Anodal tDCS shows promise for treatment-resistant depression, post-stroke motor recovery, and cognitive enhancement. However, response variability exists between controlled trials and clinical implementation, with factors including treatment parameters, patient selection, and concurrent medications which can impact the way patients respond to it (Woodham et al., 2024).

Carbamazepine, a commonly prescribed sodium channel blocker, can completely eliminate the neurophysiological effects that tDCS relies on. This isn't a minor modulation- it's a mechanistic block that prevents the treatment from working as intended.

Understanding this interaction is essential for accurate patient selection, protocol design, and outcome interpretation.

The Mechanism

How anodal tDCS normally works:

What carbamazepine does:

Blocks voltage-gated sodium channels → prevents Step 1 → entire cascade fails

KEY FINDING

Nitsche et al. (2003): Carbamazepine completely abolishes excitability increases from anodal tDCS—both during stimulation and after-effects. Cathodal effects preserved, indicating this specifically targets excitatory plasticity.

The Evidence

Study 1: Nitsche et al., 2003

• Design: Within-subject crossover, motor-evoked potentials

• Finding: CBZ selectively eliminated anodal tDCS effects

• Implication: Sodium channel depolarization is necessary for NMDA/calcium cascade

Study 2: Darmani et al., 2019

• Design: Design: Double-blind crossover (n=15), TMS-EMG/EEG (cortical excitability study)

• Finding: Single CBZ dose → increased motor thresholds, attenuated P25/P180 potentials

• Implication: Quantifiable reduction in cortical excitability after sodium channel blockade

Study 3: McLaren et al., 2018

• Design: Focused review of medication-tDCS interactions

• Finding: Multiple drug classes (sodium blockers, calcium blockers, AEDs) alter tDCS effects

• Implication: Medication screening/reporting essential in protocols

Medications to Screen For

Sodium channel blockers that interfere with anodal tDCS:

*Note: Carbamazepine has the strongest direct evidence from tDCS studies for blocking anodal effects. While phenytoin and lamotrigine share similar sodium channel blocking properties, their specific interactions with tDCS have been less extensively studied in controlled trials and are inferred based on pharmacological mechanisms."

Clinical Implications

BEFORE Starting tDCS

•  Document all concurrent sodium channel blockers in patient records

• Discuss tDCS candidacy with prescribing neurologist to determine:

• Whether anodal protocols are appropriate given the medication regimen

• Expected response patterns based on pharmacological interaction

• Whether tDCS remains a suitable treatment option

•  Document all AEDs, doses, and timing in intake assessment

DURING Treatment

• Non-response in patients taking CBZ likely reflects mechanistic blockade rather than treatment inefficacy 

• Check for new prescriptions initiated between sessions

• Focus on functional outcomes (mood scales, ADLs, QOL) rather than neurophysiological markers

• Document medication interaction in clinical notes

FOR Research/QI Protocols

•  Pre-specify AED exclusion criteria OR stratify randomization by AED use

• Report: drug names, doses, plasma levels (if available), timing relative to stimulation

• Include medication status as covariate in outcome analyses

• Power studies to detect differential effects if allowing AED patients

The Broader Principle

Neuromodulation works through existing brain physiology, not around it.

When patients need both their AED (for seizure control or pain) AND neuromodulation (for depression or stroke recovery), the challenge is:

• Designing protocols that account for mechanistic interactions

• Setting appropriate expectations

• Interpreting outcomes accurately

• Coordinating between specialties when conflicts arise

The question isn't "Does tDCS work?",  it's "Are we using it appropriately given this patient's pharmacologically modified neurophysiology?"

Quick Summary