Characterization of medication side effects in patients with mostly resistant depression in a real-world setting

<b>Objectives</b>. This study aimed to identify factors associated with side effects of psychotropic drugs in a real-world setting enriched with treatment-resistant depression patients. <b>Methods</b>. A total of 1410 depressed patients were treated in a naturalistic setting. Side effects were measured with the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU); the total score and UKU subscales were considered. Clinical-demographic variables were tested for association with side effects in univariate and then multivariate analyses. <b>Results</b>. Total, psychic, and neurological side effects were associated with depressive symptom severity, while autonomic side effects were higher in those with somatic comorbidities and other side effects were lower in patients receiving trazodone. In multivariate analyses, depressive symptom severity was associated with psychic and total side effects, while generalized anxiety disorder with neurological side effects and somatic comorbidities remained associated with autonomic side effects. Trazodone was associated with lower side effects and with augmentation treatments. Augmentation therapies showed opposite effects depending on response status, i.e., increased or decreased the risk of side effects in responders and non-responders/resistant patients, respectively. <b>Conclusions</b>. Psychic side effects may be difficult to distinguish from depressive symptoms and factors associated with different types of side effects are heterogeneous and likely interacting.