Summary of findings 2. Tricyclic antidepressants compared with placebo for insomnia.
| TCA compared with placebo for insomnia | ||||||
| Patient or population: adults with insomnia Setting: hospital outpatients Intervention: TCAs (doxepin 1 mg, 3 mg, 6 mg, 10 mg or 25‐50 mg or trimipramine 25‐200 mg) Comparison: placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Risk with placebo | Risk with TCA | |||||
| Subjective measure of sleep quality (ISI, PSQI) (at 4, 6 or 12 weeks) | ‐ | The mean subjective measure of sleep quality in the intervention group was 0.39 standard deviations lower (0.56 lower to 0.21 lower) | ‐ | 518 (4 RCTs) | ⊕⊕⊕⊝ Moderate1 | Results suggested TCA improved subjective measures of sleep quality with a moderate effect size when measured at 4‐12 weeks. |
| Adverse events (at 4, 6 or 12 weeks) | 383 per 1000 | 393 per 1000 (294 to 502) | RR 1.02 (0.86 to 1.21) | 812 (6 RCTs) | ⊕⊕⊝⊝ Low1,2 | Results showed no significant difference in adverse events between TCA and placebo, but the evidence was low quality. |
| PSG sleep outcomes: sleep latency (at 4 and 12 weeks) | The mean sleep latency in the placebo group ranged from 17.43 to 34.9 min | The mean sleep latency in the TCA group was 4.27 min shorter (9.01 shorter to 0.48 longer) | ‐ | 510 (4 RCTs) | ⊕⊕⊕⊝ Moderate1 | Results show no difference in PSG sleep latency. |
| PSG sleep outcomes: sleep efficiency (at 4 and 12 weeks) | The mean sleep efficiency in the placebo group ranged from 65% to 82.84% | The mean sleep efficiency in the TCA group was 6.29 percentage points higher (3.17 higher to 9.41 higher) | ‐ | 510 (4 RCTs) | ⊕⊕⊕⊝ Moderate1 | Results suggested TCA improved sleep efficiency by an amount that may have clinical relevance. |
| PSG sleep outcomes: total sleep time (at 4 and 12 weeks) | The mean total sleep time in the placebo group ranged from 343.7 min to 408.2 min | The mean total sleep time in the TCA group 22.88 min longer (13.17 longer to 32.59 longer) | ‐ | 510 (4 RCTs) | ⊕⊕⊕⊝ Moderate1 | Results suggested TCA improved total sleep time by an amount that is likely to have clinical relevance. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; HAM‐D: Hamilton Rating Scale for Depression; ISI: Insomnia Severity Index; min: minute; PSG: polysomnography; PSQI: Pittsburgh Sleep Quality Index; RCT: randomised controlled trial; RR: risk ratio; TCA: tricyclic antidepressant. | ||||||
| GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
1Downgraded one level for unclear risk of bias: lack of information on randomisation, allocation concealment and blinding in included studies.
2Downgraded one level for very wide confidence interval including both large benefit and some harm.