Bupropion response on sleep quality in patients with depression: Implications for increased cardiovascular disease risk
Introduction
Some literature identifies depression as an independent risk factor for cardiovascular disease (Mallik et al., 2005, Rugulies, 2002). Higher levels of depressive symptoms at the time of coronary bypass surgery were shown to be a strong predictor for lack of functional surgical benefit after 6 months (Mallik et al., 2005). In contrast, low preoperative measures of depression and sleep problems predicted better recovery 6 months after cardiac surgery (Jenkins et al., 1994). The mechanisms responsible for the relationship between depression and cardiovascular health are unknown; however a unifying hypothesis may be stress-related.
Stress often refers to a physiological, neurochemical or emotional factor related to physical or mental pressure and may be related to a disease state. An earlier study investigating bupropion response in 17 patients with depression found reduced heart rate variability (HRV) at rest compared to controls (Straneva-Meuse et al., 2004). Furthermore, unmedicated depressed women showed reduced respiratory sinus arrhythmia (RSA) compared to non-depressed controls (Cyranowski et al., 2011) although this is in contrast to other reports (Cacioppo et al., 1994, Gianaros et al., 2005, Hawkley et al., 2001). Depressed women, the authors suggested may be less likely to demonstrate enhanced cardiac vagal control during acute stress. Sleep measures were not investigated in these studies.
Cardiopulmonary coupling (CPC) analysis detects and summarizes coupled modulation of respiration and HRV (Thomas et al., 2004, Thomas et al., 2005). CPC and polysomnography (PSG) sleep quality measures equally captured the worsening of sleep under the stress of the first night in a sleep lab in primary insomnia patients and matched control subjects (Schramm et al., 2012). Decreased sleep stability and increased unstable sleep in non-medicated depressive patients was recently reported suggesting this might indicate a long term risk for adverse cardiovascular risk in depressed patients (Yang et al., 2010). In the same study, medicated depressed patients using hypnotics had significantly improved CPC sleep quality measures compared to medication-free depressed patients demonstrating CPC's functionality to assess a pharmacological response.
Bupropion is an atypical antidepressant that influences central and autonomic nervous systems (Preskorn and Othmer, 1984). In a study of 58 subjects with major depressive disorder, bupropion produced small increases in diastolic blood pressure suggesting that it may have mild cardiovascular side effects (Kiev et al., 1994). This study investigated a bupropion acute response in depressed patients. Our primary hypothesis is that the response to bupropion would be detectable using PSG and CPC variables of sleep quality.
The study was undertaken to determine: (1) possible differences in sleep quality between bupropion and placebo conditions measured by PSG and CPC variables in patients with major depressive disorder; and (2) if bupropion influenced changes would identify risk factors for cardiovascular disease.
Section snippets
Design
The study had a randomized, double-blind, crossover design.
Subjects and setting
Nineteen subjects (1M/18F; aged 33.31±7.66 years) with unipolar major depressive disorder defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (First et al., 1997) criteria were recruited. All participants provided written informed consent approved by the local Institutional Review Board before entering the study.
Inclusion criteria included: (1) age 21–55 years; (2) meeting diagnostic criteria for current
Results
Demographic and clinical information is presented in Table 1. No statistical differences in age, weight, body mass index, BDI and HDRS scores were found.
Discussion
This is the first report on the effect of bupropion in adult depressed patients using PSG and CPC variables. The key findings of our analysis are: (1) a bupropion response on REM sleep latency was observed but not for PSG sleep continuity, non-REM sleep architecture and CPC variables; (2) a trend towards increasing VLFC duration was detected; (3) bupropion increased the number of stable–unstable sleep transitions; and (4) moderate to strong correlations between PSG and CPC variables,
Conclusions
The present study found complimentary results between PSG and CPC measures. CPC analysis identified a trend towards increasing VLFC duration and augmented stable–unstable sleep transitions in response to bupropion. Increased stable–unstable sleep transitions may indicate vulnerability to cardiovascular disease likely due in part to enhanced sympathetic and decreased parasympathetic tone. Our findings have important implications for clinical treatment of depression and whether the beneficial
Role of the funding source
This work was supported in part by grants from the National Institutes of Health (RO1 DA014037, RO1 DA015131, RO1 DA017804, RO1 DA017805, RO1 MH062464, RO1 MH068391, G12 RR003032, UL1 RR024975 and U54 RR026140/U54 MD007593), and by the Endowed Chair in Brain and Behavior Research at Meharry Medical College.
Contributors
Preetam J. Schramm, Ph.D., RPSGT—PSG review, CPC analysis, statistical analysis, first and final draft.
Russell E. Poland, Ph.D.—Statistical analysis review, critical edit of final draft.
Uma Rao, MD—PSG data collection, critical edit of manuscript.
Conflict of interest
Dr. Schramm was an Embla employee and a consultant for MyCardio, LLC. All other authors declare that they have no conflicts of interest.
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