Heart-rate response to alpha2-adrenergic receptor antagonism by antipsychotics

Purpose To explore the relationship between antipsychotic-associated antagonism of alpha 2 -adrenergic receptors and resting heart rate in individuals with schizophrenia. Methods Thirty-one inpatients treated with antipsychotics were included in this exploratory analysis. Antipsychotic doses were converted to haloperidol equivalents for alpha 2 -adrenergic receptor antagonism. Resting heart rate was measured with the patient in the seated upright posture. Results After controlling for confounding variables, the relationship between alpha 2 -adrenergic receptor antagonism and resting heart rate demonstrated a positive linear effect ( P = 0.002) as well as a nonlinear effect that accounted for an additional 14% of the variability in resting heart rate ( P = 0.005). Conclusion The observed inverted-U relationship between alpha 2 -adrenergic receptor antagonism and resting heart rate can possibly be attributed to an altered response of beta 1 -adrenergic receptors to increased norepinephrine release. Further investigations are required to confirm this exploratory finding, taking into account additional variables that include other receptors which either directly or indirectly influence heart rate. ClinicalTrials.gov Identifier NCT01392885.