Adjunctive repetitive transcranial magnetic stimulation in patients with substance use disorder

To assess clinical outcomes (abstinence, craving, substance use frequency, psychiatric complications, and adverse effects) and identify factors associated with these outcomes in patients with substance use disorder (SUD) who received treatment as usual (TAU) with or without adjunctive repetitive transcranial magnetic stimulation (rTMS).

Chinese patients aged ≥18 years with a diagnosis of SUD who received TAU with or without adjunctive rTMS at United Christian Hospital, Hong Kong, between September 2022 and May 2025 were identified. Eligible patients were approached for assessment using convenience sampling. The TAU group received psychiatric assessment and treatment, detoxification, counselling, and management of comorbid mental illness; the rTMS group additionally received at least 10 sessions of high-frequency (15 Hz) rTMS targeting the left dorsolateral prefrontal cortex twice daily. Participants were followed up at 1, 3, and 6 months. Abstinence was determined based on self-reported remission of SUD, supplemented by urine toxicology results when available. Psychiatric complications were based on psychiatric admissions and accident and emergency department admissions related to substance use. Reductions in craving and substance use and adverse effects of rTMS were recorded.

Of 385 and 90 patients with SUD who received TAU alone and TAU with adjunctive rTMS, respectively, 52 and 57 patients, respectively, were approached for assessment. Of these, 37 and 43 patients, respectively, were included in the analysis. There was a trend towards earlier 1-month abstinence with rTMS (hazard ratio = 1.68, p = 0.132). In Cox regression, the rTMS and TAU groups were comparable in terms of time to 1-month abstinence (48.8% vs 32.4%), hazard ratio [HR] = 1.680, p = 0.132), time to 3-month abstinence (32.6% vs 21.6%, HR = 1.597, p = 0.272), and time to 6-month abstinence (14.0% vs 16.2%, HR = 0.873, p = 0.810). Craving reduction was significantly greater in the rTMS group than in the TAU group from baseline to 1 month (4.0 vs 0.5, p < 0.001) and from baseline to 3 months (4.0 vs 1.5, p < 0.001) but not from baseline to 6 months (3.50 vs 2.50, p = 0.217). Substance use frequency significantly decreased from baseline to 1, 3, and 6 months in both groups (all p < 0.001). The rTMS group had fewer accident and emergency department admissions, fewer psychiatric admissions, and fewer days of psychiatric admission. No rTMS-related adverse effects were reported. In the TAU group, lower baseline craving predicted a higher likelihood of 1-month abstinence and remained significant after adjustment (odds ratio = 0.659, p = 0.018). In the rTMS group, antidepressant use predicted a lower likelihood of 1-month abstinence and remained significant after adjustment (odds ratio = 0.211, p = 0.041). Allocation to the rTMS group predicted greater craving reduction at 1 month (β = 3.140, p < 0.001) and at 3 months (β = 2.089, p = 0.001). More previous psychiatric admissions (β = -0.308, p = 0.039) and receipt of rTMS in an inpatient setting (β = -1.944, p = 0.041) predicted smaller craving reductions at 3 months.

Adjunctive rTMS was associated with greater craving reduction at 1 and 3 months but did not significantly shorten the time to achieve 1-month abstinence. Higher baseline craving in the TAU group and antidepressant use in the rTMS group were associated with a lower likelihood of achieving 1-month abstinence.