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Comparative Effectiveness of Antipsychotics in Schizophrenia: A Critical Review


This article provides a critical review of “Antipsychotics in Adults With Schizophrenia: Comparative Effectiveness of First-Generation Versus Second-Generation Medications” by Hartling et al., published in the Annals of Internal Medicine. The original study offers a systematic review and meta-analysis comparing first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) in treating schizophrenia. This review highlights key findings, discusses the implications for clinical practice, and identifies areas needing further research.


Schizophrenia treatment has evolved with the introduction of second-generation antipsychotics (SGAs), aiming to improve symptom management and reduce adverse effects compared to first-generation antipsychotics (FGAs). The study by Hartling et al. (2012) provides a comprehensive comparison of these two classes of medications, assessing their effectiveness and safety profiles in adults with schizophrenia.


Hartling et al. conducted a systematic review and meta-analysis, analyzing data from randomized controlled trials (RCTs) and cohort studies. The review included studies published up to March 2012, focusing on core illness symptoms, adverse events such as diabetes mellitus, mortality, tardive dyskinesia, and metabolic syndrome.


The review found few clinically important differences between FGAs and SGAs in treating core symptoms of schizophrenia. Moderate-strength evidence suggested haloperidol’s benefit over olanzapine for positive symptoms and olanzapine’s benefit over haloperidol for negative symptoms. Low-strength evidence indicated no significant difference in mortality between chlorpromazine and clozapine or haloperidol and aripiprazole. However, olanzapine was associated with a higher incidence of metabolic syndrome.


The findings highlight the complexity of choosing between FGAs and SGAs for schizophrenia treatment. While SGAs were expected to offer superior outcomes, the evidence did not conclusively favor one class over the other for core symptoms. The study’s limitations, including high or unclear risk of bias in most studies and variability in medication comparisons, suggest the need for more robust research.


Hartling et al.’s review underscores the necessity for personalized treatment approaches in schizophrenia, considering individual patient responses and potential adverse effects. Future research should focus on long-term outcomes and the impact of specific antipsychotics within diverse patient populations to provide clearer guidance for clinicians.


Hartling, L., Abou-Setta, A. M., Dursun, S., Mousavi, S. S., Pasichnyk, D., & Newton, A. S. (2012). Antipsychotics in Adults With Schizophrenia: Comparative Effectiveness of First-Generation Versus Second-Generation Medications: A Systematic Review and Meta-analysis. Annals of Internal Medicine, 157(7), 498-511. Link to the full text.