Brief report
Transcranial direct current stimulation in severe, drug-resistant major depression

https://doi.org/10.1016/j.jad.2009.02.015Get rights and content

Abstract

Background

Though antidepressant drugs are the treatment of choice for severe major depression, a number of patients do not improve with pharmacologic treatment. This study aimed to assess the effects of transcranial direct current stimulation (tDCS) in patients with severe, drug-resistant depression.

Methods

Fourteen hospitalized patients aged 37–68, with severe major depressive disorder according to DSM-IV.TR criteria, drug resistant, with high risk of suicide and referred for ECT were included. Mood was evaluated using the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HDRS) and the Visual Analogue Scale (VAS). We also administered cognitive tasks to evaluate the possible cognitive effects on memory and attention. tDCS was delivered over the dorsolateral prefrontal cortex (DLPC) (2 mA, 20 min, anode left, cathode right) twice a day.

Results

After five days of treatment although cognitive performances remained unchanged, the BDI and HDRS scores improved more than 30% (BDI p = 0.001; HDRS p = 0.017). The mood improvement persisted and even increased at four (T2) weeks after treatment ended. The feeling of sadness and mood as evaluated by VAS improved after tDCS (Sadness p = 0.007; Mood p = 0.036).

Conclusions

We conclude that frontal tDCS is a simple, promising technique that can be considered in clinical practice as adjuvant treatment for hospitalized patients with severe, drug-resistant major depression.

Introduction

Major depressive disorder (MDD) is a common medical condition with high social costs (von Knorring et al., 2006). Studies using various functional imaging techniques demonstrated a prefrontal asymmetry with hypoactivity in the left dorsolateral prefrontal cortex (DLPFC) and relative hyperactivity in the right DLPFC (Grimm et al., 2008, Walter et al., 2007). Despite the effective therapeutic options available today, a number of patients with depression does not respond to antidepressants or fail to achieve or maintain remission (Sackeim, 2001). Drug-resistant patients can improve with adjuvant treatments as, for instance, electroconvulsive treatment (ECT). Though effective, ECT is however traumatic, has known risks, high rates of relapse (Sackeim et al., 2001), requires general anaesthesia and induces transient cognitive dysfunction (Nobler and Sackeim, 2008). Transcranial direct current stimulation (tDCS) (Boggio et al., 2007, Boggio et al., 2008, Fregni et al., 2006a, Fregni et al., 2006b, Rigonatti et al., 2008) is under investigation in depression.

Several aspects make this latter technique interesting for clinical practice. tDCS is a simple, cheap, non-invasive technique for brain stimulation that induces prolonged functional changes in the cerebral cortex (Priori, 2003). The changes (increase or decrease) in cortical excitability induced by tDCS lead to corresponding changes in cortical function and activation (Nitsche and Paulus, 2000, Priori, 2003). Seizures have not been reported with tDCS (Poreisz et al., 2007).

Given the abnormal frontal lobe activation in depression (Grimm et al., 2008, Walter et al., 2007) and the persisting functional changes elicitable by DC stimulation (Ardolino et al., 2005, Liebetanz et al., 2002, Nitsche and Paulus, 2001, Priori, 2003), tDCS has been proved effective in treating patients with mild or moderate depression (Boggio et al., 2007, Fregni et al., 2006b, Rigonatti et al., 2008). No data is however available on the efficacy and safety of tDCS in patients with severe, drug-resistant major depression. We delivered tDCS twice a day (4.8 C/day) for five days in a group of 14 patients with severe, drug-resistant major depression. Patients underwent mood and cognitive assessment before tDCS, immediately after the last tDCS session, and 4 weeks after tDCS treatment ended.

Section snippets

Patients

We studied 14 hospitalized patients aged 37–68 years, with severe MDD according to DSM-IV.TR criteria (APA American Psychiatric Association, 2004), at high risk of suicide (see Table 1) and candidate for ECT. All subjects had a chronic illness, scored more than 29 on the Beck Depression Inventory (BDI) (Beck et al., 1961), and had undergone multiple medication trials. The patients met all the following three strict criteria: documented severe depressive illness for some time, persistent

Results

All 14 patients tolerated tDCS well without adverse events and were in general satisfied of the treatment.

Discussion

After bilateral frontal twice-a-day tDCS for only 5 days most of our patients with resistant major depression improved and none of them experienced adverse reactions. Notably, only one patient had to receive ECT after tDCS.

A first important point is that this is an open design study, without a placebo group.

Nonetheless, although our patients' severe depression and previous suicide attempts precluded a placebo group (Thase, 1999), the severity of depression, the magnitude of improvement, and

Role of funding source

FISM had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Conflict of interest

Roberta Ferrucci, Dr. Marco Bortolomasi, Maurizio Vergari, Laura Tadini, Beatrice Salvoro, Dr. Mario Giacopuzi, Dr. Sergio Barbieri, and Prof. Alberto Priori reported no financial interests or potential conflict of interest.

Acknowledgment

Roberta Ferrucci was supported by FIS (Fondazione Italiana Sclerosi Multipla) grant.

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