Discontinuing Psychotropic Drugs from Participants in Randomized Controlled Trials: A Systematic Review

Background and Objective: Methods and justifications for discontinuing psychotropic drugs in randomized controlled trials (RCTs), and RCTs’ acknowledgement of possible withdrawal symptoms following discontinuation, have not been examined systematically, which this review aims to do. Study Eligibility, Data Extraction, and Synthesis: Publications in MEDLINE, EMBASE, and PsycINFO (2000–2017) randomly assigning participants diagnosed with mental disorders to discontinue antipsychotic, antidepressant, anticonvulsant, antimanic, mood-stabilizing, benzodiazepine, or stimulant drugs. Authors independently extracted data, devised a typology of trials, and assessed trials’ recognition of with-drawal symptoms. Results: Eighty RCTs (70% with industry participation) discontinued drugs from 5,757 participants to investigate relapse prevention (44%), successful dis-continuation (26%), architecture of withdrawal (14%), and practicality of discontinuation (10%). RCTs of stimulants, antidepressants, and antipsychotics mostly aimed to reach conclusions about relapse prevention by testing abrupt or rapid discontinuations; RCTs of benzodiazepines mostly aimed to reduce drug use by testing longer-lasting, supportive discontinuations. In 67% of RCTs, no justification was given for the specific discontinuation strategy, which lasted under 2 weeks in 60% of RCTs. Possible withdrawal confounding of trial outcomes was addressed in 14% of eligible RCTs. Limitations: Only the published literature was searched. Conclusions and Implications: RCTs use drug discontinuation to study several key issues in psychopharmacology but infrequently justify how they implement it or acknowledge that possible withdrawal symptoms may threaten internal validity. Reappraising the use of drug discontinuation and the recognition of withdrawal symptoms in RCTs is required.