title: Is there an interrelationship between the effects of antipsychotics on psychopathology and on metabolism?
abstract: BACKGROUND
  Increased body weight and hyperlipidemia caused by antipsychotics may be associated with improved antipsychotic efficacy in schizophrenia. If this association has a causal interrelationship via a genuine pathophysiological mechanism, then body weight loss in antipsychotic-treated patients would be accompanied by worsened psychopathology. This could have clinical implications.
  
  
  OBJECTIVE
  To explore whether the decreased body weight in these patients is associated with a worsened psychopathology.
  
  
  METHODS
  In our previously published study, a 16 week treatment period with add-on orlistat (but not placebo) resulted in body weight loss in male (but not female) clozapine- or olanzapine-treated overweight or obese patients. In the current study, we investigated whether body weight loss in those male patients could worsen psychosis. Changes in the Positive and Negative Syndrome Scale (PANSS) scores within groups and body weight changes and lipid profiles over the treatment period were analysed by the paired samples t-test. Between-group comparisons were analysed by the independent samples t-test.
  
  
  RESULTS
  Over the treatment period body weight decreased by 2.56 ± 3.25 kg from initial 106.02 ± 12.61 kg (p = 0.04) for the orlistat group, with no statistically significant changes for the placebo group. Lipid levels did not change in either group. The orlistat-induced weight decrease was not associated with worsening in the PANSS scores.
  
  
  CONCLUSIONS
  Weight loss was not associated with a worsening of psychosis. The interrelationship between the antipsychotic-induced weigh gain and improved schizophrenia psychopathology observed in earlier studies appears to be indirect. Orlistat treatment in our study did not worsen psychopathology in this population.
authors.affiliation: a Department of Psychiatry , Helsinki University Central Hospital , Finland.|b Department of Psychiatry , University of Helsinki , Finland.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Chukhin
authors.affiliation: b Department of Psychiatry , University of Helsinki , Finland.|c Department of Psychiatry , Kellokoski Hospital , Finland .
authors.forename: Viacheslav
authors.initials: V
authors.lastname: Terevnikov
authors.affiliation: d Department of Psychiatry , Vanha Vaasa Hospital , Finland .
authors.forename: Pirjo
authors.initials: P
authors.lastname: Takala
authors.affiliation: e Department of Psychiatry , Oulu University Hospital , Finland .
authors.forename: Helinä
authors.initials: H
authors.lastname: Hakko
authors.affiliation: c Department of Psychiatry , Kellokoski Hospital , Finland .|f National Institute for Health and Welfare , Finland , and.
authors.forename: Hanna
authors.initials: H
authors.lastname: Putkonen
authors.affiliation: g Department of Psychiatry , University of Oulu , Finland.
authors.forename: Pirkko
authors.initials: P
authors.lastname: Räsänen
authors.affiliation: a Department of Psychiatry , Helsinki University Central Hospital , Finland.
authors.forename: Jan-Henry
authors.initials: JH
authors.lastname: Stenberg
authors.affiliation: d Department of Psychiatry , Vanha Vaasa Hospital , Finland .
authors.forename: Markku
authors.initials: M
authors.lastname: Eronen
authors.affiliation: a Department of Psychiatry , Helsinki University Central Hospital , Finland.
authors.forename: Grigori
authors.initials: G
authors.lastname: Joffe
mesh_terms: D000328:Adult; D019440:Anti-Obesity Agents / Q000009:adverse effects* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007783:Lactones / Q000009:adverse effects* / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy*; D000077152:Olanzapine; D000077403:Orlistat; D011569:Psychiatric Status Rating Scales; D011599:Psychopathology; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology
chemical_list: D019440:Anti-Obesity Agents; D014150:Antipsychotic Agents; D007783:Lactones; D001569:Benzodiazepines; D000077403:Orlistat; D003024:Clozapine; D000077152:Olanzapine
keywords: Antipsychotics; orlistat; psychopathology; weight control; weight gain