Does clozapine decrease smoking?

Jose De Leon, Francisco J. Diaz, Richard C. Josiassen, Thomas B. Cooper, George M. Simpson

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


McEvoy et al.'s study in 1999, which used cotinine levels but had limited power, suggested that clozapine treatment may be associated with a mild smoking decrease (particularly when plasma clozapine levels are > 150 ng/ml). Some naturalistic studies also suggest that clozapine treatment may be associated with a mild smoking decrease. The present study included 38 schizophrenic daily smokers from a double-blind clozapine trial. Five analyses were tested for significant decreases in plasma cotinine levels from a haloperidol baseline to: (1) the end of clozapine trials regarding clozapine doses (100, 300 or 600 mg/day), (2) the end of the clozapine trial where the highest plasma clozapine level was achieved, (3) the end of the clozapine trial where a clozapine level in the 150-450 ng/ml range was achieved, (4) the end of the first clozapine trial regardless of clozapine dose, and (5) the end of the last clozapine trial in the study. The first and straightforward analysis by dose showed no clozapine effects on smoking. The second and the third analyses (an attempt to mimic the design by McEvoy et al. [McEvoy, J.P., Freudenreich, O., Wilson, W.H., 1999. Smoking and therapeutic response to clozapine in patients with schizophrenia. Biol. Psychiat. 46, 125-129.]) also indicated that there was not a significant effect of clozapine on smoking. The fourth and five analyses were also negative. None of the five analyses in our clozapine trial demonstrated that clozapine had major effects on smoking. This study cannot rule out that in some subjects, clozapine treatment may be associated with a small decrease in smoking. New prospective longitudinal studies using repeated cotinine and clozapine levels are needed to explore whether clozapine may reduce smoking in some patients.

Original languageEnglish
Pages (from-to)757-762
Number of pages6
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Issue number5
StatePublished - Jun 2005

Bibliographical note

Funding Information:
Drs. de Leon, Josiassen and Simpson were affiliated to the Department of Psychiatry at the Medical College of Pennsylvania, Philadelphia, PA and to the Clinical Research Center at Norristown State Hospital where this study was completed. This study was supported by the grant MH-47162 to Drs. Simpson and Josiassen from the US National Institute of Mental Health. A National Alliance for Research on Schizophrenia and Affective Disorders (NARSAD) Young Investigator Award to Dr. de Leon supported the cotinine analyses. Dr. Diaz was partially supported by the Direccion de Investigaciones of the Universidad Nacional, Medellin, Colombia (grants 030802738 and Apoyo a Grupos Reconocidos por Colciencias 2004). The Novartis Research Institute provided free medication. The authors are grateful to Albert R. Di Dario, who was Superintendent of Norristown State Hospital at the time of the study and provided administrative support. Robert W. Ehlers, R.N., and Eileen McCann, RN, helped with blood collections. Margaret Susce, R.N., helped with editing.


  • Clozapine
  • Cotinine
  • Nicotine
  • Schizophrenia
  • Smoking

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry


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