Lack of Effects of Extended Sessions of Transcranial Direct Current Stimulation (tDCS) Over Dorsolateral Prefrontal Cortex on Craving and Relapses in Crack-Cocaine Users

Abstract

Background: Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) has been investigated as additional therapeutic tool for drug use disorder. In a previous study, we showed that five sessions of tDCS applied bilaterally over the dorsolateral prefrontal cortex (dlPFC) reduced craving to the use of crack-cocaine in inpatients from a specialized clinic. In the present study, we examine if an extended number of sessions of the same intervention would reduce craving even further and affect also relapses to crack-cocaine use. Methods: A randomized, double-blind, sham-controlled, clinical trial with parallel arms was conducted (https://clinicaltrials.gov/ct2/show/NCT02091167). Crack-cocaine patients from two private and one public clinics for treatment of drug use disorder were randomly allocated to two groups: real tDCS (5 cm × 7 cm, 2 mA, for 20 min, cathodal over the left dlPFC and anodal over the right dlPFC, n = 19) and sham-tDCS (n = 16). Real or sham-tDCS was applied once a day, every other day, in a total of 10 sessions. Craving was monitored by a 5-item obsessive compulsive drinking scale once a week (one time before, three times during and once after brain stimulation) over about 5 weeks and relapse was monitored after their discharge from clinics for up to 60 days. Results: Craving scores progressively decreased over five measurements in both sham- and real tDCS groups. Corrected Hedges' within-group (initial and final) effect sizes of craving scores were of 0.77 for the sham-tDCS and of 0.97 for the real tDCS group. The between-groups effect size was of 0.34, in favor of the real tDCS group over sham-tDCS group. Relapse rates were high and quite similar between groups in the 30- and 60-days follow-up after discharge from the hospital. Conclusion: Extended repetitive bilateral tDCS over the dlPFC had no add-on effects over regular treatment when considering craving and relapses to the crack-cocaine use in a sample of crack-cocaine patients with severe use disorder. Different tDCS montages targeting other cortical regions and perhaps additional extension of sessions need to be investigated to reach more efficiency in managing craving and relapses to crack-cocaine use.

Keywords: crack-cocaine use disorder; craving; dorsolateral prefrontal cortex; relapses; tDCS.

FIGURE 1

Flow diagram according to CONSORT 2010.

FIGURE 2

Diagram of the general procedure: eligible crack-cocaine users were recruited from clinics for treatment of drug use disorder, signed the informed consent form and were randomized to receive repetitive bilateral (cathode left/anode right over the Dorsolateral Prefrontal Cortex) transcranial Direct Current Stimulation (2 mA, 35 cm², stimulation for 20 min) every other day in 10 sessions. Craving to the use of crack-cocaine was examined by 5 items from the Obsessive–Compulsive Cocaine Use Scale once a week for 5 weeks (the week before treatment, during the second, third and fourth treatment weeks, and the week after treatment). A, anterior; P, posterior; R, right; L, left; a, anode; c, cathode; BS, brain stimulation.

FIGURE 3

Craving is shown individually (A) and as the mean of the 5 item score from Obsessive-Compulsive Cocaine Use Scale score ± standard error of means (SEM) (B) in the week before treatment (1 initial), the second (2), third (3) and fourth (4) weeks during the treatment, and the week after treatment (5 final) with bilateral repetitive transcranial Direct Current Stimulation (tDCS, 2 mA, 35 cm²: cathode left/anode right over the Dorsolateral Prefrontal Cortex; stimulation for 20 min every other day of 10 sessions; n = 19) or placebo (sham-tDCS; n = 14) in crack cocaine users. Linear regression of the real tDCS group: ^∗∗p < 0.01. (C) Mean scores of craving shown in the week before and the week after treatment in the sham-tDCS and real tDCS groups. ^∗p < 0.05 and ^∗∗∗p < 0.001 when compared to initial scores (paired t-test).

FIGURE 4

Crack-cocaine use relapses in dependent patients in the 30-days (A) and 60-days (B) follow-up after ten sessions of sham- (n = 12) or real tDCS (n = 17) applied over the bilateral dorsolateral Prefrontal Cortex. Two patients from each group were lost to follow-up.