Bupropion response on sleep quality in patients with depression: Implications for increased cardiovascular disease risk

Abstract

Depression could be an independent risk factor for cardiovascular disease. We assessed bupropion response in depressed patients by polysomnography (PSG) and cardiopulmonary coupling (CPC) variables. Nineteen subjects participated in a two-session, two consecutive night PSG protocol. Participants received either placebo or bupropion-SR 150 mg, orally, in a randomized, double-blind cross-over fashion on night two. Outcome variables were: sleep stages, REM latency, stable, unstable sleep and very low frequency coupling (VLFC). CPC analysis uses heart rate variability and the electrocardiogram’s R-wave amplitude fluctuations associated with respiration to generate frequency maps. Bupropion increased REM latency (p=0.043) but did not impact PSG sleep continuity, architecture and CPC variables. A trend (p=0.092) was observed towards increasing VLFC duration. Bupropion increased the number of stable-unstable sleep transitions (p=0.036). Moderate to strong correlations between PSG and CPC variables were found on placebo and bupropion nights. Limitations include a small sample size, limited power to detect CPC changes and lack of normal controls for comparison. Increased stable-unstable sleep transitions and VLFC duration may indicate vulnerability to cardiovascular disease due to their association with low heart rate variability that has been associated with increased mortality raising the question whether the beneficial effects of the antidepressant medication outweighs the impact on cardiopulmonary dynamics.

Relationship Between Brain-Derived Neurotrofic Factor (Bdnf) and Sleep on Depression: A Critical Review

“…In a study with 126 patients with MDD, was found that increased BDFN levels has been associated with N-REM sleep improvement and enhanced slow wave activity, but on the other hand, reported no relationship between BDFN and insomnia improvement. It was found that the reduction of BDFN levels is associated with improvement in hypersomnia [ 16 ].…”

“…Giese and cols investigated if stress levels influence the association between sleep and BDNF levels, and found that the sleep quality interfere directly in the relation of stress with BDNF levels [ 16 ]. In another study they investigated BDNF serum levels in 26 patients with insomnia and compared the results with a control group and found that insomniacs present decreased serum BDNF levels, when compared to control group [ 28 ].…”

“…In most of cases, Major Depressive Disorder is accompanied by complaints about sleep quality. Sleep disturbance is one of the main residual symptoms after treatment with antidepressants and the main risk factor for relapse in major depression who are in remission [ 18 ] Some biomarkers present in the development of depression and response to treatment are linked to sleep quality [ 16 ].…”

“…The relationship between antidepressants and BDNF in rats has shown that the administration of different types of antidepressants increases the levels of BDNF production in the hippocampus [ 14 ], but this effect can been see only with nonpeptidic agonists [ 15 ]. Antidepressants that decrease BDNF levels can be effective in treatment of depression, however can alter sleep pattern [ 16 ], which may increase GABA A Rs on the membrane of excitatory cortical neurons, while increase of slow wave sleep can return to baseline levels [ 17 ], while adenosine A 1 receptors (A 1 R) plays a decisive role for antidepressant effects on sleep deprivation [ 18 ].…”

Cardiovascular side effects of psychopharmacologic therapy

“…Importantly, depression has been found to predict early onset CHD. Depression could be an independent RF for CVD and it is common among pts treated with PCI [64,65]. Numerous psychosocial factors have been linked to CHD [66].…”