Non-motor manifestations in patients with cervical dystonia. A literature review and results of a pilot single-arm study on the efficacy of a fixed-dose combination of mirtazapine and tizanidine (Dorsumio) in the management of non-motor manifestation

The article presents a literature review of non-motor disorders and the results of a single-arm interventional study evaluating the effects of Dorsumio on pain and affective manifestations in cervical dystonia. Although cervical dystonia is traditionally considered a motor disorder, contemporary studies highlight a high prevalence of its non-motor manifestations, which significantly determine the patients’ quality of life. The use of botulinum toxin type A does not always correct non-motor disorders. Furthermore, the use of conventional antidepressants (selective serotonin reuptake inhibitors) is limited due to the risk of worsening dystonic hyperkinesis. The combination of mirtazapine (exhibiting anxiolytic and analgesic properties) and tizanidine (a central muscle relaxant) may exert a synergistic effect on pain and affective syndromes. Objective. To evaluate the safety and efficacy of a fixed-dose combination of mirtazapine (15 mg) and tizanidine hydrochloride (6 mg) (Dorsumio) for the management of pain, anxiety, and depression in patients with cervical dystonia receiving stable botulinum toxin type A therapy. Material and methods. A single-arm interventional study was conducted, which included 22 patients (19 women, 3 men; mean age 51±2.9 years) with cervical dystonia. All patients regularly received botulinum toxin type A injections with a confirmed positive effect on motor manifestations (evaluated by the TWSTRS scale). In cases where non-motor symptoms (such as pain, anxiety, low mood) persisted, Dorsumio was additionally prescribed at a dose of 1 tablet in the evening for a 2-month course. Pain assessment was performed using the Visual Analogue Scale (VAS), while anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS). Statistical analysis was performed using the paired Student’s t test and the Wilcoxon signed-rank test. Results. Against the background of botulinum toxin type A therapy in combination with Dorsumio, a significant reduction in motor manifestations of cervical dystonia (clinical improvement) was noted (TWSTRS score: 42.77±9.80 before treatment vs. 33.64±8.37 after treatment; difference: 9.14±1.04; p<0.001). The addition of Dorsumio led to a statistically significant reduction in: pain on the VAS (from 7.05±1.62 points to 4.27±1.67 points; p<0.01), anxiety on the HADS (from 12.67±1.80 points to 8.42±2.08 points; p<0.001), and depression on the HADS (from 7.14±2.40 points to 5.76±1.93 points; p<0.01). Adverse events (somnolence in 13.6% of patients, dry mouth in 23.0% of patients, and increased appetite in 23.0% of patients) were mild and did not lead to treatment discontinuation. Conclusion. Analysis of the literature data on the structure of mental, sensory, and dyssomnic disorders in cervical dystonia showed that anxiety-depressive disorders occur in 20—63.6% of cases, obsessive-compulsive disorders in 6.7—21.1% of cases, pain syndrome in up to 88.9% of cases, and insomnia in 65—72% of cases. The fixed-dose combination of mirtazapine and tizanidine (Dorsumio) can be considered a safe and effective adjunct therapy option for the management of pain syndrome and affective disorders in patients with cervical dystonia who have persistent non-motor disorders despite adequate motor correction with botulinum toxin type A. The obtained data warrant confirmation in randomized controlled trials.