Amy Mahony

Extended-release mixed amphetamine salts vs placebo for comorbid adult attention-deficit/hyperactivity disorder and cocaine use disorder a randomized clinical trial

IMPORTANCE Adult attention-deficit/hyperactivity disorder (ADHD) is prevalent but often unrecognized, in part because it tends to co-occur with other disorders such as substance use disorders. Cocaine use disorder is one such disorder with high co-occurrence of ADHD. OBJECTIVE To examine whether treatment of co-occurring ADHD and cocaine use disorder with extended-release mixed amphetamine salts is effective at both improving ADHD symptoms and reducing cocaine use. DESIGN, SETTING, AND PARTICIPANTS Thirteen-week, randomized, double-blind, 3-arm, placebo-controlled trial of participants meeting DSM-IV-TR criteria for both ADHD and cocaine use disorder conducted between December 1, 2007, and April 15, 2013, at 2 academic health center substance abuse treatment research sites. One hundred twenty-six adults diagnosed as having comorbid ADHD and cocaine use disorder were randomized to extended-release mixed amphetamine salts or placebo. Analysis was by intent-to-treat population. INTERVENTIONS Participants received extended-release mixed amphetamine salts (60 or 80 mg) or placebo daily for 13 weeks and participated in weekly individual cognitive behavioral therapy. MAIN OUTCOMES AND MEASURES For ADHD, percentage of participants achieving at least a 30% reduction in ADHD symptom severity, measured by the Adult ADHD Investigator Symptom Rating Scale; for cocaine use, cocaine-negative weeks (by self-report of no cocaine use and weekly benzoylecgonine urine screens) during maintenance medication (weeks 2-13) and percentage of participants achieving abstinence for the last 3 weeks. RESULTS More patients achieved at least a 30% reduction in ADHD symptom severity in the medication groups (60 mg: 30 of 40 participants [75.0%]; odds ratio [OR] = 5.23; 95% CI, 1.98-13.85; P < .001; and 80 mg: 25 of 43 participants [58.1%]; OR = 2.27; 95% CI, 0.94-5.49; P = .07) compared with placebo (17 of 43 participants [39.5%]). The odds of a cocaine-negative week were higher in the 80-mg group (OR = 5.46; 95% CI, 2.25-13.27; P < .001) and 60-mg group (OR = 2.92; 95% CI, 1.15-7.42; P = .02) compared with placebo. Rates of continuous abstinence in the last 3 weeks were greater for the medication groups than the placebo group: 30.2% for the 80-mg group (OR = 11.87; 95% CI, 2.25-62.62; P = .004) and 17.5% for the 60-mg group (OR = 5.85; 95% CI, 1.04-33.04; P = .04) vs 7.0% for placebo. CONCLUSIONS AND RELEVANCE Extended-release mixed amphetamine salts in robust doses along with cognitive behavioral therapy are effective for treatment of co-occurring ADHD and cocaine use disorder, both improving ADHD symptoms and reducing cocaine use. The data suggest the importance of screening and treatment of ADHD in adults presenting with cocaine use disorder. TRIAL REGISTRATION clinicaltrials.gov Identifier:NCT00553319.

The Utility of Attention-Deficit/Hyperactivity Disorder Screening Instruments in Individuals Seeking Treatment for Substance Use Disorders

OBJECTIVE Several screening tools for attention-deficit/hyperactivity disorder (ADHD) have been validated in non-substance-abusing populations, but limited data are available regarding their utility in adults with current substance use disorders. The aim of this study was to determine the sensitivity, specificity, and positive and negative predictive values of 3 commonly used ADHD screening instruments in cocaine-dependent individuals. METHOD Adults seeking treatment for cocaine dependence (N = 102) were administered 3 self-report instruments between May 2009 and April 2011: the Conners Adult ADHD Rating Scale (CAARS), the Wender Utah Rating Scale (WURS), and the Adult ADHD Self-Report Scale-Version 1.1 (ASRS-V1.1). They then met with masters-level clinicians who administered the Conners Adult ADHD Diagnostic Interview for DSM-IV (CAADID). With the CAADID serving as the gold standard, the validity of the screening instruments was determined, both singly and in combination. RESULTS Twenty-five (25%) of the 102 patients met DSM-IV criteria for ADHD or ADHD not otherwise specified (NOS) based on the CAADID. Kappa scores determining agreement between the screening tools and the CAADID (with ADHD NOS labeled as ADHD or labeled as not ADHD) ranged from 0.37 to 0.69. Sensitivity scores for the broadest range of ADHD cases were 80.0%, 87.5%, and 60.9% for the CAARS, WURS, and ASRS-V1.1, respectively. Positive predictive value was highest for the CAARS, at 74.1%, and negative predictive value was highest for the WURS, at 95.1%. The highest sensitivity (96.0%) was found with coadministration of the WURS and CAARS. CONCLUSION While all of the screening instruments were found to have adequate sensitivity and specificity, the CAARS outperformed the other instruments in regard to agreement with the CAADID and positive predictive values. However, the WURS, with the highest sensitivity in regard to the broadest range of ADHD cases, may be the single best instrument for preliminary screening purposes. Further, because the ASRS-V1.1 is the simplest and shortest instrument to administer, it may have advantages when a large number of patients need to be screened.

Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial ☆

BACKGROUND Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. OBJECTIVE The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. METHODS One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. RESULTS There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. CONCLUSIONS Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder.

ADHD Is Highly Prevalent in Patients Seeking Treatment for Cannabis Use Disorders

Objective: To estimate the prevalence of ADHD and determine an effective screening test for ADHD in a population-seeking treatment for cannabis use disorders. Method: The Conners Adult ADHD Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; CAADID) was used to generate sensitivity and specificity data for ADHD screening tests, which were then administered to 99 participants seeking treatment for cannabis use disorders to estimate ADHD prevalence. Results: The prevalence estimated from the Wender Utah Rating Scale (WURS) was 45% (sensitivity = 0.88, sensitivity of 0.75), from the Conners Adult ADHD Rating Scale (CAARS) 34% (sensitivity = 0.80, specificity = 0.91), from the WURS + CAARS 36% (sensitivity = 0.71, specificity = 0.95), and from the Adult ADHD Self-Report Scale (ASRS) 46% (sensitivity = 0.61, specificity = 0.86). Conclusion: The prevalence of ADHD in adults seeking treatment for cannabis use disorders is estimated to be between 34% and 46%. The WURS paired with the CAARS provides excellent sensitivity and specificity for the diagnosis of ADHD in this population.

Abstinence and reduced frequency of use are associated with improvements in quality of life among treatment-seekers with cannabis use disorder: Quality of Life and Cannabis Treatment

BACKGROUND AND OBJECTIVE Many patients with cannabis use disorder (CUD) do not achieve or do not have abstinence as a goal of treatment, rather they reduce their use. Assessing outcome measures as they relate to functioning and reductions in cannabis use is an important area of study. Quality of life (QoL) shows promise as one such measure. Past studies have demonstrated gender differences in QoL and CUD. We aim to assess (1) the relationship between cannabis use and QoL and (2) gender effects in an outpatient medication treatment study for CUD. METHODS Data from an 11-weeks, double-blind, placebo-controlled trial of lofexidine and dronabinol for CUD (n = 62) was analyzed. Pearsons correlations between baseline QoL as measured with the Quality of Life, Enjoyment, and Satisfaction Questionnaire-Short Form (QLES-Q-SF) and cannabis use assessed with modified timeline follow-back (TLFB) were examined. Multiple linear regression models of cannabis use on end of study QLES-Q-SF were analyzed, while adjusting for baseline QLES-Q-SF, study arm, and gender. Moderation effects with gender were also tested. RESULTS No significant association between baseline cannabis use and QoL was found. End of study abstinence (F1,47   =  8.34, p = .006) and reduced proportion of using days (F1,47  = 9.48, p = .004) were each significantly associated with end of study QoL. Reduction in grams (F1,27  = 0.25, p = .62) was not associated with QoL at end of study. Gender was not a significant moderator. DISCUSSION AND CONCLUSIONS Abstinence and lower frequency of use are associated with higher QoL, regardless of gender. SCIENTIFIC SIGNIFICANCE This is the first time QoL has been demonstrated to change over the course of CUD medication treatment. QoL is an important outcome in CUD treatment. TRIAL REGISTRATION NCT01020019. (Am J Addict 2018;27:101-107).

How treatment improvement in ADHD and cocaine dependence are related to one another: A secondary analysis

BACKGROUND Attention-deficit hyperactivity disorder (ADHD) is overrepresented among individuals seeking treatment for substance use disorders. We previously reported that treatment with extended release mixed amphetamine salts (MAS-XR) increased abstinence, compared to placebo, among patients with co-occurring ADHD and cocaine dependence. This secondary analysis investigates the temporal relationship between ADHD improvement and cocaine abstinence in the first six weeks of the trial. METHODS The study was a three-arm, randomized, double-blinded, placebo-controlled, 14-week trial comparing MAS-XR (60 mg or 80 mg daily) versus placebo among 126 participants with ADHD and cocaine dependence. An autoregressive cross-lagged structural equation model was fit and evaluated weekly ADHD improvement (defined as ≥30% reduction in the Adult ADHD Investigator Symptom Rating Scale) and urine-confirmed abstinence over the first six weeks. RESULTS The proportion of patients with each of the possible overall patterns of response was: ADHD improves before cocaine abstinence: 24%; Cocaine abstinence occurs before ADHD improvement: 12%; ADHD improvement and abstinence occur during the same week: 6%; ADHD improves but abstinence never achieved: 34%; Abstinence achieved but ADHD never improves: 6%; Neither ADHD improvement nor abstinence: 18%. A significant cross-lagged association was found; subjects with ADHD improvement at week 2 had significantly higher odds of cocaine abstinence at week 3 (p = .014). CONCLUSION When treating co-occurring ADHD and cocaine dependence with stimulant medication, abstinence is most likely preceded by improvement in ADHD, which tends to occur early with medication treatment. Other observed temporal patterns suggest the potential complexity of the relationship between ADHD and cocaine dependence.

Open-label pilot study of injectable naltrexone for cannabis dependence

ABSTRACT Background: There are no FDA-approved pharmacotherapies for cannabis use disorders (CUD), despite the evaluation of numerous medications. Notably, chronic dosing of oral naltrexone decreases self-administration of cannabis in human laboratory studies. Objectives: To test the feasibility of long-acting injectable naltrexone for the treatment of CUD, while obtaining preliminary safety and efficacy data. Methods: Twelve adult participants (seven male) meeting DSM-IV-TR criteria for cannabis dependence enrolled into an 8-week, open-label pilot study conducted at an academic treatment research clinic. They received 380 mg intramuscular injections of long-acting naltrexone on study day 1 and at the start of study week 5. Outcome measures included percentages of study completers and participants who received the second injection, frequency of adverse events (AEs), and cannabis consumption measured by average daily grams, dollars, and using days per week as measured by timeline follow-back and urine oral delta-9-tetrahydrocannabinol (THC) concentrations. Results: Of the 12 participants enrolled in the study, 9 completed the study and 6 received the second injection. There were no severe AEs but an unexpected AE led to the addition of supportive medications to the protocol. Number of cannabis use days per week significantly decreased over the course of the study (p = .001). Creatinine-corrected urine THC concentrations and average daily cannabis use per study week in grams and in dollars did not decrease over the course of the study. Conclusions: Long-acting injectable naltrexone is a feasible intervention for CUD worthy of further study in a placebo-controlled, double-blinded randomized clinical trial.

Mixed-amphetamine salts increase abstinence from marijuana in patients with co-occurring attention-deficit/hyperactivity disorder and cocaine dependence

BACKGROUND AND OBJECTIVES The prevalence of ADHD is greater in substance use disorders than the general population, and ADHD and substance use disorders share neurobiological features such as dysregulation of reward circuitry. We tested the hypothesis that stimulants would decrease marijuana use in a randomized controlled trial of extended release mixed amphetamine salts (MAS-XR) for treatment of co-occurring ADHD and cocaine use disorders. METHODS Marijuana users were defined as participants reporting use in the 30 days before study initiation, collected with timeline follow-back. The original 14-week trial utilized a 3-arm randomized design, comparing placebo, MAS-XR 60 mg, and MAS-XR 80 mg. For this analysis, both MAS-XR groups were combined, leaving n = 20 in the placebo group and n = 37 in the MAS-XR group. The primary outcome was proportion of subjects reporting any marijuana use per study week. Comparisons between groups were made using a logistic mixed effects model incorporating multiple predictors and modeling time-by-treatment interactions. RESULTS There were no significant baseline differences in marijuana use frequency and quantity. There was a significant decrease in the proportion of participants using marijuana over time in the MAS-XR group, but no difference in the proportion of marijuana-use days over time. DISCUSSION AND CONCLUSIONS Treatment of ADHD and comorbid cocaine use disorders with MAS-XR is associated with increased weekly abstinence from marijuana but not with a decrease in the proportion of marijuana using days per week. SCIENTIFIC SIGNIFICANCE Stimulant treatment of ADHD and cocaine use disorders may diminish co-occurring cannabis use. (Am J Addict 2016;25:666-672).