Pilot study of feasibility of the effect of treatment with tDCS in patients suffering from treatment-resistant depression treated with escitalopram
Introduction
Treatment-resistant depression (TRD), defined as a failure to respond to at least two courses of evidence based antidepressant (AD) treatment approaches, represent a serious challenge to both patients and clinicians. Despite a wide array of pharmacological and psychological treatments, only 50% of patients respond to their first antidepressant, and the probability of remission drops significantly after the failure of two consecutive AD trials (Rush et al., 2006). Illness-related disability and limitations of conventional pharmacological interventions provide the impetus for implementation of alternative therapeutic options. Non-pharmacologic brain stimulation therapies have emerged since the mid-1990s as therapeutic options for TRD, guided by the emerging knowledge of mood-regulating systems. Among them, transcranial direct current stimulation (tDCS) is a non-invasive form of stimulation based on the application of a weak direct electrical current flowing through the cerebral cortex, producing polarity-dependent effects (Nitsche and Paulus, 2001). In line with historical observations of depression-related hypometabolism of the dorsolateral prefrontal cortex (DLPFC), the rationale for considering tDCS as a potentially efficacious treatments for TRD stem from its ability to induce functional changes in resting membrane potential and cerebral blood flow (Berlim et al., 2013). More specifically, anodal stimulation leads to a depolarization of the neurons membranes and thus invokes an increase of the spontaneous neuronal firing rate, whereas cathodal stimulation induces neuronal hyperpolarization (Nitsche et al., 2008).
Beneficial effects of anodal tDCS in depressed populations have been reported in a series of open label and randomized clinical trials (RCT), using heterogeneous stimulations parameters – i.e. current density, electrode position, and stimulation duration – with few, generally mild side effects (for review, see (Mondino et al., 2014)). Although it is increasingly accepted that tDCS has antidepressant effects, its clinical utility is uncertain as many aspects of this treatment remain incompletely investigated, including the patient characteristics that might predispose to a strong antidepressant response. Promising results have been reported in severely depressed patients (Ferrucci et al., 2009), and tDCS appears to be particularly effective in treating retardation and dysphoria (Alonzo et al., 2013).
In the field of resistant depression, one open label trial reported sustained antidepressant effects of active tDCS applied at 2 mA during at least one month in 14 resistant and severely depressed patients, with a >30% HAM-D improvement after 5 days of tDCS, while 2 controlled trials failed to reproduce this result (Ferrucci et al., 2009, Blumberger et al., 2012, Palm et al., 2012). The discrepant findings between these studies may in particular relate to inclusion of patients with a history of ECT non-response as well as differences in methodology, and highlighted the need to specify the clinical relevance of tDCS in patients considering the level of resistance. In the current study (ClinicalTrials.gov Identifier: NCT01428804), we examined the symptomatic outcomes associated with providing tDCS as an adjunct to ongoing antidepressant treatment in a rigorously defined sample of TR depressed patients, with no history of ECT failure. As previous studies suggest that tDCS could be particularly effective in treating specific symptoms such as retardation, we sought to further characterize the pattern of change in depressive symptomatology induces by tDCS, notably in motor and cognitive domains.
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Participants
Twenty-four patients (18 females, 6 males, mean 61.8 ± 16.3 years) meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for unipolar depression were recruited from the psychiatric wards of the university hospital of Besançon (France). Patients were required to have a score ⩾25 on the Montgomery Asberg Depression Rating Scale (MADRS) (Montgomery and Asberg, 1979) and to meat at least stage II treatment resistant criteria (Montgomery and Asberg, 1979, Rush et al., 2003).
Results
The subjects’ baseline demographic and clinical characteristics and their neuropsychological performances are summarized in Table 1, Table 2. Demographic characteristics did not differ across the treatment groups for age (t21 = 0.09, p = 0.93), gender (z = 1.33, p = 0.09) or educational level (t21 = 1.72, p = 0.18). Statistical analyzes revealed no difference at baseline between active and sham stimulations groups in depression severity (HDRS: t21 = 0.66, p = 0.51; MADRS: t21 = 1.72, p = 0.1; BDI: t21 = 0.25, p =
Discussion
This double blind, randomized, placebo-controlled study assessed the effects of anodal tDCS applied to the left DLPFC in a homogeneous sample of unipolar medication-resistant depressed patients. In active and sham stimulation groups, depression improved in the range of 40–47.7% from baseline in both clinician and self-ratings after 10 stimulations sessions. However, active stimulation failed to demonstrate any additional antidepressant effects compared with sham, as previously reported in
Acknowledgements
This study was supported by a Grant from Lundbeck Foundation.
Lundbeck Foundation participated in the decision to submit the article for publication.
Conflict of interest: All the authors declare they have no other financial or non-financial associations that might pose a conflict of interest in connection with this manuscript.
References (23)
- et al.
Transcranial direct current stimulation (tDCS) for depression: analysis of response using a three-factor structure of the Montgomery-Åsberg depression rating scale
J Affect Disord
(2013) - et al.
Clinical utility of transcranial direct current stimulation (tDCS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials
J Psychiatry Res
(2013) - et al.
TDCS selectively improves working memory in older adults with more education
Neurosci Lett
(2012) - et al.
Go-no-go task performance improvement after anodal transcranial DC stimulation of the left dorsolateral prefrontal cortex in major depression
J Affect Disord
(2007) - et al.
Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the major depressive episode: findings from a naturalistic study
Eur Psychiatry
(2013) - et al.
Transcranial direct current stimulation in severe, drug-resistant major depression
J Affect Disord
(2009) - et al.
Inconsistent outcomes of transcranial direct current stimulation may originate from anatomical differences among individuals: electric field simulation using individual MRI data
Neurosci Lett
(2014) - et al.
Transcranial direct current stimulation: state of the art 2008
Brain Stimul
(2008) - et al.
Transcranial direct current stimulation in treatment resistant depression: a randomized double-blind, placebo-controlled study
Brain Stimul
(2012) - et al.
Effects of transcranial direct current stimulation (tDCS) on executive functions: influence of COMT Val/Met polymorphism
Cortex
(2013)