An Algorithm-Based Approach to First-Episode Schizophrenia: Response Rates Over 3 Prospective Antipsychotic Trials With a Retrospective Data Analysis
J Clin Psychiatry 2011;72(11):1439-1444
© Copyright 2016 Physicians Postgraduate Press, Inc.
Purchase This PDF for $40.00
If you are not a paid subscriber, you may purchase the PDF.
(You'll need the free Adobe Acrobat Reader.)
Receive immediate full-text access to JCP. You can subscribe to JCP online-only ($86) or print + online ($156 individual).
With your subscription, receive a free PDF collection of the NCDEU Festschrift articles. Hurry! This offer ends December 31, 2011.
If you are a paid subscriber to JCP and do not yet have a username and password, activate your subscription now.
As a paid subscriber who has activated your subscription, you have access to the HTML and PDF versions of this item.
Click here to login.
Did you forget your password?
Still can't log in? Contact the Circulation Department at 1-800-489-1001 x4 or send email
Objective: Early, effective treatment in first-episode schizophrenia is advocated, although evidence based on a systematic approach over multiple antipsychotic trials is lacking. Employing a naturalistic design, we examined response rates over 3 circumscribed antipsychotic trials.
Method: Between June 2003 and December 2008, 244 individuals with first-episode schizophrenia or schizoaffective disorder according to DSM-IV criteria were treated at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada, following an algorithm that moved them through 2 antipsychotic trials, followed by a trial with clozapine. For the first 2 trials, treatment consisted of risperidone followed by olanzapine, or vice versa; each trial consisted of 3 stages (low-, full-, or high-dose) lasting up to 4 weeks at each level and adjusted according to response/tolerability. Clinical response was defined as a Clinical Global Impressions-Improvement score of 2 (much improved) or 1 (very much improved) and/or a Brief Psychiatric Rating Scale Thought Disorder subscale score ≤ 6. Data were analyzed retrospectively, and publication of anonymized clinical data was approved by the Research Ethics Board of the Centre for Addiction and Mental Health in May 2003.
Results: In trial 1, 74.5% of individuals responded, with rates significantly higher for olanzapine (82.1%, 115/140) versus risperidone (66.3%, 69/104; P = .005). With trial 2, response rate dropped dramatically to 16.6% but again was significantly higher for olanzapine (25.7%, 9/35) compared to risperidone (4.0%, 1/25; P = .04). Response rate climbed above 70% once more, specifically 75.0% (21/28), in those individuals who agreed to a third trial with clozapine.
Conclusions: Results confirm a high response rate (75%) to initial antipsychotic treatment in first-episode schizophrenia. A considerably lower response rate (< 20%) occurs with a second antipsychotic trial. Results here were specific to olanzapine and risperidone, suggesting clinical differences (ie, olanzapine more effective than risperidone). A subsequent trial with clozapine is clearly warranted, although it remains unclear whether outcome would be further enhanced if it were used earlier in the treatment algorithm.
J Clin Psychiatry
Submitted: October 21, 2009; accepted April 26, 2010.
Online ahead of print: March 8, 2011 (doi:10.4088/JCP.09m05785yel).
Corresponding author: Ofer Agid, MD, Schizophrenia Program, Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario, M5T 1R8, Canada (Ofer_agid@camh.net).