The purpose of this study is to investigate the short and long term clinical and cognitive effects of repetitive Transcranial Magnetic Stimulation (rTMS) at 5 Hz and/or 10 Hz frequencies on the left dorsolateral prefrontal cortex in cocaine dependent patients and to examine possible changes in brain structure and functional connectivity associated with this intervention.
Repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce craving in cocaine addicts in the short term. However, there are no studies on the long term clinical and cognitive effects of sustained rTMS therapy. Moreover, clinical improvement or decline could be related to long term changes in brain structure and function. The purpose of this study is to investigate the short and long term clinical and cognitive effects of repetitive Transcranial Magnetic Stimulation (rTMS) at 5 Hz and/or 10 Hz frequencies on the left dorsolateral prefrontal cortex in cocaine dependent patients and to examine possible changes in brain structure and functional connectivity associated with this intervention. For this purpose the investigators will recruit cocaine dependent patients and stimulate them using rTMS with a acute intervention (twice a day for 2 weeks) and a maintenance intervention (twice a week for 3 months). The investigators will follow the patients to determine clinical outcome. The investigators will also measure clinical, cognitive and brain structural and functional connectivity to asses changes related to the intervention in the short and long term (measurements at: baseline, 2 weeks and 3 months). Procedure: The projects consists of: Screening Visit, Part 1 and Part 2. First, there will be a screening visit, where a clinical interview will be conducted and tests will be applied to select study participants who meet the inclusion and exclusion criteria. Baseline clinical, cognitive and neuroimaging data will be acquired. The cognitive and neuroimaging data will be exploratory, to be associated with the outcome measures. Part 1 of the study entails the determination of the rTMS target frequency (5 or 10 Hz) for Part 2 (long term stimulation). In Part 1, all participants will be randomly assigned to one of the four treatment legs with rTMS (10Hz, 10Hz-Sham, 5Hz, 5Hz-Sham). Participants will receive 20 sessions of rTMS (intervention or sham), twice per day for 10 consecutive days. Each session lasts approximately 35 minutes. At 2 weeks, the investigators will evaluate the short term effect of treatment by measuring clinical, cognitive and neuroimaging changes and select which frequency of stimulation is the most effective in terms of clinical improvement, but also in terms of the rate of secondary effects. Our hypothesis is that 5 Hz is as effective as 10 Hz without the high rate of secondary effects (i.e. seizures). In Part 2 of the study, the sham groups will end and they will be invited to the treatment condition although they data not will be considered for later phases. Here the maintenance phase starts (long term), where rTMS will be performed twice a week for 12 months using the target frequency (5 or 10 Hz). Clinical, cognitive and neuroimaging data will be acquired at 2 weeks and 3 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
40
The investigators will use a Magpro R-30 MagVenture quick stimulator, equipped with an 8-reel, 75 mm internal diameter in each spiral. Each patient will receive consistent treatment in 2 sessions a day for 10 consecutive business days in the first two weeks, then receive 2 weekly sessions, until the year of treatment is completed. Each session will consist of the application of 30 trains of 10 seconds duration separated by intervals of one minute, at a fixed frequency (5Hz or 10Hz), to 100% of the motor threshold.
The investigators will use a Magpro R-30 MagVenture quick stimulator, equipped with an 8-reel, 75 mm internal diameter in each spiral with a coil that allows simulated stimulation (Coil AP). This condition will only last two weeks.
Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz"
Mexico City, Mexico
RECRUITINGChange in Cocaine Craving (CCQ)
The craving will be measured using a craving questionnaire for cocaine validated in Mexican population (Cocaine Craving Questionnaire or CCQ).
Time frame: Baseline, 2 weeks, 3 months
Change in Cocaine Craving (VAS)
The craving will be measured using a 100 mm visual analogue scales (VAS).
Time frame: Baseline, 2 weeks, 3 months
Change in Cocaine Urine Test
Frequency of cocaine use will be measured using reagent strips from Instant View drug screening (\> 300 ng/mL). Results are Positive or Negative.
Time frame: Baseline, 2 weeks, 3 months
Changes in Psychopathological Symptoms
Measured by the 90 Symptoms Questionnaire (SCL-90).
Time frame: Baseline, 2 weeks, 3 months
Changes in Depression
Measured by Hamilton Depression Rating Scale (HDRS) (21 items).
Time frame: Baseline, 2 weeks, 3 months
Changes in Anxiety
Measured by Hamilton Anxiety Rating Scale (HARS).
Time frame: Baseline, 2 weeks, 3 months
Changes in Drug Consumption and Related Problems
Measured by the Addiction Severity Index (ASI-lite).
Time frame: Baseline, 2 weeks, 3 months
Changes in Sleep Quality: PSQI
Measured by the Pittsburgh Sleep Quality Index (PSQI).
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Time frame: Baseline, 2 weeks, 3 months
Changes in Impulsivity
Measured by the Barrat Impulsivity Scale-11 (BIS-11).
Time frame: Baseline, 2 weeks, 3 months
Lapse rate
Lapse is defined as at least one consumption event not in the same pattern as the baseline consumption. The report of self-consumption of cocaine and urine drug tests, with special attention to the presence of traces of cocaine.
Time frame: Baseline, 2 weeks, 3 months
Relapse rate
Relapse is defined as consumption events in the same pattern as the baseline consumption. The report of self-consumption of cocaine and urine drug tests, with special attention to the presence of traces of cocaine.
Time frame: Baseline, 2 weeks, 3 months