LAI Antipsychotics Beat Oral Meds for Preventing Relapse, Hospitalization

Long-acting injectable antipsychotics may be more effective than oral antipsychotics at lowering the risk of relapse and hospitalization in patients with schizophrenia, a meta-analysis in Lancet Psychiatry has found. Three previous meta-analyses by the same authors had yielded inconsistent results depending on the type of study they analyzed: LAIs appeared to be superior at lowering risk of relapse and hospitalization in cohort and pre/post studies but not in randomized, controlled trials.

“Since evidence from randomized, controlled trials is used primarily as the basis for guidelines and since several randomized, controlled trials had been conducted since our last meta-analysis, ... we wanted to update our three meta-analyses and apply similar methods to analyze studies in all three designs with the same meta-analytic approach,” said Christoph U. Correll, M.D., a professor of psychiatry and molecular medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, N.Y., and an investigator at the Center for Psychiatric Neuroscience at the Feinstein Institute for Medical Research in Manhasset, N.Y. He added that several of the more recent randomized, controlled trials included populations who had a higher risk of nonadherence to their medications, such as those with a first episode or early phase illness and those who have substance use disorders.

In the current study, Correll and colleagues analyzed data from more than 397,000 patients in 137 studies, including 32 randomized, controlled trials; 65 cohort studies; and 40 pre/post studies. (Pre/post studies are studies that compare outcomes in the same patients before and after they start a particular intervention.) They found that the risk for hospitalization or relapse was lower for patients who took LAIs compared with those who took oral antipsychotics in all three study designs: 12% lower in randomized, controlled trials; 8% lower in cohort studies; and 56% lower in pre/post studies. The researchers also looked at secondary outcomes such as adverse events, quality of life, cognitive function, and the use of health care resources. Compared with oral antipsychotics, LAIs were significantly advantageous in 60 of 328 comparisons, no different in 252 comparisons, and less beneficial in 16 comparisons.

The researchers noted that randomized, controlled trials tend to include patients who are more likely to adhere to their medication regimens than patients in “real-world” settings, which can make it more difficult to show the benefits of LAIs. In contrast, cohort studies might be biased against LAIs in that patients who receive LAIs may have more severe illness compared with patients who receive oral antipsychotics, again making it more difficult to show the advantages of LAIs. Correll explained that the effects were largest in studies that most closely mimicked clinical use, such as pre/post studies that compared outcomes in patients after they started taking LAIs with outcomes in the same patients before they took LAIs, when they were taking oral antipsychotics.

Correll noted that one of the challenges of treatment with oral antipsychotics is that patients may be ambivalent about taking medications and can stop them at any time, which increases their risk of worsening symptoms, relapse, and hospitalization over time.

“Relapse prevention via … reduction of nonadherence through LAI treatment is the most effective way to address actionable risk factors for poor outcomes in people with schizophrenia,” he said.

Last September, APA released its Practice Guideline for the Treatment of Patients With Schizophrenia. Although the guideline does not offer definitive recommendations on the use of LAIs compared with oral antipsychotics, it does note moderate evidence to support the use of LAIs in patients who prefer them or who have a history of poor medication adherence.

“This study is consistent with what we found when we were developing the guideline and reinforces the recommendations that we made,” said George Keepers, M.D., a professor of psychiatry at Oregon Health and Science University School of Medicine in Portland and chair of the workgroup that developed APA’s guideline. “When you look at long-acting injectables versus oral agents in randomized, controlled trials, you don’t actually see much difference, but in studies of real-world practice, you find much more robust evidence that long-acting injectables can prevent hospitalizations, reduce relapse rates, and reduce mortality. The study discussion does a good job of addressing why [the differences between findings] might be.”

Correll and colleagues reported no outside funding for their study. ■

“Long-Acting Injectable Versus Oral Antipsychotics for the Maintenance Treatment of Schizophrenia: A Systematic Review and Comparative Meta-Analysis of Randomised, Cohort, and Pre-Post Studies” is posted here.

APA’s Practice Guideline for the Treatment of Patients With Schizophrenia is posted here.