Pilot study of feasibility of the effect of treatment with tDCS in patients suffering from treatment-resistant depression treated with escitalopram

https://doi.org/10.1016/j.clinph.2014.09.026Get rights and content

Highlights

  • Transcranial direct current stimulation (tDCS) efficacy in pharmacotherapy-resistant depression is limited.

  • tDCS did not induce clinically relevant effect on psychomotor and neuropsychological functioning.

  • More research on the fundamental neurobiological effects of brain electrical stimulation will help these new techniques continue to improve and evolve.

Abstract

Objective

This double-blind, sham-controlled trial investigated the effects of two daily tDCS sessions over a 5-day period in treatment-resistant depression.

Method

Twenty-four treatment-resistant depressed patients received two daily sessions of active or sham anodal tDCS to the left prefrontal cortex (2 mA, 10 sessions over 1 week). Depression severity, psychomotor retardation and cognitive function were assessed.

Results

Active tDCS was not significantly superior to sham tDCS on the HDRS at week 4, as well as on the MADRS and SRRS scales, and on neuropsychological tests. Response rates were not significantly higher with active tDCS. tDCS was well tolerated, with mild adverse events limited to transient scalp discomfort.

Conclusion

tDCS did not induce clinically relevant antidepressant effect in active and sham stimulation groups. There was no impact on psychomotor and neuropsychological functioning.

Significance

tDCS efficacy on specific symptom profiles in pharmacotherapy-resistant depression is limited. The use of optimized stimulation protocol and longer period of follow up may valuably contribute to specify the place of tDCS in treatment-resistant depression.

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.

Section snippets

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)

Cited by (0)

View full text