title: Effects of modafinil on weight, glucose and lipid metabolism in clozapine-treated patients with schizophrenia.
abstract: BACKGROUND
  Sedation is a common side effect of clozapine treatment and may exacerbate metabolic consequences of poor diet and exercise habits that are common in patients with schizophrenia. Modafinil has been proposed as a treatment for clozapine-induced sedation and metabolic abnormalities.
  
  
  OBJECTIVE
  To estimate the effect sizes and person-to-person variation in anthropometric measures, glucose and lipid metabolism, and diet on modafinil treatment for future randomized control trials.
  
  
  METHODS
  A double-blind, placebo-controlled, flexible-dosed 8-week pilot trial was conducted, adding modafinil up to 300 mg/day to stabilized schizophrenia outpatients receiving clozapine. Blood pressure, weight, BMI, laboratory assays, and dietary intake were tracked to monitor changes in metabolic markers.
  
  
  RESULTS
  Thirty-five participants were randomly assigned to treatment with study drug or placebo and were included in the analysis. Modafinil did not improve blood pressure, weight, BMI, glucose or lipid metabolism compared to placebo. Modafinil was well tolerated and did not worsen psychosis.
  
  
  CONCLUSIONS
  Results of this pilot trial do not support routine use of modafinil to counteract increased weight and metabolic diseases in patients taking clozapine. However, the effects of modafinil on weight and insulin regulation warrant further investigation with effect sizes of 0.4 to 0.6.
authors.affiliation: Massachusetts General Hospital Schizophrenia Program, 25 Staniford Street, 2nd Floor, Boston, MA 02114, USA. dchenderson@partners.org
authors.forename: David C
authors.initials: DC
authors.lastname: Henderson
authors.forename: Oliver
authors.initials: O
authors.lastname: Freudenreich
authors.forename: Christina P C
authors.initials: CP
authors.lastname: Borba
authors.forename: Xingyue
authors.initials: X
authors.lastname: Wang
authors.forename: Paul M
authors.initials: PM
authors.lastname: Copeland
authors.forename: Eric
authors.initials: E
authors.lastname: Macklin
authors.forename: Xiaoduo
authors.initials: X
authors.lastname: Fan
authors.forename: Corinne
authors.initials: C
authors.lastname: Cather
authors.forename: Donald C
authors.initials: DC
authors.lastname: Goff
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D003024:Clozapine / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced / Q000188:drug therapy*; D008875:Middle Aged; D000077408:Modafinil; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012189:Retrospective Studies; D012559:Schizophrenia / Q000188:drug therapy; D013997:Time Factors
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D018696:Neuroprotective Agents; D003024:Clozapine; D000077408:Modafinil