Transcranial Direct Current Stimulation (tDCS)

Definition and Mechanism of Action

Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain neuromodulation technique that uses low-intensity electrical currents (0.5–2 mA) to modulate neuronal excitability in the cerebral cortex. It is an emerging tool in the treatment of major depressive disorder, particularly in patients who have an inadequate response to pharmacological therapy.

During the session, two electrodes are placed on the scalp: one anode (positive) and one cathode (negative). The anode is usually positioned over the left dorsolateral prefrontal cortex, a region involved in affective regulation and often underactive in depression, while the cathode is placed contralaterally or in a neutral area (e.g., right supraorbital region).

The current modulates the neuronal membrane in a subthreshold manner, meaning it does not induce action potentials but instead facilitates or inhibits the probability of synaptic activation depending on the polarity:

• The anode increases neuronal excitability (facilitatory effect);
• The cathode decreases it (inhibitory effect).

The antidepressant mechanism of tDCS is based on:

• Modulation of fronto-limbic connectivity and the default mode network circuits;
• Increased neuroplasticity and BDNF activity;
• Anti-inflammatory effects and synergy with antidepressants or psychotherapy.

Unlike other neuromodulation techniques, tDCS does not generate magnetic pulses or induce seizures. It is silent, painless, and free from cognitive side effects, with an excellent safety profile even for supervised home use.

Indications in Depression

The main indication for tDCS is the treatment of treatment-resistant major depression, especially in patients who:

• Have partial response to one or more antidepressants;
• Present with pharmacological contraindications (e.g., pregnancy, polypharmacy, hepatic or cardiovascular comorbidities);
• Refuse invasive treatments (e.g., ECT, VNS);
• Have a preserved cognitive and functional profile, able to follow outpatient or supervised home protocols;
• Are in the maintenance phase to prevent relapse after partial remission.

tDCS is not recommended as monotherapy in severe depression with suicidal risk, in psychotic features, or in patients with significant neurocognitive impairment.

Therapeutic Protocol

A standard tDCS treatment for depression includes:

• Current: 1–2 mA;
• Session duration: 20–30 minutes;
• Frequency: 5 sessions per week for 2–4 weeks;
• Total number of sessions: at least 10–15 for clinical response, up to 20–30 for more stable effects.

Treatment can be repeated cyclically or maintained at low frequency in the consolidation phase (e.g., 1–2 times/week). In some studies, tDCS has been effectively combined with SSRIs or cognitive-behavioral therapy, enhancing their effects through induced neuroplasticity.

Tolerability and Side Effects

tDCS is generally well tolerated and considered among the neuromodulation techniques with the best safety profile. Side effects are mild, transient, and rarely lead to treatment discontinuation. The most common include:

• Tingling, burning, or itching sensations under the electrodes, usually decreasing after the first sessions;
• Transient skin redness at the application site;
• Mild fatigue, headache, or difficulty concentrating after the session, typically self-limiting;
• Sleep disturbances (rare, and usually related to evening sessions).

No serious or permanent side effects have been reported in patients treated with tDCS in clinical trials. Subthreshold stimulation does not induce seizures and does not impair cognitive function—in fact, some studies suggest possible improvements in attention and working memory.

Contraindications

Absolute contraindications are few. tDCS is not recommended in patients with:

• Active intracranial electronic devices (e.g., brain stimulators, cochlear implants);
• Recent severe focal brain injuries (e.g., trauma, hemorrhagic stroke);
• Active or inflammatory skin conditions at the electrode application sites.

Relative contraindications include:

• Severe cognitive impairment interfering with cooperation;
• Current confusional, delirious, or psychotic states;
• Inability to ensure supervision in home-based protocols.

Clinical Effectiveness

tDCS has shown positive results in treating depression in several controlled clinical studies. Clinical response rates are lower compared to rTMS and ECT, but the procedure is much simpler, cheaper, and more accessible.

Response is more frequently observed in patients with:

• Moderate, non-psychotic depression;
• Recent onset and good neurocognitive reserve;
• High compliance and adherence to protocol;
• Absence of marked somatic or melancholic symptoms.

tDCS can be considered a complementary and personalized option in long-term therapeutic plans and is also being studied as a cognitive enhancer in low-intensity mood disorders.

Guidelines and Future Perspectives

Guidelines from CANMAT, NICE, and the APA include tDCS among the recommended options for patients with mild to moderate treatment-resistant depression, in the absence of indications for ECT or rTMS. The level of evidence is considered intermediate but promising when combined with other strategies.

The simplicity of the procedure has led to the development of supervised home-use protocols using portable devices, always under medical guidance. In the future, tDCS may be used not only for depression, but also for treating anhedonia, residual cognitive symptoms, and preventing affective relapses.

References
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