Stimulant Treatment Doesn't Aggravate Substance Abuse

In the adult study, Theresa Winhusen, Ph.D., a research associate professor of psychiatry and codirector of the Cincinnati Addiction Research Center at the University of Cincinnati, and colleagues enrolled 252 smokers with a confirmed DSM-IV diagnosis of ADHD and randomized half to receive 72 mg/day of OROS-methylphenidate (Concerta) and half to get a placebo. Meanwhile, all participants received smoking-cessation treatment consisting of a nicotine patch of 21 mg/day and a brief counseling session every week.

Participants were asked to set the quit date as the end of week 4 of the study. The researchers measured the primary outcome, prolonged abstinence from smoking based on self-report, starting from week 6, thus giving the smokers some time to cut down on their cigarette use. ADHD symptom severity was measured using a standard rating scale.

Over the course of the 11-week treatment, the participants' ADHD symptoms improved significantly more in the methylphenidate group than in the placebo group. However, the ADHD treatment had very little effect on smoking-cessation outcomes. Both groups saw substantial reduction in smoking, suggesting that the smoking-cessation interventions were effective. Prolonged abstinence was achieved by 43.3 percent of the methylphenidate group and 42.2 percent of the placebo group, and the difference was not statistically significant. The methylphenidate group had a slightly lower mean number of cigarettes smoked per day during the quit period (from week 6 to the end of the study) than the placebo group, which was a statistically significant but not clinically meaningful difference, Winhusen said at the meeting.

The adolescent study, designed to test the effect of ADHD treatment on SUDs, demonstrated that these patients—generally considered hard to treat because of their comorbidities—can improve as much as their peers who had only one disorder, said Paula Riggs, M.D., the principal investigator, at the session. Riggs is an associate professor of psychiatry at the University of Colorado at Denver and Health Sciences Center.

Three hundred adolescents aged 13 to 18, recruited from the community, were enrolled in the study. All had concurrent DSM-IV diagnoses for ADHD and at least one SUD other than nicotine. At 11 sites, these adolescents were randomly assigned to either OROS-methylphenidate with dosage titrated up to 72 mg/day or placebo in a 1:1 ratio. At the same time, every participant was given manual-standardized cognitive-behavioral therapy (CBT) with individual weekly sessions designed to target substance use.

ADHD symptom severity, measured by the rating scale, was substantially reduced from baseline in both groups, but the reduction was not statistically significantly different between the methylphenidate and placebo groups. The clinicians' rating of ADHD symptom severity also showed no significant difference between the two groups. Parents' rating of ADHD symptoms did indicate a statistically significant difference favoring the active treatment group. The adolescents' problem-solving and focused-coping skills, which were specifically taught in CBT, improved significantly from baseline in the methylphenidate group but were little changed in the placebo group.

Both groups reduced their substance use. The number of days of drug use within the past 28 days decreased by 43 percent from baseline in the methylphenidate group and by 33 percent in the placebo group. The between-group difference was not statistically significant. However, the mean proportion of negative urine samples in the methylphenidate group was statistically significantly higher than the placebo group, although the clinical significance of this difference may be less clear. “Again, mixed results,” Riggs concluded.

The lack of a clear outcome difference between methylphenidate and placebo may be a result of strong therapeutic efficacy from the background CBT for all study participants, according to Riggs. She noted that the scale of ADHD symptom reduction was “unexpectedly high” for both groups and similar to or greater than previous clinical trials of stimulant medications that provided no psychosocial treatment. Although designed to target substance use, the CBT in this study may have had a spillover effect on ADHD improvement that neutralized the therapeutic difference between methylphenidate and placebo.

Both clinical trials were able to maintain excellent retention rates and treatment compliance. Over 70 percent of the adolescents with both ADHD and SUD completed the entire 16 weeks of study. About 80 percent of the adults with ADHD completed the 11-week smoking-cessation study.

Although methylphenidate-treated participants had higher rates of adverse events, such as abdominal discomfort, increased heart rate, and nervousness than placebo-treated persons in both studies, there were no signs of worsening smoking or substance use associated with the stimulant, the researchers noted.

Both studies were conducted within the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN). The network consists of various academic medical centers, community treatment centers and programs, and research support centers scattered around the country. The CTN forms a framework for NIDA-funded researchers to collaborate on large, multisite clinical trials in the community setting, and the answers generated from these trials are directly relevant and applicable to most clinicians.