title: High H1-affinity antidepressants and risk of metabolic syndrome in bipolar disorder.
abstract: BACKGROUND
  Metabolic syndrome (MetS) is common in patients with bipolar disorder, with a relative risk of 1.6-2 compared to the general population. The increased risk is believed to be due to unhealthy lifestyles and use of medications. Although antipsychotics and mood stabilizers have been associated with weight gain and MetS, the impact of antidepressants has not been comprehensively evaluated.
  
  
  OBJECTIVE
  The objective of the study is to assess the risk of MetS in patients exposed to different types of antidepressants.
  
  
  METHODS
  In this cross-sectional study, 294 patients with bipolar disorder were consecutively recruited. MetS was diagnosed according to NCEP ATP-III modified criteria. Antidepressants used by the patients were classified according to the usual nomenclature (SSRI, TCA, SNRI, and other antidepressants) and a pharmacodynamic classification taking into account histamine 1-receptor (H1-R) affinity.
  
  
  RESULTS
  Use of antidepressants in general was not associated with MetS (prevalence ratio [PR], 1.08; 95% confidence interval, 0.73 to 1.62; p = 0.70). However, subjects using H1-R high-affinity antidepressants (N = 15) showed a substantial increase in the prevalence of MetS (PR, 2.17; 95 % confidence interval, 1.24 to 3.80; p = 0.007). When we included the inhibition constant (Ki) as a continuous covariate in the models, we found an inverse association between Ki and prevalence of MetS (p = 0.004).
  
  
  CONCLUSIONS
  We observed for the first time in a clinical setting that a pharmacodynamic-based classification of antidepressants could be more useful than the traditional one to predict the risk of MetS in patients with bipolar disorder. Clinical consequences may be relevant. However larger studies are warranted to generalize these results.
authors.affiliation: Department of Neurosciences, University of Turin, Turin, Italy.
authors.forename: Virginio
authors.initials: V
authors.lastname: Salvi
authors.affiliation: Department of Pharmaceutical Sciences, University of Eastern Piedmont, Novara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Barone-Adesi
authors.affiliation: Department of Neurosciences, University of Turin, Turin, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: D'Ambrosio
authors.affiliation: Department of Neurosciences, University of Turin, Turin, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Albert
authors.affiliation: Department of Neuroscience, AOU San Luigi Gonzaga, University of Turin, Turin, Italy. giuseppe.maina@unito.it.|SCDU Psichiatria AOU San Luigi Gonzaga, Regione Gonzole 10, 10043, Orbassano, TO, Italy. giuseppe.maina@unito.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maina
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000378:metabolism* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced* / Q000453:epidemiology / Q000378:metabolism*; D008875:Middle Aged; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D012307:Risk Factors; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; D011969:Receptors, Histamine H1
keywords: Affinity; Antidepressant; Cardiovascular; Histamine; Metabolism