Extended-Release Mixed Amphetamine Salts vs Placebo for Comorbid Adult Attention-Deficit/Hyperactivity Disorder and Cocaine Use Disorder

Abstract

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 PARTICIPANTSThirteen-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 MEASURESFor 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. RESULTSMore 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

Evaluation of the “Pipeline” for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research

“…Clinical trial results suggest that amphetamine isomers are effective for treating cocaine dependence Shearer et al, 2003;Schmitz et al, 2012;Levin et al, 2015). In the seminal trial, cocaine-dependent subjects were randomly assigned to receive D-amphetamine (15 or 30 mg/day; n = 26 and 28, respectively) or placebo (n = 40) for 25 weeks .…”

“…D-Amphetamine maintenance decreased the proportion of cocaine-positive urine samples provided by subjects across the trial. Finally, Levin et al (2015) found that extended-release mixed amphetamine salts (60 and 80 mg), combined with cognitive behavioral therapy, were effective in reducing cocaine use in a population of individuals with comorbid cocaine use disorder and ADHD.…”

Tratamiento del TDAH Dual: una Gota en el Desierto

“…En esta línea, recientemente, un ECA realizado en pacientes con TDAH y dependencia de cocaína que evaluó la eficacia de dos dosis de sales mixtas de anfetaminas (60 y 80 mg/d) en comparación con placebo durante 13 semanas encontró que la disminución del consumo de cocaína a lo largo del estudio y la proporción de pacientes que conseguían estar abstinentes durante las últimas 3 semanas del estudio era mayor en el grupo que recibió 80 mg/d de MAS en comparación con el grupo que recibió 60 mg/d y el que recibió placebo (Levin et al, 2015). Otro ECA que comparó la eficacia de dosis altas de metilfenidato OROS (180 mg/d) con placebo durante 24 semanas en pacientes varones con TDAH y dependencia de anfetaminas encontró que el metilfenidato era más eficaz que el placebo en la mejora de los síntomas de TDAH, el consumo de anfetaminas y el abandono del tratamiento (Konstenius et al, 2014).…”

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

“…12 Briefly, patients seeking treatment for cocaine use disorders were enrolled at the Columbia University/New York State Psychiatric Institute (NYSPI) Substance Treatment and Research Service (STARS) or at the Ambulatory Research Center (ARC) at the University Of Minnesota Department Of Psychiatry. Inclusion criteria for the study required participants to be aged 18-60, to meet criteria for adult ADHD and current cocaine dependence as diagnosed by the Conners Adult ADHD Diagnostic Interview for DSM-IV 26 and the SCID for DSM-IV, 27 respectively, and to be medically and psychiatrically stable.…”