Original ContributionsImpact of Antipsychotics and Anticholinergics on Autonomic Modulation in Patients With SchizophreniaHuang, Wei-Lieh MD*†‡; Chang, Li-Ren MD*; Kuo, Terry B.J. MD, PhD‡§∥; Lin, Yu-Hsuan MD*†; Chen, Ying-Zai BS*; Yang, Cheryl C.H. PhD‡§ Author Information From the *Department of Psychiatry, National Taiwan University Hospital, Yun-Lin Branch, Yunlin; †Department of Psychiatry, National Taiwan University Hospital; ‡Institute of Brain Science, National Yang-Ming University; §Sleep Research Center, National Yang-Ming University, Taipei; and ∥Research Center for Adaptive Data Analysis, National Central University, Taoyuan, Taiwan. Received November 22, 2011; accepted after revision June 12, 2012. Reprints: Cheryl C.H. Yang, PhD, Sleep Research Center and Institute of Brain Science, National Yang-Ming University, No 155, Sec 2, Li-Nong St, Taipei 11221, Taiwan (e-mail: [email protected]). This study was supported by a grant (NTUHYL.99N015) from the National Taiwan University Hospital, Yun-Lin Branch; a grant (NSC 100-2627-B-010-002) from the National Science Council (Taiwan); and a grant (100AC-B3) from the Ministry of Education, Aim for the Top University Plan. Wei-Lieh Huang and Li-Ren Chang contributed equally to this work. Journal of Clinical Psychopharmacology: April 2013 - Volume 33 - Issue 2 - p 170-177 doi: 10.1097/JCP.0b013e3182839052 Buy Metrics Abstract Antipsychotics are associated with cardiovascular risk, but the relationship between their anticholinergic properties and cardiac function is not clear. We hypothesize that antipsychotics with a high muscarinic affinity (HMA) may reduce parasympathetic modulation, which should be observable by means of heart rate variability (HRV) measurement. We also assume that anticholinergics, which are commonly used in patients with schizophrenia to treat drug-induced parkinsonism, interact with antipsychotics, and this may also affect HRV. Fifty-five patients with schizophrenia were recruited into this study. Twenty-eight subjects used antipsychotics with an HMA and 27 subjects used antipsychotics with a low muscarinic affinity (LMA). Heart rate variability values between the patients on antipsychotics with HMA and those on antipsychotics with LMA were compared. Correlation and regression analysis were then performed to clarify the relationship between HMA, LMA, and HRV. The influence of anticholinergics was also assessed by correlation analysis. The HMA group showed significantly reduced low-frequency (LF) power, high-frequency (HF) power, total power (TP), and normalized LF (LF%) than the LMA group. Regression analysis supported the hypothesis that muscarinic affinity was related to LF (β = −0.447; P < 0.001), HF (β = −0.390; P = 0.002), and TP (β = −0.399; P = 0.001). The interaction between LMA and anticholinergic use also influenced LF% (β = 0.326; P = 0.006). In the LMA group, the use of anticholinergics was positively correlated with LF% and LF/HF. In the HMA group, after exclusion of the patients using anticholinergics, the equivalent dose of antipsychotics showed a negative correlation with HF. Our results suggest that the muscarinic affinity of antipsychotics affects both sympathetic and parasympathetic modulation and that anticholinergics interact with antipsychotics to influence HRV. © 2013 by Lippincott Williams & Wilkins.