Thyroid Function in Treatment-Resistant Schizophrenia Patients Treated With Quetiapine, Risperidone, or Fluphenazine

Deanna L. Kelly, Pharm.D., B.C.P.P., and Robert R. Conley, M.D.

Background: Thyroid dysfunction is relatively common in patients with schizophrenia, possibly related to a genetic linkage of the disorders and to antipsychotic treatment. Quetiapine has been implicated as causing some degree of thyroid function changes, yet it remains unclear as to what extent or why these changes may occur. Furthermore, the need for thyroid function monitoring in patients taking this medication is not definitive.

Method: Thyroid function was assessed in 38 adult DSM-IV-diagnosed schizophrenia patients after 6 weeks of prospective, double-blind, randomized treatment with quetiapine (400 mg/day), risperidone (4 mg/day), or fluphenazine (12.5 mg/day). Data were collected from 1997 to 2002.

Results: At baseline, the percentages of randomized patients with abnormal values were 18% (4/22) for serum T₃ resin uptake, 13% (4/30) for thyroid-stimulating hormone (TSH), and 9% (2/22) for total serum thyroxine (TT₄), representing fairly widespread thyroid abnormalities independent of treatment group. Little change was noted in thyroid function during the 6 weeks of treatment, except for a significant decrease in TT₄ values for those taking quetiapine (p = .01). Clinically, however, no patients demonstrated any signs or symptoms of hypothyroidism during the study, nor were any significant changes in the free thyroxine index or TSH levels noted.

Conclusions: It is expected that TT₄ levels will decrease during quetiapine treatment, and this may possibly be related to competitive metabolism of thyroid hormones and quetiapine by UDP-glucuronosyltransferase. Routine monitoring of thyroid function in quetiapine-treated patients without a history of thyroid disease is not recommended.

(J Clin Psychiatry 2005;66:80-84)

Received March 11, 2004; accepted July 6, 2004. From the Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore.

Support for this project was provided by the National Institute of Mental Health (grant MH-47311). Study medications were supplied by Janssen and AstraZeneca. Other funding included grants from the Intervention Research Center (MH-40279); The VA Capitol Network (VISN 5) Mental Illness Research, Education, and Clinical Center (MIRECC); and the University of Maryland General Clinical Research Center, General Clinical Research Centers Program, National Center for Research Resources (NCRR), National Institutes of Health (M01 RR165001).

Dr. Kelly has received grant/research support from AstraZeneca, has received honoraria from Janssen, and has served on the speakers or advisory boards of AstraZeneca and Janssen. Dr. Conley has served as a consultant for AstraZeneca, Abbott, Bristol-Myers Squibb, Eli Lilly, Zenith Goldline Pharmaceuticals, Novartis, Otsuka, and Janssen; has received grant support from AstraZeneca, Janssen, Eli Lilly, Abbott, and Novartis; and has received honoraria from Eli Lilly, Janssen, AstraZeneca, Bristol-Myers Squibb, and Otsuka.

The authors would like to thank the research team at the Maryland Psychiatric Research Center for their work on this study. They also thank Yang Yu, M.A., and Robert McMahon, Ph.D., for their assistance in data maintenance and statistical analyses.

Corresponding author and reprints: Deanna L. Kelly, Pharm.D., B.C.P.P., Maryland Psychiatric Research Center, University of Maryland, Box 21247, Baltimore, MD 21228 (e-mail: dkelly@mprc.umaryland.edu).