Do discontinuation symptoms predict depression relapse after antidepressant cessation?

Background: Discontinuing antidepressants after recovering from a depressive episode is associated with a risk for two events: discontinuation symptoms and relapse. Little is known about who can discontinue safely and whether discontinuation symptoms constitute a risk factor for relapse. This study investigated risk factors for experiencing discontinuation symptoms and whether discontinuation symptoms are associated with depression relapse.Methods: 103 patients with a currently remitted major depressive disorder were randomized to continuation or discontinuation of antidepressants. Discontinuation symptoms were assessed with the Discontinuation Emergent Signs and Symptoms (DESS) scale. The discontinuation syndrome (ADS) was defined as experiencing at least 4 DESS symptoms. We investigated the association of clinical factors with the number of discontinuation symptoms in Bayesian linear regressions. After the randomization phase, all patients discontinued their antidepressant and were followed up over 6 months. We investigated the association of discontinuation symptoms and clinical factors with relapse risk in logistic regressions and a cox proportional hazards model. Results: An ADS was experienced by 29% (95% PI [8.3%, 72%]) of patients. Women reported more discontinuation symptoms than men (factor 1.67 (95% interval [1.06, 2.56])). None of the other prespecified predictors were associated with the risk or severity of ADS. Trait anxiety (Slope = 0.42, 95% PI [-0.01, 0.90]), ADS severity (0.58, 95% PI [0.07, 1.16]) and early depressive symptoms (0.63, 95% PI [0.16, 1.17]) were associated with a higher relapse risk. Conclusion: Antidepressant discontinuation symptoms were relatively common and experienced mainly by women. Experiencing discontinuation symptoms may adversely impact relapse risk.