Treatment outcomes of patients with tardive dyskinesia and chronic schizophrenia

Abstract

Objective: We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD.

Method: This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with χ(2) tests. Data were collected from January 2001 to December 2004.

Results: Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (χ(2)(1) = 0.11, P = .743). Changes in PANSS scores were not significantly different (F(1,974) = 0.82, P = .366), but patients with TD showed less improvement in neurocognitive scores (F(1,359) = 6.53, P = .011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F(3,151) = 0.32, P = .811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a ≥ 50% decrease in AIMS score, and 7% showed a ≥ 50% increase in AIMS score.

Conclusions: Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology, but differed in neurocognitive response. There were no significant differences between treatments in the course of TD, with most patients showing either persistence of or fluctuation in observable symptoms.

Trial registration: clinicaltrials.gov Identifier: NCT00014001.

Conflict of interest statement

Potential conflicts of interest: Dr Caroff has been a consultant for Eli Lilly and has received grant/research support from Pfizer, Bristol-Myers Squibb, and Ortho-McNeil Neurologies. Dr V. G. Davis is an employee of the Collaborative Studies Coordinating Center in the Department of Biostatistics, University of North Carolina. Dr Miller has been a consultant for Otsuka, Hoffmann-La Roche, and Schering Plough and has received research funds from the National Institute of Mental Health and the Foundation for the National Institute of Health. Dr S. M. Davis is an employee of Quintiles. Dr Rosenheck has been a consultant for Eli Lilly, GlaxoSmithKline, Bristol-Myers Squibb, Organon, and Janssen; has received research support from Bristol-Myers Squibb, Eli Lilly, Janssen, AstraZeneca, and Wyeth; and provided expert testimony for the plaintiffs in UFCW Local 1776 and Participating Employers Health and Welfare Fund, et al vs Eli Lilly and Company; for the respondent in Eli Lilly Canada Inc vs Novapharm Ltd and Minister of Health, respondent; and for the Patent Medicines Prices Review Board, Canada, in the matter of Janssen Ortho Inc. and “Risperdal Consta.” Dr McEvoy has received research funding from AstraZeneca, Forest, Eli Lilly, Janssen, Pfizer, Sanofi-Aventis, and Dainippon Sumitomo; consulting or advisory board fees from Pfizer, Bristol-Myers Squibb, Indevus, and Eli Lilly; lecture fees from Janssen and Bristol-Myers Squibb; and honoraria from Eli Lilly. Dr Saltz has received research funds from Cephalon, AstraZeneca, and Novartis and lecture fees from Janssen and Novartis. Dr Chakos has been a consultant for Roche and has received grant/research support from Pfizer, Solvay, AstraZeneca, Janssen, Roche, and Organon. Dr Swartz has received consulting and education fees from AstraZeneca, Bristol-Myers Squibb, Pfizer, Eli Lilly, and Comprehensive Neuroscience and has received grant/research support and honoraria from Eli Lilly. Dr Keefe is currently receiving or in the past 12 months has received investigator-initiated research funding support from the National Institute of Mental Health, Allon, Novartis, and the Singapore National Medical Research Council and an unrestricted educational grant from AstraZeneca; and has received honoraria from or served as a consultant or advisory board member for Abbott, AstraZeneca, BiolineRx, Bristol-Myers Squibb, Cephalon, Dainippon Sumitomo, Eli Lilly, Johnson & Johnson, Lundbeck, Memory, Merck, Neurosearch, Orion, Orexigen, Otsuka, Pfizer, Roche, Targacept, Sanofi-Aventis, Shire, Wyeth, and Xenoport. In the past, he has received honoraria from or served as a consultant or advisory board member for Acadia, Cortex, Cyberonics, Forest, Gabriel, GlaxoSmithKline, Repligen, Saegis, and Schering Plough and has received research funding from AstraZeneca, Eli Lilly, Janssen, and Pfizer. He receives royalties from the Brief Assessment of Cognition in Schizophrenia (BACS) testing battery and the MATRICS Battery (BACS Symbol Coding). Dr Stroup has received research funding from Eli Lilly and consulting fees from Janssen, Eli Lilly, Lundbeck, Solvay, GlaxoSmithKline, and Bristol-Myers Squibb. Dr Lieberman has received research funding from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, and Pfizer and consulting and educational fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Novartis, Pfizer, and Solvay. Drs Campbell and Riggio report no financial or other relationship relevant to the subject of this article.

© Copyright 2011 Physicians Postgraduate Press, Inc.

Figures

Figure 1

All-Cause Discontinuation Between Patients With and Without Tardive Dyskinesia (TD) at Baselinea aP = .743 for difference between TD groups in model adjusting for treatment, age, baseline Positive and Negative Syndrome Scale score, investigator site, duration of illness, and antipsychotic medications taken prior to study entry.

Figure 2

All-Cause Discontinuation by Treatment for Patients With Tardive Dyskinesia (TD) at Baselinea aBelween-group differences significant for olanzapine vs quetiapine (P = .005), risperidone (P < .001), and ziprasidone (P = .004) in model adjusting for age, baseline Positive and Negative Syndrome Scale score, investigator site, duration of illness, and other antipsychotic medications taken prior to study entry.

Figure 3

PANSS: Adjusted Repeated-Measures Model Between Patients With and Without Tardive Dyskinesia (TD) at Baselinea aAdjusted P = .366 for overall TD effect. Model adjusted for baseline PANSS score, investigator site, treatment, age, duration of illness, and other antipsychotics taken prior to study entry. Abbreviations: LS = least squares, PANSS = Positive and Negative Syndrome Scale.

Figure 4

AIMS: Adjusted Repeated-Measures Model for Patients With Tardive Dyskinesia (TD) at Baselinea aAdjusted P = .811 for overall treatment difference. Model adjusted for baseline AIMS score, baseline PANSS score, and duration of illness. Abbreviations: AIMS = Abnormal Involuntary Movement Scale, LS= least squares, PANSS = Positive and Negative Syndrome Scale.