Abstract
Background: There is no approved neurobiological treatment for cocaine-use disorder (CocUD). Previous preliminary clinical work suggests some benefit from repetitive transcranial magnetic stimulation (rTMS) of left dorsolateral prefrontal cortex (l-DLPFC), but all published studies to date have been limited by small sample sizes and short follow-up times. Methods: This is a retrospective observational study of 284 outpatients cohort meeting DSM-5 criteria for CocUD. At treatment entry, most were using cocaine every day or several times per week. All patients underwent three months of rTMS and were followed for up to 2 years, 8 months. Self-report, reports by family or significant others, and regular urine screens were used to assess drug use. Outcome: Median time to the first lapse (resumption of cocaine use) since the last rTMS session was 91 days. For most patients, TMS was re-administered weekly, then monthly, throughout follow-up. The decrease in frequency of rTMS sessions was not accompanied by an increase in lapses to cocaine use. Mean frequency of cocaine use was less than 1·0 day/month (median 0), while serious rTMS-related adverse events were infrequent, consistent with published reports from smaller studies. Interpretation: This is the first follow-up study to show that rTMS treatment is accompanied by long-lasting reductions in cocaine use in a large cohort. Funding. Novella Fronda Foundation, Human Science and Brain Research, Padua, Italy. Declaration of Interest: The authors have no conflicts of interest to disclose. Ethical Approval: The study protocol was approved by the Local Ethics Committee of University of Padua (Protocol 2551, number code: A0A52E7461375325ABBC1C2D9C54F844).
Highlights
Cocaine is a psychostimulant drug generally used as enhancer of cognitive performances, confidence, sociability, energy, and wakefulness
Previous preliminary clinical work suggests some benefit from repetitive transcranial magnetic stimulation stimulating the prefrontal cortex (PFC), involved in inhibitory cognitive control, decision-making and attention
The decrease in frequency of repetitive transcranial magnetic stimulation (rTMS) sessions was not accompanied by an increase in lapses to cocaine use
Summary
Cocaine is a psychostimulant drug generally used as enhancer of cognitive performances, confidence, sociability, energy, and wakefulness. The traditional strategy has been to develop medications or psychological interventions to attenuate drug reward, which is mainly mediated by the dopaminergic pathway from the ventral tegmental area (VTA) to the nucleus accumbens This approach has not resulted in effective therapeutic interventions for cocaine addiction. As we and others have suggested, rTMS of left dorsolateral prefrontal cortex (l-DLPFC) may represent a human translation of preclinical findings that cocaine-seeking is attenuated by optogenetic activation of specific prefrontal circuits [2, 3]. Both preclinical and clinical findings suggest that DLPFC has a key role in top-down modulation of emotional and behavioral processes relevant to addiction [4, 5]. All published studies to date have been limited by small sample sizes and short follow-up times
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