Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation on Impulse Inhibition in Abstinent Patients With Methamphetamine Addiction: A Randomized Clinical Trial

IMPORTANCE: Impulsivity during periods of abstinence is a critical symptom of patients who use methamphetamine (MA). OBJECTIVE: To evaluate changes in impulse inhibition elicited by repetitive transcranial magnetic stimulation (rTMS) in patients with MA addiction. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted in Da Lian Shan Addiction Rehabilitation Center, Nanjing, China, from December 1, 2018, to April 20, 2019. Effects of the intervention were examined at 3 time points: after a single session (day 1), 24 hours after 10 repeated sessions (day 11), and at 3 weeks of follow-up (day 31). Men with MA addiction and healthy male control participants were recruited for this study. Data analysis was performed from March 2019 to October 2019. INTERVENTIONS: Patients who use MA were randomized to undergo sham rTMS (36 patients) and or 1-Hz rTMS (37 patients) to the left prefrontal cortex, receiving daily TMS treatments for 10 consecutive days. MAIN OUTCOMES AND MEASURES: The primary outcome was impulse inhibition, which is primarily embodied by accuracy reduction (ie, accuracy cost) from standard to deviant trials in a 2-choice oddball task (80% standard and 20% deviant trials). RESULT: The study included 73 men with MA addiction (mean [SD] age, 38.49 [7.69] years) and 33 male healthy control participants without MA addiction (mean [SD] age, 35.15 [9.68] years). The mean (SD) duration of abstinence for the men with MA addiction was 9.27 (4.61) months. Compared with the control group, patients with MA addiction exhibited greater impulsivity (accuracy cost, 3.3% vs 6.2%). The single session of 1-Hz rTMS over the left prefrontal cortex significantly increased accuracy from 91.4% to 95.7% (F(1,36) = 9.58; P < .001) and reaction time delay from 50 milliseconds to 77 milliseconds (F(1,36) = 22.66; P < .001) in deviant trials. These effects were seen consistently after 10 sessions of 1-Hz rTMS treatment (day 11 vs day 1, t(26) = 1.59; P = .12), and the behavioral improvement was maintained at least for 3 weeks after treatment (day 31 vs day 1, t(26) = 0.26; P = .80). These improvement effects of impulse inhibition were coupled with a reduction in addictive symptoms as measured by cue-induced craving. The pretest accuracy cost was positively correlated with the change in impulse inhibition (r = 0.615; P < .001) and change in craving (r = 0.334; P = .01), suggesting that these 2 behaviors may be modified simultaneously. CONCLUSIONS AND RELEVANCE: These findings suggest that repeated rTMS sessions have sustained effects on impulse inhibition in patients with MA addiction and provide novel data on impulsivity management strategies for addiction rehabilitation. TRIAL REGISTRATION: ChiCTR-ROC-16008541