Peripheral edema associated with antidepressant use: Systematic review of case reports

Background: Oedema associated with psychotropics can impose a considerable burden, leading to increased morbidity and cost. Peripheral oedema is sometimes related to the use of antidepressants, which are among the most prescribed psychotropic medications. We reviewed the reported cases of antidepressant-associated oedema to understand the risk factors, aetiology and outcome. Methods: We searched the Medline, Web of Science and Embase databases to identify reported cases of peripheral oedema associated with antidepressant use. We included studies published in English and those with full-text availability. A systematic review of the reports was done to identify the antidepressants associated with oedema, explore possible risk factors, investigate potential mechanisms, and assess the outcome. Results: We identified a total of 45 cases (27 case reports and five case series) that reported oedema associated with antidepressant use. Almost all major classes of antidepressants were found to be associated with oedema. Among these drugs, trazodone, mirtazapine, and escitalopram were the most implicated. Older age and female gender were more commonly associated with oedema. Etiologically, antagonism of α₁ adrenergic receptors and 5HT_2A receptors, leading to vasodilation and oedema, emerged as the most prevalent mechanisms. In most cases, the oedema subsided following the discontinuation of the antidepressants. Conclusions: Peripheral oedema associated with antidepressant use can represent a significant adverse drug reaction involving various classes of antidepressants. To ensure timely identification and proper management of oedema, regular monitoring is crucial.