Abstract

Problems abound when assessing the comparative acceptability and safety of antidepressant drugs. The findings of double-blind randomised placebo- and comparator-controlled trials provide a reasonable impression of the relative tolerability of antidepressants in short-term treatment, but less is confidently known about their relative acceptability and safety in long-term treatment. The findings of randomised controlled trials which are conducted in homogenous and largely physically healthy samples of trial participants do not necessarily generalise well into the mixed and highly comorbid groups of depressed patients seen in real-world clinical settings. Furthermore, many of the reported adverse effects of antidepressants include reduced sexual desire, emotional indifference, and ‘activation’ – which can make it hard to distinguish the adverse effects of treatment from persistent or emerging symptoms of the underlying condition. The quality of many reports of possible adverse drug reactions with antidepressants is poor and this further hinders the accurate assessment of comparative tolerability and potential toxicity. Certain antidepressant classes are prescribed preferentially to particular groups of patients with comorbid physical illnesses, whose presence hinders the interpretation of tolerability events in pharmacoepidemiological studies. These problems are addressed through discussing the role of mixed treatment comparisons in assessing the acceptability of antidepressant treatment, are highlighted by referring to methodological challenges in research into sexual dysfunction and emotional indifference during treatment with selective serotonin reuptake inhibitors, are illustrated by considering the quality of case reports of adverse reactions relating to hepatic function with serotonin-noradrenaline reuptake inhibitors, and are further considered when reviewing pharmacoepidemiological data on antidepressant tolerability in elderly patients.

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