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Evidence summaries

Antidepressant Plus Benzodiazepine for Major Depression

Combined antidepressant plus benzodiazepine therapy appears to be more effective than antidepressants alone in improving depression severity and response in depression in the early phase, but these effects were not maintained past 4 weeks. Level of evidence: "B"

The quality of evidence is downgraded by study limitations (unclear allocation concealment and blinding).

A Cochrane review [Abstract] 1 included 10 studies with a total of 731 subjects.

Combined therapy of benzodiazepine plus antidepressants was more effective than antidepressants alone for depression severity in the early phase (4 weeks) (SMD -0.25, 95% CI -0.46 to -0.03; 10 studies, n=598; moderate-quality evidence), but there was no difference between treatments in the acute phase (5 to 12 weeks) (SMD -0.18, 95% CI -0.40 to 0.03; 7 studies, n=347; low-quality evidence) or in the continuous phase (more than 12 weeks) (SMD -0.21, 95% CI -0.76 to 0.35; 1 study, n=50; low-quality evidence). For response in depression, combined therapy was more effective than antidepressants alone in the early phase (RR 1.34, 95% CI 1.13 to 1.58; 10 studies, n=731), but there was no evidence of a difference in the acute phase (RR 1.12, 95% CI 0.93 to 1.35; 7 studies, n=383) or in the continuous phase (RR 0.97, 95% CI 0.73 to 1.29; 1 study, n=52). There was no evidence of a difference between combined therapy and antidepressants alone for anxiety severity in the early phase (SMD -0.76, 95% CI -1.67 to 0.14; 3 studies, n=129) or in the acute phase (SMD -0.48, 95% CI -1.06 to 0.10; 3 studies, n=129).

For acceptability of treatment, there was no difference in the dropouts due to any reason between combined therapy and antidepressants alone (RR 0.76, 95% CI 0.54 to 1.07; 10 studies, n=731; moderate-quality evidence). Participants in the combined therapy group reported at least one adverse effect more often than participants who received antidepressants alone (RR 1.12, 95% CI 1.01 to 1.23; 7 studies, n=510; moderate-quality evidence).

Clinical comments

The moderate benefits of adding a benzodiazepine to an antidepressant in the early phase must be considered against possible harms such as the risk of addiction and consideration given to alternative treatment strategies when antidepressant monotherapy may be considered inadequate.

    References

    • Ogawa Y, Takeshima N, Hayasaka Y et al. Antidepressants plus benzodiazepines for adults with major depression. Cochrane Database Syst Rev 2019;(6):CD001026. [PubMed]

Primary/Secondary Keywords