Oral Antipsychotics vs Long-Acting Injectables

Leslie Citrome, MD, MPH


December 17, 2013

Long-Acting Injectable Versus Oral Antipsychotics in Schizophrenia: A Systematic Review and Meta-Analysis of Mirror-Image Studies

Kishimoto T, Nitta M, Borenstein M, Kane JM, Correll CU
J Clin Psychiatry. 2013;74:957-965

Study Summary

This is a meta-analysis of mirror-image studies that compare periods of oral antipsychotic vs long-acting injectable (LAI) antipsychotic treatment in the same patients, who served as their own controls. The data were typically gathered retrospectively using large databases. Kishimoto and colleagues analyzed a total of 25 mirror-image studies from 28 countries. These studies followed 5940 patients with schizophrenia for ≥ 12 months (≥ 6 months each on oral antipsychotic and LAI treatment). LAIs showed strong superiority over oral antipsychotics in preventing hospitalization (16 studies, n = 4066; risk ratio = 0.43; 95% confidence interval [CI], 0.35-0.53; P < .001) and in reducing the number of hospitalizations (15 studies, 6342 person-years; rate ratio = 0.38; 95% CI, 0.28-0.51; P < .001).


The same group of investigators recently conducted a meta-analysis of randomized controlled trials (RCTs) of LAI vs oral antipsychotics in the prevention of relapse in schizophrenia.[1] In that report, they found that across 21 trials (n = 5176), outcomes with LAIs were generally similar to those for oral antipsychotics.

Why the disparity in results between these 2 meta-analyses? It is thought that in RCTs, subjects are not as representative of real-world patients as they are in naturalistic studies. The investigators acknowledged that in RCTs, patients who are willing to listen to a lengthy explanation of the trial, give consent, and show up for appointments are likely to be recruited, but those who miss appointments and are less cooperative are likely to be excluded from the study recruitment procedure. Therefore, subjects in RCTs may consist of patients with better treatment adherence and lower illness severity. In essence, patients in RCTs may not be representative of the patient group for whom clinicians would routinely choose LAIs. In addition, subjects in RCTs receive reminders, reimbursement, provision of transportation, and frequent structured assessments of efficacy, safety, and adherence. The combination of patient selection bias and the amenities of being in a clinical trial reduce the opportunity to see a difference between LAIs and oral agents in RCTs.

On the other hand, the design of mirror-image studies reflects clinical practice. Eligible patients include all those who are candidates for LAIs and receive them as part of routine clinical care. Although mirror-image studies are not without biases of their own, they may more closely approximate what we can expect when using LAIs in the day-to-day care of our patients than RCTs.



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