Tolerability and Blinding of Transcranial Direct Current Stimulation in People with Parkinson’s Disease: A Critical Review

Abstract

Transcranial direct current stimulation (tDCS) is accompanied by transient sensations (e.g., tingling, itching, burning), which may affect treatment outcomes or break the blinding of the study protocol. Assessing tolerability and blinding is integral to providing ample evidence of a “real effect” from the applied stimulation and dispelling the possibility of placebo effects. People with Parkinson’s disease (PwPD) endure many motor and non-motor symptoms that might be amenable to tDCS. However, because the disease also affects sensation capabilities, these subjects might report tolerability and blinding differently than other cohorts. Therefore, the purpose of this review was to aggregate the tolerability and blinding reports of tDCS studies in PwPD and recommend a standard tolerability and blinding reporting practice. A literature search of the PubMed and Scopus databases from 1 January 2020 to 1 April 2020 was performed to identify publications that applied tDCS to PwPD. Seventy studies were potentially reviewable, but only 36 (nine with quantitative tolerability reports, 20 with qualitative tolerability reports, and seven that only reported blinding) provided sufficient information to be included in the review. Quantitative information on tDCS tolerability and blinding maintenance in PwPD is scarce, and future reviews and metanalyses should carefully consider the possibility of placebo effects in their included studies.

Current Perspectives on the Assessment and Management of Gait Disorders in Parkinson’s Disease

“…The findings should be interpreted with caution, due to study heterogeneity and methodological challenges in blinding. 193 A randomized placebo-controlled trial of direct current stimulation (DCS) combined with physical therapy demonstrated a significant improvement in cadence, but not for stride length or timed up-and-go time, and the effects were sustained with DCS compared to physiotherapy alone. However, the small extent of improvement was not felt to be clinically relevant, 194 an important concept that requires further consideration in a majority of interventional studies on PD.…”

New Approaches Based on Non-Invasive Brain Stimulation and Mental Representation Techniques Targeting Pain in Parkinson’s Disease Patients: Two Study Protocols for Two Randomized Controlled Trials

“…In addition, their comfort will be assessed using a specific comfort questionnaire specified in the protocol section. These questionnaires will be necessary to obtain quantitative information on tDCS tolerability and blinding maintenance, which is scarce in PD patients [ 36 ]. Patients recruited will not meet in waiting rooms to avoid them to comment on their experience during the protocol.…”

Alterations in Leg Muscle Glucose Uptake and Inter-Limb Asymmetry after a Single Session of tDCS in Four People with Multiple Sclerosis

“…To evaluate the tolerability and blinding, each subject was asked to report all sensations felt during the stimulation period [6]. Specifically, the subjects were asked to rate the severity of sensations felt on a 10-point Likert scale (1 = "barely perceptible"; 10 = "most I could possibly stand").…”

“…Transcranial direct current stimulation (tDCS) uses weak currents applied to the scalp to non-invasively alter cortical excitability [4] and is considered safe with only mild transient adverse side effects (e.g., temporary tingling sensations) [5,6]. It is generally accepted that anodal tDCS enhances cortical excitability [7], and cathodal tDCS decreases cortical excitability (inhibition) [8].…”