Discontinuation of antidepressant treatment: a retrospective cohort study on more than 20,000 participants

Abstract

Background: Factors influencing antidepressant treatment discontinuation are poorly understood. In the present study, we aimed to estimate the prevalence of antidepressant treatment discontinuation and identify demographic characteristics, psychiatric comorbidities, and specific side effects associated with treatment discontinuation.

Methods: We leveraged data from the Australian Genetics of Depression Study (AGDS; N = 20,941) to perform a retrospective cohort study on antidepressant treatment discontinuation. Participants were eligible if they were over 18 years of age, had taken antidepressants in the past 4 years, and provided informed consent.

Results: Among the ten antidepressants studied, the highest discontinuation rates were observed for Mirtazapine (57.3%) and Amitriptyline (51.6%). Discontinuation rates were comparable across sexes except for Mirtazapine, for which women were more likely to discontinue. The two most common side effects, reduced sexual function and weight gain, were not associated with increased odds of treatment discontinuation. Anxiety, agitation, suicidal thoughts, vomiting, and rashes were associated with higher odds for treatment discontinuation, as were lifetime diagnoses of PTSD, ADHD, and a higher neuroticism score. Educational attainment showed a negative (protective) association with discontinuation across medications.

Conclusions: Our study suggests that not all side effects contribute equally to discontinuation. Common side effects such as reduced sexual function and weight gain may not necessarily increase the risk of treatment discontinuation. Side effects linked to discontinuation can be divided into two groups, psychopathology related and allergy/intolerance.

Keywords: Antidepressant treatment; Comorbidities; Discontinuation; SNRI; SSRI; Side effects.

Fig. 1

Prevalence and factors associated with treatment discontinuation a Estimated discontinuation rates and 95% confidence intervals are shown across medications. The graph is color coded according to medication class (from left to right): SSRIs, SNRIs, and others. Purple dashed lines show the estimates for males, whereas the green solid lines show the results for females. b Heatmap depicting the odds ratio between treatment discontinuation and side effects, comorbidities, chronotype, and demographic variables. The color scale represents the odds ratios of associations between these variables and treatment discontinuation. Blue color indicates an increased risk, whereas red color indicates a decreased risk (protective effect). *Nominally significant (p-value < 0·05) odds ratio. **Significant odds ratio after Bonferroni multiple testing correction.