Optimal Doses of Specific Antipsychotics for Relapse Prevention in a Nationwide Cohort of Patients with Schizophrenia

Heidi Taipale, Antti Tanskanen, Jurjen J. Luykx, Marco Solmi, Stefan Leucht, Christoph U. Correll, Jari Tiihonen

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background and Hypothesis: Optimal doses of most antipsychotics in the maintenance treatment of schizophrenia are unknown. We aimed to study the risk of severe relapse indicated by rehospitalization for different dose categories of 15 most frequently used antipsychotics in monotherapy in Finland. Study Methods: We studied the risk of rehospitalization (Adjusted Hazard Ratio, aHR) associated with six antipsychotic monotherapy dose categories (as time-varying dose, measured in defined daily dose, DDDs/day) in a nationwide cohort of persons diagnosed with schizophrenia (n = 61 889), using within-individual analyses to eliminate selection bias. Study Results: Among the 15 most widely used antipsychotics, 13 had a U- or J-shaped dose-response curve, showing the lowest risks of relapse for doses of 0.6-<1.1 DDDs/day vs nonuse of antipsychotics. The exceptions were oral perphenazine (aHR = 0.72, 95% CI = 0.68-0.76, <0.6 DDDs/day), and olanzapine-long-acting injectable (LAI), which had the lowest aHR of any antipsychotic (aHR = 0.17, 95% CI = 0.11-0.25, 1.4-<1.6 DDDs/day). Certain risperidone and perphenazine doses <0.9 DDD/day were associated with 21%-45% lower risk of rehospitalization (P <. 001) than the standard dose of 0.9-1.1 DDD/day (ie, 5 mg for risperidone and 30 mg for perphenazine). Conclusions: For most antipsychotics, the risk of severe relapse was the lowest during use of standard dose. Our results suggest that olanzapine LAI is highly effective in dose ranges >0.9 DDD/day, and especially at 1.4-<1.6 DDDs/day (405 mg/4 weeks) associated with substantially lower risk of rehospitalization than any dose of any other antipsychotic. The current WHO standard dose definitions appear to be clearly too high for perphenazine and somewhat too high for risperidone.

Original languageEnglish
Pages (from-to)774-784
Number of pages11
JournalSchizophrenia Bulletin
Volume48
Issue number4
DOIs
StatePublished - 1 Jul 2022
Externally publishedYes

Keywords

  • hospitalization
  • prevention
  • psychosis

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