Add-on repetitive transcranial magnetic stimulation in patients with opioid use disorder undergoing methadone maintenance therapy

ABSTRACT

Background: Repetitive transcranial magnetic stimulation (rTMS) shows potential therapeutic effects for individuals with addiction, but few studies have examined individuals with opioid use disorder (OUD).

Objectives: We conducted an add-on double-blinded, sham-controlled rTMS feasibility pilot trial to examine OUD participants undergoing methadone maintenance therapy (MMT). The current report focused on the effects of rTMS on (1) craving and heroin use behavior and (2) depression, impulsivity, and attention.

Methods: Active or sham rTMS treatment was applied to the left dorsolateral prefrontal cortex (DLPFC) over a total of 11 sessions in 4 weeks (15-Hz frequency, 4 seconds per train, intertrain interval of 26 seconds, 40 trains per session) in OUD participants (ClinicalTrials.gov registration number: NCT03229642). Craving, heroin use severity, urine morphine tests, the Hamilton Depression Rating Scale (HDRS), the Barratt Impulsiveness Scale-11 (BIS-11), and the Continuous Performance Tests (CPTs) were measured.

Results: Twenty-two OUD participants were enrolled, of which eleven (8 males) were undergoing active rTMS and nine (8 males) were in the sham rTMS group. After 12 weeks of follow-up, the active rTMS group did not show significantly greater improvements than the sham group with respect to craving, heroin use, or urine morphine test results. However, HDRS scores, BIS-11 attentional subscales, and CPTs commission T-scores (C-TS) were significantly lower in the active rTMS group (P = .003, 0.04, and 0.02, respectively) than in the sham group.

Conclusion: Add-on rTMS did not appear to improve heroin use behavior but may have benefitted depressive symptoms, impulse control and attention in OUD participants undergoing MMT.

KEYWORDS:

• Repetitive transcranial magnetic stimulation
• opioid use disorder
• craving
• depression
• impulsivity

Acknowledgements

The authors would like to thank Miss Shish-Shuan Peng, Chien-Yu Tseng, Hung-Yi Chan, Yu Ting Hung, Mr. De-Cyuan Liu and Hsin-Han Wu for their assistance in the preparation of the manuscript.

Contributors

TYW designed the study and wrote the protocol. WHC, PSC, and YY contributed to the study design and discussion. TYT, YCL, PWL, TYW, and THL contributed to conducting the experiments. TYT, TYW, HHT, and KCC recruited participants. TYW wrote the first draft of the manuscript. SYL, YHC, SLC, PSC, YKY, and RBL provided laboratory and research assistance. All authors contributed to and reviewed the final version of the manuscript.

Conflicts of interest

All authors declare that they have no conflicts of interest.

Primary field of submission

General topics in psychiatry and related fields.

Secondary field of submission

Clinical neurophysiology and neuropsychology.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

The study was supported by research grants from the Ministry of Science and Technology (MOST 106-2314-B-006-037, MOST-107-2314-B-006-067, MOST- 109-2314-B-006-056 to TYW), from the Ministry of Health and Welfare (MOHW107-TDU-B-211-123003, MOHW108-TDU-B-211-133003 to TYW), and the Integrated Drug Addiction Treatment Center of the Jianan Psychiatric Center by Ministry of Health and Welfare in Taiwan. YY is supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, USA.