LAIs more beneficial for certain schizophrenia outcomes than oral antipsychotics

Long-acting injectable antipsychotics provided significant benefit in prevention of hospitalization or relapse for schizophrenia compared with oral antipsychotics, according to study results published in The Lancet Psychiatry.

“Our previous meta-analysis of randomized controlled trials (RCTs), as the largest in recent years comparing LAIs versus oral antipsychotics, did not find a significant difference between LAIs and oral antipsychotics in preventing relapse or hospitalization, or in secondary outcomes related to relapse, including drug inefficacy, all-cause discontinuation and non-adherence,” Taishiro Kishimoto, MD, of the department of neuropsychiatry at Keio University School of Medicine in Tokyo, and colleagues wrote. “Conversely, subsequent meta-analyses of pre–post studies and cohort studies showed that LAIs were associated with significantly lower risk [for] hospitalization or relapse than oral antipsychotics.”

The investigators conducted the current comprehensive systematic review and meta-analysis to compare the benefits of LAIs with those of oral antipsychotics for people with schizophrenia in three study designs, which were randomized controlled trials, cohort studies and pre-post studies. They searched five databases without language restrictions for studies published between the inception of the database and March 13, 2020, as well as ClinicalTrials.gov and unpublished studies. They included studies that lasted 6 months or longer and targeted individuals with schizophrenia and related disorders, and they excluded studies on penfluridol, case reports and case series with fewer than 20 individuals. Meta-analysis of the risk ratio for hospitalization or relapse with LAIs compared with oral antipsychotics by a random-effects model, with hospitalization used preferentially over relapse, served as the primary outcome. The researchers used the preferential order of relapse over hospitalization and evaluated hospitalization risk and relapse risk individually as secondary analyses.

The researchers analyzed 137 studies, of which 32 were randomized controlled trials, 65 were cohort studies and 40 were pre-post studies. They noted variance from low to high in the quality of studies related to risk for bias across study designs and within each study design. Results showed an association between LAI use and lower risk for hospitalization or relapse compared with oral antipsychotics among each of the three study studies, with a risk ratio of 0.88 (95% CI, 0.79-0.99) for randomized controlled trials, 0.92 (95% CI, 0.88-0.98) for cohort studies and 0.44 (95% CI, 0.39-0.51) for pre-post studies. When the researchers reversed the preferential order to risk for relapse over hospitalization, as well as in individual analysis of hospitalization risk, the association remained. However, for relapse risk alone, the association was maintained only among pre-post studies. Further, when analyzed according to study design, all other outcomes related to effectiveness, efficacy, safety, quality of life, cognitive function and other outcomes appeared more benefitted by LAIs than oral antipsychotics in 60 of 328 comparisons, not different in 252 comparisons and less beneficial in 16 comparisons. Across all three study designs, the researchers reported significant heterogeneity. They noted publication biases among cohort and pre-post studies, with similar effects after trim-and-fill analyses.

“The present results should be interpreted with care, considering the strengths and weaknesses of the study designs, potentially low quality of observational studies and heterogeneous reporting of adverse events across studies,” Kishimoto and colleagues wrote. “Nevertheless, this updated analysis of RCTs and other study designs that consistently showed LAIs to prevent hospitalization or relapse is meaningful and suggests potential benefits of increased use of LAIs in clinical practice.”

In a related editorial, Elaine H Morrato, DrPH, MPH, of the Parkinson School of Health Sciences and Public Health at Loyola University in Chicago, outlined the implications of these findings for policy makers.

“Policy makers allocating limited health budgets should also assess applicability of the findings,” Morrato wrote. “Depending on location, long-acting second-generation antipsychotics can cost considerably more than oral versions; for example, annual drug costs were four to 10 times higher for LAIs versus oral antipsychotics in Canada in 2014. Therefore, the question of whether the marginal clinical benefits estimated in the report outweigh increased drug costs should be assessed at the local level.”