The Effect of Clozapine on Factors Controlling Glucose Homeostasis

Oliver D. Howes, M.R.C.Psych.; Fiona P. Gaughran, F.R.C.P.I., M.R.C.Psych., M.D.; Stephanie A. Amiel, B.Sc., M.D., F.R.C.P.; Robin M. Murray, F.R.C.Psych., D.Sc.;and Lyn S. Pilowsky, M.R.C.Psych., Ph.D.

Background: This prospective study examines the effect of clozapine on factors determining glucose homeostasis.

Method: The sample consisted of all patients meeting DSM-IV criteria for schizophrenia who commenced clozapine treatment within the South London and Maudsley hospitals during 1 year (2000-2001). Growth hormone (GH), insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) were measured in 19 patients (10 female; mean age = 31.1 years [SD = 5.8]; 9 black British/African, 10 white British) before and after a mean of 2.5 (SD = 0.9) months of clozapine treatment.

Results: Baseline IGFBP-1 was low. IGFBP-1, GH, and IGF-1 were not significantly changed by clozapine treatment.

Conclusions: Clozapine does not alter GH, IGF-1, or IGFBP-1 within 3 months of commencing treatment, indicating that alteration in glucose tolerance associated with clozapine treatment involves other mechanisms yet to be elucidated. Baseline abnormalities in IGFBP-1 indicate a preexisting susceptibility to glucoregulatory dysfunction.

(J Clin Psychiatry 2004;65:1352-1355)

Received Dec. 17, 2003; accepted March 23, 2004. From the Division of Psychological Medicine, Institute of Psychiatry (Drs. Howes, Gaughran, Murray, and Pilowsky) and the Department of Diabetic Medicine, GKT School of Medicine, King's College (Dr. Amiel), London, United Kingdom.

Financial support for this study was provided by the Stanley Medical Research Institute, Bethesda, Md.

Dr. Howes has previously received charitable, unrestricted research grants from AstraZeneca and Eli Lilly. Dr. Gaughran has been a speaker/advisory board member for Bristol-Myers Squibb, Janssen-Cilag, and AstraZeneca; has received an honorarium from AstraZeneca; and has a family member who works for Eli Lilly. Dr. Murray has received honoraria from Bristol-Myers Squibb, Janssen, Pfizer, Eli Lilly, and AstraZeneca. Dr. Pilowsky is a U.K. Medical Research Council Senior Fellow and has received investigator-led charitable research grants from Novartis, AstraZeneca, Janssen, and Sanofi-Synthelabo.

The authors thank David Taylor; Brian Smith; the staff of the Pharmacy and Pathology Departments, Maudsley Hospital; the Medical Toxicology Department, Guy's Hospital; and Rebecca Walwyn, Department of Biostatistics, Institute of Psychiatry.

Corresponding author and reprints: Oliver Howes, M.R.C.Psych., Box 63, Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, SE5 8AF, United Kingdom
(e-mail: O.Howes@iop.kcl.ac.uk).