Six RCTs met the inclusion criteria, of which five (n=861) provided sufficient data to be included in the meta-analyses.
The 4 studies reported in full scored from 7 to 11 (out of 11 points) for validity. All reported blinding of treatment, three reported blinding of carers, and none reported blinding of the assessor. Two studies reported follow-up greater than 80%.
Nortriptyline versus placebo (4 RCTs, n=641): no statistically significant heterogeneity was found (P=0.37). Nortriptyline significantly increased prolonged (at least 6 months) abstinence rates compared with placebo; the RR was 2.4 (95% CI: 1.7, 3.6) and the RD was 0.11 (95% CI: 0.07, 0.15). The AP decreased significantly faster in the nortriptyline group compared with the placebo group (-1.5% per month versus -0. 2%, P<0.01).
Nortriptyline versus bupropion (1 RCT, n=220): the difference in AP between treatments was small but significantly higher with bupropion compared with nortriptyline (45.2% versus 43.1%,P<0.01). At 12 months there was no significant difference in AP between treatments(RR 1.7, 95% CI: 0.7, 4.1).
Adverse effects: significantly more adverse effects were reported with nortriptyline compared with placebo. The most common adverse effects were dry mouth and constipation or gastrointestinal upset.
The study of nortriptyline versus bupropion did not directly compare adverse effects between treatments.