Elsevier

Drug and Alcohol Dependence

Volume 87, Issue 1, 23 February 2007, Pages 20-29
Drug and Alcohol Dependence

Treatment of cocaine dependent treatment seekers with adult ADHD: Double-blind comparison of methylphenidate and placebo

https://doi.org/10.1016/j.drugalcdep.2006.07.004Get rights and content

Abstract

The purpose of this double-blind 14-week trial was to compare the efficacy of sustained-release methylphenidate (MPH) to placebo (PBO) in treating adult attention deficit hyperactivity disorder (ADHD) symptoms in current cocaine dependent (CD) treatment seekers. The randomized sample consisted of 106 participants who were predominately male (83%) and 60% Caucasian, 14% Hispanic, 20% African-American and 6% other. All participants met DSM-IV criteria for ADHD and CD. There were no significant demographic differences between the two treatment groups. All participants received weekly individual cognitive behavioral therapy. There was no difference in retention rate based on treatment group (p = .91). The majority of the PBO group and the MPH group reported >30% improvement in their ADHD symptoms (55% versus 47%), with no significant difference between the two groups (p = .44). Using a combined outcome measure (>30% reduction in ADHD symptoms and CGI <3), the response rates were similar for both groups (28% PBO versus 30% MPH; p = .83). Longitudinal analyses of the urine toxicology data using generalized estimating equations, revealed a decrease in the probability of cocaine positive urine samples during the trial for the MPH group compared to the PBO group (p = .001). Further analysis suggested that for the MPH group, ADHD treatment responders, based on a semi structured clinical interview, were more likely to have a reduction in cocaine use compared to the non-ADHD responders. Although sustained-release MPH did not show superiority over PBO in treating ADHD symptoms, this trial provides some evidence that improvement in ADHD symptoms (clinician rated) among those patients receiving MPH, but not placebo, was associated with a reduction in cocaine use.

Introduction

Recent studies in treatment-seeking substance abusers have found that the rates of adult ADHD range from 10 to 33% (Clure et al., 1999, King et al., 1999, Levin et al., 1998a, Schubiner et al., 2000). Further, adolescents and adults with ADHD are less likely to progress well or complete treatment (Carroll and Rounsaville, 1993, Levin et al., 2004, Wise et al., 2001). Several clinicians have hypothesized that substance abusers with ADHD, particularly those with cocaine dependence, may seek out alcohol or other drugs to self-medicate ADHD symptoms (Khantzian, 1983, Khantzian et al., 1984, Weiss and Hechtman, 1986). Alternatively, some individuals with ADHD may not specifically choose substances to “treat” themselves, but rather initiate alcohol and drug use because they make impulsive choices. Then, because the drugs are euphorigenic and/or the individual has underlying genetic vulnerabilities, problematic use develops. Regardless of how the substance dependence develops, it is reasonable to hypothesize that reduction of ADHD symptoms may lead to a reduction or cessation of drug use.

To date, there have been numerous case reports and open trials suggesting that stimulants may reduce both ADHD symptoms and alcohol/drug use in adult outpatients (Castaneda et al., 2000, Levin et al., 1998b, Somoza et al., 2004). However, to our knowledge, only three randomized, double-blind, placebo-controlled trials have targeted current substance abusers with ADHD. In 69 substance-abusing adolescents (Riggs et al., 2004), pemoline was more effective than placebo (PBO) in reducing ADHD symptoms, but had no impact on substance use. In 48 cocaine-dependent adults with ADHD (Schubiner et al., 2002), methylphenidate (MPH) was more effective in treating ADHD symptoms based on clinician ratings, but not self-report ratings. Finally, we recently reported (Levin et al., 2006) that neither MPH nor bupropion (BPR) was superior than PBO in reducing ADHD symptoms in methadone-maintained patients.

Given the paucity of randomized, placebo-controlled trials targeting substance abusers with ADHD, it remains unclear if medication targeting ADHD symptoms in active adult substance users reduces ADHD symptoms and/or substance use. Although there are several studies with treatment seeking substance abusers suggesting that stimulants can be given safely to those with and without ADHD (Castaneda et al., 2000, Grabowski et al., 2004, Grabowski et al., 1997, Levin et al., 2006, Levin et al., 1998b, Schubiner et al., 2002, Shearer et al., 2003, Somoza et al., 2004), more support for this notion is needed. Considering that the only existing double-blind trial comparing MPH to PBO was relatively small (n = 48) and had mixed results (Schubiner et al., 2002), further evaluation of MPH in cocaine-dependent individuals with ADHD under double-blind placebo controlled conditions is warranted. We hypothesized that adult cocaine-dependent individuals with ADHD who received MPH along with individual cognitive behavioral therapy would have greater improvements in their ADHD symptoms and cocaine use than those who received PBO.

Section snippets

Participants

All participants were seeking outpatient treatment for problems related to cocaine use and were recruited by local advertising or by referrals in the New York City metropolitan area. Two types of advertisements were placed: those that recruited individuals who were seeking treatment for cocaine dependence and those that recruited individuals who were seeking treatment for cocaine dependence and might have problems with inattention and or hyperactivity. The study was initiated in January 1998

Participant flow

Fig. 1 outlines the participant flow during the screening process and throughout the randomized trial. A total of 1125 cocaine-dependent treatment seekers began screening for the trial. Of these, 124 individuals met inclusion/exclusion criteria and entered the study, with 106 participants completing the PBO lead-in and randomized to either the MPH group (n = 53) or the PBO group (n = 53).

In the PBO group, three individuals were removed from the protocol because of worsening of pre-existing

Discussion

The results of this randomized, placebo-controlled trial do not suggest that sustained-release MPH produced a greater reduction in ADHD symptoms compared to PBO based on data collected using standard outcome measures. Although there was no substantial improvement in cocaine abstinence in either group, those receiving MPH had a reduced likelihood of cocaine use over time. The finding that MPH did not offer an advantage over PBO in reducing ADHD symptoms based on self-reported information and/or

Acknowledgements

This research was supported by NIDA grants R01 DA11755 and KO2 00465. We want to thank the staff of the Substance Treatment and Research Service (STARS) of the New York State Psychiatric Institute and of Project Outreach of the Long Island Jewish Medical Center for their clinical support. Dr. Levin is a consultant for Eli Lily and Company, Shire Pharmaceuticals Group, AstraZeneca, Cephalon/Alkermes and OrthoMcNeil Pharmaceutical Inc. Also she has research support from Eli Lily and Company, UCB

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