Do withdrawal symptoms predict depression relapse after antidepressant cessation?

Discontinuing antidepressants after remission poses risks of withdrawal symptoms and relapse. This study addressed four questions: Can withdrawal symptoms be differentiated from relapse? What are their risk factors? Are withdrawal symptoms associated with relapse? Can discontinuation be optimized? 103 patients with a remitted major depressive disorder were randomized to continue or discontinue antidepressants. Withdrawal symptoms were assessed using the Discontinuation Emergent Signs and Symptoms scale (DESS). Withdrawal syndrome was defined as experiencing at least four new or worsened DESS symptoms. Associations between clinical factors and symptom count were examined using linear regressions. After the randomization phase, all patients discontinued treatment and were monitored for six months. The relationship between withdrawal symptoms, clinical factors, and relapse risk was analyzed via logistic regression and a Cox proportional hazards model. Ten symptoms were reported exclusively in the discontinuation group and may aid in distinguishing withdrawal syndrome from relapse. Withdrawal syndrome occurred in 29% (95% PI [8.3%, 72%]) of patients. Women reported more withdrawal symptoms than men (factor 1.67 (95% PI [1.06, 2.56])). None of the other predictors were associated with symptom count. Of 83 patients with outcome data, 54 (65%) remained well and 29 (35%) relapsed. Withdrawal symptoms (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. Tapering duration was not associated with either withdrawal symptoms or relapse rate. Withdrawal symptoms were common and more frequent in women. Experiencing withdrawal symptoms may increase relapse risk.