Interventions to help patients withdraw from depression drugs: A systematic review

Article type: Review Article

Authors: Gøtzsche, Peter C.^a; | Demasi, Maryanne^a

Affiliations: [a] Institute for Scientific Freedom, Hørsholm, Denmark

Correspondence: [*] Address for correspondence: Peter C. Gøtzsche, DrMedSci. E-mail: pcg@scientificfreedom.dk

Abstract: BACKGROUND:Depression drugs can be difficult to come off due to withdrawal symptoms. Gradual tapering with tapering support is needed to help patients withdraw safely. OBJECTIVE:To review the withdrawal success rates, using any intervention, and the effects on relapse/recurrence rates, symptom severity, quality of life, and withdrawal symptoms. METHODS:Systematic review based on PubMed and Embase searches (last search 4 October 2022) of randomised trials with one or more treatment arms aimed at helping patients withdraw from a depression drug, regardless of indication for treatment. We calculated the mean and median success rates and the risk difference of depressive relapse when discontinuing or continuing depression drugs. RESULTS:We included 13 studies (2085 participants). Three compared two withdrawal interventions and ten compared drug discontinuation vs. continuation. The success rates varied hugely between the trials (9% to 80%), with a weighted mean of 47% (95% confidence interval 38% to 57%) and a median of 50% (interquartile range 29% to 65%). A meta-regression showed that the length of taper was highly predictive for the risk of relapse (P = 0.00001). All the studies we reviewed confounded withdrawal symptoms with relapse; did not use hyperbolic tapering; withdrew the depression drug too fast in a linear fashion; and stopped it entirely when receptor occupancy was still high. CONCLUSION:The true proportion of patients on depression drugs who can stop safely without relapse is likely considerably higher than the 50% we found.

Keywords: Depression drugs, withdrawal symptoms, relapse, tapering

DOI: 10.3233/JRS-230011

Journal: International Journal of Risk & Safety in Medicine, vol. Pre-press, no. Pre-press, pp. 1-14, 2023