Effects of antipsychotic drugs on cardiovascular variability in participants with bipolar disorder

Abstract

Objective The risk for cardiovascular diseases is elevated in persons with bipolar disorder. However, it remains unknown how much of this excess risk is secondary to pharmacologic treatment. We tested the hypothesis that current and cumulative antipsychotic drug exposure is associated with increased cardiovascular risk as indicated by lower heart rate variability (HRV) and increased blood pressure variability (BPV). Methods 55 individuals with bipolar disorder (33±7 years; 67% female) underwent non-invasive electrocardiogram assessment of time- and frequency-domain HRV, as well as BPV analysis. Medication histories were obtained through systematic review of pharmacy records for the past five years. Results Current antipsychotic exposure was associated with lower SDNN. Second generation antipsychotics were associated with lower SDNN and RMSSD. There was no significant relationship between five-year antipsychotic exposure and HRV in subjects with bipolar disorder. Exploratory analysis revealed a possible link between SSRI exposure and increased low frequency spectral HRV. Conclusions Current antipsychotic use (particularly second generation antipsychotics with high affinities for the D2S receptor) is associated with reduced autonomic-mediated variability of heart rate. The absence of an association with cumulative exposure suggests that the effects are acute in onset, and may therefore relate more to altered autonomic function than structural cardiovascular abnormalities. Future studies should prospectively examine effects of these antipsychotics on autonomic function.

Heart Rate Variability and Omega-3 Index in Euthymic Patients with Bipolar Disorders

“…Therefore, our results are very much in line with previous studies in which patients with bipolar disorders showed significantly reduced heart rate variability, defined as the standard deviation of the successive difference in RR intervals [11,22,23,26]. Similarly, regarding LF and HF, our data are in line with some [8,26], but not all previous studies [11], reporting a significantly reduced LF and HF, compared to healthy controls.…”

“…However, one study suggested that current use of atypical antipsychotics, classified as high-potency based on their pharmacodynamic affinity for the presynaptic D 2S receptor (i.e. aripiprazole, risperidone, and paliperidone) is associated with lower SDNN [23]. In our study, only 14.1% of all patients were on aripiprazole, and less than 10% on risperidone, with paliperidone not being used at all.…”

Diminution of Heart Rate Variability in Bipolar Depression

“…These negative effects on HRV also appear to be dose-dependent, with higher doses being associated with further decreases in HRV ( 52 ). There have been other findings that atypical antipsychotics decrease HRV, but these papers do not specify which specific medications were used ( 53 , 54 ). It is worth speculating, however, that atypical antipsychotics with a lower anticholinergic profile may be less prone to reduce HRV parameters.…”

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

“…In an observational study of patients with BD, SGAs were shown to decrease heart rate variability (HRV), in particular those drugs with high affinity for the D2 receptor 102. Since HRV is a recognized predictor of SCD, routine monitoring of HRV may help in identifying at-risk subjects and possibly prevent SCD 103.…”