Increasing versus maintaining the dose of olanzapine or risperidone in schizophrenia patients who did not respond to a modest dosage

A double-blind randomized controlled trial

Hitoshi Sakurai, Takefumi Suzuki, Robert Bies, Bruce G. Pollock, Masaru Mimura, Shitij Kapur, Hiroyuki Uchida

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: While doctors often increase the dose of an antipsychotic when there is insufficient response, there is limited evidence that this intervention is any better than waiting longer on the lower dose. We put the proposition to test. Method: In this 4-week, double-blind, randomized controlled trial conducted in psychiatric care from September 2012 to March 2015, 103 patients with schizophrenia (ICD-10) who did not respond to olanzapine 10 mg/d or risperidone 3 mg/d were randomly allocated to a dose-increment or -continuation group. In the increment group, antipsychotic doses were doubled for 4 weeks, whereas in the continuation group, doses were not changed. Completion rate (primary outcome measure); changes in psychopathology, function, and extrapyramidal symptoms; and response rate were compared between the groups. The relationship between baseline plasma antipsychotic concentrations and changes in psychopathology was examined. Results: The completion rate was significantly lower in the increment group than in the continuation group (69.2% [36/52] vs 86.3% [44/51], P = .038). No significant superiority was observed in any of the outcome measures in the increment group compared to the continuation group, except the Positive and Negative Syndrome Scale (PANSS) positive subscale score change in intentionto- treat analysis. Those with lower plasma concentrations of olanzapine on their initial treatment showed a greater improvement on the PANSS positive subscale when their dose was increased (P = .042). Conclusions: As a general strategy, patients with schizophrenia failing to respond to moderate antipsychotic doses may not benefit from an increase in dose. The possibility of benefit in those whose plasma antipsychotic concentrations at baseline are still low cannot be ruled out. Trial Registration: UMIN.ac.jp/ctr/index.htm identifier: UMIN000008667.

Original languageEnglish (US)
Pages (from-to)1381-1390
Number of pages10
JournalJournal of Clinical Psychiatry
Volume77
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

olanzapine
Risperidone
Antipsychotic Agents
Schizophrenia
Randomized Controlled Trials
Psychopathology
Outcome Assessment (Health Care)
International Classification of Diseases
Psychiatry

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Increasing versus maintaining the dose of olanzapine or risperidone in schizophrenia patients who did not respond to a modest dosage : A double-blind randomized controlled trial. / Sakurai, Hitoshi; Suzuki, Takefumi; Bies, Robert; Pollock, Bruce G.; Mimura, Masaru; Kapur, Shitij; Uchida, Hiroyuki.

In: Journal of Clinical Psychiatry, Vol. 77, No. 10, 01.10.2016, p. 1381-1390.

Research output: Contribution to journalArticle

Sakurai, Hitoshi ; Suzuki, Takefumi ; Bies, Robert ; Pollock, Bruce G. ; Mimura, Masaru ; Kapur, Shitij ; Uchida, Hiroyuki. / Increasing versus maintaining the dose of olanzapine or risperidone in schizophrenia patients who did not respond to a modest dosage : A double-blind randomized controlled trial. In: Journal of Clinical Psychiatry. 2016 ; Vol. 77, No. 10. pp. 1381-1390.
@article{b70f1e38219c482988995e9c974817c3,
title = "Increasing versus maintaining the dose of olanzapine or risperidone in schizophrenia patients who did not respond to a modest dosage: A double-blind randomized controlled trial",
abstract = "Objective: While doctors often increase the dose of an antipsychotic when there is insufficient response, there is limited evidence that this intervention is any better than waiting longer on the lower dose. We put the proposition to test. Method: In this 4-week, double-blind, randomized controlled trial conducted in psychiatric care from September 2012 to March 2015, 103 patients with schizophrenia (ICD-10) who did not respond to olanzapine 10 mg/d or risperidone 3 mg/d were randomly allocated to a dose-increment or -continuation group. In the increment group, antipsychotic doses were doubled for 4 weeks, whereas in the continuation group, doses were not changed. Completion rate (primary outcome measure); changes in psychopathology, function, and extrapyramidal symptoms; and response rate were compared between the groups. The relationship between baseline plasma antipsychotic concentrations and changes in psychopathology was examined. Results: The completion rate was significantly lower in the increment group than in the continuation group (69.2{\%} [36/52] vs 86.3{\%} [44/51], P = .038). No significant superiority was observed in any of the outcome measures in the increment group compared to the continuation group, except the Positive and Negative Syndrome Scale (PANSS) positive subscale score change in intentionto- treat analysis. Those with lower plasma concentrations of olanzapine on their initial treatment showed a greater improvement on the PANSS positive subscale when their dose was increased (P = .042). Conclusions: As a general strategy, patients with schizophrenia failing to respond to moderate antipsychotic doses may not benefit from an increase in dose. The possibility of benefit in those whose plasma antipsychotic concentrations at baseline are still low cannot be ruled out. Trial Registration: UMIN.ac.jp/ctr/index.htm identifier: UMIN000008667.",
author = "Hitoshi Sakurai and Takefumi Suzuki and Robert Bies and Pollock, {Bruce G.} and Masaru Mimura and Shitij Kapur and Hiroyuki Uchida",
year = "2016",
month = "10",
day = "1",
doi = "10.4088/JCP.15m10490",
language = "English (US)",
volume = "77",
pages = "1381--1390",
journal = "Journal of Clinical Psychiatry",
issn = "0160-6689",
publisher = "Physicians Postgraduate Press Inc.",
number = "10",

}

TY - JOUR

T1 - Increasing versus maintaining the dose of olanzapine or risperidone in schizophrenia patients who did not respond to a modest dosage

T2 - A double-blind randomized controlled trial

AU - Sakurai, Hitoshi

AU - Suzuki, Takefumi

AU - Bies, Robert

AU - Pollock, Bruce G.

AU - Mimura, Masaru

AU - Kapur, Shitij

AU - Uchida, Hiroyuki

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Objective: While doctors often increase the dose of an antipsychotic when there is insufficient response, there is limited evidence that this intervention is any better than waiting longer on the lower dose. We put the proposition to test. Method: In this 4-week, double-blind, randomized controlled trial conducted in psychiatric care from September 2012 to March 2015, 103 patients with schizophrenia (ICD-10) who did not respond to olanzapine 10 mg/d or risperidone 3 mg/d were randomly allocated to a dose-increment or -continuation group. In the increment group, antipsychotic doses were doubled for 4 weeks, whereas in the continuation group, doses were not changed. Completion rate (primary outcome measure); changes in psychopathology, function, and extrapyramidal symptoms; and response rate were compared between the groups. The relationship between baseline plasma antipsychotic concentrations and changes in psychopathology was examined. Results: The completion rate was significantly lower in the increment group than in the continuation group (69.2% [36/52] vs 86.3% [44/51], P = .038). No significant superiority was observed in any of the outcome measures in the increment group compared to the continuation group, except the Positive and Negative Syndrome Scale (PANSS) positive subscale score change in intentionto- treat analysis. Those with lower plasma concentrations of olanzapine on their initial treatment showed a greater improvement on the PANSS positive subscale when their dose was increased (P = .042). Conclusions: As a general strategy, patients with schizophrenia failing to respond to moderate antipsychotic doses may not benefit from an increase in dose. The possibility of benefit in those whose plasma antipsychotic concentrations at baseline are still low cannot be ruled out. Trial Registration: UMIN.ac.jp/ctr/index.htm identifier: UMIN000008667.

AB - Objective: While doctors often increase the dose of an antipsychotic when there is insufficient response, there is limited evidence that this intervention is any better than waiting longer on the lower dose. We put the proposition to test. Method: In this 4-week, double-blind, randomized controlled trial conducted in psychiatric care from September 2012 to March 2015, 103 patients with schizophrenia (ICD-10) who did not respond to olanzapine 10 mg/d or risperidone 3 mg/d were randomly allocated to a dose-increment or -continuation group. In the increment group, antipsychotic doses were doubled for 4 weeks, whereas in the continuation group, doses were not changed. Completion rate (primary outcome measure); changes in psychopathology, function, and extrapyramidal symptoms; and response rate were compared between the groups. The relationship between baseline plasma antipsychotic concentrations and changes in psychopathology was examined. Results: The completion rate was significantly lower in the increment group than in the continuation group (69.2% [36/52] vs 86.3% [44/51], P = .038). No significant superiority was observed in any of the outcome measures in the increment group compared to the continuation group, except the Positive and Negative Syndrome Scale (PANSS) positive subscale score change in intentionto- treat analysis. Those with lower plasma concentrations of olanzapine on their initial treatment showed a greater improvement on the PANSS positive subscale when their dose was increased (P = .042). Conclusions: As a general strategy, patients with schizophrenia failing to respond to moderate antipsychotic doses may not benefit from an increase in dose. The possibility of benefit in those whose plasma antipsychotic concentrations at baseline are still low cannot be ruled out. Trial Registration: UMIN.ac.jp/ctr/index.htm identifier: UMIN000008667.

UR - http://www.scopus.com/inward/record.url?scp=84992731172&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992731172&partnerID=8YFLogxK

U2 - 10.4088/JCP.15m10490

DO - 10.4088/JCP.15m10490

M3 - Article

VL - 77

SP - 1381

EP - 1390

JO - Journal of Clinical Psychiatry

JF - Journal of Clinical Psychiatry

SN - 0160-6689

IS - 10

ER -