Drug Addiction, Executive Dysfunction
Conditions
Keywords
crack-cocaine addiction, tDCS, dlPFC, craving, cognition
Brief summary
In this study, eligible crack-cocaine addicted inpatients recruited from specialized clinics for substance abuse disorder treatment, filling inclusion criteria and not showing any exclusion criteria, were randomized to receive the repetitive (10 sessions, every other day) bilateral dorsolateral Prefrontal Cortex (dlPFC: cathodal left / anodal right) tDCS (2 milliamperes, 3x7 cm2, for 20 min) or placebo (sham-tDCS). Craving to the use of crack-cocaine was examined before (baseline), during and after the end of the tDCS treatment. Based in our previous data, our hypothesis was that repetitive bilateral tDCS over dlPFC would favorably change clinical, cognitive and brain function in crack-cocaine addiction and these would be long-lasting effects.
Detailed description
Before (baseline) and after tDCS or sham-tDCS treatment, subjects were examined: (1) clinically, regarding craving (obsessive compulsive scale) and relapses to the drug use. They were followed-up for clinical examination at least 60 days after treatment.
Interventions
DEVICEtranscranial Direct Current Stimulation
Direct currents are transferred via a pair of carbonated-silicone electrodes (35 cm2) with a thick layer of high conductive gel for EEG underneath them. The electric current is delivered by an electric stimulator. To stimulate the left DLPFC, the cathode electrode is placed over F3 according to the 10-20 international system while the anode is placed over the contralateral F4 region. The currents flows continuously for 20 minutes with an intensity of 2 milliamperes.
Sponsors
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Harvard Medical School (HMS and HSDM)
University of Göttingen
Federal University of Espirito Santo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention model description
Sham-controlled double-blind randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* patients between the age of 18 and 60 years; * met criteria for crack-cocaine dependence according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), as determined by clinical evaluation; * in stable clinical condition with no need for inpatient care; * able to read, write, and speak Portuguese; and * no severe withdrawal signs or symptoms at baseline.
Exclusion criteria
* a condition of intoxication or withdrawal due to a substance other than crack-cocaine; * unstable mental or medical disorder or substance abuse or addiction other than crack-cocaine dependence, except nicotine and/or caffeine; * a diagnosis of epilepsy, convulsions; * a previous history of drug hypersensitivity or adverse reactions to diazepam or other benzodiazepines and haloperidol; * any contraindication for electrical brain stimulation procedures such as electronic implants or metal implants; * suspected pregnancy for female participants;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Craving | Five applications: once in the week before tDCS treatment (baseline), second, third and fourth weeks, during the treatment, and in the fith week, after the end of the tDCS treatment. | Five items from the original obsessive compulsive drinking scale, which are believed to reliably assess craving in a narrow sense were used. Questions of this brief scale allow quantification of thoughts and feelings (obsessions), and behavioral intentions, and are answered on a scale ranging from 0 to 4, resulting in a total score between 0 and 20. Higher scores reflect more severe craving. These items were applied at the beginning, during and at the end of the treatment with sham-tDCS or tDCS. |
| Relapses | 30 and 60 days after discharge from clinics | A use relapse was defined as the first episode of return to the previous uncontrolled pattern of crack-cocaine use (rocks per day). Information about relapse were gathered directly when patients regularly returned to the hospital for clinical follow-up after their discharge and/or by self-report or reports of family members by telephone calls. |
Countries
Brazil
Participant flow
Recruitment details
There were two dropouts in the sham-tDCS group that were excluded after randomization. One patient escaped from the treatment facility and the other had to be discontinued because of precocious discharge from the clinic for misconduct.
Participants by arm
| Arm | Count |
|---|---|
| Real tDCS Ten sessions (every other day) of bilateral transcranial Direct Current Stimulation (tDCS: 2 milliamperes, 3 x 7 cm2, during 20 minutes) over dorsolateral Prefrontal Cortex (cathodal left / anodal right).
transcranial Direct Current Stimulation: Direct currents are transferred via a pair of carbonated-silicone electrodes (35 cm2) with a thick layer of high conductive gel for EEG underneath them. The electric current is delivered by an electric stimulator. To stimulate the left DLPFC, the cathode electrode is placed over F3 according to the 10-20 international system while the anode is placed over the contralateral F4 region. The currents flows continuously for 20 minutes with an intensity of 2 milliamperes. | 19 |
| Sham-tDCS Ten sessions (every other day) of placebo control (sham procedure) of transcranial Direct Current Stimulation (sham-tDCS) during 20 minutes with electrodes placed over the dorsolateral Prefrontal Cortex (cathodal left / anodal right). Current was delivered for 30 seconds and was turned off for the rest of the stimulation period. In this way, subjects experienced the initial itching sensation at the beginning of stimulation, but received no current for the rest of the session.
transcranial Direct Current Stimulation: Direct currents are transferred via a pair of carbonated-silicone electrodes (35 cm2) with a thick layer of high conductive gel for EEG underneath them. The electric current is delivered by an electric stimulator. To stimulate the left DLPFC, the cathode electrode is placed over F3 according to the 10-20 international system while the anode is placed over the contralateral F4 region. The currents flows continuously for 20 minutes with an intensity of 2 milliamperes. | 14 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 |
Baseline characteristics
| Characteristic | Sham-tDCS | Total | Real tDCS |
|---|---|---|---|
| Age, Continuous | 35.0 years STANDARD_DEVIATION 8.2 | 35.03 years STANDARD_DEVIATION 8.7 | 35.1 years STANDARD_DEVIATION 9.6 |
| Employment situation Formal job | 4 Participants | 6 Participants | 2 Participants |
| Employment situation Freelance | 1 Participants | 8 Participants | 7 Participants |
| Employment situation Retired | 1 Participants | 2 Participants | 1 Participants |
| Employment situation Unemployed | 8 Participants | 17 Participants | 9 Participants |
| Marital state Common-law | 1 Participants | 1 Participants | 0 Participants |
| Marital state Divorced | 2 Participants | 3 Participants | 1 Participants |
| Marital state Married | 0 Participants | 2 Participants | 2 Participants |
| Marital state Non reported | 0 Participants | 4 Participants | 4 Participants |
| Marital state Single | 10 Participants | 22 Participants | 12 Participants |
| Marital state Widow | 1 Participants | 1 Participants | 0 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 2 Participants | 6 Participants | 4 Participants |
| Sex: Female, Male Male | 12 Participants | 27 Participants | 15 Participants |
| Tobacco use No | 3 Participants | 11 Participants | 8 Participants |
| Tobacco use Yes | 11 Participants | 22 Participants | 11 Participants |
| Years of education Above 13 | 3 Participants | 7 Participants | 4 Participants |
| Years of education Between 10 to 13 | 7 Participants | 15 Participants | 8 Participants |
| Years of education Between 6 to 9 | 4 Participants | 11 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 2 / 14 |
| other Total, other adverse events | 16 / 19 | 8 / 14 |
| serious Total, serious adverse events | 0 / 19 | 0 / 14 |
Outcome results
Primary
Craving
Five items from the original obsessive compulsive drinking scale, which are believed to reliably assess craving in a narrow sense were used. Questions of this brief scale allow quantification of thoughts and feelings (obsessions), and behavioral intentions, and are answered on a scale ranging from 0 to 4, resulting in a total score between 0 and 20. Higher scores reflect more severe craving. These items were applied at the beginning, during and at the end of the treatment with sham-tDCS or tDCS.
Time frame: Five applications: once in the week before tDCS treatment (baseline), second, third and fourth weeks, during the treatment, and in the fith week, after the end of the tDCS treatment.
Population: Two patients from each group were lost to follow-up after their discharge from the hospital.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real-tDCS | Craving | 2 | 4.74 scores on a scale | Standard Deviation 4.1 |
| Real-tDCS | Craving | 4 | 2.63 scores on a scale | Standard Deviation 3.4 |
| Real-tDCS | Craving | 3 | 3.63 scores on a scale | Standard Deviation 3.9 |
| Real-tDCS | Craving | 5 | 2.26 scores on a scale | Standard Deviation 2.9 |
| Real-tDCS | Craving | 1 | 6.53 scores on a scale | Standard Deviation 5.2 |
| Sham-tDCS | Craving | 5 | 4.07 scores on a scale | Standard Deviation 3.4 |
| Sham-tDCS | Craving | 1 | 7.0 scores on a scale | Standard Deviation 3.8 |
| Sham-tDCS | Craving | 2 | 4.43 scores on a scale | Standard Deviation 2.9 |
| Sham-tDCS | Craving | 3 | 4.0 scores on a scale | Standard Deviation 3.2 |
| Sham-tDCS | Craving | 4 | 3.5 scores on a scale | Standard Deviation 3.1 |
Comparison: We powered for a medium effect size based on our previous study with effect size (partial ղ2) of 0.10384 for the main within-subject factor in the two-way ANOVA with repeated measures. With a power of 80%, and a two-sided probability of a type I error of 5%, the resulting minimum sample size was 30 participants. To account for waiving or dropouts we increased the estimated sample size to approximately 10%, resulting in 33 subjects in total (approximately 16 to 17 subjects in each group).p-value: 0.05ANOVA
Primary
Relapses
A use relapse was defined as the first episode of return to the previous uncontrolled pattern of crack-cocaine use (rocks per day). Information about relapse were gathered directly when patients regularly returned to the hospital for clinical follow-up after their discharge and/or by self-report or reports of family members by telephone calls.
Time frame: 30 and 60 days after discharge from clinics
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Real-tDCS | Relapses | 30-days follow-up | Not relapsed | 10 Participants |
| Real-tDCS | Relapses | 30-days follow-up | Relapsed | 7 Participants |
| Real-tDCS | Relapses | 60-days follow-up | Not relapsed | 8 Participants |
| Real-tDCS | Relapses | 60-days follow-up | Relapsed | 9 Participants |
| Sham-tDCS | Relapses | 60-days follow-up | Relapsed | 8 Participants |
| Sham-tDCS | Relapses | 30-days follow-up | Not relapsed | 7 Participants |
| Sham-tDCS | Relapses | 60-days follow-up | Not relapsed | 4 Participants |
| Sham-tDCS | Relapses | 30-days follow-up | Relapsed | 5 Participants |
Comparison: Two patients from each group were lost to follow-up after their discharge from the hospital.p-value: 0.05Fisher Exact