Incidence of antidepressant withdrawal reactions: A prospective longitudinal cohort study in primary care patients
Andri Rennwald, Mark A. Horowitz, Oliver Senn, Stefan Neuner-Jehle, Michael P. HengartnerBackground
The incidence of antidepressant withdrawal reactions in longer-term users and the influence of dosage is insufficiently understood.
Objectives
Informed by neuropharmacological models and user surveys, this study examined change in withdrawal symptoms during tapering and if increases were specifically associated with dose reductions that lowered the dose below 75% of the minimum effective dose.
Design
This was a prospective longitudinal cohort study with seven assessments over six months.
Methods
Altogether 32 Swiss adult primary care patients who were on antidepressants for at least six months and in stable remission were assessed at baseline (week 0) before they started tapering and after 2, 4, 6, 8, 16, and 26 weeks. Withdrawal symptoms were measured repeatedly using an adapted version of the Discontinuation-Emergent Signs and Symptoms Scale (DESS) and the main outcome was intra-individual symptom change during intervals. Antidepressant dose was standardized relative to the minimum effective dose in the treatment of depressive and anxiety disorders.
Results
Across intervals, dose reductions that lowered the dose below 75% of the minimum effective dose were associated with increases in withdrawal symptoms, while reductions above that threshold or no reductions were associated with symptom decreases. After adjusting for potential confounders, the rate of clinically relevant increases in withdrawal symptoms after dose reductions below 75% of the minimum effective dose was 33%, as compared to 13% during intervals with no dose reductions (OR=3.2, 1.4 to 7.4). We thus estimated that 60% of the risk of clinically relevant symptom increases was attributable to pharmacological withdrawal effects. The adjusted cumulative incidence rates for clinically relevant moderate and severe withdrawal reactions were 32% and 11%, respectively.
Conclusions
Consistent with neuropharmacological research findings, we found that antidepressant withdrawal symptoms emerge predominantly once the dose is reduced below 75% of the minimum effective dose, affecting about one-third of patients. Even small reductions may trigger clinically relevant withdrawal reactions in this lowest dose-range, stressing the need for personalized tapering plans. Given the small sample size, incidence estimates could be imprecise and require replication in larger cohorts.