Antipsychotic Sedation Peaks in First 2 Weeks, Emphasizing Importance of Early Monitoring
A meta-analysis of randomized controlled trials (RCTs) of antipsychotic monotherapy for the acute phase of schizophrenia and schizoaffective disorder (SSD) found that sedation onset peaked within the first 2 weeks of treatment initiation. The study, published in The Lancet Psychiatry, aimed to better understand the timing of sedation onset and resolution in antipsychotic treatments for patients with schizophrenia.
“Sedative adverse events, such as sedation, somnolence, and fatigue, are frequent in patients receiving antipsychotic treatment for schizophrenia, and negatively affect quality of life and treatment adherence,” wrote lead author Nobuyuki Nomura, MD PhD, Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Munich, Germany, and study co-authors. “However, there is little understanding of the temporal trajectory of these events, including their onset and resolution, across different antipsychotic drugs.”
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The authors conducted a meta-analysis of 19 placebo-controlled RCTs of antipsychotic monotherapy for the acute phase of SSD. Six of the trials assessed long-acting injectable (LAI) antipsychotic use and 13 assessed oral antipsychotic use. Of the 6791 participants, 6125 (90.2%) were diagnosed with schizophrenia and 666 (9.8%) were diagnosed with schizoaffective disorder. The researchers created Kaplan–Meier curves to analyze the probability of sedation onset and the time until sedation resolution after treatment initiation.
The meta-analysis found that 418 (83%) of the 505 documented sedation events occurred within the first 2 weeks of treatment initiation and peaked on the first 2 days after initiation for patients receiving antipsychotics. The median onset was 4 days from treatment initiation, with 50% of symptoms resolving in 1 week and 75% in 1 month. While the majority of antipsychotic and placebo distributions were similar for each of the drugs, haloperidol and LAI risperidone showed later median onset at 9 days and 16 days, respectively. Sedation persisted in only 24% (95% CI 19·7–29·3) of participants after 4 weeks.
“Our results emphasize the need for careful monitoring of patients during the early treatment phase and suggest that additional factors, beyond the antipsychotic itself, should be considered if sedation persists for more than 1 month,” the authors wrote.
The researchers noted several limitations of the study, including the variability in drug type and drug dose across the selected RCTs, and the lack of controls for potential time-varying effects for each of the assessed drugs. The study also did not include individuals with lived experience, which may impact its generalizability.
Still, the authors emphasize that the meta-analysis offers a more comprehensive understanding of the dynamics of sedation onset and resolution, which may encourage more competent patient care during the initiation of antipsychotics.
“Our study offers valuable guidance for managing sedative adverse events during antipsychotic treatment, potentially improving patient care and potentially reducing early treatment discontinuation due to sedation,” they concluded.
