists in Alcoholism and Addictions
Lobmaier PP; Kunoe N; Gossop M; Katevoll T; Waal H. Naltrexone implants compared to methadone: Outcomes six months after prison release. European Addiction Research 16(3): 139-145, 2010. (62 refs.)Background: After prison release, offenders with heroin use problems are at high risk of relapse and overdose death. There is a particular need for treatments that can be initiated in prison and continued after release into the community. Methadone maintenance treatment has been shown to reduce heroin use, criminality and mortality. Naltrexone implant treatment has not previously been evaluated in prison settings. Methods: This study compares the effects of naltrexone implants and methadone treatment on heroin and other illicit drug use, and criminality among heroin-dependent inmates after release from prison. Results: Forty-six volunteers were randomly allocated to naltrexone implants or methadone before release. Intention-to-treat analyses showed reductions in both groups in frequency of use of heroin and benzodiazepines, as well as criminality, 6 months after prison release. Conclusions: Naltrexone implants may be a valuable treatment option in prison settings. Copyright 2010, Karger
Lundholm L; Kall K; Wallin S; Thiblin I. Use of anabolic androgenic steroids in substance abusers arrested for crime. Drug and Alcohol Dependence 111(3): 222-226, 2010. (42 refs.)Background: Use of anabolic androgenic steroids (AASs) has been associated with both violent crime and the use of illicit drugs . The scientific literature on polysubstance abuse as a confounder for AAS-related violence is sparse and ambiguous With the Intent of further investigating this issue we have gathered data concerning drug abuse and AAS experience among substance abusers who have been arrested for a variety of crimes. Methods: Data were collected from structured interviews with substance abusers (n = 3597) apprehended at two remand prisons in Sweden from 2002 through 2008 Analyses concerned type of criminal act primary drug used during the past year and experience of AAS use Results: Those stating AAS experience (n = 924 20 women and 904 men) were more often apprehended for violent crimes (OR = 1 65). This association remained significant after controlling for age and sex (OR = 1 28). AAS users and non-users claimed similar primary substances of use during the past year with the exception of benzodiazepine use which was more common in the AAS group (OR = 2 30) although this did not affect the frequency of violent crime. Among MS-experienced participants there was no difference in violent crime incidence between current users and former users. Conclusions: Study results suggest that AASs do not function as a proximal trigger for violence but still involve an Increased risk for violence in users of illicit drugs. These findings also suggest that AAS use is highly overrepresented in women who commit crimes. Copyright 2010, Elsevier Science
Mackesy-Amiti ME; Fendrich M; Johnson TP. Symptoms of substance dependence and risky sexual behavior in a probability sample of HIV-negative men who have sex with men in Chicago. Drug and Alcohol Dependence 110(1-2): 38-43, 2010. (44 refs.)Objective: This study examines the relationship between self-reported symptoms of substance dependence and risky sexual behavior among 187 HIV-negative men who have sex with men. Method: In a supplement to a Chicago household survey, using random probability sampling, men who reported consensual sex with other men or who identified as gay or bisexual were selected for interviews. Participants reported on sexual behavior, substance use, and symptoms of substance dependence related to past year use of alcohol, marijuana, cocaine, and sedatives, tranquilizers or pain relievers. Risky sexual behavior was defined as unprotected insertive or receptive anal intercourse plus having multiple partners, casual partners, or a partner who was HIV positive or of unknown serostatus. Results: Risky sexual behavior in the past six months was significantly and positively associated with alcohol dependence symptoms, cocaine dependence symptoms (receptive only), and prescription drug dependence symptoms (insertive only). Confirmatory factor analyses revealed that dependence symptoms loaded on separate factors by substance, which in turn loaded on an overarching dependence symptoms factor. In structural equation models, individual substance factors were not significantly associated with sexual risk behavior, however the higher order dependence symptoms factor was significantly and positively associated with both receptive and insertive risk behavior. Conclusions: MSM with symptoms of multiple substance use dependencies are more likely to be engaged in sexual behavior that places them at risk for acquiring HIV and other sexually transmitted infections. Alcohol and drug abuse treatment providers should be aware of the need for HIV testing and counseling in this population. Copyright 2010, Elsevier Science
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
Marin GH; Canas M; Carlson S; Silvestrini MP; Corva S; Mestorino N; Errecalde J et al. Self-medication, substance abuse and alcohol consumption in students attending to La Plata National University, Argentina. Latin American Journal of Pharmacy 29(8): 1425-1430, 2010. (32 refs.)The World Health Organization raises self-care as a strategy for health promotion. Although self-medication is included in self-care strategy, often it is associate to an irrational medicine's usage. This factor associated with illicit drugs and alcohol consumption becomes in a public health problem. In order to establish frequency of self-medication and the prevalence of illicit drugs and alcohol consumption among university students of La Plata, Argentina, was started the present project. Information was collected by anonymous survey, that evaluated age, sex, origin, cohabitants, type, frequency of consumption, and career. A total of 5170 students were polled. 46.64 % consumes regularly some medicine and 50.11 % of this consumption was self-medication. Mainly this consumption consisted in analgesics (88 %) and antibiotics (45 %). Benzodiazepines were also consumed in 6.9 ck (39 % by self-medication). The consumption of illicit drugs was 38.1 % (29 % marihuana, 4 % cocaine, 1,2 % "paco" and 2.9 % "ecstasy"). The consumption of alcoholic drinks was 82 % for beer, 56 % fernet, 55 % wine and 48 % whiskey. Medicines were obtained outside pharmacies in 30.1 % of the cases. The major consumption of cocaine was given among students of Social Careers [Odds Ratio (OR) 2.3], and in those that lives without their families (1.5). The results indicate that self-medication is common among university students. Those students that live alone had a significant higher risk of being self-medicated than those that lives with their families. More than 30 % of the medicines were obtained at the informal market (other place that pharmacies). Copyright 2010, Colegio Farmaceuticos Provincia De Buenos Aires
Martinotti G; di Nicola M; Frustaci A; Romanelli R; Tedeschi D; Guglielmo R et al. Pregabalin, tiapride and lorazepam in alcohol withdrawal syndrome: A multi-centre, randomized, single-blind comparison trial. Addiction 105(2): 288-299, 2010. (85 refs.)Introduction: The aim of this trial was to compare lorazepam with non-benzodiazepine medications such as pregabalin and tiapride in the treatment of alcohol withdrawal syndrome (AWS). These drugs were chosen for their inhibitorial effects on the hypersecretion of neurotransmitters usually observed in AWS. Craving reduction and improvement of psychiatric symptoms were the secondary end-points. Methods: One hundred and ninety subjects affected by current alcohol dependence were considered consecutively: 111 were enrolled and divided into three groups of 37 subjects each. Within a treatment duration of 14 days, medication was given up to the following maximum doses (pregabalin 450 mg/day; tiapride 800 mg/day; lorazepam 10 mg/day). Withdrawal (CIWA-Ar), craving [visual analogue scale (VAS); Obsessive and Compulsive Drinking Scale (OCDS)], psychiatric symptoms [Symptom Check List 90 Revised (SCL-90-R)] and quality of life (QL-index) rating scales were applied. Results: On the CIWA-Ar score, all the groups showed a significant reduction between times (P < 0.001) with a higher reduction for the pregabalin group (P < 0.01) on items regarding headache and orientation. Retention in treatment was lower in the tiapride group (P < 0.05), while the number of subjects remaining alcohol free was higher in the pregabalin group (P < 0.05). Significant reduction between baseline and the end of the treatment was found in all the groups at the OCDS and the VAS for craving, at the SCL-90-R and QL-index (P < 0.001). Discussion: All the medications in the trial showed evidence of safety and efficacy in the treatment of uncomplicated forms of AWS, with some particular differences. The efficacy of pregabalin was superior to that of tiapride, used largely in research trials and, for some measures, to that of the 'gold standard', lorazepam. Accordingly, pregabalin may be considered as a potentially useful new drug for treatment of AWS, deserving further investigation. Copyright 2010, Society for the Study of Addiction to Alcohol and Other Drugs
Maxwell HG; Dubois S; Weaver B; Bedard M. The additive effects of alcohol and benzodiazepines on driving. Canadian Journal of Public Health 101(5): 353-357, 2010. (25 refs.)Objectives To examine the relationship between the combination of alcohol and benzodiazepines and the risk of committing an unsafe driver action, Methods: We used data from the Fatality Analysis Reporting Systemem (1993 2006) on drivers aged 20 or older who were tested for both alcohol and drugs Using a case control design, we compared drivers who had at least one unsafe driver action (UDA, e g, weaving) recorded in relation to the crash (cases) to drivers who did not (controls). Results: Drivers who tested positive for intermediate and long acting benzodiazepines in combination with alcohol had significantly greater odds of a UDA compared to those under the influence of alcohol alone, up to blood alcohol concentrations (BACs) of 0 08 and 0 05 g/100 ml respectively. The odds of a UDA with short acting benzodiazepines combined with alcohol were no different than for alcohol alone. Conclusions: This study demonstrates that the combination of alcohol and benzodiazepines can have detrimental effects on driving beyond those of alcohol alone. By describing these combined effects in terms of BAC equivalencies, this study also allows for the extrapolation of simple, concrete concepts that communicate risk to the average benzodiazepine user Copyright 2010, Canadian Public Health Association
Minett WJ; Moore TL; Juhascik MP; Nields HM; Hull MJ. Concentrations of opiates and psychotropic agents in polydrug overdoses: A surprising correlation between morphine and antidepressants. Journal of Forensic Sciences 55(5): 1319-1325, 2010. (25 refs.)The relationship between postmortem concentrations of morphine and co-detected psychoactive drugs in fatal overdoses is examined. Morphine and other drugs were detected in 161 medicolegal autopsy cases. Subsets of these morphine-positive cases based on drug class were established, including opioids, antidepressants, ethanol, benzodiazepines, and "other." Each subset was split into high or low concentration groups based on median drug concentrations. Morphine concentrations of the [high] and [low] groups were compared, with no significant difference in morphine concentration identified in the opioid, ethanol, or benzodiazepine subsets. The "other" drug class was too heterogeneous for statistical assessment. Morphine concentrations did show a significant direct relationship (p = 0.01) with antidepressants, namely increased concentrations of antidepressant drugs are associated with an increased concentration of morphine. This trend probably remains even after excluding cocaine-positive cases. The unsuspected finding that postmortem concentrations of antidepressants positively correlate with morphine levels may be important in the treatment of depression in drug addicts. Copyright 2010, Wiley-Blackwell
Mistry V; Jeffery AJ; Madira W; Padfield CJH; Rutty GN. Methadone toxicity in infants: A report of two fatalities. Forensic Science. Medicine and Pathology 6(2): 116-120, 2010. (27 refs.)Fatalities in infants resulting from methadone toxicity are rare within the United Kingdom. We report two cases of fatality attributed to methadone toxicity in infants aged 3-1/2 and 15 months of age, respectively. One of the two cases was also associated with diazepam ingestion. We discuss the difficulties with the interpretation of paediatric forensic toxicology and review the current literature related to methadone and diazepam toxicity in infants and older children. Copyright 2010, Humana Press
Mordal J; Holm B; Morland J; Bramness JG. Recent substance intake among patients admitted to acute psychiatric wards: Physician's assessment and on-site urine testing compared with comprehensive laboratory analyses. Journal of Clinical Psychopharmacology 30(4): 455-459, 2010. (21 refs.)This cross-sectional study of acute psychiatric admissions compared physicians' assessments of recent substance intake and on-site urine testing with comprehensive laboratory drug analyses. The sample comprised 325 consecutive admissions from 2 acute psychiatric wards. Physicians on call were asked to judge if the patient had recently taken benzodiazepines, opiates, alcohol, amphetamines, cannabis, or cocaine. Blood and urine samples were obtained and analyzed with chromatographic laboratory methods for a wide range of substances. A routine on-site urine screening test was performed in 92 of the cases. Physicians' assessments and on-site urine testing were compared with the reference standard of laboratory analyses. The sensitivity of the physician's assessment was highest for amphetamines (76%), followed by benzodiazepines (61%), opiates (57%), cannabis (55%), and cocaine (50%), whereas specificity was greater than 90% for all substances. The sensitivity of the on-site test ranged from 76% for amphetamine to 97% for cannabis, and specificity ranged from 82% for cannabis to 100% for cocaine. The study indicates clinical underdetection of recent substance intake among acute psychiatric admissions. On-site urine testing identified substance use that was not recognized by the physician's initial assessment, although specificity for cannabis and benzodiazepines was low. Chromatographic methods, which offered important supplementary information about substance use, should be considered for the routine screening of acutely admitted psychiatric patients. Copyright 2010, Lippincott, Williams & Wilkins
Musshoff F; Trafkowski J; Lichtermann D; Madea B. Comparison of urine results concerning co-consumption of illicit heroin and other drugs in heroin and methadone maintenance programs. International Journal of Legal Medicine 124(5): 499-503, 2010. (23 refs.)Urine samples of patients from a heroin maintenance program (FIMP) and a methadone maintenance program (MMP) were chromatographically analyzed 1 month before and 6 and 12 months into treatment for the presence of classical markers of heroin use as well as for the presence of markers for illicit heroin abuse. Furthermore, the samples were immunochemically tested for cannabinoids, cocaine metabolites, amphetamine, methylendioxyamphetamines and benzodiazepines. A co-consumption of illicit heroin (HER) in the HMP was determined to be 50% but was significantly lower compared to the MMP with a co-use of 71%. The incidence was high because not only acetylcodeine (AC) as a very specific marker was considered but also other marker substances for illicit HER use. Amphetamines played only a minor part in both collectives, and the proportion of HER and methadone patients using cocaine was similar and decreased during treatment. Also, the benzodiazepine use decreased, and cannabis use was high in both collectives during treatment. Considering only the AC in the present study, a co-use of illicit HER in the HMP was similar to previous reports concerning HER-assisted treatment programs. If additional marker substances were examined, the suspicion of a co-use of illicit HER is markedly enhanced. Copyright 2010, Springer
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
Oulis P; Konstantakopoulos G. Pregabalin in the treatment of alcohol and benzodiazepines dependence. (review). CNS Neuroscience & Therapeutics 16(1): 45-50, 2010. (39 refs.)We review all available studies on the use of the newer anticonvulsant drug pregabalin (PGB) in the treatment of both alcohol dependence (AD) and benzodiazepine dependence (BD). In AD, the available evidence includes one open-label and one double-blind randomized studies, whereas in BD, only a few case reports and one open-label study are as yet available. In both conditions, PGB was found efficacious with significant improvement in withdrawal symptoms at the dosage ranges of 150-450 mg/day (AD) and 225-900 mg/day (BD). Moreover, its side effects were mild and transient. Despite the limited quality of the studies design, their findings suggest that PGB might constitute a novel efficacious and safe option in the treatment of both AD and BD. Copyright 2010, Wiley-Blackwell Publishing
Pelissier-Alicot AL; Sastre C; Baillif-Couniou V; Gaulier JM; Kintz P; Kuhlmann E et al. Buprenorphine-related deaths: Unusual forensic situations26. International Journal of Legal Medicine (6): 647-651, 2010. (26 refs.)The success of high-dose buprenorphine (HDB) as substitution therapy for major opioid dependence is related to its partial agonist effect on opioid receptors, which in theory makes it very safe to use. However, numerous deaths directly attributable to buprenorphine have been described in the literature. These deaths are generally related to misuse of HDB with intravenous administration and/or concomitant use of benzodiazepines, and they usually occur in patients on HDB substitution therapy for opioid dependence. We present three deaths attributed to HDB which arose from uncommon mechanisms and led to unusual forensic situations. The first death was that of a patient admitted to hospital after simultaneous prescription of HDB, clonazepam, oxazepam, and cyamemazine. The second death followed forcible administration of a very low dose of HDB to a patient with post-hepatitis C cirrhosis and heart failure. The third death was subsequent to an HDB overdose, probably with suicidal intent, in a young woman who had not been prescribed the drug as opiate substitute. Such deaths raise the question of the mechanisms involved and draw attention to the resulting unusual forensic situations. Copyright 2010, Springer
Pradel V; Delga C; Rouby F; Micallef J; Lapeyre-Mestre M. Assessment of abuse potential of benzodiazepines from a prescription database using 'doctor shopping' as an indicator. CNS Drugs 24(7): 611-620, 2010. (32 refs.)Background: Benzodiazepines are widely used for different purposes because of their pharmacological properties, but their abuse potential may represent a limitation to their use. Data suggest that this abuse potential may vary between products and available dosages. Doctor shopping (the simultaneous use of several physicians by a patient) is one of the most important ways in which prescription drugs, in particular benzodiazepines, are diverted. Objective: To assess the potential for abuse of several benzodiazepines using doctor shopping in a French administrative area as a proxy for abuse. Methods: All prescriptions reimbursed during the year 2003 in Haute-Garonne, France (one million inhabitants) for benzodiazepines that were available in ambulatory care through community pharmacies as solid oral forms were extracted from a reimbursement database. The benzodiazepines were alprazolam (0.25 mg, 0.50 mg), bromazepam 6 mg, clonazepam 2 mg, clorazepate (5 mg, 10 mg, 50 mg), diazepam (1 mg, 5 mg, 10 mg), flunitrazepam 1 mg, lorazepam (1 mg, 2.5 mg) and tetrazepam 50 mg. For each patient, the quantities prescribed, dispensed and obtained by doctor shopping (i.e. overlap between prescriptions from different prescribers) were computed. Benzodiazepines were compared using their 'doctor shopping indicator' (DSI, the percentage of each drug obtained through doctor shopping among the total reimbursed quantity). Results: About 128 000 patients received at least one benzodiazepine during the year. Four groups of benzodiazepines were identified according to their abuse potential: very high abuse potential (flunitrazepam, DSI=42.8%); high abuse potential (diazepam 10 mg, DSI = 3.2%; clorazepate 50 mg, DSI = 2.7%); intermediate abuse potential (alprazolam 0.50 mg, bromazepam, clonazepam, DSI ranging from 1.8% to 1.9%); and low abuse potential (other benzodiazepines and dosages, DSI ranging from 0.3% to 1.1%). Conclusion: The DSI can be used to assess the relative abuse liability of benzodiazepines and to detect signals of new patterns of abuse in settings where centralized records of prescription or deliveries are available for the great majority of patients. Copyright 2010, Adis International
Quan VM; Aramrattana A; Vongchak T; Latkin C; Donnell D; Liu TY et al. Mortality among injection drug users in northern Thailand: A prospective cohort study. Journal of Addiction Medicine 4(4): 217-222, 2010. (21 refs.)Objectives: To measure mortality rates and assess predictors of all-cause mortality in a cohort of Thai injection drug users (IDUs) who were enrolled and followed up from 2004 through 2006. Methods: In this prospective cohort study, we enrolled 314 community- dwelling IDUs (95% being men; 42% of ethnic minority; median age, 29 years [range, 18-69 years]) and followed up them at 6-month intervals. Mortality rates were calculated based on person-years of follow-up. Marginal Cox proportional hazards models for clustered data were constructed to determine the factors associated with all-cause mortality. Findings: During 445.7 person-years of follow-up, 17 of 314 (5.4%) IDUs died. The all-cause mortality rate was 3.8 per 100 person-years (95% confidence interval [CI] = 2.2-6.1). The standardized mortality ratio was 5.8 (95% CI = 3.5-9.1). The mortality rate among HIV-positive IDUs was 13.4 per 100 person-years (95% CI = 5.4-27.6). In a marginal Cox proportional-hazards model for clustered data, the excess mortality was associated with HIV-positivity (hazard ratio [HR] = 7.0, 95% CI = 2.8-17.6), benzodiazepine use (HR = 3.1, 95% CI = 1.1-9.4), and excessive alcohol consumption at enrollment (HR = 3.5, 95% CI = 1.3-9.1). Conclusions: The all-cause mortality among the drug injectors is high. The increased mortality was associated with HIV infection, benzodiazepine use, and excessive alcohol consumption. Copyright 2010, Lippincott, Williams & Wilkins
Ribeiro DSM; Prior JAV; Santos JLM; Lima JLFC. Automated determination of diazepam in spiked alcoholic beverages associated with drug-facilitated crimes. Analytica Chimica Acta 668(1, special issue): 67-73, 2010. (20 refs.)In this work, a multipumping flow system (MPFS) coupled to a photodegradation unit was developed, for the first time, for the determination of diazepam (a benzodiazepine) in spiked alcoholic beverages by fluorimetry. The main features of MPFS such as, high portability, versatility and straightforward automation and control combined with the efficiency and simplicity of photodegradation and the selectivity and sensitivity of fluorimetric detection makes the developed analytical methodology an attractive tool and a valuable contribution for the prevention of drug-facilitated crimes (DFC). Drug-facilitated crimes involve the unauthorized administration of strong central nervous system depressant drugs, which have the capability of preventing victims from resist to the action of the perpetrator or fighting off. Most often, the drugs identified as being used in DFC are surreptitiously placed in drinks served to potential victims in entertainment places, like night clubs. Five commercial alcoholic beverages (Eristoff(R), Smirnoff(R), Bacardi(R), Dry Gin(R) and Brazilian Cachaca 51(R)) spiked with diazepam were analyzed by the proposed methodology, and the results revealed good agreement with those obtained through a HPLC comparison procedure. Relative deviations comprised between -1.97 and 2.05% were achieved, and additionally, the application of a paired t-test, revealed the absence of any statistical difference for a confidence level of 95% (n = 5). The detection limit was approximately 2.02 mg L-1. Copyright 2010, Elsevier Science
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
Senna MC; Augsburger M; Aebi B; Briellmann TA; Donze N; Dubugnon JL et al. First nationwide study on driving under the influence of drugs in Switzerland. Forensic Science International 198(1-3): 11-16, 2010. (41 refs.)In Switzerland, a two-tier system based on impairment by any psychoactive substances which affect the capacity to drive safely and zero tolerance for certain illicit drugs came into force on 1 January 2005. According to the new legislation, the offender is sanctioned if Delta(9)-tetrahydrocannabinol THC is >= 1.5 ng/ml or amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), cocaine, free morphine are >= 15 ng/ml in whole blood (confidence interval +/- 30%). For all other psychoactive substances, impairment must be proven in applying the so-called "three pillars expertise". At the same time the legal blood alcohol concentration (BAC) limit for driving was lowered from 0.80 to 0.50 g/kg. The purpose of this study was to analyze the prevalence of drugs in the first year after the introduction of the revision of the Swiss Traffic Law in the population of drivers suspected of driving under the influence of drugs (DUID). A database was developed to collect the data from all DUID cases submitted by the police or the Justice to the eight Swiss authorized laboratories between January and December 2005. Data collected were anonymous and included the age, gender, date and time of the event, the type of vehicle, the circumstances, the sampling time and the results of all the performed toxicological analyses. The focus was explicitly on DUID; cases of drivers who were suspected to be under the influence of ethanol only were not considered. The final study population included 4794 DUID offenders (4243 males, 543 females). The mean age of all drivers was 31 +/- 12 years (range 14-92 years). One or more psychoactive drugs were detected in 89% of all analyzed blood samples. In 11% (N = 530) of the samples, neither alcohol nor drugs were present. The most frequently encountered drugs in whole blood were cannabinoids (48% of total number of cases), ethanol (35%), cocaine (25%), opiates (10%), amphetamines (7%), benzodiazepines (6%) and methadone (5%). Other medicinal drugs such as antidepressants and benzodiazepine-like were detected less frequently. Poly-drug use was prevalent but it may be underestimated because the laboratories do not always analyze all drugs in a blood sample. This first Swiss study points out that DUID is a serious problem on the roads in Switzerland. Further investigations will show if this situation has changed in the following years. Copyright 2010, Elsevier Science
Shannon LM; Havens JR; Hays L. Examining differences in substance use among rural and urban pregnant women. American Journal on Addictions 19(6): 467-473, 2010. (52 refs.)Substance use during pregnancy is a major public health concern. This study examined differences in substance use among pregnant women from rural and urban areas. Participants were 114 pregnant women entering a hospital-based inpatient detoxification unit primarily for Opiate Dependence who voluntarily agreed to a face-to-face interview. Substance use measures were based on the Addiction Severity Index gathering information about lifetime, past 12 months, and 30 days prior to admission. Rural pregnant women had higher rates of illicit opiate use, illicit sedative/benzodiazepine use, and injection drug use (IDU) in the 30 days prior to admission. Additionally, a greater proportion of rural pregnant women reported the use of multiple illegal/illicit substances in the 30 days prior to entering detoxification. More specifically, pregnant women from rural areas were 8.4 times more likely to report illicit opiate use, 5.9 times more likely to report IDU, 3.3 times more likely to report illicit sedative/benzodiazepine use, and 2.8 times more likely to report the use of multiple illegal/illicit substances in the 30 days prior to entering inpatient detoxification, after adjustment for socio-demographic characteristics (including education and income), pregnancy characteristics, physical and mental health indicators, and criminal justice system involvement. The increased rates of prescription opiate and benzodiazepine use as well as IDU among rural pregnant women are concerning. In order to begin to understand the elevated rates of substance abuse among rural pregnant women, substance use must be considered within the context of demographic, geographic, social, and economic conditions of the region. Copyright 2010, Wiley-Blackwell
Skurtveit S; Furu K; Bramness J; Selmer R; Tverdal A. Benzodiazepines predict use of opioids: A follow-up study of 17,074 men and women. Pain Medicine 11(6): 805-814, 2010. (39 refs.)Objective. To evaluate the effect of the use of benzodiazepines on prescription of opioids 4-7 years later in patients with noncancer pain. Design. A cohort of 7,991 men and 9,083 women aged 40, 45 and 60 years who reported no use of opioids in health surveys in 2000-2001 was linked to the nationwide Norwegian Prescription Database, and their prescriptions of opioids during 2004-2007 were analyzed. Moderate-high prescription frequency of opioids was defined as at least 12 prescriptions during the period January 2004-December 2007. Results. The unadjusted odds ratio for moderate-high prescription frequency of opioids for individuals who had previously used benzodiazepines was 7.7 (95% confidence interval 5.6-10.5) as compared with previous nonusers. After adjustment for musculoskeletal pain, alcohol, smoking habits, and socioeconomic variables, the odds ratio was lowered to 3.1 (2.1-4.6). The analysis of the effect of benzodiazepines and chronic pain individually and in combination suggest that use of benzodiazepines is an even stronger predictor of later opioid use than self-reported chronic pain. Conclusions. Our study suggests that earlier use of benzodiazepines may predict repeated use of opioids. Before starting pain treatment with opioids, clinicians should take into consideration the possibility of substance abuse and mental health disorders. A central issue when prescribing opioids for chronic noncancer pain is to balance the risk of problematic use of these drugs with the benefits of pain relief. Copyright 2010, Wiley-Blackwell
Smith AJ; Tett SE. Improving the use of benzodiazepines-Is it possible? A non-systematic review of interventions tried in the last 20 years. BMC Health Services Research 10: e-article 321, 2010. (69 refs.)Background: Benzodiazepines are often used on a long term basis in the elderly to treat various psychological disorders including sleep disorders, some neurological disorders and anxiety. This is despite the risk of dependence, cognitive impairment, and falls and fractures. Guidelines, campaigns and prescribing restrictions have been used to raise awareness of potentially inappropriate use, however long term use of benzodiazepine and related compounds is currently increasing in Australia and worldwide. The objective of this paper is to explore interventions aimed at improving the prescribing and use of benzodiazepines in the last 20 years. Methods: Medline, EMBASE, PsychINFO, IPA were searched for the period 1987 to June 2007. Results: Thirty-two articles met the study eligibility criteria (interventions solely focusing on increasing appropriate prescribing and reducing long term use of benzodiazepines) and were appraised. Insufficient data were presented in these studies for systematic data aggregation and synthesis, hence critical appraisal was used to tabulate the studies and draw empirical conclusions. Three major intervention approaches were identified; education, audit and feedback, and alerts. Conclusions: Studies which used a multi-faceted approach had the largest and most sustained reductions in benzodiazepines use. It appears that support groups for patients, non-voluntary recruitment of GPs, and oral delivery of alerts or feedback may all improve the outcomes of interventions. The choice of outcome measures, delivery style of educational messages, and requests by GPs to stop benzodiazepines, either in a letter or face to face, showed no differences on the success rates of the intervention. Copyright 2010, BioMed Central
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
Stapleton RD; Comiskey CM. Alcohol usage and associated treatment outcomes for opiate users entering treatment in Ireland. Drug and Alcohol Dependence 107(1): 56-61, 2010. (20 refs.)Evidence has shown that frequency and quantity of drug usage are reduced after treatment but the effect of opioid addiction treatment on alcohol consumption remains unclear. As part of the national Research Outcome Study in Ireland Evaluating drug treatment effectiveness (ROSIE, see www.nuim.ie/rosie) comprehensive drug and alcohol data on 404 opiate users were collected. This study recruited and followed up at 1 and 3 years a prospective cohort of 404 users entering a new treatment episode. Descriptive and inferential statistics were computed and logistic modelling was used to identify key factors effecting outcomes. The cohort represented 8.2% of all new treatments. Follow-up interview rate at 3 years was 88%. Analysis revealed that those who abstained from alcohol use at 3 years were less likely to be using heroin at 3 years than non-abstainers. In addition, those who abstained from alcohol use at 3 years were also less likely to be using methadone, benzodiazepines and cocaine at 3 years than alcohol users. Outcomes for medium and heavy drinkers were found not to be as good as alcohol abstainers. Finally males tended to reduce the frequency and level of alcohol usage after entering treatment more than females. Results: demonstrate to clinicians that an alcohol strategy is a key component of opiate treatment planning and a comprehensive and regular assessment of the client's alcohol and drug use profile is essential if treatment interventions are to have maximum impact on outcomes. Copyright 2010, Elsevier Science
Starer J; Chang G. Hyperammoneic encephalopathy, valproic acid, and benzodiazepine withdrawal: A case series. American Journal of Drug and Alcohol Abuse 36(2): 98-101, 2010. (13 refs.)Background: Benzodiazepine withdrawal is accompanied by a risk of seizures, delirium, and death. While a gradual outpatient taper off of benzodiazepines is the most commonly recommended method for discontinuation, acute inpatient detoxification and seizure prophylaxis may be necessary for some. Complications related to the use of valproic acid for seizure prophylaxis are presented. Objectives: The study's objectives are to highlight an uncommon and possibly unrecognized complication of valproic acid when used for seizure prophylaxis during acute inpatient detoxification from benzodiazepines in the context of current practice. Methods: Case series. Results: Three patients with hyperammoneic encephalopathy are described. Conclusions: Hyperammoneic encephalopathy can occur as a distinct entity separate from hepatotoxicity with the use of valproic acid and may be an unrecognized complication among patients receiving this drug during benzodiazepine detoxification. Scientific Significance: A previously unreported complication among the addiction patient population is reported. This underscores the need for a better evidence base regarding the prevention of seizures during acute benzodiazepine detoxification, particularly in terms of indications, safety, and efficacy. Copyright 2010, Taylor & Francis
Subelj M; Vidmar G; Svab V. Prescription of benzodiazepines in Slovenian family medicine: A qualitative study26. Wiener Klinische Wochenschrift 122(15-16): 474-478, 2010. (26 refs.)INTRODUCTION: Previous quantitative research showed large variations in prescribing volume and prescribing patterns of benzodiazepines among Slovenian family physicians. We performed a qualitative interview study to investigate how high-prescribing family physicians explain their own prescription. METHODS: Five family physicians with benzodiazepine prescriptions in volumes larger than 4000 defined daily doses per month and five who prescribed volumes smaller than 2000 defined daily doses per month, selected randomly from the representative sample of Slovenian family physicians, were interviewed. Physicians' self-explanations about their daily decisions regarding benzodiazepine prescribing, patients' and practice characteristics and their attitudes towards patients were analysed. RESULTS: Family physicians were reporting about patients' needs and their demands, co-morbidity of older patients, previous good experience with benzodiazepines, concerns about decreasing dosage or discontinuation of benzodiazepines, high workload and time constraints, limited access to mental health workers and insufficient education and training. CONCLUSION: Family physicians consider the task of initiating, withdrawing or reducing benzodiazepines as demanding due to complexity of psychosocial problems, co-morbidity, workload, time-consumingness, need to master counselling skills, demands of their patients, particularly the long-term ones and due to low access to mental health services. The majority of family physicians agreed with restrictions in their prescription based on the guidelines. Copyright 2010, Springer Wien
Tenore PL. Advanced urine toxicology testing. Journal of Addictive Diseases 29(4): 436-448, 2010. (63 refs.)Urine toxicology screening testing is an important standard of care in the addiction and pain treatment setting, offering a reproducible, unbiased, and accurate laboratory test to monitor patients and provide objective support for clinical observations. It has been shown that physicians do not have proficiency in the ordering or interpretation of these tests. This article is an attempt to respond to that need. Current antibody-based enzymatic immunoassays (EIAs) used for urine toxicology screening are useful to detect classes of drugs (ex., opiate) but cannot determine which specific drug (ex., morphine) is present. Gas chromatography and mass spectroscopy can determine exactly which drugs are present, allowing prescribed (or illicit) opiates and benzodiazepines to be identified. This article will discuss principles and details of opiate and benzodiazepine EIA and gas chromatography and mass spectroscopy urine toxicology testing. The approach to detecting patients attributing positive opiate EIAs to prescription opiates who are using heroin or other opioids will be reviewed. Cases of controlled prescription drugs that do not produce the expected positive urine tests (ex., oxycodone producing negative opiate screening tests) will be discussed. How to differentiate codeine from heroin and the role of poppy seeds in toxicology will be examined. The case of an anti-depressant drug that produces false-positive benzodiazepine results and antibiotics that cause positive opiate urine toxicology results will be reviewed. Common benzodiazepines (ex., clonazepam and lorazepam) that do not reliably produce positive benzodiazepine EIAs will be discussed. The approach to detection and management of all these types of toxicology cases will be reviewed, and it is hoped that the analyses presented will impart an adequate information base to medical providers and staff members of drug treatment and pain centers, enabling them to order and interpret these tests in the clinic more effectively as an integrated part of whole patient care. Copyright 2010, Haworth Press
Toblin RL; Paulozzi LJ; Logan JE; Hall AJ; Kaplan JA. Mental illness and psychotropic drug use among prescription drug overdose deaths: A medical examiner chart review. Journal of Clinical Psychiatry 71(4): 491-496, 2010. (25 refs.)Objective: Between 1999 and 2006, there was a 120% increase in the rate of unintentional drug overdose deaths in the United States. This study identifies the prevalence of mental illness, a risk factor for substance abuse, and chronic pain among prescription drug overdose deaths in West Virginia and ascertains whether psychotropic drugs contributing to the deaths were used to treat mental illness or for nonmedical purposes. Method: In 2007, we abstracted data on mental illness, pain, and drugs contributing to death from all unintentional prescription drug overdose deaths in 2006 recorded by the West Virginia Office of the Chief Medical Examiner. Decedent prescription records were obtained from the state prescription drug monitoring program. Results: Histories of mental illness and pain were documented in 42.7% and 56.6% of 295 decedents, respectively. Psychotropic drugs contributed to 48.8% of the deaths, with benzodiazepines involved in 36.6%. Benzodiazepines contributing to death were not associated with mental illness (adjusted odds ratio [AOR] =1.1; 95% CI, 0.6-1.8), while all other psychotropic drugs were (AOR = 3.9; 95% CI, 2.0-7.6). Of decedents with contributory benzodiazepines, 46.3% had no prescription for the drug. Conclusions: Mental illness may have contributed to substance abuse associated with deaths. Clinicians should screen for mental illness when prescribing opioids and recommend psychotherapy as an adjunct or an alternate to pharmacotherapy. Benzodiazepines may have been used nonmedically rather than as a psychotropic drug, reflecting drug diversion. Restricting benzodiazepine prescriptions to a 30-day supply with no refills might be considered. Copyright 2010, Physicians Postgraduate Press
Toprak S; Sam B; Akgul E; Silan C; Baysal E. Psychoactive drug related traumatic deaths in Istanbul between 1990-2000. Romanian Journal of Legal Medicine 18(1): 69-74, 2010. (43 refs.)The objective of this study was to identify characteristics of drug related traumatic deaths in Istanbul between 1990 and 2000. This retrospective descriptive study was set in the Council of Forensic Medicine, Ministry of Justice. During the period studied 143 people (86 % males, 14 % females) who took a drug died after traumatic events. The mean age was 37.7 +/- 13.6 years. The most common causes of deaths were asphyxia and blunt force injury. Benzodiazepines, cannabis and heroin were the most commonly used drugs. While benzodiazepines are common in self-directed violence cases such as suicide by asphyxia, cannabis was frequent among interpersonal violence cases as homicide by shooting. Heroin was approximately equally seen in all traumatic deaths. Benzodiazepine and heroin use are especially frequent among non-violence deaths (road traffic accidents). Copyright 2010, Romanian Legal Medical Society
Vikander B; Koechling UM; Borg S; Tonne U; Hiltunen AJ. Benzodiazepine tapering: A prospective study. Nordic Journal of Psychiatry 64(4): 273-282, 2010. (42 refs.)Background: Benzodiazepines (BZD) are the most widely used sedative-hypnotics, and evidence is rapidly accumulating suggesting potential BZD dependence, association of chronic use with adverse effects and a definite abstinence syndrome produced by withdrawal. Aims: The present investigation followed prospectively long-term BZD users over 1 year following graded BZD withdrawal in terms of clinical and withdrawal symptoms. Methods: Clinical symptoms were measured by the Comprehensive Psychopathological Rating Scale (CPRS) and by the Newcastle Anxiety and Depression Diagnostic Index (NADDI) in a sample of BZD users over a 50-week period following graded BZD withdrawal. Results: The results showed that the frequency and severity of clinical symptomatology measured by both scales significantly decreased over time. A detailed analysis of possible patterns of symptoms on both scales revealed four patterns: 1) a gradual decrease over the 50-week time period; 2) an increase in the severity of symptoms at the onset of tapering and a decrease in severity post-tapering; 3) an increase in the severity of symptoms 4 weeks after the cessation of BZD tapering; and 4) no change over the 50-week time period. Rate of BZD withdrawal was associated with CPRS ratings of global illness at admission and at end of treatment, but was not associated with duration or dosage of BZDs, type of BZD, prescriptive and/or non-prescriptive drug use prior to admission, marital status, sex or age. Conclusions: The results of the present study provide a detailed picture of the pattern of symptoms, their time course and multidimensional determinants of the BZD withdrawal symptoms. Copyright 2010, Taylor & Francis
Voyer P; Roussel ME; Berbiche D; Preville M. Effectively detect dependence on benzodiazepines among community-dwelling seniors by asking only two questions. Journal of Psychiatric and Mental Health Nursing 17(4): 328-334, 2010. (41 refs.)Consumption of benzodiazepines (BZDs) is common among seniors. When used over a long period of time, BZDs can induce dependence. The present study aimed to equip nurses with valid screening questions for detecting BZD dependence among seniors, applicable to clinical practice and based on the DSM-IV-TR version. A random sample of 707 BZD users aged 65 years and over was screened for BZD dependence using the DSM-IV-TR criteria for substance dependence. To predict a diagnosis of BZDs dependence, sensitivity and specificity were computed for each pair of items. Results showed that an affirmative answer to 'Have you tried to stop taking this medication?' and 'Over the past 12 months, have you noticed any decrease in the effect of this medication?' led to a sensitivity of 97.1% and a specificity of 94.9% to detect BZD dependence. Asking these two simple questions can be easily integrated into clinical practice and have considerable potential for identifying cases of BZD dependence. Copyright 2010, Wiley-Blackwell
Wedekind D; Jacobs S; Karg I; Luedecke C; Schneider U; Cimander K; Baumann P; Ruether E; Poser W; Havemann-Reinecke U. Psychiatric comorbidity and additional abuse of drugs in maintenance treatment with L- and D,L-methadone. World Journal of Biological Psychiatry 11(2, Part 2): 390-399, 2010. (48 refs.)Sixty D,L-or L-methadone treated patients in maintenance therapy were interviewed for additional drug abuse and psychiatric comorbidity; 51.7% of the entire population had a comorbid Axis-I disorder, with a higher prevalence in females (P < 0.05). Comorbid patients tended to have higher abuse of benzodiazepines, alcohol, cannabis, and cocaine, but not of heroin. They had received a significantly lower D,L- (P<0.05) and L-methadone dose than non-comorbid subjects. The duration of maintenance treatment showed an inverse relationship to frequency of additional heroin intake (P<0.01). Patients with additional heroin intake over the past 30 days had been treated with a significantly lower L-methadone dosage (P<0.05) than patients without. Axis-I comorbidity appears to be decreased when relatively higher dosages of D,L-(and L-methadone) are administered; comorbid individuals, however, were on significantly lower dosages. Finally, L-, but not D,L-methadone seems to be more effective in reducing additional heroin abuse. Copyright 2010, Taylor & Francis
Wilsey BL; Fishman SM; Gilson AM; Casamalhuapa C; Baxi H; Zhang H et al. Profiling multiple provider prescribing of opioids, benzodiazepines, stimulants, and anorectics. Drug and Alcohol Dependence 112(1-2): 99-106, 2010. (41 refs.)Background: The main objective of this study was to determine the prevalence of multiple providers for different controlled substances using the largest electronic prescription monitoring program (PMP) in the United States. A secondary objective was to explore patient and medication variables associated with prescriptions involving multiple providers. PMPs monitor the final allocation of controlled substances from pharmacist to patient. The primary purpose of this scrutiny is to diminish the utilization of multiple providers for controlled substances. Methods: This is a secondary data analysis of the California PMP, the Controlled Substance Utilization Review and Evaluation Systemem (CURES). The prevalence of multiple provider episodes was determined using data collected during 2007. A series of binomial logistic regressions was used to predict the odds ratio (OR) of multiple prescriber episodes for each generic type of controlled substance (i.e., opioid, benzodiazepine, stimulant, or diet pill (anorectic) using demographic and prescription variables. Results: Opioid prescriptions (12.8%) were most frequently involved in multiple provider episodes followed by benzodiazepines (4.2%), stimulants (1.4%), and anorectics (0.9%), respectively. The greatest associations with multiple provider episodes were simultaneously receiving prescriptions for different controlled substances. Conclusions: Opioids were involved in multiple provider prescribing more frequently than other controlled substances. The likelihood of using multiple providers to obtain one class of medications was substantially elevated as patients received additional categories of controlled substances from the same provider or from multiple practitioners. Polypharmacy represents a signal that requires additional vigilance to detect the potential presence of doctor shopping. Copyright 2010, Elsevier Science
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