Antipsychotic Withdrawal - Individual Patient Data Analysis of the Placebo Groups in Randomized Controlled Trials

• Applicants: Dr. Stefan Gutwinski; Professor Dr. Stefan Leucht
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 428509362

Background: Antipsychotics are used in the treatment of several disorders. Schizophrenia is one of the main treatment indications, but other mental disorders, such as bipolar affective disorder and disruptive behavior disorders are also treated antipsychotics. Rapid discontinuation of treatment with antipsychotics occurs frequently, for example because of occurrence of side effects or low adherence. Withdrawal symptoms and relapse are among the known risks when discontinuing antipsychotics. Avoiding withdrawal symptoms and relapse after antipsychotic discontinuation, reduction, or switch is a key factor when planning a safe and successful therapy. However, data about withdrawal symptoms after antipsychotic discontinuation are scarce.Objective: Systematic examination of withdrawal symptoms and relapse after stopped antipsychotic treatment.
Study Design: Examination of a cohort of individual patient data of 4419 patients from 45 randomized controlled trials (RCTs). Importantly, this study will not focus on effects of the study medication of the RCTs. The present analysis focuses on patients in the placebo group who stopped their prestudy antipsychotic treatment. In these patients, frequency, duration, and severity of withdrawal symptoms and relapse will be examined. These patients, who have stopped their prestudy medication before receiving a placebo, will serve as a target group in the present analysis. Patients who have not been taking prestudy antipsychotics before receiving placebo will serve as a control group. Baseline is the first clinical assessment of the patient after randomized allocation to the placebo arm. Endpoint is 12 weeks after baseline. Data were made available for this study by Yale University Data Open Access (YODA). Participants: Schizophrenia, bipolar affective disorder, schizoaffective disorder, and children with disruptive behavior disorders.
Primary statistical analysis: Examination with a generalized linear mixed model (GLMM) of baseline and endpoint in patients in the placebo arm who stopped individual prestudy antipsychotics (target group) versus patients in the placebo arm without individual prestudy antipsychotics (control group).

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Alkomiet Hasan; Professor Dr. Andreas Heinz