Methylphenidate for treating tobacco dependence in non-attention deficit hyperactivity disorder smokers: A pilot randomized placebo-controlled trial

To investigate potential efficacy for relieving nicotine withdrawal symptoms and promoting smoking abstinence, we conducted a randomized, double-blind, placebo-controlled, phase II study of once-a-day osmotic-release oral system methylphenidate (OROS-MPH, Concerta？) at a target dose of 54-mg/day for 8 weeks compared with placebo in 80 adult cigarette smokers.Of the 80 randomized subjects and median smoking rate was 20 cigarettes per day. At the end of the medication phase, the biochemically confirmed 7-day point prevalence smoking abstinence was 10% (4/40) for the placebo group and 2.5% (1/40) for the OROS-MPH group.Nicotine withdrawal was not found to differ significantly between treatment groups during the first 14 days following the start of medication prior to the target quit date (p = 0.464) or during the first 14 days following the target quit date (p = 0.786).We observed no evidence of efficacy of OROS-MPH to aid smokers to stop smoking. Although there are biologically plausible hypotheses that support the use of OROS-MPH for treating tobacco dependence, we found no evidence to support such hypotheses. In addition to no increase in smoking abstinence, we saw no effect of OROS-MPH for tobacco withdrawal symptom relief and no change in smoking rates was observed in the OROS-MPH group compared to the placebo group.Expansion of pharmacologic options for treating tobacco dependence is needed. A large part of the positive reinforcement from cigarettes is due to the delivery of nicotine to the central nervous system (CNS), resulting in increased concentrations of dopamine in the reward centers of the brain [1]. Methylphenidate was considered as a potential treatment for smokers because of its action to block the re-uptake of dopamine by binding to the dopamine transporter in the presynaptic cell membrane and increase extracellular dopamine levels [2,3]. Similarities in neuropsychologic effects between nicotine and methylphenidate have also made methylphenidate an in