David D Kim1, Donna J Lang2, Darren E R Warburton3, Melissa L Woodward2, Randall F White4, Alasdair M Barr1, William G Honer4, Ric M Procyshyn5. 1. Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada. 2. Department of Radiology, University of British Columbia, Vancouver, BC, Canada. 3. Cardiovascular Physiology and Rehabilitation Laboratory, Physical Activity Promotion and Chronic Disease Prevention Unit, University of British Columbia, Vancouver, BC, Canada. 4. Department of Psychiatry, University of British Columbia, Room A3-111, 938 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. 5. Department of Psychiatry, University of British Columbia, Room A3-111, 938 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. rprocyshyn@bcmhs.bc.ca.
Abstract
PURPOSE: To explore the relationship between antipsychotic-associated antagonism of alpha2-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 alpha2-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 alpha2-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 alpha2-adrenergic receptor antagonism and resting heart rate can possibly be attributed to an altered response of beta1-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.
PURPOSE: To explore the relationship between antipsychotic-associated antagonism of alpha2-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 alpha2-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 alpha2-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 alpha2-adrenergic receptor antagonism and resting heart rate can possibly be attributed to an altered response of beta1-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.
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