Background: Anxiety frequently coexists with depression. There is no systematic review to show if adding benzodiazepines to antidepressants can bring about any advantage over antidepressants alone in the treatment of depression, although such a combination prescription appears to be widely practiced worldwide
Objectives: To determine whether, among adult patients with major depression, adding benzodiazepines to antidepressants brings about any benefit in terms of symptomatic recovery or side-effects in the short term (less than 8 weeks) and long term (more than 2 months), in comparison with treatment by antidepressants alone.
Search strategy: Electronic searches of MEDLINE, EMBASE, International Pharmaceutical Abstracts, Biological Abstracts, LILACS, PsycLit, the Cochrane Library and the trial register of the Cochrane Depression, Anxiety and Neurosis Group (January 1972 to December 1998), combined with hand searching, reference searching, SciSearch and personal contacts.
Selection criteria: All randomized controlled trials that compared combined antidepressant-benzodiazepine treatment with antidepressant alone for adult patients with major depression (Feighner criteria, RDC, DSM-III, DSM-III-R, DSM-IV or ICD-10). Exclusion criteria are: antidepressant dosage lower than 100 mg of imipramine or its equivalent daily and duration of trial shorter than 4 weeks.
Data collection and analysis: Two reviewers independently assessed the eligibility and quality of the studies. Two reviewers independently extracted the data. Standardized weighted mean differences and relative risks were estimated with random effects model. The dropouts were assigned the least favorable outcome. Two sensitivity analyses examined the effect of this assumption as well as the effect of including medium quality studies. Three a priori subgroup analyses were performed with regard to the patients with or without comorbid anxiety and with regard to the types of benzodiazepines tested.
Main results: Aggregating nine studies with a total of 679 patients, the combination therapy group was 37% (95%CI: 19 to 51%) less likely to drop out than the antidepressant alone group. The intention-to-treat analysis showed that the former were 63% (18 to 127%) to 38% (15 to 66%) more likely to show response (defined as 50% or greater reduction in the depression scale from baseline) up to 4 weeks.
Reviewer's conclusions: The potential benefits of adding a benzodiazepine to an antidepressant must be balanced judiciously against possible harms including development of dependence and accident proneness, on the one hand, and against continued suffering following no response and drop-out, on the other.