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CORK Bibliography: Prescription Drugs

69 citations. October 2010 to present

Prepared: June 2011

Advokat C. What are the cognitive effects of stimulant medications? Emphasis on adults with attention-deficit/hyperactivity disorder (ADHD. (review). Neuroscience and Biobehavioral Reviews 34(8): 1256-1266, 2010. (104 refs.)

The relevant literature concerning cognitive effects of amphetamine and methylphenidate, was reviewed, with an emphasis on research conducted in adults diagnosed with attention-deficit/hyperactivity disorder. As first-line treatment for ADHD, stimulant drugs are well-known to improve attention and concentration. Yet, there is increasing evidence that (as with children and adolescents), they do not promote learning and academic achievement in adult college students with ADHD. A review of neuropsychological studies indicates that, although response latencies are reduced, performance of ADHD adults on tests of 'distractibility' and 'planning' is also not consistently improved by stimulants. Studies in non-ADHD adults suggest that stimulants do not promote acquisition of new information, might improve retention of previously acquired information, and facilitate memory consolidation, but may actually impair performance of tasks that require adaptation, flexibility and planning. It is still not clear if improvement only occurs when there is a baseline deficit. Stimulants may influence cognition by their effects on physiological arousal. Regardless, the evidence does not support the conclusion that stimulants are cognitive 'enhancers.

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.

Apodaca TR; Moser NC. The use and abuse of prescription medication to facilitate or enhance sexual behavior among adolescents. Clinical Pharmacology & Therapeutics 89(1): 22-24, 2011. (5 refs.)

Adolescents naturally experience an increased interest in sexual behavior, but they usually lack much experience. Thus, any prescription medication that holds the potential to ease or facilitate sexual matters holds a unique allure. Widespread cultural awareness of medications to treat erectile dysfunction (ED) has combined with a recent trend toward increased adolescent prescription drug abuse to create unique challenges for industry, clinicians, and researchers.

Benotsch EG; Koester S; Luckman D; Martin AM; Cejka A. Non-medical use of prescription drugs and sexual risk behavior in young adults. Addictive Behaviors 36(1-2): 152-155, 2011. (27 refs.)

In recent years the non-medical use of prescription drugs (without a doctor's prescription) has increased dramatically particularly in young adults Previous work has noted associations between the non-medical use of prescription drugs and the use of illicit drugs and associations between the use of illicit drugs and sexual risk behavior Investigations examining associations between the non medical use of prescription drugs (NMUPD) and sexual risk behavior are sparse In the present study undergraduate students (n = 435) ages 18-25 completed an instrument assessing these behaviors Overall 35 6% of participants reported NMUPD Individuals who reported NMUPD were more likely to also report the use of alcohol, marijuana, ecstasy, cocaine, methamphetamine, and poppers Participants who indicated they had used prescription medications without a doctor's consent had significantly higher rates of sexual risk behavior including more sexual partners and more instances of unprotected sex in the previous 3 months. Results: suggest that a significant minority of young adults are using prescription medication recreationally and are risking negative consequences including the potential for addiction dangerous interactions between prescription and recreational drugs and greater risk for contracting sexually transmitted infections.

Benotsch EG; Martin AM; Koester S; Cejka A; Luckman D. Nonmedical use of prescription drugs and HIV risk behavior in gay and bisexual men. Sexually Transmitted Diseases 38(2): 105-110, 2011. (56 refs.)

Background: Previous research has demonstrated associations between substance use and sexual risk behavior in men who have sex with men (MSM). Recent trends in substance use show increasing use of prescription medications (e. g., Vicodin) without a physician's prescription, yet associations between the nonmedical use of prescription drugs (NMUPD) and HIV risk behavior have not been well examined in MSM. Methods: MSM attending a gay pride festival completed a self-report measure assessing NMUPD, motivations for use, use of traditional recreational drugs, and HIV risk behavior. Results: More than one-third of the sample (38%) reported lifetime NMUPD and 17% reported NMUPD in the previous 3 months. The most common class of medications used was prescription analgesics. Men reporting NMUPD also reported higher rates of the use of marijuana, poppers, ecstasy, cocaine, methamphetamine, GHB, ketamine, heroin, and rohypnol, and had significantly higher rates of HIV risk behaviors, including more sexual partners and more unprotected sex. Conclusions: A significant minority of MSM are using prescription medications without a doctor's consent. Men who do so are risking negative consequences of such use, including the potential for addiction, potentially dangerous interactions between prescription and recreational drugs, and greater risk for contracting HIV.

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

Catalano RF; White HR; Fleming CB; Haggerty KP. Is nonmedical prescription opiate use a unique form of illicit drug use? Addictive Behaviors 36(1-2): 79-86, 2011. (35 refs.)

Nonmedical prescription opiate (NMPO) use is of great concern because of its high addiction potential, cognitive impairment effects and other adverse consequences (e g hormonal and Immune system effects hyperalgesia and overdose). Due to the combination of drugs used by those who are NMPO users it is difficult to isolate the negative effects of NMPO use from the effects of other legal and illicit drugs. Based on a stage model of substance use this study tested whether NMPO use represents a unique form of illicit drug use among emerging adults and whether there are unique consequences of early NMPO use We used longitudinal data from 912 emerging adults from the Raising Healthy Children study who were interviewed at least annually from the first or second grade through age 21. The findings indicated that almost all NMPO users have also used marijuana and a large majority has also used other drugs such as cocaine and ecstasy In addition more frequent users of NMPOs are also more frequent users of other drugs. Except for violent behavior NMPO use explained little unique variance in negative outcomes of use (e g drug use disorder mood disorder nonproductive behavior poor health and property crime) beyond that explained by other illicit drug use. Future studies examining the predictors or consequences of NMPO use and nonmedical use of other prescription drugs need to consider use within the context of other drug use.

Dahl MS; Nielsen J; Mojtabai R. The effects of becoming an entrepreneur on the use of psychotropics among entrepreneurs and their spouses. Scandinavian Journal of Public Health 38(8): 857-863, 2010. (28 refs.)

Aims: Entering entrepreneurship (i.e. becoming an entrepreneur) is known to be a demanding activity with increased workload, financial uncertainty and increased levels of stress. However, there are no systematic studies on how entering entrepreneurship affects the people involved. Methods: The authors investigated prescriptions of psychotropics for 6,221 first-time entrepreneurs from 2001-2004 and their 2,381 spouses in the first two years after becoming entrepreneurs in a matched case-control study using linked data from three Danish national registries: The Danish database for Labor Market Research, the Danish Entrepreneurship database and the Danish Prescription database. Results: Entrepreneurs were more likely to fill prescriptions at pharmacies for sedatives/hypnotics (adjusted odds ratio (AOR): 1.45 [95% CI: 1.26-1.66], p < .0001). However, they were less likely to fill prescriptions for antidepressants (AOR: 0.74 [95% CI: 0.59-0.92] p = 0.007). Spouses of these entrepreneurs were also more likely to fill prescriptions for sedatives/hypnotics (AOR: 1.36 [95% CI: 1.10-1.67], p = 0.005). No difference in prescription of antidepressants was found for spouses. Conclusions: This study showed that there was a significant relation between entering entrepreneurship and receiving prescriptions for sedative/ hypnotics both among the entrepreneurs themselves and their spouses, suggesting that entering entrepreneurship may be associated with increased stress for both the entrepreneurs and their families.

Damm J; Eser D; Moeller HJ; Rupprecht R. Severe dependency on zolpidem in a patient with multiple sclerosis suffering from paraspasticity. World Journal of Biological Psychiatry 11(2, Part 2): 516-518, 2010. (19 refs.)

Zolpidem, a non-benzodiazepine hypnotic, acts selectively via the alpha(1)-subunit of GABA(A) receptors at therapeutic doses. It is therefore thought to lack both benzodiazepine properties such as anxiolysis, anticonvulsion, muscle relaxation, and side effects such as dependency. We report a case of severe dependency of zolpidem taken because of percieved myorelaxation in a patient with multiple sclerosis and paraspasticity. The observations in the patient described here suggest that zolpidem looses alpha 1-receptor selectivity at higher doses, thereby leading to the same risks and benefits such as benzodiazepines. This should be taken into account by doctors when prescribing higher doses. Zolpidem may improve symptoms of spasticity in high doses via affection of GABA alpha 2-receptor and alpha 3-receptor subunits.

Darcin AE; Dilbaz N; Okay IT. Barbexaclone abuse in a cannabis ex-user. Substance Abuse 31(4): 270-272, 2010. (6 refs.)

Abuse of drugs including addictive ingredients is common among patients with initial addiction history. This article reports a patient who had experienced a panic attack due to cannabis intoxication and has began to abuse an antiepileptic drug barbexaclone after he had quitted cannabis.

DeSantis A; Noar SM; Webb EM. Speeding through the frat house: A qualitative exploration of nonmedical ADHD stimulant use in fraternities. Journal of Drug Education 40(2): 157-171, 2010. (24 refs.)

Qualitative methods were used to investigate the use of nonmedical Attention Deficit Hyperactivity Disorder (ADHD) stimulants by fraternity members. The primary goal of the study was to determine students' levels of understanding and motivations for use of these Schedule II controlled substances. Seventy-nine in-depth interviews were conducted. Key findings highlighted how: a) easy it was for subjects to obtain stimulants; b) little health information nonmedical users have about stimulants; c) academic stress created a fertile context for stimulant use; and d) a small number of prescribed users supply the vast majority of nonmedical users with their stimulants. Most nonmedical users claimed to primarily use ADHD stimulants in periods of high academic stress and believed that they not only reduced fatigue, but also increased reading comprehension, interest, cognition, and memory. These qualitative data have supplied a rich and complex understanding behind nonmedical ADHD stimulant use among fraternity members.

Edlund MJ; Martin BC; Fan MY; Devries A; Braden JB; Sullivan MD. Risks for opioid abuse and dependence among recipients of chronic opioid therapy: Results from the TROUP Study. Drug and Alcohol Dependence 112(1-2): 90-98, 2010. (54 refs.)

Objective: To estimate the prevalence of and risk factors for opioid abuse/dependence in long-term users of opioids for chronic pain, including risk factors for opioid abuse/dependence that can potentially be modified to decrease the likelihood of opioid abuse/dependence, and non-modifiable risk factors for opioid abuse/dependence that may be useful for risk stratification when considering prescribing opioids. Methods: We used claims data from two disparate populations, one national, commercially insured population (HealthCore) and one state-based, publicly insured (Arkansas Medicaid). Among users of chronic opioid therapy, we regressed claims-based diagnoses of opioid abuse/dependence on patient characteristics, including physical health, mental health and substance abuse diagnoses, sociodemographic factors, and pharmacological risk factors. Results: Among users of chronic opioid therapy, 3% of both the HealthCore and Arkansas Medicaid samples had a claims-based opioid abuse/dependence diagnosis. There was a strong inverse relationship between age and a diagnosis of opioid abuse/dependence. Mental health and substance use disorders were associated with an increased risk of opioid abuse/dependence. Effects of substance use disorders were especially strong, although mental health disorders were more common. Concerning opioid exposure; lower days supply, lower average doses, and use of Schedule III-IV opioids only, were all associated with lower likelihood of a diagnosis of opioid abuse/dependence. Conclusion: Opioid abuse and dependence are diagnosed in a small minority of patients receiving chronic opioid therapy, but this may under-estimate actual misuse. Characteristics of the patients and of the opioid therapy itself are associated with the risk of abuse and dependence.

Fischer B; Bibby M; Bouchard M. The global diversion of pharmaceutical drugs. Non-medical use and diversion of psychotropic prescription drugs in North America: a review of sourcing routes and control measures. Addiction 105(12): 2062-2070, 2010. (90 refs.)

Aims North America features some of the world's highest consumption levels for controlled psychoactive prescription drugs (PPDs; e.g. prescription opioids, benzodiazepines, stimulants), with non-medical use and related harms (e.g. morbidity, mortality) rising in key populations in recent years. While the determinants, characteristics and impacts of these 'use' problems are increasingly well documented, little is known about the 'supply' side of non-medical PPD use, much of which is facilitated by 'diversion' as a key sourcing route. This paper provides a select review of the phenomenon of PPD diversion in North America, also considering interventions and policy implications. Methods A conceptual and empirical review of select-peer- and non-peer-reviewed research literature from 1991 to 2010 focusing upon PPD diversion in North America was conducted. Results The phenomenon of PPD diversion is heterogeneous. Especially among general populations, a large proportion of PPDs for non-medical use are obtained from friends or family members. Other PPD diversion routes involve 'double doctoring' or 'prescription shopping'; street drug markets; drug thefts, prescription forgeries or fraud; as well as PPD purchases from the internet. Conclusions: The distinct nature and heterogeneity make PPD diversion a complex and difficult target for interventions. Prescription monitoring programs (PMPs) appear to reduce overall PPD use, yet their impact on reducing diversion or non-medical use is not clear. Law enforcement is unlikely to reach PPD diversion effectively. Effective reduction will probably require reductions in overall PPD consumption volumes, although such will need to be accomplished without compromising standards of good medical (e.g. pain) care.

Fortuna RJ; Robbins BW; Caiola E; Joynt M; Halterman JS. Prescribing of controlled medications to adolescents and young adults in the United States. Pediatrics 126(6): 1108-1116, 2010. (39 refs.)

OBJECTIVE: The nonmedical use of prescription drugs by adolescents and young adults has surpassed all illicit drugs except marijuana, yet little is known about prescribing patterns. We examined the prescribing of controlled medications to adolescents aged 15 to 19 and young adults aged 20 to 29. METHODS: We used cross-sectional data from the National Ambulatory Medical Care Survey (N = 4304 physicians) and the National Hospital Ambulatory Medical Care Survey (N = 2805 clinics; N = 1051 emergency departments) between 2005 and 2007. We also used consecutive data from 1994 to describe trends. RESULTS: A controlled medication was prescribed at 2.3 million visits by adolescents and 7.8 million visits by young adults in 2007. Between 1994 and 2007, controlled medications were prescribed at an increasing proportion of visits from adolescents (6.4%-11.2%) and young adults (8.3%-16.1%) (P < .001 for trend). This increase was seen among males and females, in ambulatory offices and emergency departments, and for injury-related and non-injury-related visits (all P < .001). A controlled medication was prescribed during 9.6% of all adolescent visits and 13.8% of young-adult visits for non-injury-related indications and at 14.5% of adolescent visits and 27.0% of young-adult visits for injury-related reasons. Controlled medications were prescribed at a substantial proportion of visits for common conditions, such as back pain, to both adolescents (23.4%) and young adults (36.9%). CONCLUSIONS: Controlled medications are prescribed at a considerable proportion of visits from adolescents and young adults, and prescribing rates have nearly doubled since 1994. This trend and its relationship to misuse of medications warrants further study.

Galloway GP; Buscemi R; Coyle JR; Flower K; Siegrist JD; Fiske LA et al. A randomized, placebo-controlled trial of sustained-release dextroamphetamine for treatment of methamphetamine addiction. Clinical Pharmacology & Therapeutics 89(2): 276-282, 2011. (49 refs.)

Sixty treatment-seeking individuals with methamphetamine (MA) dependence entered a randomized, placebo-controlled, double-blind clinical trial of oral dextroamphetamine (d-AMP) as a replacement therapy for MA dependence. The subjects took 60 mg sustained-release d-AMP for 8 weeks, during which time they received eight 50-min sessions of individual psychotherapy. Adverse events and urine toxicology for MA were assessed two times a week. There were no serious adverse events. Urine samples containing < 1,000 ng/ml of MA were classified as negative for MA. The MA-negative scores in the d-AMP group (3.1 +/- SD 4.6) were no higher than those in the placebo group (3.3 +/- SD 5.3; P > 0.05). However, withdrawal and craving scores were significantly lower in the d-AMP group (P < 0.05 for both). Although subjects taking d-AMP did not reduce their use of MA, the significant reductions observed in withdrawal and craving scores in this group support the need for further exploration of d-AMP as a pharmacologic intervention for MA dependence, possibly at higher doses.

Gracious B; Abe N; Sundberg J. The importance of taking a history of over-the-counter medication use: A brief review and case illustration of "prn" antihistamine dependence in a hospitalized adolescent. Journal of Child and Adolescent Psychopharmacology 20(6): 521-524, 2010. (22 refs.)

Over-the-counter (OTC) and prescription medication abuse has been rapidly increasing, yet publications on OTC abuse in adolescents are limited. We present a brief literature review and a novel report of antihistamine dependence emerging after admission in an adolescent, subsequently treated with naltrexone. This case highlights the need to take a thorough history of OTC, herbal, and prescription drug use from parents and patients separately and repeatedly, at initial presentation, and again if withdrawal symptoms emerge. General strategies for combating OTC and prescription abuse are given.

Hansen RN; Oster G; Edelsberg J; Woody GE; Sullivan SD. Economic costs of nonmedical use of prescription opioids. Clinical Journal of Pain 27(3): 194-202, 2011. (36 refs.)

Objectives: Although the economic costs of substance misuse have been extensively examined in the published literature, information on the costs of nonmedical use of prescription opioids is much more limited, despite being a significant and rapidly growing problem in the United States. Methods: We estimated the current economic burden of nonmedical use of prescription opioids in the United States in terms of direct substance abuse treatment, medical complications, productivity loss, and criminal justice. We distributed our broad cost estimates among the various drugs of misuse, including prescription opioids, down to the individual drug level. Results: In 2006, the estimated total cost in the United States of nonmedical use of prescription opioids was $53.4 billion, of which $42 billion (79%) was attributable to lost productivity, $8.2 billion (15%) to criminal justice costs, $2.2 billion (4%) to drug abuse treatment, and $944 million to medical complications (2%). Five drugs-OxyContin, oxycodone, hydrocodone, propoxyphene, and methadone-accounted for two-thirds of the total economic burden. Discussion: The economic cost of nonmedical use of prescription opioids in the United States totals more than $50 billion annually; lost productivity and crime account for the vast majority (94%) of these costs.

Havens JR; Young AM; Havens CE. Nonmedical prescription drug use in a nationally representative sample of adolescents evidence of greater use among rural adolescents. Archives of Pediatrics & Adolescent Medicine 165(3): 250-255, 2011. (44 refs.)

Objectives: To compare the prevalence of nonmedical prescription drug use among adolescents residing in urban, suburban, and rural areas of the United States and to determine factors independently associated with rural nonmedical prescription drug use among adolescents aged 12 to 17 years. Design: Cross-sectional, population-based survey. Setting: Noninstitutionalized residents in the United States. Participants: Participants included adolescents aged 12 to 17 years (N = 17 872), most of whom were residing in urban areas (53.2%), male (51%), and white (59%). Main Exposure: Living in rural compared with urban area. Main Outcome Measures: Nonmedical use of prescription drugs (pain relievers, tranquilizers, sedatives, and stimulants). Data were from the 2008 National Survey on Drug Use and Health. Results: Rural adolescents were 26% more likely than urban adolescents to have used prescription drugs nonmedically (adjusted odds ratio, 1.26; 95% confidence interval, 1.01-1.57) even after adjustment for race, health, and other drug and alcohol use. When examining the rural adolescents in particular, factors positively associated with nonmedical use of prescription drugs included decreased health status, major depressive episode(s), and other drug (marijuana, cocaine, hallucinogens, and inhalants) and alcohol use. Protective factors for nonmedical prescription drug use among rural adolescents included school enrollment and living in a 2-parent household. Conclusions: Rural adolescents were significantly more likely than urban adolescents to report nonmedical prescription drug use. However, these results suggest there are multiple potential points of intervention to prevent initiation or progression of use among rural adolescents including preventing school dropout, increased parental involvement, and increased access to health, mental health, and substance abuse treatment.

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.

Iravani FS; Akhgari M; Jokar F; Bahmanabadi L. Current trends in tramadol-related fatalities, Tehran, Iran 2005-2008. Substance Use & Misuse 45(13): 2162-2171, 2010. (48 refs.)

Tramadol is a widely prescribed drug. Abuse of tramadol as well as tramadol-related deaths have been increasing in Iran. The objective of the present study is to evaluate the trends of tramadol-related deaths that occurred between 2005 and 2008 in Tehran, Iran. Biological samples obtained during the autopsy were analyzed. Tramadol was detected in 294 cases by itself or together with other drugs. The majority of the cases were young male adults. Tramadol-related deaths in 2008 were 32.5 times more than in 2005. These results suggest that tramadol-related fatalities are growing in Iran especially among substance abusers.

Kirkpatrick MG; Haney M; Vosburg SK; Comer SD; Foltin RW; Hart CL. Zolpidem does not serve as reinforcer in humans subjected to simulated shift work. Drug and Alcohol Dependence 112(1-2): 168-171, 2010. (25 refs.)

Zolpidem attenuates shift-change-related sleep and performance disruptions. It is unknown whether these benefits alter the reinforcing effects of the drug during shift work. This study examined zolpidem-related reinforcing effects during simulated shift work. Eleven volunteers (3F, 8M) completed this 16-day within-participant, residential laboratory study.. Each day participants were given an opportunity to self-administer oral zolpidem (10 mg) or receive a $1 voucher immediately following a 9-h work period and immediately before going to bed. Participants worked under two shift conditions: (1) during the night shift, participants completed computerized task batteries from 00:30 to 09:30 h and went to bed at 16:00 h and (2) during the day shift, participants completed task batteries from 08:30 to 17:30 h and went to bed at 24:00 h. Shift conditions alternated three times during the study. Despite the fact that sleep, psychomotor performance, and some ratings of mood were disrupted during night-shift work, there was no significant effect of shift on choice to take zolpidem. Overall, participants selected markedly fewer zolpidem doses than monetary vouchers (17% versus 83%). Thus, zolpidem did not serve as a reinforcer even when sleep was disrupted. These data are consistent with previous reports indicating that sedatives produce limited reinforcing effects in individuals without a history of drug abuse.

Lewis ET; Trafton JA. Opioid use in primary care: Asking the right questions. (review). Current Pain and Headache Reports 15(2): 137-143, 2011. (55 refs.)

Pain is one of the most common reasons that patients seek treatment from health care professionals, often their primary care providers. One tool for treating pain is opioid therapy, and opioid prescriptions have increased dramatically in recent years in the United States. This article will review recent research about opioids that is most relevant to treating chronic pain in the context of a typical primary care practice. It will focus on four key practices that providers can engage in before and during the course of opioid therapy that we believe will enhance the likelihood that opioids, when used, are an effective tool for pain management: avoiding sole reliance on opioids; using adequate opioid doses to address pain; mitigating the risk of opioid misuse by patients; and fostering collaborative relationships for treating complex patients.

Liebschutz JM; Saitz R; Weiss RD; Averbuch T; Schwartz S; Meltzer EC et al. Clinical factors associated with prescription drug use disorder in urban primary care patients with chronic pain. Journal of Pain 11(11): 1047-1055, 2010. (59 refs.)

This study examined characteristics associated with prescription drug use disorder (PDUD) in primary care patients with chronic pain from a cross sectional survey conducted at an urban academically affiliated safety net hospital Participants were 18 to 60 years old had pain for >= 3 months took prescription or nonprescription analgesics and spoke English Measurements included the Composite International Diagnostic Interview (PDUD other substance use disorders (SUD) Posttraumatic Stress Disorder [PTSD]) Graded Chronic Pain Scale smoking status family history of SUD and time spent in jail Of 597 patients (41% male 61% black mean age 46 years) 110 (18 4%) had PDUD of whom 99 (90%) had another SUD. In adjusted analyses those with PDUD were more likely than those without any current or past SUD to report jail time (OR 5 1 95% Cl 2 8-9 3) family history of SUD (OR 3 4 1 9 6) greater pain related limitations (OR 3 8 1 2 11 7) cigarette smoking (OR 3 6 2-6 2) or to be white (OR 3 2 1 7-6) male (OR 1 9 1 1-3 5) or have PTSD (OR 1 9 1 1-3 4) PDUD appears increased among those with easily identifiable characteristics. The challenge is to determine who among those with risk factors can avoid with proper management developing the increasingly common diagnosis of PDUD. Perspective: This article examines risk factors for prescription drug use disorder (PDUD) among a sample of primary care patients with chronic pain at an urban academic safety net hospital. The findings may help clinicians identify those most at risk for developing PDUD when developing appropriate treatment.

Lin AYC; Wang XH; Lin CF. Impact of wastewaters and hospital effluents on the occurrence of controlled substances in surface waters. Chemosphere 81(5): 562-570, 2010. (43 refs.)

We have investigated the occurrence of controlled drugs in two rivers, two wastewater treatment plants (WWTPs) and five hospital effluents in Taipei, Taiwan, and report here the concentrations of controlled drugs used as prescription medication or drugs of abuse. Of the target drugs, morphine, codeine, meth-amphetamines and ketamine were observed in significant quantities in hospital effluents, with maximum concentrations of 1240, 378, 260 and 206 and L-1, respectively. The other six compounds (including metabolites) were found at trace levels or below the method detection limits. In addition, the high occurrence in river waters of methamphetamine, codeine and ketamine (maximum values 405, 57, and 341 ng L-1, respectively) indicated the significant prevalence of these controlled drugs. This study demonstrated that effluents from hospitals and clinics and treated WWTP effluents contribute to the controlled substances that eventually reach natural rivers. We hypothesize that the occurrence of controlled drugs in the environment can be attributed to two main sources: (1) substance abuse by individuals and (2) treatment with prescription medication for acute and chronic pain. The presence of these contaminants in the aquatic environment may pose significant risk to aquatic and human life. Further studies are needed for verification and may contribute to the development of sustainable strategies for environmental remediation.

Lingford-Hughes A; Watson B; Kalk N; Reid A. Neuropharmacology of addiction and how it informs treatment. British Medical Bulletin 96(1): 93-110, 2010. (67 refs.)

Our knowledge about the neuropharmacology of addiction is increasing and is leading to more informed development of pharmacotherapy. Although the dopaminergic mesolimbic system plays a central role in 'liking', reward and motivation, medications directly targeting it have not proved a very fruitful approach to treating addictions. A review of the literature was performed to find articles relating current and developing pharmacological treatments in the clinic and their underlying neuropharmacology. We focussed on the most common addictions for which pharmacology plays an important role. By characterizing what neurotransmitters modulate this dopaminergic pathway, new medications are now in the clinic and being successfully applied to treat a variety of addictions. In addition to modulating this reward pathway, alternative approaches in the future will target learning and memory, improving impulse control and decision-making.

Lofwall MR; Walsh SL. Clinical challenges in managing buprenorphine diversion. (editorial). Journal of Addiction Medicine 4(4): 243-243, 2010. (3 refs.)

Lust EB; Barthold C; Malesker MA; Wichman TO. Human health hazards of veterinary medications: Information for emergency departments. Journal of Emergency Medicine 40(2): 198-207, 2011. (59 refs.)

Background: There are over 5000 approved prescription and over-the-counter medications, as well as vaccines, with labeled indications for veterinary patients. Of these, there are several products that have significant human health hazards upon accidental or intentional exposure or ingestion in humans: carfentanil, clenbuterol (Ventipulmin), ketamine, tilmicosin (Micotil), testosterone/estradiol (Component E-H and Synovex H), dinoprost (Lutalyse/Prostamate), and cloprostenol (Estromate/EstroPlan). The hazards range from mild to life-threatening in terms of severity, and include bronchospasm, central nervous system stimulation, induction of miscarriage, and sudden death. Objective: To report medication descriptions, human toxicity information, and medical management for the emergent care of patients who may have had exposure to veterinary medications when they present to an emergency department (ED). Discussion: The intended use of this article is to inform and support ED personnel, drug information centers, and poison control centers on veterinary medication hazards. Conclusion: There is a need for increased awareness of the potential hazards of veterinary medications within human medicine circles. Timely reporting of veterinary medication hazards and their medical management may help to prepare the human medical community to deal with such exposures or abuses when time is of the essence.

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.

McLarnon ME; Monaghan TL; Stewart SH; Barrett SP. Drug misuse and diversion in adults prescribed anxiolytics and sedatives. Pharmacotherapy 31(3): 262-272, 2011. (62 refs.)

Study Objective. To identify patterns of misuse and diversion of anxiolytic and sedative drugs among a sample of adults prescribed these drugs. Design. Cross-sectional study. Setting. University research center in Canada. Participants. Sixty-seven adults (aged 19-61 yrs) who had current prescriptions for anxiolytic or sedative drugs. Intervention. Face-to-face interviews and questionnaires were used to gather information on demographics as well as variables relating to drug misuse and diversion such as personality dimensions, psychiatric symptoms, and other substance use. Measurements and Main Results. Of the 67 participants, 36 (54%) reported misusing their drugs on at least one occasion, and 35 (52%) reported diverting their drugs at least once. A variety of forms of anxiolytic or sedative misuse were reported, including exceeding the recommended dosage (28 participants [42%]), deliberately using the drug with alcohol or another drug (27 [40%]), or taking it by an alternate route of administration (5 [7%]). Misuse and diversion were associated with a history of substance use and substance-related problems, as well as personality characteristics relating to impulsivity and hopelessness. Diversion was also associated with an increased likelihood of having taken any psychoactive prescription drug without having a valid prescription for it. Conclusion. A variety of forms of drug misuse and diversion occurred among this population of adults who were prescribed anxiolytics or sedatives. Likelihood of engaging in misuse or diversion was associated with other substance use, substance use disorders, and personality characteristics. Despite the modest sample size and cross-sectional design, this study identified substantial heterogeneity in prescription anxiolytic and sedative misuse, suggesting that the use of clearly defined operational criteria will be essential in future efforts to further characterize this phenomenon.

Meltzer EC; Rybin D; Saitz R; Samet JH; Schwartz SL; Butler SF et al. Identifying prescription opioid use disorder in primary care: Diagnostic characteristics of the Current Opioid Misuse Measure (COMM). Pain 152(2): 397-402, 2011. (31 refs.)

The Current Opioid Misuse Measure (COMM), a self-report assessment of past-month aberrant medication-related behaviors, has been validated in specialty pain management patients. The performance characteristics of the COMM were evaluated in primary care (PC) patients with chronic pain. It was hypothesized that the COMM could identify patients with prescription drug use disorder (PDD). English-speaking adults awaiting PC visits at an urban, safety-net hospital, who had chronic pain and had received any opioid analgesic prescription in the past year, were administered the COMM. The Composite International Diagnostic Interview served as the "gold standard," using DSM-IV criteria for PDD and other substance use disorders (SUDs). A receiver operating characteristic (ROC) curve demonstrated the COMM's diagnostic test characteristics. Of the 238 participants, 27 (11%) met DSM-IV PDD criteria, whereas 17 (7%) had other SUDs, and 194 (82%) had no disorder. The mean COMM score was higher in those with PDD than among all others (ie, those with other SUDs or no disorder, mean 20.4 [ SD 10.8] vs 8.4 [SD 7.5], P < .0001). A COMM score of >= 13 had a sensitivity of 77% and a specificity of 77% for identifying patients with PDD. The area under the ROC curve was 0.84. For chronic pain patients prescribed opioids, the development of PDD is an undesirable complication. Among PC patients with chronic pain-prescribed prescription opioids, the COMM is a promising tool for identifying those with PDD.

Nagarnaik P; Batt A; Boulanger B. Source characterization of nervous system active pharmaceutical ingredients in healthcare facility wastewaters. Journal of Environmental Management 92(3): 872-877, 2011. (33 refs.)

Nervous system active pharmaceutical ingredients (APIs), including anti-depressants and opioids, are important clinically administered pharmaceuticals within healthcare facilities. This study provides source characterization data describing the composition and magnitude of nervous system APIs present in healthcare facility wastewaters. Concentrations and mass loadings of ten nervous system APIs and three nervous system API metabolites are reported for wastewaters from a hospital, nursing, assisted living, and independent living facility within a single municipality. Concentrations of nervous system APIs ranged from non-detectable levels for alprazolam in all four facility wastewaters to a high of 290 ng/L amitriptyline in nursing facility wastewater. The summed mean concentration of all thirteen analytes ranged from 402 ng/L in independent living facility wastewater to 624 ng/L in assisted living facility wastewater. Wastewater flow rates from each facility were combined with concentration data to estimate the daily mass loading of nervous system APIs leaving each facility through wastewater discharge to the municipal sewer system. The total mass loading of all thirteen analytes for the hospital, nursing, assisted living, and independent living facility was 228, 44, 29.5, and 28.1 mg/day, respectively. The total mass loading of nervous system APIs contributed to the municipality's wastewater from all four facilities was 330 mg/day.

Nattala P; Leung KS; Ben Abdallah A; Cottler LB. Heavy use versus less heavy use of sedatives among non-medical sedative users: Characteristics and correlates. Addictive Behaviors 36(1-2): 103-109, 2011. (45 refs.)

Non-medical use of sedatives is an ongoing problem. However, very little is known about the characteristics of individuals who use sedatives non-medically or the motives behind such use. The present analysis involving a sample of individuals reporting non-medical use of sedatives in the past 12 months (N=188) examined the relationship between socio demographic variables, past year use of other licit and illicit drugs, type of non-medical use (use in ways other than as prescribed use when not prescribed or both) motives, and past 12-month sedative use. Past 12-month sedative use was dichotomized as Heavy Use (>90 pills in past 12 months) and Less Heavy Use (<= 90 pills) using a median split. Multivariate logistic regression analyses indicated that Heavy Use of sedatives was significantly associated with positive diagnoses for sedative use disorder and prescription opioid use disorder, a higher number of motives for sedative use, and reporting sedative use in ways other than as prescribed, and both forms of non-medical use, namely other than as prescribed and when not prescribed compared to non prescribed use. Although in univariate analyses a positive diagnosis for past 12 month cocaine use disorder and individual motives for sedative use, such as to get high and for pain relief, significantly predicted past 12 month Heavy Use their effects diminished and became non-significant after adjusting for other covariates. Findings underscore the need for considering differential risk factors in tailoring preventive interventions for reducing non-medical sedative use.

Orriols L; Delorme B; Gadegbeku B; Tricotel A; Contrand B; Laumon B et al. Prescription medicines and the risk of road traffic crashes: A French registry-based study. PLoS Medicine 7(11): e-article 1000366, 2010. (32 refs.)

Background: In recent decades, increased attention has been focused on the impact of disabilities and medicinal drug use on road safety. The aim of our study was to investigate the association between prescription medicines and the risk of road traffic crashes, and estimate the attributable fraction. Methods and Findings: We extracted and matched data from three French nationwide databases: the national health care insurance database, police reports, and the national police database of injurious crashes. Drivers identified by their national health care number involved in an injurious crash in France, between July 2005 and May 2008, were included in the study. Medicines were grouped according to the four risk levels of the French classification system (from 0 [no risk] to 3 [high risk]). We included 72,685 drivers involved in injurious crashes. Users of level 2 (odds ratio [OR] = 1.31 [1.24-1.40]) and level 3 (OR = 1.25 [1.12-1.40]) prescription medicines were at higher risk of being responsible for a crash. The association remained after adjustment for the presence of a long-term chronic disease. The fraction of road traffic crashes attributable to levels 2 and 3 medications was 3.3% [2.7%-3.9%]. A within-person case-crossover analysis showed that drivers were more likely to be exposed to level 3 medications on the crash day than on a control day, 30 days earlier (OR = 1.15 [1.05-1.27]). Conclusion: The use of prescription medicines is associated with a substantial number of road traffic crashes in France. In light of the results, warning messages appear to be relevant for level 2 and 3 medications and questionable for level 1 medications. A follow-up study is needed to evaluate the impact of the warning labeling system on road traffic crash prevention.

Passik SD; Messina J; Golsorkhi A; Xie F. Aberrant drug-related behavior observed during clinical studies involving patients taking chronic opioid therapy for persistent pain and fentanyl buccal tablet for breakthrough pain. Journal of Pain and Symptom Management 41(1): 116-125, 2011. (21 refs.)

Context. Information on aberrant drug-related behaviors in the clinical study setting is limited. Objectives. This retrospective analysis was designed to identify the types and frequency of aberrant drug-related behaviors (including misuse and abuse) and associated patient characteristics in opioid-tolerant patients with chronic pain. Methods. Data from opioid-tolerant patients participating in clinical studies of fentanyl buccal tablet (FBT) for breakthrough pain (up to 18 months of clinical study case-report forms) were retrospectively reviewed and coded for abuse, overdose, and aberrant behavior. Aberrant behaviors were categorized as those involving FBT (overuse, lost or stolen study drug) and those not involving FBT (patients seeking prescriptions from other sources, not returning for follow-up). Results. Of the 1,160 patients evaluated, 10 (<1%) patients had an abuse-related event, 18 (<2%) had a positive urine drug screening (nonprescribed drug or illicit substance), and 12 (1%) had an event consistent with opioid overdose; 124 (11%) had aberrant behaviors related to FBT, and 68 (6%) had aberrant behaviors that were not. Aberrant behaviors were more frequent in men (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.1, 2.1; P < 0.01), in patients 42 years or younger (OR: 2.5; 95% CI: 1.6, 4.0; P < 0.01), and in patients 43 years to 49 years (OR: 1.9; 95% CI: 1.2, 3.1; P < 0.01). Conclusion. The incidence of drug abuse events and aberrant drug-related behaviors was relatively low, probably because of the implementation of universal precautions and the controlled clinical study setting. Even in this setting, events occurred, highlighting the limits of screening and the need for ongoing monitoring of aberrant behavior.

Pauly V; Frauger E; Pradel V; Rouby F; Berbis J; Natali F et al. Which indicators can public health authorities use to monitor prescription drug abuse and evaluate the impact of regulatory measures? Controlling high dosage buprenorphine abuse. Drug and Alcohol Dependence 113(1): 29-36, 2011. (46 refs.)

Background: Two methods have been recently developed from a drug reimbursement database to provide useful indicators for public health authorities concerning the abuse potential of psychotropic drugs. The doctor-shopping indicator (DSI) measures the proportion of the drug obtained by doctor shopping among the overall quantity of the drug reimbursed and the clustering method reveals subgroups of deviant patients. Objective: The objective of the study was to analyze and compare indicators resulting from these two methods, applied to High Dosage Buprenorphine (HDB) (a product well-known to be diverted in France), in order to determine which public health authorities needs they answer. Data analysis: The patients with reimbursed HDB were grouped using the clustering method in terms of drug dispensations characteristics over a nine month period. The characteristics of the resulting subgroups, including their DSI, were then compared. Results: 4787 Patients (73.4%) had no measurable doctor-shopping behaviour. But the comparison of the two methods demonstrated that the more a patient's profile was characterized by deviant behavior, the higher was the DSI: from 0.4% in a subgroup with a median profile to 72% in a subgroup with a deviant profile. Conclusion: These two methods are useful surveillance tools for public health authorities: the clustering method may help devise pertinent intervention strategies to reduce prescription drug abuse while the DSI method provides quantitative information demonstrating whether these strategies are useful. We discuss the advantages and disadvantages of using these two methods as useful indicators for public health authorities.

Pedrelli P; Bitran S; Shyu I; Baer L; Guidi J; Tucker DD et al. Compulsive alcohol use and other high-risk behaviors among college students. American Journal on Addictions 20(1): 14-20, 2011. (34 refs.)

The association between heavy alcohol consumption and risky behaviors has been amply investigated among college students. However, less is known with regard to types of drinking behaviors associated with high-risk activities. The present study extends this area of research by examining the relationship between compulsive drinking and hazardous behaviors in this population. Nine hundred and four college students completed measures on compulsive drinking and other risky behaviors in the context of mental health screenings at three campuses. Results showed that in males, compulsive drinking increased the risk for compulsive street drugs use, compulsive prescription drugs use, compulsive sexual activities, and gambling. Among females, compulsive drinking increased the risk for compulsive street drugs use, and compulsive sexual activities. These findings suggest that inquiring about compulsive drinking among college students may have great utility in identifying those at greater risk for other risky behaviors. The high co-occurrence of compulsive drinking, illicit substances, compulsive sexual activities, and gambling in college students suggests the need for comprehensive programs addressing high-risk behaviors together.

Peltzer K; Ramlagan S; Johnson BD; Phaswana-Mafuya N. Illicit drug use and treatment in South Africa: A review. (review). Substance Use & Misuse 45(13): 2221-2243, 2010. (45 refs.)

This review synthesizes available epidemiological data on current drug use and substance user treatment admissions in South Africa since 1994, and how changes in the political, economic, and social structures within South Africa, both before and after Apartheid, has made the country more vulnerable to drug use. Based on national surveys, current use of cannabis ranged among adolescents from 2% to 9% and among adults it was 2%, cocaine/crack (0.3%), mandrax/sedatives (0.3%), club drugs/amphetamine-type stimulants (0.2%), opiates (0.1%), and hallucinogens (0.1%). The use of primary illicit substance at admission to South African drug user treatment centers was cannabis 16.9%, methamphetamine (tik) 12.8%, crack/cocaine 9.6%, cannabis and mandrax 3.4%, heroin/opiates 9.2%, and prescription and OTC drugs 2.6%. An increase in substance user treatment admissions has increased. While the prevalence of illicit drug use in South Africa is relatively low compared to the United States and Australia, prevention and intervention policies need to be designed to reduce these levels by targeting the more risky subpopulations identified from this review.

Ponizovsky AM; Marom E; Zeldin A; Cherny NI. Trends in opioid analgesics consumption, Israel, 2000-2008. European Journal of Clinical Pharmacology 67(2): 165-168, 2011. (19 refs.)

Objective: To describe trends in opioid consumption in Israel (morphine, methadone, oxycodone, pethidine, fentanyl, buprenorphine, codeine, and dextropropoxyphene) over the 9 years, 2000-2008, and to explore explanations for changes in consumption, in amounts and the pattern. Methods: Data for the 2000-2008 period (all treatment settings, private and public) were drawn from the database maintained by the Israel Ministry of Health's Pharmaceutical Administration. The data were converted into a defined daily dose (DDD)/1,000 inhabitants/day. Results: Consumption of the five strong opioids (requiring a special prescription form) increased by 47%, from 2.46 DDD/1,000 inhabitants per day in 2000 to 3.61 DDD/1,000 inhabitants per day in 2008. This rise was mainly the result of a 4-fold increase in fentanyl consumption from 0.32 DDD/1,000 inhabitants per day in 2000 to 1.28 DDD/1,000 inhabitants per day in 2008. Oxycodone and methadone consumption levels increased moderately, and buprenorphine and dextropropoxyphene consumption rose drastically, whereas morphine, pethidine, and codeine use significantly fell. Conclusion: There has been a modest increase in opioid consumption in the years 2000-2008. This has been associated with substantial changes in the pattern of differential opioid prescribing characterized by increased prescription of oxycodone, fentanyl, buprenorphine, and dextropropoxyphene, and decreases in morphine, pethidine, and codeine.

Porucznik CA; Sauer BC; Crook J; Rolfs RT. Adult use of prescription opioid pain medications --- Utah, 2008. MMWR. Morbidity and Mortality Weekly Review 59(6): 153-157, 2010. (9 refs.)

In 2005, Utah had the highest rates in the nation of reported nonmedical use of pain relievers, as well as an increase in prescription opioid--related deaths. In 2008, the Utah Department of Health added 12 questions to the state's Behavioral Risk Factor Surveillance System (BRFSS) survey to assess how residents obtain and use prescription pain medication. Findings from the survey indicated that an estimated 20.8% of Utah adults aged �18 years had been prescribed an opioid pain medication during the preceding 12 months. Of those prescribed an opioid pain medication, 3.2% reported using their medication more frequently or in higher doses than had been directed by their doctor; 72.0% reported having leftover medication, and 71.0% of those with leftover medication reported that they had kept the medication. Approximately 1.8% of all adults reported using prescription opioids that had not been prescribed to them. In 2009, the Utah Department of Health published a set of guidelines to reduce morbidity, mortality, and disability associated with misuse or abuse of prescription drugs, especially narcotics. The guidelines include recommendations that providers 1) counsel patients to dispose of unused medication properly once the pain has resolved and 2) prescribe no more than the number of doses needed based on the usual duration of pain severe enough to require opioids for that condition. The following guidelines are presented, for physicians and public policy. Providers can reduce the amount of opioid medication available for nonmedical use by: Using opioid medications for acute or chronic pain only after determining that alternative therapies do not deliver adequate pain relief. The lowest effective dose of opioids should be used. Reserving use of long-acting or sustained-release opioids (e.g., OxyContin or methadone) for the treatment of long-term pain. Seeking specialty consultation if patients continue to experience severe pain without functional improvement despite treatment with opioids. Periodically requesting a report on the prescribing of opioids to their patients by other providers. Such reports generally are available from the state prescription drug monitoring program. State and federal agencies can reduce the risks resulting from misuse of opioid analgesics by: Making substance abuse treatment services widely available; Monitoring Medicaid prescription claims information for signs of inappropriate use of opioid medication (e.g., multiple prescriptions for the same medication from different physicians), and notifying the physicians that the patient might be misusing the medication; Proactively using state prescription drug monitoring programs to identify patients and providers with signs of inappropriate use, prescribing, or dispensing of opioid medications.

Public Domain

Radat F; Lanteri-Minet M. What is the role of dependence-related behavior in medication-overuse headache? Headache 50(10): 1597-1611, 2010. (85 refs.)

Medication-overuse headache (MOH) can be viewed as an interaction between the worsening of the primary headache course and individual predispositions for dependence. We present here a review of the clinical and biological data raising the role of dependence-related behavior in MOH. Indeed, several clinical studies show that acute headache medications containing psychoactive components (barbiturates, opiates) are associated with an increased risk of MOH. Diagnostic and Statistical Manual of Mental Disorders, 4th edition substance dependence criteria were identified in a sub-group of MOH patients. Comorbidity between MOH and substance-related disorders has also been showed. Recent neuroimaging, biological, and pharmacogenetic studies suggest the existence of an overlap between the pathophysiological mechanisms of MOH and those of substance-related disorders. These data support the proposition of separating 2 sets of MOH patients: the first one in which the illness is mainly due to the worsening of the headache course, and the second one in which behavioral issues are a major determinant of the illness. Detection of a psychological dependence component in a sub-group of MOH patients should have direct relevance to disease management.

Rigg KK; March SJ; Inciardi JA. Prescription drug abuse & diversion: Role of the pain clinic. Journal of Drug Issues 40(3): 681-701, 2010. (35 refs.)

The goal of this research is to better understand the role that South Florida pain management clinics may be playing in the abuse and diversion of prescription drugs This study explores 1) the characteristics and practices of pain clinics that may be facilitating the drug-seeking endeavors of prescription drug abusers and 2) the drug-seeking behaviors of prescription drug abusers who use pain clinics as a primary source for drugs Thirty in-depth interviews were conducted with prescription drug abusers in South Florida. Interviews were transcribed verbatim and codes were generated based on thematic analyses of the data. Using grounded theory strategies the analyses revealed six main themes: pill mills on-site pharmacies, liberal prescribing habits, drug diversion, pain doctor/pharmacy shopping, and falsifying symptoms/documentation. These findings should provide insights for law enforcement regulatory agencies and industry as they attempt to develop appropriate policy initiatives and recommendations for best practices

Skurtveit S; Furu K; Selmer R; Handal M; Tverdal A. Nicotine dependence predicts repeated use of prescribed opioids. prospective population-based cohort study. Annals of Epidemiology 20(12): 890-897, 2010. (53 refs.)

PURPOSE: The aim of this study was to evaluate prospectively smoking dependence as a predictor of repeated use of prescribed opioids in non-cancer patients. METHODS: We conducted a prospective population-based study cohort of 12,848 men and 15,894 women 30-75 years of age in health surveys in Norway during 2000-2002 with repeated opioid prescriptions (12+, during 2004-2007) recorded in the Norwegian Prescription Database as the outcome measure. Information on history of smoking and potential confounders was obtained at baseline by self-administered questionnaires. For smoking, participants were divided into categories: never; previously heavy (stopped maximum of 5 years earlier; 10+ cigarettes daily); daily not heavy (1-9 cigarettes); dependent daily smokers (10+ cigarettes), and other (previously and/or not daily). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by logistic regression. RESULTS: During follow-up, 335 (1.5%) of survey participants were registered with 12+ prescriptions of opioids during the period 2004-2007. The prevalence of repeated prescription frequency of opioids was higher for men and women with a history of smoking. The adjusted OR for prescribed opioids for dependent daily smokers was 3.1(95% Cl: 2.3-4.1), for daily non-heavy smokers 1.8 (1.2-2.7), and for previous heavy smokers 1.8 (1.1-3.0), compared with never-smokers as reference. CONCLUSIONS: Results of the study suggest that smoking dependence may predict more frequent use of opioids.

Sobolevsky T; Rodchenkov G. Sulbutiamine in sports. Drug Testing and Analysis 2(11-12, special issue): 643-646, 2010. (9 refs.)

Sulbutiamine (isobutyryl thiamine disulfide) is a lipophilic derivative of thiamine used for the treatment of asthenia and other related pathological conditions. It is available over-the-counter in several countries either as a component of nutritional supplements or as a pharmaceutical preparation. The presence of sulbutiamine in urinary doping control samples was monitored to evaluate the relevance of its use in sports. As one of the sulbutiamine metabolites has very close retention time and the same characteristic ion (m/z 194) as the main boldenone metabolite, the raw data files generated from the screening for anabolic steroids were automatically reprocessed to identify the samples containing sulbutiamine. It was found that of ca. 16000 samples analyzed in the Russian laboratory during 2009, about 100 samples contained sulbutiamine. It is important to note that most of these samples were collected in-competition, and sulbutiamine concentration was estimated to be greater than 500 ng/ml. This may indicate that sulbutiamine was intentionally administered for its ergogenic and mild stimulating properties.

Waiser MJ; Humphries D; Tumber V; Holm J. Effluent-dominated streams. Part 2: Presence and possible effects of pharmaceuticals and personal care products in Wascana Creek, Saskatchewan, Canada. Environmental Toxicology and Chemistry 30(2): 508-519, 2011. (58 refs.)

Recent worldwide surveys have not only established incomplete removal of pharmaceuticals and personal care products (PPCPs) by sewage treatment plants, but also their presence in surface waters receiving treated sewage effluent. Those aquatic systems where sewage effluent dominates flow are thought to be at the highest risk for ecosystem level changes. The city of Regina, Saskatchewan, Canada (population 190,400) treats its sewage at a modern tertiary sewage treatment facility located on Wascana Creek. The Wascana Creek hydrograph is dominated by one major event: spring snow melt. Thereafter, creek flow declines considerably and in winter treated sewage effluent makes up almost 100% of stream flow. Four water surveys conducted on the creek from winter 2005 to spring 2007 indicated that PPCPs were always present, in nanogram and sometimes microgram per liter concentrations downstream of the sewage treatment plant. This mixture included antibiotics, analgesics, antiinflammatories, a lipid regulator, metabolites of caffeine, cocaine and nicotine, and an insect repellent. Not surprisingly, concentrations of some PPCPs were highest in winter. According to hazard quotient calculations and homologue presence, ibuprofen, naproxen, gemfibrozil, triclosan, erythromycin, trimethoprim, and sulfamethoxazole were present in Wascana Creek at concentrations that may present a risk to aquatic organisms. The continual exposure to a mixture of pharmaceuticals as well as concentrations of un-ionized ammonia that far exceed Canadian and American water quality guidelines suggests that Wascana Creek should be considered an ecosystem at risk. Although the Wascana Creek study is regional in nature, the results highlight the considerable risks posed to aquatic organisms in such effluent-dominated ecosystems.

Warner M; Chen LH; Makuc DM. QuickStats. Number of poisoning deaths involving opioid analgesics and other drugs or substances --- United States, 1999--2007. MMWR. Morbidity and Mortality Weekly Review 59(32): 1026, 2010. (3 refs.)

Data is presented on the number of poisoning deaths involving opioid analgesics and other drugs or substances in the United States during 1999-2007. From 1999 to 2007, the number of U.S. poisoning deaths involving any opioid analgesic (e.g., oxycodone, methadone, or hydro-codone) more than tripled, from 4,041 to 14,459, or 36% of the 40,059 total poisoning deaths in 2007. In 1999, opioid analgesics were involved in 20% of the 19,741 poisoning deaths. During 1999-2007, the number of poisoning deaths involving specified drugs other than opioid analgesics increased from 9,262 to 12,790, and the number involving nonspecified drugs increased from 3,608 to 8,947.

Public Domain

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.

Wu LT; Woody GE; Yang CM; Blazer DG. How do prescription opioid users differ from users of heroin or other drugs in psychopathology: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. Journal of Addiction Medicine 5(1): 28-35, 2011. (26 refs.)

Objectives: To study substance use and psychiatric disorders among prescription opioid users, heroin users, and nonopioid drug users in a national sample of adults. Methods: Analyses of data from the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Results: Four groups were identified among 9140 illicit or nonprescribed drug users: heroin-other opioid users (1.0%; used heroin and other opioids), other opioid-only users (19.8%; used other opioids but never heroin), heroin-only users (0.5%; used heroin but never other opioids), and nonopioid drug users (78.7%; used drugs but never heroin or other opioids). After adjusting for variations in socioeconomic characteristics, history of substance abuse treatment, and familial substance abuse, heroin-other opioid users had greater odds of several substance use disorders (SUDs; cocaine, hallucinogen, sedative, amphetamine, and tranquilizer) when compared with the other groups; heroin-only users had reduced odds of sedative and tranquilizer use disorders when compared with other opioid-only users. Nonopioid drug users had reduced odds of all SUDs and other mental disorders (mood, anxiety, pathologic gambling, and personality) when compared with other opioid-only users. Past-year other opioid-only users also reported slightly lower scores on quality of life than past-year nonopioid drug users. Conclusions: All opioid users had higher rates of SUDs than nonopioid drug users, and these rates were particularly increased among heroin-other opioid users. The findings suggest the need to distinguish between these 4 groups in research and treatment as they may have different natural histories and treatment needs.

Yang YH; Lai JN; Lee CH; Wang JD; Chen PC. Increased risk of hospitalization related to motor vehicle accidents among people taking zolpidem: A case-crossover study. Journal of Epidemiology 21(1): 37-43, 2011. (21 refs.)

Background: Several epidemiological and experimental studies have found a positive association between the risk of motor vehicle accidents (MVAs) and use of zopiclone and benzodiazepines. There is, however, little evidence of any risk of MVA attributable to the use of zolpidem 1 day before such accidents. We attempted to determine whether the use of zolpidem 1 day before is associated with an increased risk of an MVA. Methods: Using a 1-million-person randomly sampled cohort from the Taiwan National Health Insurance reimbursement database, 12 929 subjects were identified as having been hospitalized between 1998 and 2004 due to an MVA. Using a case-crossover design, we selected the day before an MVA as the case period for each subject, and the 91st, 182nd, and 273rd days before the case period as 3 retrospective control periods. Conditional logistical regression models were constructed to calculate the odds ratio (OR) of having an MVA and the exposure of zolpidem 1 day before. We calculated doses of benzodiazepines, zopiclone, and zolpidem based on their defined daily dose. Results: The adjusted OR for involvement in an MVA after taking 1 defined daily dose of zolpidem was 1.74 (95% confidence interval: 1.25-2.43). There were also positive effects for different washout periods and cumulative doses at 7, 14, 21, and 28 days before the occurrence of an MVA. Conclusions: Use of zolpidem 1 day before might be associated with an increased risk of MVA. Thus, precautionary warnings should be provided when prescribing zolpidem.

Yee LM; Wu D. False-positive amphetamine toxicology screen results in three pregnant women using labetalol. Obstetrics and Gynecology 117(2, Part 2 Supplement): 503-506, 2011. (8 refs.)

BACKGROUND: Labetalol is commonly used for control of hypertension in pregnancy. A component of the workup for new-onset hypertension in pregnancy often includes a urine drug screen. A labetalol metabolite is structurally similar to amphetamine and methamphetamine, thus causing potential cross-reactivity in drug immunoassays. CASES: We present one case of cocaine-induced hypertensive crisis superimposed on chronic hypertension and two cases of severe preeclampsia for which patients required escalating doses of labetalol for hypertension, with subsequent false-positive amphetamine urine drug screen results. CONCLUSION: In pregnant women requiring labetalol for treatment of hypertensive disease, a urine drug screen may be falsely positive for amphetamines and methamphetamines. Providers should be cognizant of this possibility when interpreting the results of urine drug screens.

Zacny JP; Jun JM. Lack of sex differences to the subjective effects of nitrous oxide in healthy volunteers. Drug and Alcohol Dependence 112(3): 251-254, 2010. (30 refs.)

Background: Although numerous studies have assessed subjective effects of nitrous oxide few studies have analyzed for sex differences. Since sex differences have been reported in subjective effects of several drugs such as opioids nicotine and alcohol we sought to determine if sex modulates the subjective effects of the inhalant nitrous oxide in healthy volunteers Methods: Thirty-eight females and seventy-two males from nine studies that were conducted in our laboratory were included in this retrospective analysis. All experimental studies utilized randomized placebo-controlled repeated measures designs in which subjects Inhaled 30% nitrous oxide in oxygen and 100% oxygen (placebo) Dependent measures in this analysis were subjective effects measured at baseline and 15 min into the inhalation period. Results: Nitrous oxide produced a number of subjective effects including those that could be considered abuse liability-related ( elated having pleasant thoughts drug liking) but sex did not modulate these effects. Conclusions: Females and males showed similar subjective responses to 30% nitrous oxide. Future prospective studies might assess other concentrations other measures (choice analgesic response) and other inhaled general anesthetics to more comprehensively characterize the role of sex in response to inhalants.artmouth e-journal