title: Varenicline Effects on Smoking, Cognition, and Psychiatric Symptoms in Schizophrenia: A Double-Blind Randomized Trial.
abstract: Schizophrenic patients have a high rate of smoking and cognitive deficits which may be related to a decreased number or responsiveness of nicotinic receptors in their brains. Varenicline is a partial nicotinic agonist which is effective as an antismoking drug in cigarette smokers, although concerns have been raised about potential psychiatric side-effects. We conducted a double-blind placebo controlled study in 87 schizophrenic smokers to evaluate the effects of varenicline (2 mg/day) on measures of smoking, cognition, psychiatric symptoms, and side-effects in schizophrenic patients who were cigarette smokers. Varenicline significantly decreased cotinine levels (P<0.001), and other objective and subjective measures of smoking (P < .01), and responses on a smoking urges scale (P = .02), more than placebo. Varenicline did not improve scores on a cognitive battery designed to test the effect of drugs on cognitive performance in schizophrenia (the MATRICS battery), either in overall MATRICS battery Composite or individual Domain scores, more than placebo. There were no significant differences between varenicline vs. placebo effects on total symptom scores on psychiatric rating scales, PANSS, SANS, or Calgary Depression scales, and there were no significant drug effects in any of these scales sub-scores when we used Benjamin-Hochberg corrected significance levels (α = .05). Varenicline patients did not show greater side-effects than placebo treated patients at any time point when controlled for baseline side-effect scores. Our study supports the use of varenicline as a safe drug for smoking reduction in schizophrenia but not as a cognitive enhancer.
  
  
  BACKGROUND
  ClinicalTrials.gov 00802919.
authors.affiliation: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, United States of America.|NYU Langone Medical Center, Department of Psychiatry, New York, New York, United States of America.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Smith
authors.affiliation: Chaim Sheba Medical Center, Ramat-Gan, Israel.|Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Revital
authors.initials: R
authors.lastname: Amiaz
authors.affiliation: Peking University Institute of Mental Health, The Key Laboratory for Mental Health, Ministry of Health, Beijing, China.
authors.forename: Tian-Mei
authors.initials: TM
authors.lastname: Si
authors.affiliation: Albany Medical Center, Albany, New York, United States of America.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Maayan
authors.affiliation: University of California San Diego, Department of Psychiatry, San Diego, California, United States of America.|VA San Diego Healthcare System, San Diego, California, United States of America.
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.affiliation: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, United States of America.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Boules
authors.affiliation: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, United States of America.|NYU Langone Medical Center, Department of Psychiatry, New York, New York, United States of America.
authors.forename: Henry
authors.initials: H
authors.lastname: Sershen
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Ren
authors.affiliation: Peking University Institute of Mental Health, The Key Laboratory for Mental Health, Ministry of Health, Beijing, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Youseff
authors.affiliation: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, United States of America.|NYU Langone Medical Center, Department of Psychiatry, New York, New York, United States of America.
authors.forename: Abel
authors.initials: A
authors.lastname: Lajtha
authors.affiliation: Psychiatric Institute University of Illinois, Chicago, Illinois, United States of America.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Guidotti
authors.affiliation: Chaim Sheba Medical Center, Ramat-Gan, Israel.|Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Mark
authors.initials: M
authors.lastname: Weiser
authors.affiliation: Psychiatric Institute University of Illinois, Chicago, Illinois, United States of America.
authors.forename: John M
authors.initials: JM
authors.lastname: Davis
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects*; D003367:Cotinine / Q000097:blood; D003863:Depression / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D018722:Nicotinic Agonists / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D011581:Psychological Tests; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy; D012565:Schizophrenic Psychology; D012907:Smoking / Q000097:blood / Q000188:drug therapy*; D016540:Smoking Cessation; D063189:Symptom Assessment; D061485:Tobacco Use Cessation Devices / Q000009:adverse effects; D000068580:Varenicline / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D018722:Nicotinic Agonists; D003367:Cotinine; D000068580:Varenicline