High H1-affinity antidepressants and risk of metabolic syndrome in bipolar disorder

Rationale 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 bipo- lar disorder were consecutively recruited. MetS was diag- nosed according to NCEP ATP-III modified criteria. Antide- pressants used by the patients were classified according to the usual nomenclature (SSRI, TCA, SNRI, and other antidepres- sants) and a pharmacodynamic classification taking into ac- count histamine 1-receptor (H1-R) affinity. Results Use of antidepressants in general was not associated with MetS (prevalence ratio [PR], 1.08; 95% confidence in- terval, 0.73 to 1.62; p=0.70). However, subjects using H1-R high-affinity antidepressants (N = 15) showed a substantial in- crease in the prevalence of MetS (PR, 2.17; 95 % confidence interval, 1.24 to 3.80; p = 0.007). When we included the inhi- bition constant (Ki) as a continuous covariate in the models, we found an inverse association between Ki and prevalence of MetS (p = 0.004). Conclusion We observed for the first time in a clinical setting that a pharmacodynamic-based classification of antidepres- sants 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.