INTRODUCTION

Musician’s dystonia is the manifestation of dystonic symptoms only when playing a musical instrument [1]. Treatment of musician’s dystonia includes oral medications and botulinum toxin treatment, but neurosurgical treatment is considered when these treatments fail [1,2]. Because neurosurgical treatment can have irreversible complications, its indication should be considered a last resort for treatment.

The efficacy of zolpidem for treating movement disorders in patients with dystonia and Parkinson’s disease has been reported [3-7]. We previously reported that zolpidem was significantly effective in treating residual dystonic symptoms in patients who had undergone neurosurgical treatments for dystonia [3]. Because of the high efficacy of zolpidem in patients with upper extremity focal dystonia in that study, we started to use zolpidem for the treatment of focal dystonia. Here, we report the efficacy and safety of zolpidem for treating musician’s dystonia.

MATERIALS & METHODS

Patient population

We retrospectively reviewed medical records between January 2021 and December 2023 to identify patients with musician’s dystonia who had been prescribed zolpidem. Patients were excluded if they had incomplete data for the Tubiana Musician’s Dystonia Scale (TMDS) assessment, no reported duration of zolpidem’s effect, or if they used additional medications or botulinum toxin injections after starting zolpidem.

Medication

A single dose of 5 mg of zolpidem was prescribed daily. The dose was subsequently increased to a single dose of 10 mg daily. In the case of difficulty in continuing zolpidem owing to side effects, such as drowsiness, the dose was decreased to a single dose of 2.5 mg per dose. The patients were allowed to take zolpidem several times per day if the daily dose was <10 mg.

Evaluation

Evaluations were performed 1–2 h after oral administration of zolpidem via video at home. The TMDS was used: 1) plays several notes but stops because of blockage or lack of facility; 2) plays short sequences without rapidity and with unsteady fingering; 3) plays easy pieces but is unable to perform more technically challenging pieces; 4) plays almost normally but difficult passages are avoided because of fear or motor problems; and 5) returns to concert performances [8]. Patients rated themselves using the TMDS. Patients were instructed to videotape their performances at home, and these recordings were subsequently reviewed by both the patients and their physicians to validate the accuracy of the self-assessments. The duration of zolpidem’s effect was assessed by asking patients to report the time from administration until the end of the effect during musical performances. Side effects were reported by patients during follow-up consultations.

Statistical analysis

Statistical analysis was performed using the JMP statistical package, version 15.0.0 (SAS Institute, Cary, NC, USA). Because the data were nonnormally distributed, nonparametric tests were performed. Therefore, the Wilcoxon signed-rank test was performed to compare pre- and posttreatment TMDS scores. Statistical significance was set at a p value < 0.05.

Ethical considerations

The data for this study were retrospectively collected and analyzed. The Ethics Committee of Tokyo Women’s Medical University approved this study (2021-0169), and considering its observational nature, the requirement for patient consent was waived. Written informed consent was obtained for the publication of the videos.

Data sharing

The data are available from the corresponding author upon reasonable request.

RESULTS

The patient demographics and clinical characteristics are presented in Table 1. Fifteen patients were analyzed in this study, including 12 with focal hand dystonia, 2 with embouchure dystonia, and 1 with dystonic head tremor. Nine participants were professional musicians, 5 were music teachers, and 1 was a music college student. The mean effective dose of zolpidem was 5.3 ± 2.0 mg. The mean effective duration of zolpidem was 4.3 ± 1.2 h. With zolpidem administration, the TMDS score significantly improved from 2.2 ± 1.0 to 4.3 ± 0.8 (48.9% improvement, p < 0.001). Two patients (Cases 12 and 13, 13.3%) discontinued the medication due to insufficient efficacy, whereas another two patients (Cases 14 and 15, 13.3%) discontinued due to severe drowsiness. The remaining 11 patients (73.3%) experienced significant symptomatic improvement and continued the medication. One patient (Case 9) with dystonic head tremors responded well to zolpidem; however, because tremors occurred not only during instrumental playing but also at other times, the limited duration of zolpidem’s effect was insufficient to significantly improve the patient’s quality of life. Therefore, the patient underwent deep brain stimulation (DBS) 2 years after receiving oral medication. Two patients (Cases 12 and 13) were unable to continue their careers as professional musicians. One patient (Case 12) experienced complete remission of dystonia through stereotactic ventro-oral thalamotomy and successfully returned to their professional musical career. One patient (Case 13) continues to experience significant difficulties due to the lack of efficacy of zolpidem and other medications. All other patients were able to maintain their professional careers. The effectiveness of zolpidem can be demonstrated through videos of three representative cases (Supplementary Video 1 in the online-only Data Supplement).

Five patients did not experience any drowsiness owing to the effective dose of zolpidem. Ten patients felt drowsy, but 8 of them were drowsy enough to not interfere with the performance itself. One patient experienced a right-hand fracture due to a traffic accident caused by drowsy driving. Despite this, the medication was effective, and the patient continued its use. The accident occurred 4 h after the participants took zolpidem for a concert and was thought to have been caused by zolpidem.

DISCUSSION

The effective duration of zolpidem was 4.4 h, which covered the time required to play the instrument in rehearsals, concerts, and examinations. Eleven patients continued to take zolpidem for continue their work as musicians. None of the patients required any other pharmacological treatment or botulinum toxin injection. Two professional musicians (Cases 9 and 12) underwent surgery because of insufficient response to zolpidem, other oral medications, and botulinum toxin treatment. As a result, the patients experienced dramatic improvement in their dystonia symptoms and returned to their occupations. One disadvantage of zolpidem is that it induces severe drowsiness. Drowsiness occurred in 10 of the 15 patients, and 2 patients discontinued the drug owing to strong drowsiness and inadequate effects. Two patients developed amnesia after taking 10 mg of the drug. Taking zolpidem during the day increases the risk of falls due to unsteady gait and traffic accidents due to drowsy driving. It is extremely important to advise patients not to drive while under zolpidem treatment.

There are extremely few reports on medical treatment for musician’s dystonia. In a report by Jabusch and Altenmüller [1], 69 patients with musician’s dystonia were treated with an average of 11 mg/day of trihexyphenidyl. Among these patients, 23 (33%) experienced symptomatic improvement, and 20 (29%) discontinued the treatment within 2 months owing to side effects and a lack of efficacy [1]. Bledsoe et al. [9] reported the clinical characteristics of 12 patients with drummer’s dystonia. Pharmacological treatments, including carbidopa/levodopa, trihexyphenidyl, clonazepam, diazepam, lorazepam, and baclofen, which are largely ineffective, were prescribed [9]. Only two patients (16.7%) experienced mild benefits. One patient showed mild benefit with trihexyphenidyl, and another patient showed some improvement with diazepam [9].

We have previously documented surgical interventions, including radiofrequency, gamma knife and focused ultrasound ablation, for treating musician’s dystonia [2,10-13]. In cases where dystonia affects the upper or lower limbs, we perform thalamotomy targeting the Vo nucleus of the thalamus [2,10-12], whereas for embouchure dystonia, which impacts the lip region, we conduct pallidotomy targeting the internal segment of the globus pallidus [13]. The efficacy of DBS for the Vo nucleus of the thalamus has also been verified by Poncelet et al. [14] These surgical targets are located adjacent to the posterior limb of the internal capsule, posing a risk of irreversible motor deficits due to potential cerebral hemorrhage. Such complications could hinder musicians from performing. Additionally, excessive reduction in muscle tone from lesions in the Vo nucleus or internal segment of the globus pallidus could compromise the rapid and precise motor functions required for professional musical performance, even if the dystonia is relieved. To mitigate these risks, DBS is recommended, as it is less likely to cause such side effects. However, DBS presents its own challenges, including reluctance to undergo device implantation and device-related complications such as infections or rejection. Ideal candidates for these surgical procedures are those musicians whose dystonia is so severe that it completely prevents them from playing. For upper limb dystonia, this often means that the symptoms are present during all hand movements, not just when playing an instrument. In the initial stages, musician’s dystonia is typically instrument specific. During this period, nonsurgical treatments such as medication or botulinum toxin therapy should be considered before opting for surgery.

We used clonazepam, trihexyphenidyl, and baclofen in our daily clinical practice and did not observe a dramatic improvement in symptoms compared with zolpidem use. Zolpidem is superior to other agents in its ability to produce dramatic symptomatic improvement over a short period. In contrast, zolpidem should be administered orally several times a day to control dystonia because it causes severe drowsiness or sleepiness. We believe that zolpidem can be an effective medication for musician’s dystonia that requires symptomatic improvement only when playing musical. Our findings revealed that 86.7% of patients experienced symptomatic improvement and continued their professional musical careers. Since the use of zolpidem for musician’s dystonia, few cases have been indicated for surgery at our hospital. This study has several limitations: it is retrospective, open-label, and involves a small patient cohort. In the evaluation of TMDS, one limitation is that patients scored themselves, which introduces the potential for bias. Additionally, the study did not aim to ascertain the optimal dosage of zolpidem for musician’s dystonia. To address these limitations, future double-blind controlled trials with more participants are necessary to confirm the efficacy of zolpidem and determine the optimal dosage.

In conclusion, this study suggests that zolpidem may be an alternative treatment option for musician’s dystonia.

Supplementary Materials

Video 1.

Zolpidem-off and zolpidem-on conditions in Cases 8, 11, and 14.

Notes

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

This work was supported by the Japan Society for the Promotion of Science KAKENHI (Grant JP21K09113) and the Japan Brain Foundation.

Author Contributions

Conceptualization: Shiro Horisawa. Formal analysis: Shiro Horisawa. Funding acquisition: Shiro Horisawa. Investigation: Shiro Horisawa, Kilsoo Kim, Masato Murakami, Masahiko Nishitani. Project administration: Shiro Horisawa. Resources: Shiro Horisawa. Supervision: Takakazu Kawamata, Takaomi Taira. Writing—original draft: Shiro Horisawa. Writing—review & editing: Shiro Horisawa.

Acknowledgments

None

REFERENCES

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