A systematic review found no indication that antidepressive drugs are less safe, efficacious or well tolerated in people with chronic health problems.

Depression frequently occurs in people with chronic health problems, and coexistence predicts poorer health status and greater functional disability. Treatment with antidepressive drugs may be expected to improve quality of life and function, however there may be reluctance to prescribe them because of concerns over safety and efficacy. The authors of this systematic review aimed to determine whether there was reliable evidence on the efficacy, safety, and tolerance of antidepressive drugs in patients with chronic illness.

They carried out a comprehensive literature search for randomised controlled trials that compared antidepressive drugs with placebo or another antidepressive in patients with chronic illness; a range of specific conditions were specified, and patients with mixed and unspecified conditions were classed as general medical illness. Outcomes assessed were efficacy and safety / tolerability. Efficacy was evaluated using depression scale scores (physician and patient-related as available), remission, and physical health symptoms; safety and tolerability were evaluated using withdrawals from trials for adverse effects and also withdrawals for all reasons.

The initial searches yielded 38,166 potentially relevant papers, of which 136 were assessed in full and 63 (n=5,794) were eligible and included in the review. Only three papers specifically addressed safety, all used in patients after MI. Trials with selective serotonin reuptake inhibitors (SSRI) were published from mid-1994 to 2008; most trials with tricyclic antidepressives (TCA) were published between 1984 and 2000, with one appearing in 2008.

In placebo-controlled trials, both SSRI and TCA showed efficacy for response: relative risk (RR) for SSRI 0.83 (95% CI 0.71 to 0.97), RR for TCA 0.55 (95% 0.43 to 0.70). Compared to placebo, SSRI showed significant efficacy for remission (RR 0.81; 95% CI 0.73 to 0.91), whereas TCA did not, (RR 0.70; 95% CI 0.40 to 1.25), however only two trials reported this outcome for TCA. For SSRI, seven trials reported on quality of life with wide variation in results but overall an indication of benefit; there was inadequate evidence for quantification on quality of life measures for TCA.

Both groups of drugs were less well tolerated than placebo, using the outcome of leaving study early due to adverse effects: for SSRI, RR 1.80 (95% CI 1.16 to 2.78), for TCA, RR 2.00 (95% CI 0.99 to 3.57). Three studies examined safety in patients post MI – two with SSRI and one with mirtazapine: none indicated any safety issues compared to placebo.

In 14 trials comparing SSRI and TCA, there were no significant differences between the groups in any of the main outcomes.

Single studies evaluated trazodone (post stroke), duloxetine (general medical illness), and mirtazapine (post MI), and two trials examined mianserin.

The authors conclude that both SSRI and TCA drugs are effective in treatment of depression in people with chronic illness, with no robust evidence to indicate that either group is superior. They suggest that given that there is some evidence for improvements in quality of life with SSRI, and the demonstration of safety in post MI patients, these drugs may be considered first choice.