Trial of Escitalopram versus tDCS for Depression

Further, they advised caution when judging the failure to show non-inferiority to escitalopram. The study team noted that patients were able to guess their group allocation with escitalopram, but not with tDCS. In other words, the placebo control with escitalopram was not reliable. This is important because the uncertainty as to whether the patient is receiving an active intervention may negatively impact response and remission rates. In this case, the negative effect from uncertainty might’ve only affected the tDCS group.

tDCS protocol used in the study consisted of 22 half-hour sessions with 2 mA current. The sessions were administered five times a week for first three weeks, after which weekly sessions were given until week 10. Treatment outcomes for tDCS group at week 10:

HDRS-17 response: tDCS 41% – 22% Placebo

HDRS-17 remission: tDCS 24% – 13% Placebo

MADRS response: tDCS 40% – 23% Placebo

MADRS remission: tDCS 32% – 20% Placebo

The most surprising result of the study was the conclusion that tDCS was associated with more adverse events than escitalopram. Traditionally, tDCS is considered to have a favourable side effect profile as highlighted by the safety review by Bikson et al. in 2016.

This is also in contrast to our patient data, where treatment tolerability has been excellent and drop out rates low. When interviewed, many of our patients have also underlined the tolerability of the treatment when compared to their previous experiences with medication.

We looked into the supplementary materials of the study for more information on reported adverse events. The study used 2 questionnaires for adverse events: SAFTEE and a questionnaire focused on common tDCS side effects. Figure 3 lists the items included in both questionnaires.

Figure 3: Items included in adverse event questionnaires. Note how the questionnaires overlap: discomfort and headache are part of both.

Predictably, adverse events were more common with escitalopram in SAFTEE and with tDCS in stimulation focused questionnaire. When answers from both questionnaires were put together, there were no significant between-group differences as can be seen from Figure 4:

Figure 4: Prevalence of adverse events in the study groups. 36% to 43% of patients reported at least one adverse event that they classified as severe.

Looking at the adverse events data from supplementary materials revealed the most common side-effects:

• 96 out of 202 patients reported at least mild improvement in mood
• 61 reported at least a mild headache
• 57 reported at least mild itching
• 56 reported at least mild sleepiness

In the adverse effects classified as severe, the only significant between-group difference was in Sleepiness: Severe sleepiness was more frequently associated with escitalopram than tDCS or placebo. Largely owing to this, there was also a between-group difference in severe adverse effects per patient as shown in Figure 5.