Rapid vs. slow antipsychotic initiation in schizophrenia: A systematic review and meta-analysis

Background: How antipsychotics should be initiated/titrated in patients with acute schizophrenia as well as patients undergoing an antipsychotic switch remains a question. Methods: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were systematically searched. Randomized controlled trials examining rapid vs. slow antipsychotic initiation in patients with schizophrenia were selected. Data on study discontinuation, psychopathology, extrapyramidal symptoms (EPS), and treatment-emergent adverse events (TEAEs) were extracted and synthesized in studies including clinically different populations of acute patients and stable patients undergoing an antipsychotic switch. Results: Among 11 studies that met eligibility criteria, 8 and 3 studies involving 809 and 777 patients were identified as acute patient studies and stable patient switching studies, respectively. Rapid antipsychotic initiation was not significantly different from slow antipsychotic initiation in acute patient studies for all-cause study discontinuation, while the former was significantly inferior to the latter in stable patient switching studies (N = 3, n = 777, RR = 1.45, 95% CI = 1.05-2.00, P = 0.02). In contrast, rapid initiation was significantly superior to slow initiation for all psychopathology outcomes including the PANSS/BPRS total score (N = 3, n = 336, SMD = -0.28, 95% CI = -0.51--0.05, P = 0.02) in acute patient studies, but not different in stable patient switching studies. Any other outcomes except for nausea did not significantly differ between the 2 groups. Conclusions: Rapid initiation of antipsychotics may represent a reasonable option for the treatment of acute schizophrenia, while slower initiation may be a safer strategy when switching antipsychotics in stable schizophrenia. Because of the low to very low quality of evidence, findings should be considered preliminary.