Table 2.
Characteristics of the included studies.
| Author (Year), Country | Study Design | Population | No. of Participants | Intervention | Stimulation Area | Stimulation Protocol | Frequency (Hz) and Intensity (% RMT) | Comparator | Outcomes | Measures |
|---|---|---|---|---|---|---|---|---|---|---|
| Bolloni (2016) [41], Italy, USA and Israel | RCT | CUD (DSM-5) Male: n=16 Female: n = 2 Mean age: 27–48 years |
n = 18 | Deep rTMS | Bilateral PFC | 12 rTMS sessions were administered three times a week for 4 weeks | 10 Hz 100–120% |
Sham | Cocaine intake (hair analysis) | Baseline, after 1 month and 3 and 6 months later |
| Gómez (2020) [20], Italy | CS | CUD (DSM-5) Male: n = 85 Female: n = 2 Mean age: 37.67 years |
n = 87 | rTMS | Left-DLPFC | 2 sessions per day for the first 5 consecutive days of treatment (10 sessions), and 2 sessions per week for the following 12 weeks. | 15 Hz 100% |
NA | Cocaine use (self-report and urine screens) Craving (CCQ) Sleep Quality (PSQI) Depression (BDI-II) Anxiety (SAS) Symptoms (SCL-90) |
Baseline, and after 5, 30, 60, and 90 days of rTMS treatment. |
| Hanlon (2015) [15], USA |
RCT | Cocaine users Male: n = 9 Female: n = 2 Mean age: 39 years |
n = 11 | cTBS | MPFC | 2 stimulation visits (occurring within 7–14 days of each other). | 5 Hz 110% |
Sham | Craving (VAS) | Before and after the cTBS session |
| Hanlon (2017) [42], USA |
RCT | Cocaine users Male: n = 12 Female: n = 3 Mean age: 42 years |
n = 25 | cTBS | MPFC | 2 stimulation visits (occurring within 7–14 days of each other) with exposure to 6 trains of cBTS. | 5 Hz 110% |
Sham | Craving (VAS) | Before and after the cTBS session |
| Madeo (2020) [43], Italy and USA |
CS | CUD (DSM-5) Male: n = 139 Female: n = 8 Mean age: 36.6 years |
n = 147 | rTMS | Left-DLPFC | 2 rTMS sessions per day for the first 5 days, then weekly, twice per day on each session day for 11 consecutive weeks. | 15 Hz 100% |
NA | Cocaine use (urine screening, self-report and reports by collateral informants) | Baseline, after 3 months of rTMS and up to 2 years. |
| Martínez (2018) [44], USA and Israel | RCT | CUD (DSM-5) Male: n = 17 Female: n = 1 Mean age: 43.3 years |
n = 18 | rTMS | MPFC | The rTMS was delivered on weekdays, over the course of 3 weeks. | HF: 10 Hz LF: 1 Hz 90–110% |
Sham | Number of doses chosen during self-administration Craving (VAS) |
Baseline, after 4 days and after 13 days of rTMS. |
| Pettorruso (2019) [45], Italy and UK | CS | CUD (DSM-5) Male: n = 4 Female: n = 2 Mean age: 36.63 years |
n = 16 | rTMS | Left-DLPFC | 20 stimulation sessions (2 daily, 5 d/week) for 2 weeks and 2 consecutive maintenance rTMS sessions once a week for 2 weeks. | 15 Hz 100% |
NA | Cocaine use (urine test) Cocaine withdrawal signs and symptoms (CSSA) Craving (CSSA) Depression (BDI) Anxiety (SAS) Global Psychopathology (SCL-90) Insomnia (ISI) |
Baseline, after 2 and after 4 weeks of rTMS treatment. |
| Politi (2008) [46], Italy | CS | CUD (DSM-IV) Male: n = 31 Female: n = 5 Mean age: NI |
n = 36 | rTMS | Left-DLPFC | 10 daily sessions of rTMS. | 15 Hz 100% |
NA | Craving (VAS) | During sessions of rTMS. |
| Rapinesi (2016) [17] Italy | CS | CUD (DSM-IV) Male: n = 7 Female: n = 0 Mean age: 48.71 years |
n = 7 | Deep TMS | Bilateral PFC | 3 weekly sessions on alternate days for 4 consecutive weeks, for a total of 12 sessions. | 20 Hz 100% |
NA | Craving (VAS) | Baseline and after 2, 4 and 8 weeks of treatment. |
| Sanna (2019) [47], Italy | nRCT | CUD (DSM-5) Male: n = 45 Female: n = 2 Mean age: 37.40 years |
n = 47 | iTBS | PFC | 20 stimulations over 4 weeks: 10 stimulations during the 1st week, 4 stimulations during the 2nd week, 3 stimulations during the 3rd and 4th week. |
HF rTMS: 15 Hz; 100% iTBS: 5 Hz; 80% |
HF rTMS | Cocaine use (urine test) Craving (CCQ-brief) Risk for developing problems due to the use of cocaine (ASSIST) |
Baseline, weekly during treatment and at the end of treatment. |
| Steele (2019) [48], USA | CS | CUD (DSM-5) Male: n = 13 Female: n = 6 Mean age: 47.4 years |
n = 19 | iTBS | Left-DLPFC | 3 iTBS sessions per day, with an interval of approximately 60-min between sessions, for 10 days over a 2-week period (30 total iTBS sessions). | 5 Hz 90–120% |
NA | Amount of money spent on cocaine consumption Craving (CCS and CCQ) iTBS side effects Depression (MADRS) |
Baseline, during, and after the intervention and at 1-and 4-week follow-up visits. |
| Terraneo (2016) [13], Italy | RCT | CUD Male: n = 30 Female: n = 2 Mean age: 40.28 years |
n = 32 | rTMS | Left-DLPFC | 1 rTMS session per day during the first 5 days of treatment, and then once a week for the following 3 weeks, for a total of 8 rTMS sessions. | 15 Hz 100% |
Pharmacological agents | Cocaine use (urine test) Craving (VAS) Adverse events Depression (SCL-90) |
Baseline, after 29-day treatment and after 63-day follow-up. |
ASSIST: Alcohol, Smoking and Substance Involvement Screening Test; BDI-II: Beck Depression Inventory-II; cBTS: continuous theta burst stimulation; CCQ: Cocaine Craving Questionnaire; CCQ: Cocaine Craving Questionnaire; CCSA: Cocaine Selective Severity Assessment; CIP: Cocaine-Induced Psychosis Screener; CS: case-series; CUD: cocaine use disorder; DLPFC: dorsolateral prefrontal cortex; DSM: Diagnostic and Statistical Manual of Mental Disorders; HF: high frequency; ISI: Insomnia Severity Index; cTBS: continuous theta burst stimulation; iTBS: intermittent theta burst stimulation; LF: low frequency; MADRS: Montgomery–Asberg Depression Rating Scale; MPFC: medial prefrontal cortex; NA: Not applicable; NA: not applicable; RCT: randomized controlled trial; NI: No Information; nRCT: non-randomized controlled trial; PFC: prefrontal cortex; PSQI: Pittsburgh Sleep Quality Index; RMT: resting motor threshold. rTMS: repetitive transcranial magnetic stimulation; SAS: Self-rating Anxiety Scale; SAS: Zung Self-Rating Anxiety Scale; SCL-90: Symptom checklist 90-revised; UK: United Kingdom; USA: United States of America; VAS: visual analogue scale.