A Systematic Review of Non-Invasive Brain Stimulation Therapies and Cardiovascular Risk: Implications for the Treatment of Major Depressive Disorder

Abstract

Major depressive disorder (MDD) and cardiovascular diseases are intimately associated. Depression is an independent risk factor for mortality in cardiovascular samples. Neuroendocrine dysfunctions in MDD are related to an overactive hypothalamus-pituitary-adrenal (HPA) axis and increased sympathetic activity. Novel intervention strategies for MDD include the non-invasive brain stimulation (NIBS) techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). In fact, although these techniques have being increasingly used as a treatment for MDD, their cardiovascular effects were not sufficiently investigated, which would be important considering the dyad MDD/cardiovascular disorders. We investigated this issue through a systematic review for published articles from the first date available to May 2012 in MEDLINE and other databases, looking for main risk factors and surrogate markers for cardiovascular disease such as: cortisol, heart rate variability (HRV), alcohol, smoking, obesity, hypertension, glucose. We identified 37 articles (981 subjects) according to our eligibility criteria. Our main findings were that NIBS techniques might be effective strategies for down-regulating HPA activity and regulating food, alcohol, and cigarette consumption. NIBS’s effects on HRV and blood pressure presented mixed findings, with studies suggesting that HRV values can decrease or remain unchanged after NIBS, while one study found that rTMS increased blood pressure levels. Also, a single study showed that glucose levels decrease after tDCS. However, most studies tested the acute effects after one single session of rTMS/tDCS; therefore further studies are necessary to investigate whether NIBS modifies cardiovascular risk factors in the long-term. In fact, considering the burden of cardiac disease, further trials in cardiovascular, depressed, and non-depressed samples using NIBS should be performed.

Cytokines plasma levels during antidepressant treatment with sertraline and transcranial direct current stimulation (tDCS): results from a factorial, randomized, controlled trial

“…Nonetheless, the effects of rTMS and tDCS on the HPA and SAM axes, which are directly linked to the neuroimmunological response, have been evaluated in healthy volunteers and neuropsychiatric disorders. On this matter, two recent reviews (Sampaio et al 2012; Schestatsky et al 2013) found mixed evidence regarding possible neuromodulatory effects on these systems, with positive results obtained from studies generally employing designs in which participants were submitted to physiological or psychological stress (e.g., (Brunoni et al 2013c)). Using data from SELECT-TDCS, we observed that tDCS-only and combined with sertraline did not modulate heart rate variability, a marker of sympathetic/parasympathetic activity, throughout the trial (Brunoni et al 2013a) and also, that these therapies had no specific antidepressant effects on vegetative symptoms (Brunoni et al, in press), as similarly observed in another tDCS trial (Alonzo et al 2013).…”

Heart rate variability is a trait marker of major depressive disorder: evidence from the sertraline vs. electric current therapy to treat depression clinical study

“…Recently, our group (Brunoni et al, 2013a) observed HF HRV to increase during anodal tDCS while participants viewed negative-valence images, indicating that tDCS may counterbalance the physiological stress associated with viewing of negative images. In this regard we recently proposed -in a systematic review (Sampaio et al, 2012) -that acute tDCS effects on cardiovascular activity occur during stress-induced paradigms.…”

“…Moreover, tDCS is an intervention with minimal, systemic side-effects (Brunoni et al, 2010). In fact, acute tDCS seems to have either no or favorable effects on sympathovagal balance (Sampaio et al, 2012;Vandermeeren et al, 2010;Montenegro et al, 2011;Brunoni et al, 2013a) -the latter effects possibly due to the role of the prefrontal cortex in inhibiting cardio-acceleratory circuitry, thereafter increasing vagal activity (Thayer et al, 2010). Therefore, our hypothesis was that reductions in HRV following antidepressant drugs and increases in HRV following tDCS would demonstrate the adverse effects of pharmacological vs. non-pharmacological treatments.…”

Unraveling the Mechanisms Responsible for the Comorbidity between Metabolic Syndrome and Mental Health Disorders

“…Heart rate variability is not the only measurement that highlights the link between components of MetS and MHDs; non-invasive brain stimulation strategies can improve depressive symptoms in patients with depression or bipolar disorder [226] and may be effective in reducing HPA activity [227]. …”