BDNF plasma levels after antidepressant treatment with sertraline and transcranial direct current stimulation: Results from a factorial, randomized, sham-controlled trial

Abstract

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention that modifies cortical excitability according to the stimulation parameters. Preclinical and clinical studies in healthy volunteers suggest that tDCS induces neuroplastic alterations of cortical excitability, which might explain its clinical effects in major depressive disorder (MDD). We therefore examined whether tDCS, as compared to the antidepressant sertraline, increases plasma brain-derived neurotrophic factor (BDNF) levels, a neurotrophin associated with neuroplasticity. Patients (n=73) with major depressive disorder were randomized to active/sham tDCS and sertraline/placebo (four groups) in this 6-week, double-blind, placebo-controlled trial. We measured BDNF plasma levels at baseline and endpoint, observing no significant changes of BDNF levels after treatment. In addition, no significant changes were observed in responders and non-responders as well as no relationships between BDNF levels and clinical and psychopathological variables related to depression. Thus, in one of the few placebo-controlled trials evaluating BDNF changes over an antidepressant treatment course, we did not observe BDNF increase regardless of clinical improvement in depressed patients. Regarding tDCS, BDNF plasma levels might not be a good candidate biomarker to evaluate depression improvement or be a predictor of response in patients treated with tDCS, as our results showed that BDNF increase was not necessary to induce clinical response. Finally, our findings do not support a relationship between BDNF and improvement of depression.

A prospective, longitudinal study of platelet serotonin and plasma brain-derived neurotrophic factor concentrations in major depression: effects of vortioxetine treatment

“…Our results are in agreement with reports showing increased plasma BDNF in depressed patients treated with SSRIs such as sertraline (Brunoni et al 2014),…”

“…There is evidence that both serum and plasma BDNF concentrations are decreased in patients with MDD (Piccinni et al 2008) and antidepressants are reported to normalize these abnormalities (Aydemir et al 2006;Piccinni et al 2008;Sen et al 2008). Some research supports ((Sen et al 2008) the use of increased peripheral levels of BDNF as a screening tool for novel antidepressant agents, while other research opposes ( (Brunoni et al 2014;Buttenschøn et al 2015;Deuschle et al 2013;Knorr et al 2015) this proposition. Antidepressants influence both peripheral BDNF and platelet 5-HT concentrations.…”

Role of Serum Brain Derived Neurotrophic Factor and Central N-Acetylaspartate for Clinical Response under Antidepressive Pharmacotherapy

“…While peripheral BDNF reduction during depression has often been replicated, there are open questions about the exact role of BDNF in the pathophysiology and especially in the psychopharmacological treatment of depression. Thus the results, showing that especially the reduction of BDNF must be restored to achieve antidepressant response, are questioned by contrary findings in rather recent clinical and preclinical studies [17,18,19,20,21]. So, there is even evidence that there could be a clinical response in the absence of a BDNF increase [22,23,24,25,26].…”

The Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS): rationale and study design of a non-inferiority, triple-arm, placebo-controlled clinical trial

“…tDCS does not seem to induce peripheral effects in cases of depression, such as changes to blood neurotrophic factors. 77,90,91 However, it increases central neuroplasticity as indexed by paired associative stimulation, 92 modulates cortical activity as indexed by electroencephalography 93 and improves working memory and affective processing. [94][95][96] Finally, since the same analyses will be performed in the escitalopram group, we will also explore whether the biological predictors and mediators are different between tDCS and escitalopram responders.…”

“…74,75 Nonetheless, recent meta-analyses showed that ECT increases BDNF levels in blood, but not rTMS or tDCS. 76,77 The possible explanations for this are the low number of rTMS/tDCS studies that used non-optimal treatment protocols and the lower period of observation between measurements. In ELECT-TDCS, BDNF levels in blood are assessed at baseline, week 3 and the endpoint.…”