Seventeen studies were included in the review (n=2,885 participants): 16 RCTs and one non-randomised trial. Three studies had a quality score of 1 or 2, six studies scored 3, six scored 4 and two scored 5. The randomisation process was not described in 14 trials. Sixteen trials were described as double-blind. The method of double-blinding was only described in eight. Treatment duration ranged from four to 52 weeks.
There were no reports of death or life-threatening adverse events.
Compared with comparator groups, nortriptyline was significantly associated with orthostatic hypotension (RR 3.2, 95% CI 1.9 to 5.4, I2=67%; three studies), but not with other cardiovascular adverse events; sensitivity analyses did not alter these findings. No significant increase in heart rate (two studies, I2=0%) or unspecified cardiovascular events (one study) were observed for nortriptyline-treated patients.
Compared with comparator groups, nortriptyline was significantly associated with the adverse events: anticholinergic-related effects including dry mouth (RR 2.3, 95% CI 2.1 to 2.5; 14 studies), constipation (RR 2.1, 95% CI 1.8 to 2.4), blurry vision (RR 1.9, 95% CI 1.4 to 2.6; five studies), light headache (RR 1.4, 95% CI 1.1 to 1.8; two studies), shaky hands (RR 4.1, 95% CI 2.8 to 5.8; two studies), drowsiness (RR 1.9, 95% CI 1.4 to 2.6; nine studies), dizziness (RR 1.8, 95% CI 1.3 to 2.4; nine studies), gastrointestinal disturbance (RR 1.7, 95% CI 1.3 to 2.1; four studies) and dysgeusia (RR 2.0, 95% CI 1.1 to 3.5; two studies). There was significant heterogeneity for dry mouth (I2=43%), light headache (I2=59%), shaky hand (I2=90%) and gastrointestinal disturbance (I2=66%).
Sensitivity analyses impacted upon outcomes for dizziness and drop-out due to adverse effects, but not on other adverse outcomes.