Overview of transcranial direct current stimulation

  • Non-invasive transcranial direct current stimulation (tDCS) is a safe, effective, and affordable therapeutic option for several psychiatric disorders.
  • tDCS relieves depression symptoms by modulating cortical excitability through a weak current. Specifically, treatment increases the excitability of the left dorsolateral prefrontal cortex (DLPFC), which has been shown to be hypoactive in depressive patients. tDCS does not cause direct action potentials.

  • tDCS is well tolerated, and no serious side effects have been reported.
  • Meta-analyses have found active tDCS treatment to be significantly superior to sham tDCS in depressed patients, and results have been clinically meaningful.
  • tDCS can be used both as a monotherapy or as an adjunct to antidepressant medication and psychotherapy, and the treatment effects may be additive.

Mode of action

Sooma depression therapy targets the dorsolateral prefrontal cortex (DLPFC) using a low-intensity (2 mA) direct current (Figure 1).

The current induces changes in neuronal excitability in a polarity-dependent manner: positive anodal stimulus increases cortical excitability (depolarization) without triggering action potentials, whereas negative cathodal stimulus decreases excitability (hyperpolarization).

To date, several studies have demonstrated hypoactivity of the left dorsolateral prefrontal cortex (DLPFC) in depressed patients, which may explain why anodal tDCS of the left DLPFC leads to symptom relief in depression patients (Figure 2) (Fitzgerald 2006, Grimm 2008).

Neurobiological studies have demonstrated that tDCS mediates a cascade of events at a cellular and molecular level, including effects on the N-methyl-D-aspartate receptors (Liebetanz 2002Nitsche 2003a). In addition to acute transient membrane potential changes that can last up to one hour, tDCS is associated with longer-lasting synaptic changes (Nitsche 2000, Nitsche 2003b).

Sooma Depression Treatment session

Figure 1.

tDCS stimulation graph

Figure 2.

Safety

There are no tDCS-related serious adverse events reported. The review of adverse events by Brunoni and colleagues, which included 1851 healthy volunteers and patients, indicates that the safety profile of tDCS is very good. A systematic review by NICE further concluded that the evidence raises no major safety concerns.

Mild, transient adverse events such as itching, tingling or skin redness have been reported both after active and sham tDCS treatment. According to the safety evaluations (NICE 2015, Brunoni 2011, Meron 2015), the difference between groups was not statistically significant. Likewise, dropout-rates have not differed significantly between active and sham groups in the studies conducted, indicating good tolerability of the treatment.

The largest controlled trial on tDCS in depression to date investigated the frequency of adverse events as well as the effect on cognitive capabilities (Brunoni 2013). Neither of them differed between the treatment groups and the sham group.

Efficacy

A group of key opinion leaders published evidence-based guidelines on the therapeutic use of transcranial direct current stimulation, where they concluded tDCS treatment to have probable efficacy (level B evidence) in depression treatment (Lefaucheur, 2016).

A meta-analysis of six RCTs on tDCS in depression treatment, enrolling a total of 289 patients, demonstrated significantly greater improvement in patients treated with active vs. sham tDCS (Brunoni 2016). Effect size, evaluated with number needed to treat (NNT) for response and remission, was found to be comparable with those reported for repetitive transcranial magnetic stimulation (rTMS) and antidepressant drug treatment in primary care. Another recent overview was published in the fall of 2015, when an interventional procedure guidance, “Transcranial direct current stimulation (tDCS) for depression”, was published by the The National Institute for Health and Care Excellence (NICE) in the United Kingdom (NICE 2015).

The largest RCT conducted to date enrolled 120 patients and randomised them into four treatment groups to compare the treatment effect of active vs. sham tDCS, combined either with sertraline (50mg/day), a selective serotonin reuptake inhibitor (SSRI), or placebo drug (Brunoni 2013). As seen in Figure 3, only 16.7% of the placebo group but 43.3% of the patients treated with active tDCS responded. Response was defined as >50% improvement in depression scores (on HAMD or MADRS depression scales) from baseline.

Similarly, 13.3% of the placebo group reached remission, compared to 40.0% in the active tDCS group. Remission was defined as MADRS score under 10.

Importantly, the study found the combined group (Active tDCS + Active SSRI) response to be superior already at week 2, suggesting that starting both treatments simultaneously may bring added benefits.

Figure 3.

The relapse rate after successful tDCS depression treatment was investigated in two studies. They found a mean response duration of 11.7 weeks and a sustained response rate of 47% at 24 weeks (Valiengo 2013), and sustained response rates of 83.7% at 3 months and 51.1% at 6 months (Martin 2013), respectively.

Sooma is currently supporting a multi-center randomised controlled trial on tDCS in depression treatment, which will enroll 120 patients. The study is ongoing and currently recruiting patients. More details on the study and its protocol can be found here.

Case examples

Clinical outcome in patient I after Sooma tDCS treatment as measured by A) MADRS or B) BDI depression rating scales. The score was evaluated before the first tDCS treatment session and after the last treatment session.

Patient 1 (Female, 52 years old)

The patient was diagnosed with severe treatment-resistant depression in 2005. She also suffered from colitis and musculoskeletal disorders. Since 2007, she had been on continuous antidepressant medication with low efficacy and intolerable side effects. In 2013 she was treated with electroconvulsive therapy (ECT) and achieved a good clinical response. However, with ECT the patient experienced highly unpleasant side effects that affected her memory. Sooma tDCS treatment was initiated in 2015 as an alternative treatment strategy to ECT.

  • 2 mA, 30 minutes, 17 sessions.
  • Acute phase: 5 weekly sessions for 3 weeks
  • Maintenance: One weekly session for 2 weeks.

During the treatment, the patient was treated with venlafaxine (titrated up to 112.5 mg/day), and psychotherapy was included in each of the treatment sessions. She responded well to Sooma tDCS treatment as demonstrated by a significant improvement from severe to mild depression during the 5-week treatment period.

According to the patient and her psychotherapist, her mood was already improved during the second treatment week. She had had improved activities of daily living, less anxiety, and normalised appetite and sleep patterns.

Patient 2 (Male, 48 years old)

The patient suffered from severe treatment-resistant depression since 2013. He also had moderate panic disorder, unspecified personality disorder, and sleep apnea. During two years of continuous treatment, the patient received psychotherapy and various antidepressant medications, including bupropion, pregabalin, and venlafaxine. In 2015, he received two separate interventions of Sooma tDCS treatment, as previous therapy options did not provide sufficient clinical response or were poorly tolerated.

  • 2 mA, 30 minutes, 17 sessions.
  • Acute phase: 5 weekly sessions for 3 weeks
  • Maintenance: One weekly session for 2 weeks.

Escitalopram (20mg/day) and quetiapine (25 mg, 1–2 doses per day) were administered during the treatment. In addition, the patient continued to use diazepam (10 mg, 4–10 doses per day, if needed), simvastatin (10 mg/day), and analgesics for migraine. Simultaneous psychotherapeutic sessions were included in the treatment.

During the first intervention, the patient had a good clinical response during the initial 3-week treatment period. However, during the maintenance treatment period, he suffered from panic symptoms while traveling on vacation. Three months later, the patient underwent an additional intervention with Sooma tDCS. At that time, he had a good clinical response demonstrated by a significant improvement after the 5-week treatment period.

According to the patient, his mood was significantly better already during the second treatment week. The psychotherapist stated that the Sooma tDCS treatment also positively affected sensations of pain and anxiety.

Clinical outcome in patient 2 after Sooma tDCS treatment as measured by A) MADRS or B) BDI depression rating scales. The score was evaluated before the first tDCS treatment session and after the last treatment session.

Literature

Top Picks

Lefaucheur, JP et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 128, 56-92 (2016). Available online.

Brunoni, AR et al. Transcranial direct current stimulation for acute major depressive episodes: meta-analysis of individual patient data. Br J Psychiatry. 208, 522-31 (2016). Available online.

National Institute for Health and Care Excellence (United Kingdom). Transcranial direct current stimulation (tDCS) for depression. NICE Interv. Proced. Guid. 1–9 (2015). Available online.

Further reading

Brunoni, A. et al. The Sertraline vs Electrical Current Therapy for Treating Depression Clinical Study. JAMA Psychiatry 70, 383 (2013). Available online.

Valiengo, L. et al. The sertraline versus electrical current therapy for treating depression clinical study (select-tDCS): results of the crossover and follow-up phases. Depress. Anxiety 30, 646–653 (2013). Available online.

Martin, D. et al. Continuation transcranial direct current stimulation for the prevention of relapse in major depression. J. Affect. Disord. 144, 274–278 (2013). Available online.

Bikson, M. et al. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimul. 9, 641-61 (2016). Available online.

Brunoni, A. et al. A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Int. J. Neuropsychopharmacol. 14, 1133–1145 (2011). Available online.

Palm, U. et al. Transcranial direct current stimulation in children and adolescents: a comprehensive review. J Neural Transm. 123, 1219-34 (2016). Available online.

Brunoni, A. et al. Treatment-emergent mania/hypomania during antidepressant treatment with transcranial direct current stimulation (tDCS): A systematic review and meta-analysis. Brain Stimul. Nov 2016 (2016). Available online.

Kessler, S. et al. Differences in the experience of active and sham transcranial direct current stimulation. Brain Stimul. 2, 155-62 (2012). Available online.

Hyvärinen, P. et al. Self-Administered Domiciliary tDCS Treatment for Tinnitus: A Double-Blind Sham-Controlled Study. PLoS One 11 (2016). Available online.

Kasschau, M. et al. Transcranial Direct Current Stimulation Is Feasible for Remotely Supervised Home Delivery in Multiple Sclerosis. Neuromodulation. 8, 824-831 (2016). Available online. 

Cha, Y. et al. Randomized Single Blind Sham Controlled Trial of Adjunctive Home-Based tDCS after rTMS for Mal De Debarquement Syndrome: Safety, Efficacy, and Participant Satisfaction Assessment. Brain Stimul. 9, 537-44 (2016). Available online.

Nitsche, M. et al. Level of action of cathodal DC polarisation induced inhibition of the human motor cortex. Clin. Neurophysiol. 114, 600–604 (2003). Available online.

Nitsche, M. et al. Modulation of cortical excitability by weak direct current stimulation-technical, safety and functional aspects. Suppl Clin Neurophysiol. 56, 255–76 (2003). Available online.

Liebetanz, D. et al. Pharmacological approach to the mechanisms of transcranial DC stimulation induced after effects of human motor cortex excitability. Brain 125, 2238–2247 (2002). Available online.

Nitsche, M. & Paulus, W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. The Journal of Physiology 527 Pt 3, (2000). Available online.

Grimm, S. 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 63, 369–376 (2008). Available online.

Fitzgerald, P. et al. An analysis of functional neuroimaging studies of dorsolateral prefrontal cortical activity in depression. Psychiatry Res. 148, 33–45 (2006). Available online.

Fibromyalgia treatment 

Zhu, CE. et al. Effiectiveness and safety of transcranial direct current stimulation in fibromyalgia: A systematic review and meta-analysis. J Rehabil Med. Dec 16 (2016). Available online.

Neuropathic pain after SCI treatment 

Mehta, S. et al. Effectiveness of transcranial direct current stimulation for the management of neuropathic pain after spinal cord injury: a meta-analysis. Spinal Cord. 53, 780-5 (2015). Available online.

Stroke treatment 

Figlewski, K. et al. Transcranial Direct Current Stimulation Potentiates Improvements in Functional Ability in Patients With Chronic Stroke Receiving Constraint-Induced Movement Therapy. Stroke, Nov 2016 (2016). Available online. 

Chhatbar, P. et al. Transcranial Direct Current Stimulation Post-Stroke Upper Extremity Motor Recovery Studies Exhibit a Dose-Response Relationship. Brain Stimul. 9, 16-26 (2016). Available online.

OCD treatment 

D’Urso, G. et al. Transcranial direct current stimulation for obsessive–compulsive disorder: A randomized, controlled, partial crossover trial. Depress Anxiety 33. 1132-1140 (2016). Available online.

Schizophrenia treatment

Kekic, M. et al. A systematic review of the clinical efficacy of transcranial direct current stimulation (tDCS) in psychiatric disorders. J Psychiatr Res. 74, 70-86 (2016). Available online.

Alzheimer’s disease treatment

Hsu, W. et al. Effects of noninvasive brain stimulation on cognitive function in healthy aging and Alzheimer‘s disease: a systematic review and meta-analysis. Neurobiol Aging. 36, 2348-59 (2015). Available online.

Khedr, E. et al. A double-blind randomized clinical trial on the efficacy of cortical direct current stimulation for the treatment of Alzheimer’s disease. Front Aging Neurosci. 6, 275 (2014). Available online.

Marceglia, S. et al. Transcranial Direct Current Stimulation Modulates Cortical Neuronal Activity in Alzheimer’s Disease. Front Neurosci. 10, 134 (2016). Available online.

Sooma tDCS can replicate used tDCS protocols from all aforementioned studies. Contact us for research co-operation.