Brief reportTranscranial direct current stimulation in 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.
References (28)
- 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.
Decreased prefrontal myo-inositol in major depressive disorder
Biol. Psychiatry
(2005) - et al.
Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment: an fMRI study in severe major depressive disorder
Biol. Psychiatry
(2008) - et al.
Transcranial direct current stimulation: state of the art 2008
Brain Stimulation
(2008) - et al.
Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients
Brain Res. Bull.
(2007) Brain polarization in humans: a reappraisal of an old tool for prolonged non-invasive modulation of brain excitability
Clin. Neurophysiol.
(2003)- et al.
Transcranial direct stimulation and fluoxetine for the treatment of depression
Eur. Psychiatry
(2008) - et al.
Cost of depression: effect of adherence and treatment response
Eur. Psychiatry
(2006) - et al.
Increased left prefrontal activation in patients with unipolar depression: an event-related, parametric, performance-controlled fMRI study
J. Affect. Disord.
(2007) Diagnostic and Statistical Manual of Mental Disorders, DSM-IV-TR Edition
(2004)
Non-synaptic mechanisms underlie the after-effects of cathodal transcutaneous direct current stimulation of the human brain
J. Physiol.
An inventory for measuring depression
Arch. Gen. Psychiatry
A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression
Int. J. Neuropsychopharmacol.
Treatment of major depression with transcranial direct current stimulation
Bipolar. Disord.
Cited by (191)
High-definition transcranial direct current stimulation modulates eye gaze on emotional faces in college students with alexithymia: An eye-tracking study
2022, Progress in Neuro-Psychopharmacology and Biological PsychiatryTranscranial Direct Current Stimulation Over the Prefrontal Cortex in Depression Modulates Cortical Excitability in Emotion Regulation Regions as Measured by Concurrent Functional Magnetic Resonance Imaging: An Exploratory Study
2022, Biological Psychiatry: Cognitive Neuroscience and NeuroimagingA wake-up call: Sleep physiology and related translational discrepancies in studies of rapid-acting antidepressants
2021, Progress in Neurobiology