AT APA

SAN DIEGO (FRONTLINE MEDICAL NEWS) – A new meta-analysis suggests that second-generation long-acting injectable antipsychotics (LAIs) are slightly better than oral antipsychotics at preventing relapse after a first psychotic incident.

The meta-analysis, released at the annual meeting of the American Psychiatric Association, is limited because it looks at only three studies. Still, study lead author Christine Tran-Boynes, DO, said the findings are useful for psychiatrists.

“For a long time, LAIs were associated with severely ill psychotic patients who were frequently hospitalized and not compliant with their oral meds,” Dr. Tran-Boynes , a resident at the University of Maryland, Baltimore, said in an interview. “The purpose of this paper is to change the perception of LAIs. They are not just a medication of last resort in those with severe, chronic psychosis but, instead, can be used in the early stages of psychosis as prophylaxis against relapse.”

Injectable antipsychotics are more commonly used in Europe, where “there also seemed to be a greater willingness among patients to receive this treatment,” said Peter F. Buckley, MD , dean of the medical school at Virginia Commonwealth University, Richmond.

The APA’s schizophrenia treatment guidelines recommend LAIs for patients with “recurrent relapses related to nonadherence” and patients who prefer the shots. Dr. Tran-Boynes notes that “the most common cause of relapse in patients with schizophrenia is partial adherence or nonadherence to oral antipsychotics. If LAIs can improve adherence in patients and monitoring of adherence for clinicians, they could have a role in preventing relapse during this critical period in psychosis.”

The meta-analysis examines three randomized controlled studies – two from 2015 and one from 2013 – that compare second-generation LAIs to first- and second-generation oral antipsychotics after first episodes of psychosis. Dr. Tran-Boynes said researchers could not find any studies comparing first-generation long-acting antipsychotics to oral antipsychotics.

The largest study had 769 participants; the others had 85 and 86. The subjects, all adults, had diagnoses of schizophrenia, schizoaffective disorder, or schizophreniform disorder. Their diagnoses must have been made within the previous 5 years.

According to the meta-analysis, relapses after first-episode psychosis were more likely (relative risk, 1.078; 95% confidence interval, 1.007-1.154; P = 0.012) in patients taking first- or second-generation oral antipsychotics, compared with those on second-generation LAIs.

“There was an 8% greater efficacy for LAIs preventing relapse after early psychosis, compared to oral antipsychotics,” Dr. Tran-Boynes said. She calculated the number needed to treat as 14.

The percentages of patients who did not relapse while taking second-generation LAIs ranged from 73% (31 of 42 patients randomized to an injectable risperidone arm over 24 months) to 95% (38 of 40 patients over a 12-month study, also of injectable risperidone), Dr. Tran-Boynes said.

When asked about the meta-analysis, Robert Rosenheck, MD , expressed concern.

“While well done, it is based on too few studies to give useful guidance to practice,” said Dr. Rosenheck, professor of psychiatry, epidemiology and public health at Yale University, New Haven, Conn.

Dr. Buckley also noted that the meta-analysis includes a small number of studies. “The effect is sizable for a first-episode population, but other studies to date are more mixed,” he added. “For instance, in a study among a more chronic schizophrenic population, we found no difference between a group receiving long-acting injectable risperidone and oral second-generation antipsychotics” ( Schizophr Bull. 2015 Mar;41[2]:449-59 ).

What should psychiatrists know when they consider prescribing LAIs to prevent psychotic relapse? “If a patient expresses willingness to take an oral antipsychotic on a daily basis and/or has someone to monitor his medication intake, then prescribing an oral antipsychotic would be the ideal route,” Dr. Tran-Boynes said. “However, I would recommend LAIs to patients who have demonstrated poor compliance with previous medications in general, poor awareness of psychosis, poor awareness of need for treatment, poor availability of social support to ensure that the patient will take his/her medication daily, and/or if a patient expresses preference for LAIs.”

She cautioned that LAIs have disadvantages. Compared with oral antipsychotics, it’s harder to adjust patients’ dosages in response to side effects or when they improve, she said. LAIs are also more expensive in the short term, she said.

However, LAIs also may have produced fewer side effects, and there aren’t any questions about compliance, she said. In addition, “there’s less pain at the injection site with second-generation LAIs, compared to first-generation LAIs, due to the water-based solution of the former. The oil-based solutions that are characteristic of first-generation LAIs have been shown in studies to be very painful.”

Dr. Tran-Boynes and Dr. Rosenheck reported no relevant disclosures. Dr. Buckley disclosed that he is a research consultant for the National Institute of Mental Health.

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