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In Stable Schizophrenia, Lower Antipsychotic Doses Offer Efficacy for Relapse Prevention
Antipsychotic doses higher than about 5-mg/d risperidone equivalent had limited additional benefit for preventing relapse in patients with stable schizophrenia and were associated with more adverse events. Researchers published their findings in JAMA Psychiatry.
Amid ongoing debate on appropriate antipsychotic drug dosing for relapse prevention in schizophrenia, researchers conducted a meta-analysis of data from 72 dose arms of 26 randomized clinical trials that spanned 4776 participants. The studies compared fixed doses of a second-generation antipsychotic, haloperidol, or fluphenazine for relapse prevention among patients with stable schizophrenia.
“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; 95% CI, 0.31-0.57; standardized mean difference for Positive and Negative Syndrome Scale total score reduction, −0.55; 95% CI, −0.68 to −0.41), but flattened thereafter,” they wrote.
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However, doses higher than 5-mg/d risperidone equivalent were linked with increased discontinuations among study participants because of adverse events, according to the findings.
The investigation also revealed that doses as low as 2.5-mg/d risperidone equivalent may be sufficient for patients in remission or for patients receiving high-potency, first-generation antipsychotics.
Researchers cautioned that patients receiving low doses may experience a disproportionally higher risk of relapse with further dose decreases.
“Moreover,” they wrote, “the observations are averages, and factors such as slow or rapid metabolism, age, illness stage, comorbidities, and drug-drug interactions suggest that individual patients will often need higher or lower doses.”
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