title: Predicting Weight Gain in Patients Treated With Clozapine: The Role of Sex, Body Mass Index, and Smoking.
abstract: OBJECTIVE
  Weight gain on clozapine is highly variable and poorly predictable. Its mechanisms are not well understood. This study explores the factors that predict weight gain between 3 and 12 months of clozapine therapy in community-dwelling patients.
  
  
  METHODS
  We conducted a retrospective audit of patients attending an outpatient clozapine clinic. Weight change from 3 to 12 months of therapy was recorded, expressed as a percentage of the 3-month weight. Univariate analyses compared percent weight change according to sex, smoking status, country of birth, and baseline body mass index. Correlations between weight gain, age, and clozapine dose were explored. A general linear model identified independent predictors of weight gain.
  
  
  RESULTS
  The mean weight change from 3 to 12 months in 117 patients was +3.1% (range, -17% to +30%). Females gained more weight than males (+5.5% vs +1.3%, P = 0.01), smokers gained more than nonsmokers (+5.1% vs +1.2%, P = 0.02), and obese patients gained less than normal or overweight individuals (0.15% vs 4.6% and 5.2%, respectively, P = 0.01). Age and clozapine dose had no relation to weight change. On multivariate analysis, baseline BMI and smoking status remained independent predictors of percent weight change in females. These 2 predictors explained 25% of weight change in females in the first 3 to 12 months of therapy. These associations were not observed in males.
  
  
  CONCLUSIONS
  We hypothesize that smoking affects weight change by promoting clozapine metabolism to norclozapine via cytochrome P450 enzymes. Verifying this hypothesis and exploring the mechanisms underpinning the sex dichotomy are areas for further research.
authors.affiliation: From the *Blacktown Clinical School and Research Centre, University of Western Sydney, Parramatta; †St Vincent's Hospital, Darlinghurst; ‡Blacktown City Mental Health Service, Blacktown Hospital, Blacktown; and §Centre for Big Data Research in Health, University of New South Wales, Kensington, New South Wales, Australia.
authors.forename: Sue Lynn
authors.initials: SL
authors.lastname: Lau
authors.forename: Christopher
authors.initials: C
authors.lastname: Muir
authors.forename: Yolinda
authors.initials: Y
authors.lastname: Assur
authors.forename: Rhonda
authors.initials: R
authors.lastname: Beach
authors.forename: Bich
authors.initials: B
authors.lastname: Tran
authors.forename: Roger
authors.initials: R
authors.lastname: Bartrop
authors.forename: Mark
authors.initials: M
authors.lastname: McLean
authors.forename: Dorgival
authors.initials: D
authors.lastname: Caetano
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D015992:Body Mass Index; D003024:Clozapine / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D012727:Sex Characteristics; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine