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Methylphenidate for ADHD in adults with substance dependence: A 24-week randomized placebo-controlled trial
Abstracts / Drug and Alcohol Dependence 140 (2014) e86–e168
cigarette smokers the relationship between menthol cigarette and marijuana use. Methods: We analyzed data obtained from a high school survey (749 non-smokers, 57 sporadic smokers [defined as smoking at least 1 cigarette per day but not daily in the past month], 40 daily smokers) and from a high school-based intervention trial (132 daily smokers) conducted in Connecticut. Chi-square tests were used to assess the differences between smoking statuses (non-smoking vs. sporadic vs. daily smoking) and menthol cigarette vs. non-menthol cigarette use on study variables (demographics, cigarette and marijuana use). Multivariate-adjusted logistic regression assessed the relationship between smoking status and marijuana use in all adolescents and then between menthol cigarette smoking and marijuana use in smokers only. Results: Compared to non-smokers, smokers (sporadic, daily) were more likely to be male (p = .03) and older (p < .01). Sporadic (OR = 9.23; 95% CI: 5.18–16.44) and daily smokers (OR = 12.74; 95% CI: 6.15–26.38) were more likely than non-smokers to use marijuana. Of the 229 smokers, 82% of the daily smokers and 18% of the sporadic smokers reported smoking menthol cigarettes (p < .01). Among smokers, sporadic and daily smoking was not associated with marijuana use; however, menthol cigarette smoking, when compared with non-menthol cigarette smoking was associated with marijuana use (OR = 1.87; 95% CI: 1.04–3.34). Conclusions: Smoking cigarettes is associated with marijuana use, and menthol cigarette smoking further increased the odds of marijuana use. Future research is needed to understand neuropharmacology and social norms surrounding the promotion of dual use to inform prevention and treatment of substance use, as well as public health policy surrounding menthol cigarettes and marijuana. Financial support: P50DA09421and R01DA026450. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.313 Tamper-resistant properties of oxycodone DETERx: Intranasal administration and in vitro tampering studies E.A. Kopecky, Alison B. Fleming, R.K. Varanasi, S.P. Mayock, S. Saim Collegium Pharmaceutical, Cumberland, RI, United States Aims: Oxycodone DETERx is a multiparticulate, extendedrelease (ER), tamper-resistant formulation designed to retain ER properties following common methods of tampering such as crushing, chewing, and preparation for IV injection. The small size of the DETERx beads (median diameter ∼300 m) allows them to be administered by sprinkling or via feeding tube for medical use; this size also makes it feasible to snort for non-medical use. In this study, plasma concentrations achieved in rabbits following intranasal administration of DETERx beads were compared with a non-tamper-resistant reference (original OxyContin OC). In order to assess the effect of tampering on drug release rate, in vitro crushing and dissolution studies were also conducted. Methods: A single-dose pharmacokinetic study was conducted in female New Zealand White rabbits. DETERx beads or crushed reference tablets containing 2 mg oxycodone were introduced intranasally with a puff of air (N = 6 per group). Separate in vitro studies assessed the effect of 10 household tampering tools (e.g., hammer, coffee grinder, mortar and pestle) on drug release. Results: Intranasal delivery of DETERx beads in rabbits resulted in lower Cmax and lower early plasma exposure compared to crushed OC tablets; mean Cmax was 3.5 times lower and mean AUC(0–2) was 3.4 times lower. DETERx beads also exhibited a
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longer elimination half-life than crushed OC (mean half-lives of 3.1 and 0.8 h, respectively). In the in vitro studies, dissolution demonstrated that crushed DETERx retained ER properties for all tools tested. Conclusions: The results of the rabbit study suggest that DETERx retains ER properties when dosed intranasally compared with crushed OC. Together, the studies presented demonstrate robustness of the DETERx formulation ER mechanism in an animal model of snorting and when subjected to tampering by physical manipulations. The Oxycodone DETERx formulation may afford decreased abuse liability through its tamper-resistant properties offering a new approach to mitigation of the recreational drug abuse public health issue. Financial support: Collegium Pharmaceutical, Inc. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.314 Methylphenidate for ADHD in adults with substance dependence: A 24-week randomized placebo-controlled trial Maija Konstenius 1 , N. Jayaram-Lindström 1 , J. Guterstam 1 , O. Beck 2 , B. Philips 3 , J. Franck 1 1 Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden 2 Medicine, Karolinska Institutet, Stockholm, Sweden 3 Psychology, Linköping University, Linkoping, Sweden
Aims: The aim of this trial was to test the efficacy and safety of 180 mg OROS methylphenidate for treating ADHD in patients with amphetamine dependence. The primary end point was relapse to any illicit drugs measured by urine toxicology. Secondary endpoints included relapse to amphetamine use, change in self-rated ADHD symptoms and retention to treatment. Methods: This was a double-blind randomized placebocontrolled trial with parallel groups design. Fifty-four incarcerated men, 18–65 years, meeting DSM-IV criteria for amphetamine dependence and ADHD, were randomized to MPH or placebo. The trial duration was 24-weeks. The medication started within two weeks before release from prison and continued in outpatient care with twice weekly visits. All subjects received once weekly cognitive behaviour therapy targeting relapse prevention. Results: The MPH treated group had significantly fewer drug positive urines compared to the placebo group, fewer amphetamine positive urines and better retention to treatment. Compared to the placebo group, the MPH group significantly reduced their self-rated ADHD symptoms during the trial. Conclusions: This is, to our knowledge, the first randomized clinical trial to demonstrate the efficacy of a stimulant treatment for ADHD in individuals with substance dependence. The results of the study indicated that treatment with MPH led to a reduction in drug use and an improvement of ADHD symptoms in severely dependent individuals. Financial support: The trial was supported by the Swedish National Board of Health and Welfare, the Swedish Research Council and Stockholm County Council. Trial registration. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.315
cigarette smokers the relationship between menthol cigarette and marijuana use. Methods: We analyzed data obtained from a high school survey (749 non-smokers, 57 sporadic smokers [defined as smoking at least 1 cigarette per day but not daily in the past month], 40 daily smokers) and from a high school-based intervention trial (132 daily smokers) conducted in Connecticut. Chi-square tests were used to assess the differences between smoking statuses (non-smoking vs. sporadic vs. daily smoking) and menthol cigarette vs. non-menthol cigarette use on study variables (demographics, cigarette and marijuana use). Multivariate-adjusted logistic regression assessed the relationship between smoking status and marijuana use in all adolescents and then between menthol cigarette smoking and marijuana use in smokers only. Results: Compared to non-smokers, smokers (sporadic, daily) were more likely to be male (p = .03) and older (p < .01). Sporadic (OR = 9.23; 95% CI: 5.18–16.44) and daily smokers (OR = 12.74; 95% CI: 6.15–26.38) were more likely than non-smokers to use marijuana. Of the 229 smokers, 82% of the daily smokers and 18% of the sporadic smokers reported smoking menthol cigarettes (p < .01). Among smokers, sporadic and daily smoking was not associated with marijuana use; however, menthol cigarette smoking, when compared with non-menthol cigarette smoking was associated with marijuana use (OR = 1.87; 95% CI: 1.04–3.34). Conclusions: Smoking cigarettes is associated with marijuana use, and menthol cigarette smoking further increased the odds of marijuana use. Future research is needed to understand neuropharmacology and social norms surrounding the promotion of dual use to inform prevention and treatment of substance use, as well as public health policy surrounding menthol cigarettes and marijuana. Financial support: P50DA09421and R01DA026450. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.313 Tamper-resistant properties of oxycodone DETERx: Intranasal administration and in vitro tampering studies E.A. Kopecky, Alison B. Fleming, R.K. Varanasi, S.P. Mayock, S. Saim Collegium Pharmaceutical, Cumberland, RI, United States Aims: Oxycodone DETERx is a multiparticulate, extendedrelease (ER), tamper-resistant formulation designed to retain ER properties following common methods of tampering such as crushing, chewing, and preparation for IV injection. The small size of the DETERx beads (median diameter ∼300 m) allows them to be administered by sprinkling or via feeding tube for medical use; this size also makes it feasible to snort for non-medical use. In this study, plasma concentrations achieved in rabbits following intranasal administration of DETERx beads were compared with a non-tamper-resistant reference (original OxyContin OC). In order to assess the effect of tampering on drug release rate, in vitro crushing and dissolution studies were also conducted. Methods: A single-dose pharmacokinetic study was conducted in female New Zealand White rabbits. DETERx beads or crushed reference tablets containing 2 mg oxycodone were introduced intranasally with a puff of air (N = 6 per group). Separate in vitro studies assessed the effect of 10 household tampering tools (e.g., hammer, coffee grinder, mortar and pestle) on drug release. Results: Intranasal delivery of DETERx beads in rabbits resulted in lower Cmax and lower early plasma exposure compared to crushed OC tablets; mean Cmax was 3.5 times lower and mean AUC(0–2) was 3.4 times lower. DETERx beads also exhibited a
e109
longer elimination half-life than crushed OC (mean half-lives of 3.1 and 0.8 h, respectively). In the in vitro studies, dissolution demonstrated that crushed DETERx retained ER properties for all tools tested. Conclusions: The results of the rabbit study suggest that DETERx retains ER properties when dosed intranasally compared with crushed OC. Together, the studies presented demonstrate robustness of the DETERx formulation ER mechanism in an animal model of snorting and when subjected to tampering by physical manipulations. The Oxycodone DETERx formulation may afford decreased abuse liability through its tamper-resistant properties offering a new approach to mitigation of the recreational drug abuse public health issue. Financial support: Collegium Pharmaceutical, Inc. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.314 Methylphenidate for ADHD in adults with substance dependence: A 24-week randomized placebo-controlled trial Maija Konstenius 1 , N. Jayaram-Lindström 1 , J. Guterstam 1 , O. Beck 2 , B. Philips 3 , J. Franck 1 1 Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden 2 Medicine, Karolinska Institutet, Stockholm, Sweden 3 Psychology, Linköping University, Linkoping, Sweden
Aims: The aim of this trial was to test the efficacy and safety of 180 mg OROS methylphenidate for treating ADHD in patients with amphetamine dependence. The primary end point was relapse to any illicit drugs measured by urine toxicology. Secondary endpoints included relapse to amphetamine use, change in self-rated ADHD symptoms and retention to treatment. Methods: This was a double-blind randomized placebocontrolled trial with parallel groups design. Fifty-four incarcerated men, 18–65 years, meeting DSM-IV criteria for amphetamine dependence and ADHD, were randomized to MPH or placebo. The trial duration was 24-weeks. The medication started within two weeks before release from prison and continued in outpatient care with twice weekly visits. All subjects received once weekly cognitive behaviour therapy targeting relapse prevention. Results: The MPH treated group had significantly fewer drug positive urines compared to the placebo group, fewer amphetamine positive urines and better retention to treatment. Compared to the placebo group, the MPH group significantly reduced their self-rated ADHD symptoms during the trial. Conclusions: This is, to our knowledge, the first randomized clinical trial to demonstrate the efficacy of a stimulant treatment for ADHD in individuals with substance dependence. The results of the study indicated that treatment with MPH led to a reduction in drug use and an improvement of ADHD symptoms in severely dependent individuals. Financial support: The trial was supported by the Swedish National Board of Health and Welfare, the Swedish Research Council and Stockholm County Council. Trial registration. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.315