Sustained anxiolytic and antidepressant effects of botulinum toxin A in blepharospasm patients beyond motor symptom control

doi:10.5498/wjp.v16.i1.112973

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World Journal of Psychiatry

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World J Psychiatry. Jan 19, 2026; 16(1): 112973
Published online Jan 19, 2026. doi: 10.5498/wjp.v16.i1.112973

Sustained anxiolytic and antidepressant effects of botulinum toxin A in blepharospasm patients beyond motor symptom control

Xin-Yi He, Min-Ye Xu, Li-Ying Feng, Jian-Ting Zhang, Li-Zuo Jin, Ling Jin, Jian-Chao Ge, Liang Zhang, Wen-Bin Zhang, Li Zhang, Hong Shen, Jun Yan

Xin-Yi He, Min-Ye Xu, Li-Ying Feng, Jian-Ting Zhang, Ling Jin, Jian-Chao Ge, Liang Zhang, Li Zhang, Jun Yan, Department of Geriatrics, Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China

Li-Zuo Jin, School of Automation, Southeast University, Nanjing 210096, Jiangsu Province, China

Wen-Bin Zhang, Department of Functional Neurosurgery, Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China

Hong Shen, Neuro-Psychiatric Institute, Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China

Co-first authors: Xin-Yi He and Min-Ye Xu.

Author contributions: Jin LZ, Shen H, and Yan J conceived and designed the study; He XY, Xu MY, Feng LY, Jin L, Ge JC, and Zhang L collected the data; He XY, Jin LZ, Shen H, and Yan J conducted the data analysis; He XY, Shen H, and Yan J drafted the manuscript; Zhang JT revised the manuscript; Zhang L, Zhang WB, and Yan J obtained the funding. All authors contributed to the article and approved the submitted version. He XY and Xu MY have contributed equally to this work and share the first authorship.

Supported by the Special Funds of Jiangsu Provincial Key Research and Development Projects, No. BE2019612; Scientific Research Project Cooperated by Lanzhou Biotechnology Development Co., Ltd.; the Key R&D Program of Jiangsu Science and Technology Project, No. BE2022049 and No. BE2022049-1; National Natural Science Foundation of China, No. 82171249; Nanjing Rehabilitation Medicine Center Project; and Jiangsu Provincial Health Commission Special Fund for Aging and Health.

Institutional review board statement: The study protocol was reviewed and approved by the Medical Ethics Committee of Nanjing Brain Hospital (approval No. 2019-KY027-01).

Informed consent statement: Written informed consents were obtained from all enrolled patients or their legal guardians.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: No additional data are available.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Jun Yan, MD, Chief Physician, Department of Geriatrics, Affiliated Brain Hospital of Nanjing Medical University, No. 264 Guangzhou Road, Nanjing 210029, Jiangsu Province, China. yanjun2008@njmu.edu.cn

Received: August 14, 2025
Revised: September 27, 2025
Accepted: November 7, 2025
Published online: January 19, 2026
Processing time: 141 Days and 19.5 Hours

Abstract

BACKGROUND

The previous studies have primarily focused on the influence of botulinum toxin A (BoNT-A) injection on emotions during the period of peak motor symptom improvement in blepharospasm patients, based on facial feedback hypothesis.

AIM

To evaluate the sustained anxiolytic and antidepressant effects of BoNT-A in blepharospasm patients beyond motor symptom control.

METHODS

We recruited benign essential blepharospasm patients with BoNT-A treatment and collected their data to compare scale scores of Jankovic Rating Scale, Blepharospasm Disability Index, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Hamilton Anxiety Scale and Hamilton Depression Scale between pre-treatment (baseline) and pre-reinjection (treatment), to further assess the effects of repeated treatments with BoNT by using sub-group analyses in the certain special states.

RESULTS

A total of 21 eligible blepharospasm patients were with the mean age of 58.4 years and a male-to-female ratio of 1:6. Significantly decreases in the subscale scores of SDS and SAS, including SDS well-being index, decreased capacity and hard to decide, SAS inability to sit still and headache were showed at post-a single BoNT-A injection when scale scores of Jankovic Rating Scale and Blepharospasm Disability Index were matched between baseline and post-treatment. With each additional BoNT-A injection, the odds ratio of patients with the moderate depressive symptoms decreased by 92.6%. Moreover, BoNT treatment remained a decrease in the subscale scores of SDS and SAS in patients with repeated injections.

CONCLUSION

This study is to demonstrate that repeated BoNT-A injection have a long-lasting relief for anxiety and depressive symptoms in blepharospasm even after its motor symptom-modulating effects have diminished.

Keywords: Botulinum toxin A; Repeated injection; Neuromuscular junction; Anxiety; Depression; Blepharospasm

Core Tip: Botulinum toxin A (BoNT-A) injection significantly decreases subscale scores of Self-rating Anxiety Scale and Self-rating Depression Scale in blepharospasm even after its effects on facial muscle activity have subside. BoNT-A treatment is an independent factor for the depressive symptom improvement, especially, well-being index in the certain state. BoNT-A might alleviate somatic anxiety but not mental anxiety at a relative long follow-up. Repeated BoNT-A treatment may improve the anxiety and depressive symptoms.