Lower antipsychotic doses likely effective in stable schizophrenia, but relapse risk higher

Reuters Health - 27/08/2021  - Lower doses of antipsychotics may be effective in patients with schizophrenia who are in remission or receiving high-potency, first-generation drugs, but the relapse risk is higher, a meta-analysis shows.

By contrast, higher doses of antipsychotics may help prevent relapse, but are associated with more adverse events.

"Because patients often need to use antipsychotics for many years, adverse events, such as movement disorders and weight gain, can accumulate and result in even more severe problems, such as tardive dyskinesia or cardiovascular problems, (as well as excess mortality)," write Dr. Stefan Leucht of Technical University of Munich and colleagues. "Therefore, psychiatrists need to know which doses are sufficient for maintenance treatment."

To investigate, the team searched the literature for randomized clinical trials that compared fixed doses of a second-generation antipsychotic, haloperidol, or fluphenazine for relapse prevention in patients with stable schizophrenia, according to their JAMA Psychiatry report.

The primary outcome was relapse, as defined in the study. Secondary outcomes were rehospitalization; reduction from baseline in the Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale total score; all-cause discontinuation; and adverse events-related dropouts.

The analysis included evidence from 72 dose arms in 26 studies with a total of 4,776 participants.

The efficacy-related dose-response curves had a hyperbolic shape, meaning that the probability to relapse decreased rapidly with doses of up to 5-mg/d risperidone equivalent (relative relapse risk, 0.43; standardized mean difference for Positive and Negative Syndrome Scale total score reduction, −0.55), but flattened thereafter.

However, dropouts due to adverse events continued to increase beyond this dose (relative risk at 5 mg/d, 1.38; at 15 mg/d, 2.68).

Further, a subgroup analysis of patients in remission showed that a plateau was reached earlier, at approximately 2.5-mg/d risperidone equivalent.

The authors conclude that doses higher than approximately 5-mg/d risperidone equivalent may provide "limited additional benefit for relapse prevention but more adverse events."

"For patients in remission or who are receiving high-potency first-generation antipsychotics, doses as low as 2.5-mg/d risperidone equivalent may be sufficient," they note. "However, caution is needed at this low dose end when further decreases of dose may be accompanied by a disproportionally higher relapse risk."

These observations are averages, they add. "Factors such as slow or rapid metabolism, age, illness stage, comorbidities, and drug interactions suggest that individual patients will often need higher or lower doses."

The work is part of the dissertation of coauthor Sofia Bauer at the Technical University of Munich, School of Medicine.

SOURCE: https://bit.ly/3sQTiPO JAMA Psychiatry, online August 18, 2021

By Marilynn Larkin



Posted on 27 August 20213 September 2021