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Schizophr Bull. 2014 Jan;40(1):192-213. doi: 10.1093/schbul/sbs150. Epub 2012 Dec 17.

Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials.

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To whom correspondence should be addressed; Division of Psychiatry Research, the Zucker Hillside Hospital, 75-59 263rd Street, Glen Oaks, NY 11004, US; tel: (718) 470-4812, fax: (718) 343-1659, e-mail:



While long-acting injectable antipsychotics (LAIs) are hoped to reduce high relapse rates in schizophrenia, recent randomized controlled trials (RCTs) challenged the benefits of LAIs over oral antipsychotics (OAPs).


Systematic review/meta-analysis of RCTs that lasted ≥ 6 months comparing LAIs and OAPs. Primary outcome was study-defined relapse at the longest time point; secondary outcomes included relapse at 3, 6, 12, 18, and 24 months, all-cause discontinuation, discontinuation due to adverse events, drug inefficacy (ie, relapse + discontinuation due to inefficacy), hospitalization, and nonadherence.


Across 21 RCTs (n = 5176), LAIs were similar to OAPs for relapse prevention at the longest time point (studies = 21, n = 4950, relative risk [RR] = 0.93, 95% confidence interval [CI]: 0.80-1.08, P = .35). The finding was confirmed restricting the analysis to outpatient studies lasting ≥ 1 year (studies = 12, RR = 0.93, 95% CI:0.71-1.07, P = .31). However, studies using first-generation antipsychotic (FGA)-LAIs (studies = 10, RR = 0.82, 95% CI:0.69-0.97, P = .02) and those published ≤ 1991 (consisting exclusively of all 8 fluphenazine-LAI studies; RR = 0.79, 95% CI: 0.65-0.96, P = 0.02) were superior to OAPs regarding the primary outcome. Pooled LAIs also did not separate from OAPs regarding any secondary outcomes. Again, studies using FGA-LAIs and those published ≤ 1991 were associated with LAI superiority over OAPs, eg, hospitalization and drug inefficacy.


In RCTs, which are less representative of real-world patients than naturalistic studies, pooled LAIs did not reduce relapse compared with OAPs in schizophrenia patients. The exceptions were FGA-LAIs, mostly consisting of fluphenazine-LAI studies, which were all conducted through 1991. Because this finding is vulnerable to a cohort bias, studies comparing FGA-LAI vs second-generation antipsychotics-LAI and LAI vs OAP RCTs in real-world patients are needed.


adherence; antipsychotics; depot; long-acting injection; meta-analysis; relapse; schizophrenia; treatment discontinuation

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