Which Antipsychotics Are Best for Your Patients?

Psychiatrists in the United States currently have 12 second-generation antipsychotics (including some with multiple formulations) to choose from when considering treatment for patients with schizophrenia. Given these options, it is important that psychiatrists have updated information on how these medications stack up against each other.

A team of researchers at Oregon Health and Science University (OHSU) has conducted a meta-analysis comparing the efficacy and side effects of these U.S.-approved antipsychotics. Their findings reaffirm the current consensus that clozapine, olanzapine, and risperidone are generally the most effective treatment options for patients with schizophrenia. The report also provided new evidence that patients were more likely to stick with their recommended treatment if receiving long-acting injectable (LAI) formulations compared with oral formulations.

The analysis, published in Psychiatric Research and Clinical Practice, was part of a larger study carried out by OHSU’s Evidence-Based Practice Center (EPC) comparing the effectiveness of both pharmacological and psychosocial treatments for schizophrenia. OHSU’s center—which is one of nine in the country funded by the Agency for Healthcare, Research, and Quality (AHRQ)—is tasked with producing comprehensive evidence reviews on a range of medical topics. Stakeholders submit proposals to AHRQ for topics they believe need an evidence-based review.

APA submitted a proposal to AHRQ requesting a comprehensive review of schizophrenia treatments, since several new antipsychotics or new formulations of existing antipsychotics had been approved for use since APA’s last schizophrenia practice guideline update in 2009. Marian McDonagh, Pharm.D., a professor of medical informatics and clinical epidemiology at OHSU and associate director of OHSU’s Evidence-Based Practice Center, was lead author on the resulting report.

This systematic review as well other clinical studies helped to inform the development of APA’s practice guideline on schizophrenia (see story).

McDonagh and colleagues compiled data from 278 clinical trials of FDA-approved antipsychotics, comparing the effects of second-generation antipsychotics with other first- and second-generation antipsychotics. The researchers then assessed a range of outcomes, including symptom improvement, quality of life, side effects, and mortality risk.

The data for oral medications showed that clozapine, olanzapine, and risperidone provided the strongest symptom response. Oral olanzapine also appeared to be the best option for preventing treatment discontinuation, while clozapine was superior to other medications in reducing suicide risk. There were no significant differences among the SGAs in the proportions of patients reporting any adverse event.

For most of the antipsychotic medications, particularly the newer ones, few or no comparative data were available, the researchers noted. This made it difficult for the researchers to make strong statements about LAIs or newer drugs such as cariprazine or lurasidone compared with the older medications.

Following their initial analysis, McDonagh and colleagues made the first draft of their review available for public comment. “We received a lot of comments that our analysis should have kept oral medications and LAIs in separate categories,” she said. Ultimately, McDonagh and her expert panel considered all formulations together since APA had emphasized a desire to compare the benefits of all the available formulations.

The researchers found little evidence to suggest LAIs are superior to oral medications, as there are fewer clinical data on these newer injectables relative to more established oral drugs. The analysis did, however, reveal that LAI risperidone was superior to several oral antipsychotics in preventing people from stopping their prescriptions due to adverse events; LAI risperidone also scored well at improving quality of life relative to some oral antipsychotics.

“Looking ahead, there are so many other things to consider beyond schizophrenia symptoms,” McDonagh said. “We need studies that address factors related to patient recovery, such as employment and independent living.” She acknowledged studies like this are difficult projects that would take years. “However, this is a long-term disease, and we need long-term outcomes.”

This study was funded by a grant from AHRQ. ■

“Updating the Comparative Evidence on Second-Generation Antipsychotic Use With Schizophrenia“ is posted here.

The full report, “Treatments for Schizophrenia in Adults: A Systematic Review,” is posted here.