TY - JOUR
T1 - Optimal Doses of Specific Antipsychotics for Relapse Prevention in a Nationwide Cohort of Patients with Schizophrenia
AU - Taipale, Heidi
AU - Tanskanen, Antti
AU - Luykx, Jurjen J.
AU - Solmi, Marco
AU - Leucht, Stefan
AU - Correll, Christoph U.
AU - Tiihonen, Jari
N1 - Publisher Copyright:
© 2022 The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - 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.
AB - 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.
KW - hospitalization
KW - prevention
KW - psychosis
UR - http://www.scopus.com/inward/record.url?scp=85132453851&partnerID=8YFLogxK
U2 - 10.1093/schbul/sbac039
DO - 10.1093/schbul/sbac039
M3 - Article
C2 - 35524479
AN - SCOPUS:85132453851
SN - 0586-7614
VL - 48
SP - 774
EP - 784
JO - Schizophrenia Bulletin
JF - Schizophrenia Bulletin
IS - 4
ER -