4.1. Analysis.

Comparison 4 Bupropion and nortriptyline. Adverse events, Outcome 1 Nortriptyline vs placebo. 'No report' = no information, 'None occurred' = explicit statement.

Nortriptyline vs placebo. 'No report' = no information, 'None occurred' = explicit statement
Study	Serious events	Other adverse events	Withdrawal due to AE
Aveyard 2008	2 admissions to hospital (1 intervention, 1 control) with collapse or palpitations judged possibly caused by treatment	Dry mouth (80% vs 'more than half, OR 6.67, 5.12 to 8.69), Constipation (OR 2.06, 1.66 to 2.56) and Sweating (OR 1.37, 1.11 to 1.68) significantly more common	No report
Da Costa 2002	None occurred	No significant differences between groups. Dry mouth 44% vs 24%, constipation 29% vs 12%, irritation 18% vs 24%, anxiety 18% vs 28%.	No report
Haggsträm 2006	None occurred	Dry mouth (67.3% vs 31.4%) and drowsiness (19.2% vs 11.8%) significantly more common with nortriptyline Constipation (15.4% vs 9.8%) NS	No report
Hall 1998	None occurred	Dry mouth (78% vs 33%), lightheadedness (49% vs 22%), shaky hands (23% vs 11%) and blurry vision (16% vs 6%) were significantly more common.	4 (4%) dropouts due to side effects in drug and 1 (1%) in placebo group. Total dropout rates 30% in drug and 17% in placebo groups
Hall 2002	None occurred	Dry mouth (72% vs 33%) and constipation ( 32% vs 14%) significantly more common with nortriptyline	No report
Hall 2004	None occurred	Dry mouth (85% vs 40%), lightheadedness (44% vs 22%), shaky hands (30% vs 14%) constipation (38% vs 15%), blurry vision (23% vs 7%), difficulty urinating (13% vs 2%), all p<0.01. Sexual difficulties (19% vs 2% p <0.02)	4 (10%) in active brief treatment, 10 (25%) in active extended treatment, 9 (11%) in placebo stopped medication due to adverse effects (active vs placebo p=0.18, Fisher's exact test)
Prochazka 1998	None occurred	Dry mouth (64% vs 23%), dysgeusia (20% vs 8%), GI upset (41% vs 24%), drowsiness (24% vs 8%) significantly more common	10 (9%) treatment withdrawal due to adverse events in nortriptyline group, vs 3 (3%) in placebo group.
Prochazka 2004	None occurred	Dry mouth (38% vs 8%) & sedation (20% vs 3%) significantly more common.	10 (13%) discontinued nortriptyline including 1 subject with a normal baseline ECG who developed asymptomatic prolongation of QT interval, vs 1 placebo
Wagena 2005	One death in placebo group, previously hospitalised with dermatological reactions	Dry mouth (61% vs 20%), diarrhoea or constipation (48% vs 26%) and fatigue (20% vs 9%) significantly more common in nortriptyline group	24% discontinued nortriptyline vs 9% placebo