Antidepressants for depression in physically ill people

Depression in physical illness is common. Antidepressants have been shown to improve depression in people who are physically healthy, but there has been doubt about whether they are appropriate for people who are physically ill. This review examined clinical trials of antidepressants in physically ill people to determine whether antidepressants help these patients, and in particular if they lessen depression. We used standard methods recommended by Cochrane to identify and select studies and to collect and analyse the information. We extracted information on fifty-one studies in the review. Our results found that antidepressants are better than a placebo (inactive) drug in treating depression in physically ill people. Both the two main classes of antidepressant, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), were shown to be more effective than a placebo. Antidepressants improved depressive symptoms within 4-5 weeks of treatment, and this benefit persisted after 18 weeks. However, patients taking an antidepressant were more likely to experience sexual dysfunction and dry mouth, and were more likely to stop taking their medication after 6-8 weeks of treatment. There are no grounds to recommend one antidepressant over another on the basis of this review. We conclude that antidepressants appear to be useful in treating depression and should be considered for physically ill patients. The decision to prescribe antidepressants should take account of patients' preferences, symptoms, and possible interactions with other medicines they are taking.

Authors' conclusions: 

This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population.

Read the full abstract...

There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill’s Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context.


To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness.

Search strategy: 

Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009.

Selection criteria: 

Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria.

Data collection and analysis: 

The primary outcome was efficacy 6-8 weeks after randomisation. Data were also extracted at three additional time-points (4-5 weeks, 9-18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop-outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model.

Main results: 

Fifty-one studies including 3603 participants were included in the review. Forty-four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80-3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time-points. At 6-8 weeks, fewer patients receiving placebo dropped out compared to patients treated with an antidepressant. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant.