Comparative assessment of the efficacy and safety of various pharmacological forms of anticholinergic drugs and botulinum therapy for sialorrhea in patients with amyotrophic lateral sclerosis

Background. The problem of sialorrhea treatment in amyotrophic lateral sclerosis remains relevant due to the fact that the symptom significantly worsens the quality of life of patients, is not always immediately treatable, requires selection of therapy and is dangerous -saliva aspiration can cause pneumonia, which is fatal in 50% of cases. Clinical trials for treatments for sialorrhea are few. In the present work, an attempt to study the effect of the entire spectrum of possible drugs for the treatment of this symptom in amyotrophic lateral sclerosis (ALS) was made for the first time. Objective. Comparative assessment of the efficacy and safety of the use of various pharmacological forms of anticholinergic drugs and botulinum therapy in the treatment of sialorrhea in ALS. Methods. 70 ALS patients with bulbar disorders and sialorrhea (30 men, 40 women, age from 39 to 74 years, mean age 55±10.9 years, 55 bulbar onsets, 15 spinal onsets) were examined and consistently included in various therapeutic groups. Efficacy and safety of botulinum therapy (Dysport 250 IU in combination with amitriptyline 25 mg and Dysport 500 IU) and various pharmacological forms of anticholinergics (drops of atropine sulfate alone and in combination with a solution of ipratropium bromide 0.25 mg/ml, amitriptyline 25 mg at night separately and in combination with atropine and ipratropium bromide, Scopoderm patch, hyoscine butylbromide - Buscopan 40 mg/day) were evaluated. An objective assessment was carried out by saliva gravimetry before, 3 days (for Dysport) and 3 months after treatment for all drugs in parallel with the assessment of cognitive functions (Montreal Scale) and emotional-volitional disorders (FTD - Frontotemporal Dysfunction Scale). Results. Anticholinergic cocktail of atropine, ipratropium bromide and amitriptyline did not significantly affect sialorrhea (2.09±1.3 and 1.24±0.84 ml/5 min; P=0.083), but significantly and reversibly worsened cognitive functions (23.1±2.4, 18.1±1.4 and 21±2.1 points; P<0.05), whereas, when administered separately, these drugs did not have a significant effect on either sialorrhea or cognitive functions, as well as the selective peripheral anticholinergic hyoscine butylbromide (1.79±1.26 and 0.87±0.57 ml/5 min; P=0.061). Scopoderm patch effectively reduced sialorrhea (2.14±1.2 and 0.63±0.25 ml/5 min; P=0.03), but reversibly worsened cognitive functions (25.9±1.9, 17.3±2.1 and23.3±1.9points, P=0.03). The combination of Dysport 250 U and amitriptyline 25 mg effectively reduced sialorrhea (2.45±1.39 and 1.19±0.99 ml/5 min; P=0.048) and did not affect cognitive functions, while not adversely affecting the speech of patients. At the same time, an effective decrease in sialorrhea with Dysport at a dose of 500 IU (2.69±0.76 and 1.37±0.42 ml/5 min; P=0.02) was accompanied by an acceleration of the onset of anarthria in ALS patients with dysarthria (82±22 and 36±6 days; P=0.019), however, in ALS patients with anarthria, it was absolutely effective and safe.

amyotrophic lateral sclerosis, cognitive functions, botulinum toxin therapy, anticholinergics