Effect of Nicotine Replacement Therapy on Agitation in Smokers With Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled Study

Objective: The authors conducted a randomized, placebo-controlled study of nicotine replacement therapy for the reduction of agitation and aggression in smokers with schizophrenia. Method: Participants were 40 smokers 18-65 years of age admitted to a psychiatric emergency service with a diagnosis of schizophrenia confirmed by the Mini International Neuropsychiatric Interview. Patients were screened for agitation with the excited component subscale of the Positive and Negative Syndrome Scale (PANSS) and for nicotine dependence with the Fagerstrom Test for Nicotine Dependence. A score of at least 14 on the PANSS excited component subscale and at least 6 on the Fagerstrom test were required for study eligibility. Participants in the nicotine replacement group received a 21-mg nicotine transdermal patch, and those in the placebo group were treated with a placebo patch. Participants received usual care with antipsychotics. The Agitated Behavior Scale and other agitation measures were administered at baseline and again at 4 and 24 hours. Results: At baseline, participants were at least moderately agitated, and 28% reported aggressive behavior in the previous week. The mean Agitated Behavior Scale score for the nicotine replacement group was 33% lower at 4 hours and 23% lower at 24 hours than for the placebo group. Participants with lower levels of nicotine dependence responded better than those with higher levels of dependence. Conclusions: The drug-placebo difference in this study was similar to that obtained in trials of parenteral antipsychotics in similar populations. This finding suggests that in patients with schizophrenia, smoking status should be included in the assessment of agitation and nicotine replacement included in the treatment of those who are smokers.