Long-Term Outcome of Repetitive Transcranial Magnetic Stimulation in a Large Cohort of Patients With Cocaine-Use Disorder: An Observational Study

Abstract

Background: Cocaine is a psychostimulant drug used as performance enhancer throughout history. The prolonged use of cocaine is associated with addiction and a broad range of cognitive deficits. Currently, there are no medications proven to be effective for cocaine-use disorder (CocUD). Previous preliminary clinical work suggests some benefit from repetitive transcranial magnetic stimulation (rTMS) stimulating the prefrontal cortex (PFC), involved in inhibitory cognitive control, decision-making and attention. 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 (of whom 268 were men) meeting DSM-5 criteria for CocUD. At treatment entry, most were using cocaine every day or several times per week. All patients underwent 3 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.Results: Median time to the first lapse (resumption of cocaine use) since the beginning of treatment 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 <1·0 day/month (median 0), while serious rTMS-related adverse events were infrequent, consistent with published reports from smaller studies.Conclusions: 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.

The role of repetitive transcranial magnetic stimulation (rTMS) in the treatment of behavioral addictions: Two case reports and review of the literature

“…Notably, the clinical recovery persisted at 1-year followup after the treatment although both patients experienced unpleasant situations, recognized as triggers for inducing craving for gaming or porn watching in the past. This longlasting clinical improvement over the addictive behaviours with no relapses in both patients is in support of a minimized placebo response and is in line with our previous findings showing that rTMS treatment is accompanied by long-lasting reductions of substance consumption behaviours in a large cohort of patients with cocaine use disorder clinically followed-up for 2 years and 8 months (Madeo et al, 2020).…”

“…This approach has been associated to clinically relevant behavioral changes in patients with addictive disorders (Ekhtiari et al, 2019), affecting craving, intake and relapse (Diana et al, 2017). To date, high-frequency rTMS protocols over the dorsolateral prefrontal cortex, a key node for the executive control network (Shirer, Ryali, Rykhlevskaia, Menon & Greicius, 2012), are effective in reducing craving, substance consumption and withdrawal symptoms of SUD, including alcohol (Addolorato et al, 2017;Mishra, Nizamie, Das & Praharaj, 2010;Mishra, Praharaj, Katshu, Sarkar & Nizamie, 2015), tobacco (Amiaz, Levy, Vainiger, Grunhaus & Zangen, 2009;Eichhammer et al, 2003;Hayashi, Ko, Strafella & Dagher, 2013;Johann et al, 2003;Li et al, 2013), cocaine (G omez P erez et al, 2020;Hanlon et al, 2015;Madeo et al, 2020;Pettorruso et al, 2019;Politi, Fauci, Santoro, & Smeraldi, 2008;Sanna et al, 2019;Steele, Maxwell, Ross, Stein, & Salmeron, 2019;Terraneo et al, 2016), methamphetamine (Liang, Wang & Yuan, 2018;Su et al, 2017) and heroin (Shen et al, 2016). Preliminary findings also suggest that these protocols might ameliorate gambling disorder symptoms (Cardullo et al, 2019;Pettorruso et al, 2020).…”

A Retrospective Comparative Study in Patients With Cocaine Use Disorder Comorbid With Attention Deficit Hyperactivity Disorder Undergoing an rTMS Protocol Treatment

“…Firstly, we considered the lapse to cocaine use. In this analysis, for consistency with our previous works ( 30 , 34 ), the “zero” day for follow-up monitoring was set at 8 days after the initial 5-day course of rTMS. After that 8-day grace period, any indication of cocaine use was coded as a lapse.…”

“…To best identify the L-DLPFC [Montreal Neurological Institute (MNI) coordinates x: −50, y: 30, z: 36], we used an optical TMS navigator (Localite, St. Augustin, Germany) and a magnetic resonance image (MRI) template. Treatment characteristics are the same described in our previous studies ( 30 , 34 ): twice-daily rTMS sessions for the first five consecutive days of treatment, followed by twice-daily rTMS sessions once a week over eleven weeks. The time interval between the two sessions within each day was 45–60 min.…”

Commentary: Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation on Impulse Inhibition Methamphetamine in Abstinent Methamphetamine Patients

“…It is possible that this finding might be generalize to other substances of abuse as well and warrants future large trials investigating the effects of chronic rTMS on impulsive drug seeking behaviors and relapse. Recent studies emphasized the potency of rTMS treatment on drug intake behavior, improve sleep quality and cognition, and efficiency to reduced cue reactivity or craving in a variety of drug dependents (9)(10)(11)(12)(13)(14)(15)(16)(17). It should be noted that most of these results focused on high-frequency (e.g., 10 Hz) rTMS stimulation at left PFC region (18).…”