Safety of Nortriptyline at Equivalent Therapeutic Doses for Smoking Cessation A Systematic Review and Meta-Analysis

Background: The limited use of nortriptyline for smoking cessation is likely due to concerns about its serious adverse effects. Objective: To examine the safety of nortriptyline at doses equivalent to those used in aiding smoking cessation. Data Sources: A systematic search of relevant articles in MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, CINAHL, PsychINFO, WHO publications and the Clinical Trials database (through November 2008). Study Selection: All studies of nortriptyline at doses between 75 and 100 mg in any indication were reviewed. Data Extraction: The quality of included studies was assessed based on the Jadad score. Data were extracted using a data extraction form. Data Synthesis: From 442 potentially relevant articles identified, 17 studies met our selection criteria and were included for data analysis. Indications for nortriptyline in these studies were smoking cessation (eight studies), depression (five studies), neuropathic pain (three studies) and schizophrenia (one study). 2885 individuals participated in these studies, with exposure time ranging between 4 and 12 weeks. The major comparator used in these trials was placebo. Overall, no life-threatening events occurred in these studies. Orthostatic hypotension was significantly higher in nortriptyline users than in comparator groups (relative risk 2.8; 95% CI 1.4, 5.3). Other adverse events significantly associated with nortriptyline were anticholinergic-related effects including drowsiness, dizziness, gastrointestinal disturbance and dysgeusia. Conclusions: Current evidence suggests that nortriptyline, at doses between 75 and 100 mg, is not significantly associated with serious adverse events when administered in patients without underlying cardiovascular disease.