Does improvement in symptoms of attention deficit hyperactivity disorder (ADHD) mediate an effect of long-acting OROS-methylphenidate on cigarette smoking? A secondary analysis of CTN-0029.

Protocol CTN-0029 was a multisite, randomized, double-blind placebo-controlled trial of long-acting OROS-methylphenidate (OROS-MPH) for treatment of patients with both nicotine dependence and attention deficit hyperactivity disorder (ADHD). The principal outcome analysis found, as expected, a robust beneficial effect of OROS-MPH in improving symptoms of ADHD, but no clear effect of OROS-MPH on cigarette smoking outcomes. Since OROS-MPH is primarily a treatment for ADHD, it is reasonable to hypothesize that a beneficial effect on smoking outcome might occur only in those patients who experience a substantial improvement in their ADHD during treatment. This ancillary investigation used a linear model in which prolonged abstinence at week 10 (end of the acute treatment phase) was modeled as a function of medication treatment (OROS-MPH versus placebo), the change in the ADHD symptom severity score between baseline and end of study, and the interaction between ADHD improvement and treatment. The interaction was significant, suggesting that among those patients with the greatest improvement in ADHD symptoms during treatment, OROS-MPH was superior to placebo in promoting prolonged abstinence from nicotine. This secondary analysis suggests that OROS-MPH may be effective in promoting smoking cessation among the subset of patients whose ADHD response well to methylphenidate treatment.