Outcome Following Clozapine Discontinuation: A Retrospective Analysis

James M. Atkinson, M.Pharm., M.R.Pharm.S.; Petrina Douglas-Hall, B.Pharm., M.R.Pharm.S.; Catrin Fischetti, M.Pharm., M.R.Pharm.S.; Anna Sparshatt, M.Pharm., M.R.Pharm.S.; and David M. Taylor, M.Sc., Ph.D., M.R.Pharm.S.

Background: Clozapine is uniquely effective in refractory schizophrenia, but treatment attrition is high. There has been minimal formal study of the outcomes of stopping clozapine, beyond published observations of the time period immediately after cessation. Our aim was to establish medium-term outcome in patients stopping clozapine in normal clinical practice.

Method: This study was a retrospective analysis of all subjects registered with Clozaril Patient Monitoring Service and treated in South London and Maudsley National Health Service (NHS) Trust who stopped clozapine between March 2002 and March 2005 after at least 1 year's treatment. Case note review was performed to determine relevant information for 1 year before and 1 year after discontinuation of clozapine, including subject details, reasons for stopping, and clinical outcome 1 year after discontinuation. The primary outcome measure was the Global Assessment of Functioning scale.

Results: Thirty-five patients met inclusion criteria. Twelve had died while receiving clozapine. Of those followed up for 1 year after cessation (N = 23), mean Global Assessment of Functioning scores fell by 15 points (95% CI = 6.6 to 24.3; p = .002). Days spent in hospital rose from a mean of 74.1 (SD = 137.3) to 119.8 (SD = 143.5) (p = .214).

Conclusion: Discontinuation of clozapine has a marked negative impact on clinical status. Death is a common cause of clozapine cessation.

(J Clin Psychiatry 2007;68:1027-1030)

Received Sept. 6, 2006; accepted Dec. 7, 2006. From the South London and Maudsley National Health Service (NHS) Trust, Pharmacy Department, Maudsley Hospital, London, United Kingdom.

All authors are employees of the U.K. National Health Service Trust. Dr. Taylor is a consultant for Bristol-Myers Squibb; has received grant/research support from AstraZeneca, Bristol-Myers Squibb, and Lundbeck; has received honoraria from Bristol-Myers Squibb, Sanofi-Aventis, and Wyeth; and is a member of the speakers or advisory board of Sanofi-Aventis. Mr. Atkinson and Mss. Douglas-Hall, Fischetti, and Sparshatt report no additional financial or other relationships relevant to the subject of this article.

Corresponding author and reprints: James M. Atkinson, M.R.Pharm.S., Medicines Information, St. Mary's Hospital, 20 South Wharf Road, London W2 1PD, United Kingdom (e-mail: jamesatkinson@nhs.net).