To compare the efficacy and tolerability of tricyclic antidepressants with selective serotonin reuptake inhibitors in depression in primary care.
Systematic review and meta-analysis of randomised controlled trials.
Register of the Cochrane Collaboration's depression, anxiety, and neurosis group. Reference lists of initial studies and other relevant review papers. Selected authors and experts.
Selection of studies
Studies had to meet minimum requirements on: adequacy of sample size, adequate allocation concealment, clear description of treatment, representative source of subjects, use of diagnostic criteria or clear specification of inclusion criteria, details regarding number and reasons for withdrawal by group, and outcome measures described clearly or use of validated instruments.
Main outcome measures
Standardised mean difference of final mean depression scores and relative risk of response when using the clinical global impression score. Relative risk of withdrawing from treatment at any time, and the number withdrawing due to side effects.
11 studies (2951 participants) compared a selective serotonin reuptake inhibitor with a tricyclic antidepressant. Efficacy between selective serotonin reuptake inhibitors and tricyclics did not differ significantly (standardised weighted mean difference, fixed effects 0.07, 95% confidence interval −0.02 to 0.15; z=1.59, P<0.11). Significantly more patients receiving a tricyclic withdrew from treatment (relative risk 0.78, 95% confidence interval 0.68 to 0.90; z=3.37, P<0.0007) and withdrew specifically because of side effects (0.73, 0.60 to 0.88; z=3.24, P<0.001). Most studies included were small and supported by commercial funding. Many studies were of low methodological quality or did not present adequate data for analysis, or both, and were of short duration, typically six to eight weeks.
The evidence on the relative efficacy of selective serotonin reuptake inhibitors and tricyclic antidepressants in primary care is sparse and of variable quality. The study setting is likely to be an important factor in assessing the efficacy and tolerability of treatment with antidepressant drugs.
What is already known on this topic
Previous meta-analyses have included comparatively large numbers of secondary care based studies that indicate no significant differences in efficacy between selective serotonin reuptake inhibitors and tricyclics
Previous meta-analyses are conflicting regarding the relative tolerability between selective serotonin reuptake inhibitors and tricyclics, but do suggest a small but significant difference in favour of selective serotonin reuptake inhibitors
Such meta-analyses show notable heterogeneity
What this study adds
Selective serotonin reuptake inhibitors are better tolerated than tricyclics by primary care patients and may be better tolerated by primary care patients than secondary care patients
Study setting seems to be important and should be considered before licences are given to specific antidepressants
Although there are limited high quality data, available evidence shows that the most commonly prescribed classes of antidepressants in primary care (selective serotonin reuptake inhibitors and tricyclics) are equally effective in the short term for primary care patients, but the literature has many gaps