Primary care

Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and meta-analysis

Steve MacGillivray, research fellow, ^a Bruce Arroll, associate professor of general practice, ^d Simon Hatcher, senior lecturer in psychiatry, ^e Simon Ogston, lecturer in medical statistics, ^a Ian Reid, professor of psychiatry, ^b Frank Sullivan, professor of primary care, ^c Brian Williams, senior lecturer in behavioural science, ^a Iain Crombie, professor of epidemiology and public health. ^a

^a Department of Epidemiology and Public Health, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, ^b Department of Psychiatry, Ninewells Hospital and Medical School, ^c Tayside Centre for General Practice, Ninewells Hospital and Medical School, ^d Department of General Practice, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1, New Zealand, ^e Division of Psychiatry, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92010

Correspondence to: S MacGillivray
s.a.macgillivray{at}dundee.ac.uk

Objective: To compare the efficacy and tolerability of tricyclic antidepressants with selective serotonin reuptake inhibitors in depression in primary care.
Design: Systematic review and meta-analysis of randomised controlled trials.
Data sources: 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.
Results: 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.
Conclusion: 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