Intensive sequential tDCS–rTMS over left DLPFC for biperiden dependence: A case report

Antonio Romeo; Antonio Bruno; Maria Rosaria Anna Muscatello; Fabrizio Turiaco; Antonio Romeo; Antonio Bruno; Maria Rosaria Anna Muscatello; Fabrizio Turiaco

doi:10.3934/Neuroscience.2026021

AIMS Neuroscience

2026, Volume 13, Issue 3: 476-482. doi: 10.3934/Neuroscience.2026021

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Case report

Intensive sequential tDCS–rTMS over left DLPFC for biperiden dependence: A case report

1.
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
2.
Psychiatry Unit, Polyclinic Hospital University of Messina, Messina, Italy

Received: 20 February 2026 Revised: 24 June 2026 Accepted: 02 July 2026 Published: 20 August 2026

Background
Anticholinergic misuse is an underrecognized form of substance use disorder that can be difficult to treat. Noninvasive neuromodulation targeting prefrontal control networks has shown promise across substance use disorders but has not been described for biperiden dependence.
Objective
To report feasibility, tolerability, and preliminary clinical outcomes of a brief, intensive combined neuromodulation protocol; sequential anodal transcranial direct current stimulation (tDCS) followed by high frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (lDLPFC) in a single patient with refractory intramuscular biperiden dependence.
Case and Methods
A 38-year-old man with schizoaffective disorder and borderline personality disorder self-administered up to 15 mg/day of intramuscular biperiden. He underwent an intensive course of neuromodulation consisting of two daily sessions (separated by a 20 minute break) for five consecutive days; each session comprised anodal tDCS to the lDLPFC (1.5 mA; 20 min 6 s) immediately followed by high frequency rTMS to the lDLPFC (15 Hz; 2400 pulses/session; 100% motor threshold). Addictive behavior was assessed with the Addictive Behavior Questionnaire (ABQ, 7DAS subscale) at baseline (T0), end of treatment (T1), and one month follow up (T2); daily vial consumption was recorded.
Results
The 7DAS score decreased from 51 at T0 to 38 at T1, with a partial rebound to 46 at T2. Reported vial consumption fell from ≈3/day at baseline to 0/day by the end of treatment and remained between 0 and 1/day at one month. The intervention was well tolerated; only transient scalp discomfort and mild, short lived headaches were reported.
Conclusions
In this single case, a brief intensive sequential tDCS→rTMS protocol was feasible, well tolerated, and temporally associated with rapid reduction in biperiden use and improvement in addictive behavior scores. Findings are preliminary and hypothesis generating; controlled studies with objective toxicology, standardized stimulation parameters, and longer follow up are needed to evaluate efficacy, mechanisms, and durability.
- biperiden dependence,
- tDCS,
- rTMS,
- left DLPFC,
- neuromodulation
Citation: Antonio Romeo, Antonio Bruno, Maria Rosaria Anna Muscatello, Fabrizio Turiaco. Intensive sequential tDCS–rTMS over left DLPFC for biperiden dependence: A case report[J]. AIMS Neuroscience, 2026, 13(3): 476-482. doi: 10.3934/Neuroscience.2026021

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Abstract

Background

Anticholinergic misuse is an underrecognized form of substance use disorder that can be difficult to treat. Noninvasive neuromodulation targeting prefrontal control networks has shown promise across substance use disorders but has not been described for biperiden dependence.

Objective

To report feasibility, tolerability, and preliminary clinical outcomes of a brief, intensive combined neuromodulation protocol; sequential anodal transcranial direct current stimulation (tDCS) followed by high frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (lDLPFC) in a single patient with refractory intramuscular biperiden dependence.

Case and Methods

A 38-year-old man with schizoaffective disorder and borderline personality disorder self-administered up to 15 mg/day of intramuscular biperiden. He underwent an intensive course of neuromodulation consisting of two daily sessions (separated by a 20 minute break) for five consecutive days; each session comprised anodal tDCS to the lDLPFC (1.5 mA; 20 min 6 s) immediately followed by high frequency rTMS to the lDLPFC (15 Hz; 2400 pulses/session; 100% motor threshold). Addictive behavior was assessed with the Addictive Behavior Questionnaire (ABQ, 7DAS subscale) at baseline (T0), end of treatment (T1), and one month follow up (T2); daily vial consumption was recorded.

Results

The 7DAS score decreased from 51 at T0 to 38 at T1, with a partial rebound to 46 at T2. Reported vial consumption fell from ≈3/day at baseline to 0/day by the end of treatment and remained between 0 and 1/day at one month. The intervention was well tolerated; only transient scalp discomfort and mild, short lived headaches were reported.

Conclusions

In this single case, a brief intensive sequential tDCS→rTMS protocol was feasible, well tolerated, and temporally associated with rapid reduction in biperiden use and improvement in addictive behavior scores. Findings are preliminary and hypothesis generating; controlled studies with objective toxicology, standardized stimulation parameters, and longer follow up are needed to evaluate efficacy, mechanisms, and durability.

Acknowledgments

Informed consent was obtained from the patient for publication of this case report.

Conflict of interest

Antonio Bruno is an editorial board member for AIMS Neuroscience and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests.

Authors' contributions

AR: investigation, data curation, formal analysis, and writing – original draft; AB: conceptualisation, methodology, supervision, writing – original draft, and writing – review & editing; MRAM: conceptualisation, methodology, supervision, writing – original draft, and writing – review & editing; FT: investigation, data curation, formal analysis, and writing – original draft. All authors have read and approved the final manuscript and agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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