Summary of findings for the main comparison. Antidepressants plus benzodiazepines compared to antidepressants alone for major depression in adults.
Antidepressants plus benzodiazepines compared to antidepressants alone for major depression in adults | ||||||
Patient or population: people with major depression Setting: inpatients and outpatients Intervention: antidepressants + benzodiazepines Comparison: antidepressants alone | ||||||
Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Quality of the evidence (GRADE) | Comments | |
Risk with antidepressants alone | Risk with antidepressants plus benzodiazepines | |||||
Depression severity: early phase (2 weeks, range 1–4 weeks) Follow‐up: range 1–4 weeks | — | The mean depression severity in the early phase in the combination group was 0.25 standard deviations lower (0.46 lower to 0.03 lower). | — | 598 (10 RCTs) | ⊕⊕⊕⊝ Moderatea | — |
Depression severity: acute phase (8 weeks, range 5–12 weeks) | — | The mean depression severity in the acute phase in the combination group was 0.18 standard deviations lower (0.40 lower to 0.03 higher). | — | 347 (7 RCTs) | ⊕⊕⊝⊝ Lowa,b | — |
Depression severity: continuous phase (> 12 weeks) | — | The mean depression severity in the continuous phase in the combination groups was 0.21 standard deviations lower (0.76 lower to 0.35 higher) | — | 50 (1 RCT) | ⊕⊕⊝⊝ Lowa,b | — |
Acceptability of treatment (dropout for any reason) | Study population | RR 0.76 (0.54 to 1.07) | 731 (10 RCTs) | ⊕⊕⊕⊝ Moderatea | — | |
332 per 1000 | 253 per 1000 (180 to 356) | |||||
Moderate | ||||||
200 per 1000 | 152 per 1000 (108 to 214) | |||||
Anxiety severity: early phase (2 weeks, range 1–4 weeks) | — | The mean depression severity in early phase in the combination groups was 0.76 standard deviations lower (1.67 lower to 0.14 higher) | — | 129 (3 RCTs) | ⊕⊝⊝⊝ Very lowa,b, c | — |
Adverse effects (dropouts) | Study population | RR 0.54 (0.32 to 0.90) | 731 (10 RCTs) | ⊕⊕⊕⊝ Moderatea | — | |
119 per 1000 | 64 per 1000 (38 to 107) | |||||
Moderate | ||||||
85 per 1000 | 46 per 1000 (27 to 77) | |||||
*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; OR: odds ratio; RR: risk ratio. | ||||||
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. |
aWe downgraded the evidence by one level because of risk of bias. Studies were described as "double‐blind", but information on the procedure followed to guarantee the blindness, and if blinding was successful, was not reported in all randomised controlled trials. Also, information on randomisation procedures and allocation concealment was lacking in all studies. Moreover, half of the included studies had high attrition rate. bWe downgraded the evidence by one level because of low number of participants included in the analysis and 95% confidence interval included both no effect and appreciable benefit. cWe downgraded the evidence by one level because of high heterogeneity between studies.