Sixty-four trials met the inclusion criteria, involving 4071 children. The quality of many trials was poor, with comparisons addressed by single studies. Minor adverse effects were common, and reported in 30 trials. These included dizziness, headache, mood changes, gastrointestinal discomforts and neutropenia . More serious side-effects can occur but were not reported. Seven trials reported no adverse effects .

Tricyclics are more effective than placebo , particularly for short-term outcomes. Compared to placebo , imipramine resulted in one fewer wet nights per week ( mean difference ( MD ) -0.95, 95% confidence interval ( CI ) -1.40 to -0.50; 4 trials, 347 children), with fewer failing to achieve 14 consecutive dry nights (78% versus 95% for placebo , RR 0.74, 95% CI 0.61 to 0.90; 12 trials, 831 children). Amitriptyline and desipramine were more effective than placebo , but nortriptyline and mianserin showed no difference. Most tricyclics did not have a sustained effect after ceasing treatment, with 96% wetting at follow-up for imipramine versus 97% for placebo .

Imipramine combined with oxybutynin is also more effective than placebo , with 33% failing to achieve 14 consecutive dry nights at the end of treatment versus 78% for placebo ( RR 0.43, 95% CI 0.23 to 0.78; 1 trial , 47 children) and 45% wetting at follow-up versus 79% for placebo ( RR 0.58, 95% CI 0.34 to 0.99; 1 trial , 36 children).

There was insufficient evidence to judge the effect between different doses of tricyclics, and between different tricyclics. Treatment outcomes between tricyclic and desmopressin were similar, but were mixed when tricyclic was compared with an anticholinergic. However, when imipramine was compared with desmopressin plus oxybutynin (1 trial , 45 children), the combination therapy was more effective, with one fewer wet nights per week ( MD 1.07, 95% CI 0.06 to 2.08) and 36% failing to achieve 14 consecutive dry nights versus 87% for imipramine ( RR 2.39, 95% CI 1.35 to 4.25). Tricyclics were also more effective or showed no difference in response when compared to other drugs which are no longer used for enuresis.

Tricyclics were less effective than alarms. Although there was no difference in the number of wet nights, 67% failed to achieve 14 consecutive dry nights for imipramine versus only 17% for alarms ( RR 4.00, 95% CI 1.06 to 15.08; 1 trial , 24 children). Alarm therapy also had a more sustained effect after ceasing treatment with 100% on imipramine versus 58% on alarms wetting at follow-up ( RR 1.67, 95% CI 1.03 to 2.69; 1 trial , 24 children).

Imipramine was more effective than simple behavioural therapies during treatment, with one fewer wet nights per week compared with star chart plus placebo ( MD -0.80, 95% CI -1.33 to -0.27; 1 trial , 250 children). At follow-up 40% were wet with imipramine versus 80% with fluids and avoiding punishment ( RR 0.50, 95% CI 0.28 to 0.89; 1 trial , 40 children). However, imipramine was less effective than complex behavioural therapies, with 61% failing to achieve 14 consecutive dry nights for imipramine versus 33% for the three-step programme ( RR 1.83, 95% CI 1.08 to 3.12; 1 trial , 72 children) and 16% for the three-step programme combined with motivational therapy and computer-led education ( RR 3.91, 95% CI 2.30 to 6.66; 1 trial , 132 children) at the end of treatment, with similar results at follow-up.

Tricyclics were more effective than restricted diet, with 99% failing to achieve 14 consecutive dry nights versus 84% for imipramine ( RR 0.84, 95% CI 0.75 to 0.93; 1 trial , 147 children).There was insufficient evidence to judge the effect of tricyclics compared to the other miscellaneous interventions studied.

At the end of treatment there were about two fewer wet nights for imipramine plus oxybutynin compared with imipramine monotherapy ( MD -2.10, 95% CI -2.99 to -1.21; 1 trial , 63 children) and 48% on imipramine plus oxybutynin failed to achieve 14 consecutive dry nights compared with 74% on imipramine monotherapy ( RR 0.68, 95% CI 0.50 to 0.92; 2 trials, 101 children). At follow-up, 45% on imipramine plus oxybutynin were wetting versus 83% on imipramine monotherapy ( RR 0.55, 95% CI 0.32 to 0.92; 1 trial , 36 children).