Dear Editor,

Hemifacial spasm (HFS) is an involuntary contraction of facial muscles caused by facial nerve dysfunction that affects approximately 10 out of 100,000 individuals worldwide. It causes not only functional discomfort but also social isolation due to psychological distress, which greatly affects quality of life [1].

Botulinum toxin injection is the most common treatment, providing symptom relief in approximately 85% of patients. However, repeated injections every 3–6 months are needed because of its short duration of action [2]. Microvascular decompression of the facial nerve is effective when the facial nerve is adjacent to the blood vessels, with approximately 90% surgical success. However, complications such as facial paresis, hearing loss, and vertigo-ataxia may occur [2]. In addition, various drugs, such as anticonvulsants, anticholinergics, benzodiazepines, and muscle relaxants, can be used to relieve symptoms; however, none have been proven effective, and descriptive analyses of their effects are limited [2]. Oral medications are easily accessible and have a lower risk of long-term or permanent complications than other treatment options do.

Therefore, this study aimed to describe patient-perceived responses to four medications commonly used for HFS.

We reviewed the medical records of 117 patients with HFS who received pharmacological treatment at the Movement Disorder Clinic, Seoul National University Hospital, between 2011 and 2020. Upon diagnosis, patients received 7-day doses of four medications: 1.5 mg/day clonazepam, 6 mg/day trihexyphenidyl, 200 mg/day carbamazepine, and 30 mg/day baclofen, sequentially. This protocol was part of the standard clinical practice at our institution. Patients could discontinue or reduce the dose if they experienced adverse effects. At the 4-week follow-up, the patients self-reported their therapeutic responses to each medication dichotomously (beneficial vs. not beneficial). Cochran’s Q test was used to compare the responses among the four drugs.

Among the 117 patients who were prescribed medications, 30 did not return for follow-up, two discontinued use due to adverse effects, and 11 did not try all the medications. The therapeutic response data were missing for 11 patients. Therefore, 63 patients were included in the final analysis. The baseline characteristics of the included and excluded patients are shown in (Supplementary Table 1. The mean age was 58.1±11.0 years, and 70% were women. Forty patients underwent magnetic resonance imaging (MRI) of the internal auditory canal, 27 of whom had neurovascular contacts that compressed the facial nerve. Among the 12 patients with prior facial palsy, four underwent electrophysiological studies: two demonstrated lateral spread responses consistent with HFS, one showed facial neuropathy, and one had normal findings. No abnormalities in the blink reflex system suggestive of synkinesis were detected.

Carbamazepine had a favorable response in 19 of the 63 patients (30%), followed by clonazepam (17/63, 27%), baclofen (16/63, 25%), and trihexyphenidyl (12/63, 19%) (Figure 1A and Supplementary Table 2). No significant differences were found among the four drugs (p=0.400). In addition, 26 patients found all of the drugs to be ineffective (Figure 1B). With respect to overlap, 22 patients (35%) responded to only one medication, seven (11%) to two medications, and four each (6%) to three and four medications (Figure 1C).

Patients with neurovascular contact as revealed by MRI showed similar therapeutic responses to clonazepam (9/27, 33%), trihexyphenidyl (9/27, 33%), carbamazepine (9/27, 33%), and baclofen (8/27, 30%), with no significant differences detected among the four drugs (p=0.972) (Figure 1A and Supplementary Table 2). The drugs showed overall lower therapeutic responses across patients without neurovascular contact (n=13): clonazepam (3/13, 23%), carbamazepine (3/13, 23%), baclofen (3/13, 23%), and trihexyphenidyl (2/13, 15%), with no significant differences (p=0.925). When the two groups were compared, the response rates for each medication tended to be higher in patients with neurovascular contact, but they did not significantly differ (all p>0.05) (Supplementary Table 3).

Although previous studies have reported the effects of various medications for treatment of HFS, most have been limited to case reports [3]. Only one randomized clinical trial from Korea evaluated the efficacy and safety of clonazepam in patients with HFS; however, the results were not statistically significant [4].

This study describes patient-reported therapeutic responses to medications commonly used for HFS. We chose clonazepam, carbamazepine, and baclofen, which act as γ-aminobutyric acid receptor agonists, to reduce the hyperactivity of facial motor neurons, and we chose trihexyphenidyl, which acts as a muscarinic acetylcholine receptor antagonist in the facial motor nucleus, to reduce excessive stimulation of the facial nerve and muscles [5]. Overall, 59% of the patients (37/63) reported a favorable response to at least one medication. However, none of the drugs showed superiority, with comparable response rates of 20%–30%. Similarly, no significant differences were observed among responses to the four medications in patients with neurovascular contact on MRI. Therefore, selecting a drug that has no adverse effects on the patient may be reasonable.

Considering that the doses used in our patients were lower than the commonly used ranges (clonazepam, 0.5–4 mg/day; carbamazepine, 400–1,200 mg/day; and baclofen, 15–80 mg/day), it is possible that the patients did not feel a sufficient effect because of the use of suboptimal doses [2]. However, higher doses may increase the risk of adverse effects. Unfortunately, we did not collect data on adverse effect profiles, which are important to consider in clinical practice because drug adherence is influenced by both efficacy and tolerability.

This study has several limitations. First, because this was a retrospective chart review, placebo effects could not be excluded, as drug responses were evaluated subjectively without a control group. Second, drug doses were determined empirically on the basis of the clinician’s experience. Third, we used medications sequentially, without a washout period and in a fixed order. Given that clonazepam, which has the longest half-life (30–40 h) among the four drugs, may have caused carry-over effects that influenced responses to subsequent agents, particularly trihexyphenidyl, the reported responses to individual medications should be interpreted with caution. Fourth, therapeutic responses were assessed dichotomously on the basis of patient self-reports, which might reflect subjective satisfaction rather than objective or graded symptom improvement.

Despite these limitations, because few studies have established oral drug protocols or compared therapeutic responses in clinical practice, the findings of this study may be beneficial for clinicians managing patients with HFS. Notably, 60% of patients reported symptomatic benefit, suggesting that oral medication could be considered a potential initial option before botulinum toxin injection or surgical treatment.

Supplementary Materials

Notes

Ethics Statement

This study was approved and deemed exempt by the Institutional Review Board of Seoul National University Hospital (IRB No. 2406-018-1540). The requirement for informed consent was waived due to the retrospective design of the study.

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

None

Acknowledgments

None

Author Contributions

Conceptualization: Han-Joon Kim. Data Curation: Su Hyeon Ha. Formal analysis: Su Hyeon Ha. Investigation: Su Hyeon Ha. Methodology: Han-Joon Kim. Project administration: Su Hyeon Ha. Supervision: Han-Joon Kim. Writing—original draft: Su Hyeon Ha. Writing—review & editing: Han-Joon Kim, Seoyeon Kim, Seungmin Lee, Bora Jin, Kyung Ah Woo, Jung Hwan Shin.

Figure 1.

Medication response patterns in patients with hemifacial spasm. A: Percentage of favorable responses to each medication in the overall population and across subgroups defined by disease duration, history of facial palsy, and internal auditory canal magnetic resonance imaging (IAC MRI) findings. B: Proportion of patients who responded to at least one medication versus none. C: Distribution of overlapping responses according to the number of medications to which patients responded.

REFERENCES

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• 2. Green KE, Rastall D, Eggenberger E. Treatment of blepharospasm/hemifacial spasm. Curr Treat Options Neurol 2017;19:41.ArticlePubMedPDF
• 3. Alexander GE, Moses H 3rd. Carbamazepine for hemifacial spasm. Neurology 1982;32:286–287.ArticlePubMed
• 4. Baek SH, Shin JY, Sohn SY, Park KH, Kim JS, Kim B, et al. Safety and efficacy of clonazepam in patients with hemifacial spasm: a double-blind, randomized, placebo-controlled trial. Parkinsonism Relat Disord 2022;103:1–6.ArticlePubMed
• 5. Ollat H. Pharmacology of hemifacial spasm. In: Sindou M, Keravel Y, Møller AR. Hemifacial Spasm: A Multidisciplinary Approach. Vienna: Springer Vienna. 1997;125-134. Article

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