REVIEW ARTICLE

Year : 2022  |  Volume : 5  |  Issue : 3  |  Page : 153-158

Treatment of sialorrhea in Parkinson’s disease

Sahil Mehta, Vivek Lal
Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Correspondence Address:
Dr. Sahil Mehta
Associate Professor, Department of Neurology, Post Graduate Institute of Medical Sciences and Research, Chandigarh - 160 012
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AOMD.AOMD_9_22

Sialorrhea is a common disabling nonmotor symptom of Parkinson’s disease. It can lead to several ill effects such as poor orodental hygiene, speech and feeding difficulty, depressive symptoms, poor quality of life, and aspiration pneumonia. It most likely occurs secondary to swallowing dysfunction due to a combination of factors such as lingual bradykinesia, oropharyngeal dysphagia, and esophageal dysmotility, leading to impaired salivary clearance. Various tools are available for its objective assessment to assess drooling in patients with Parkinson’s disease. The treatment options include use of anticholinergic medications and optimization of dopaminergic therapy. However, their use is limited due to the occurrence of adverse effects. Botulinum toxin injections into the parotid and submandibular glands is the most effective and safest treatment available at present.

Keywords: Anticholinergics, botulinum toxin, glycopyrrolate, Parkinson’s disease, sialorrhea

Introduction

Treatment options

• 1. The first step is to withdraw medications that may aggravate drooling, if possible, such as antipsychotics (clozapine or quetiapine) and cholinesterase inhibitors (donepezil and rivastigmine).^[6],[7]



• 2. The second step is optimization of dopaminergic treatment or use of invasive therapies such as deep brain stimulation, if clinically indicated and justified.



• 3. The third step is to begin specific adjunctive treatment as described below:
  • A. Anticholinergics: Anticholinergics reduce salivary secretion by inhibiting the binding of acetylcholine to muscarinic receptors (especially M3) in the salivary glands. The commonly used drugs from this class include oral glycopyrrolate, oral trihexyphenidyl, sublingual atropine, and sublingual ipratropium bromide. The potential adverse effects with these medications include confusion, hallucinations, urinary retention, and constipation. Since glycopyrrolate is a quaternary ammonium compound, it does not readily cross the blood–brain barrier and has less potential to induce the abovementioned side effects. It can be used at a dose of 1–2 mg two or three times daily. Arbouw et al.^[8] demonstrated a >30% improvement on the sialorrhea rating scale at 4 weeks in their double-blind placebo-controlled trial. Mestre et al.^[9] recently demonstrated the efficacy of glycopyrrolate for sialorrhea-related disability and severity in PD (mean duration 10 years) up to 3 months at a dose of 4.5 mg/day. The results were statistically significant (p < 0.05) at 6 weeks of treatment. Adverse effects occurred with a dose of >3 mg/day. In addition, sublingual atropine drops can be used in doses of 0.5 mg twice daily; however, the evidence is scarce.^[10]
  
  
  
  • B. Adrenergic receptor agonists: At present, there are no recommendations on using these drugs to treat drooling in PD. However, studies with small sample sizes have demonstrated the beneficial effects of clonidine (0.15 mg daily) and modafinil (100 mg daily) on drooling in PD.^[11]
  
  
  
  • C. Dihydroergotoxin mesylate: It is a selective alpha adrenergic blocking agent with some affinity to dopaminergic and serotonin receptors. A dose of 2.5 mg twice daily is generally administered after meals. In a single-center study with a sample size of 30 patients, Cheng et al.^[12] demonstrated significant decrease in sialorrhea using SCS–PD with a response rate of 60% (defined as at least 30% reduction in the SCS–PD score) at 3 weeks in the open-label phase. In addition, a significant improvement with a response rate of 55% was observed at 6 weeks in the second phase of this crossover trial. No major adverse effects were observed. However, further research is needed to establish the efficacy of this drug in routine clinical practice.
  
  
  
  • D. Botulinum toxin injections: Botulinum toxins A and B have shown to be effective in the treatment of drooling in PD.^{[13],[14],[15],[16]} The mechanism of action involves presynaptic inhibition of acetylcholine release in the parasympathetic and sympathetic cholinergic ganglia, leading to reduced salivary secretion. Botulinum toxin can be injected using anatomical landmarks or under ultrasound guidance. The landmark for the parotid gland injection is the midpoint of an imaginary line extending from the tragus to the angle of the mandible. The anatomical landmark for the submandibular gland is a one finger-breadth medial to the midline of an imaginary line along the length of the body of the mandible starting from the mandibular angle to the tip of the chin ([Figure 1]). Ultrasound guidance may aid in efficacy and accuracy. The onset of the botulinum toxin injection usually starts at 1 week and may last for approximately 3–5 months. The dose administered in various studies range from 10 to 50 units of onabotulinum toxin per each parotid gland and 5 to 15 units per each submandibular gland.^{[13],[14],[15]} The doses for abobotulinum toxin range from 18.75 to 146.25 units and 18.75 to 78.75 units per each parotid and submandibular gland, respectively.^[16],[17] The adverse effects include transient dryness of the mouth and mild dysphagia. Ondo et al.^[18] used 1000 units and 250 units of botulinum toxin B in each parotid and submandibular gland, respectively. In a randomized controlled trial, Jost et al.^[19] recently demonstrated the long-term efficacy and safety of incobotulinum toxin for chronic sialorrhea over 64 weeks. In their study, 70% of the patients had PD, and 75 units and 100 units of incobotulinum toxin were administered into the bilateral parotid and submandibular glands, respectively. There was improvement in the unstimulated salivary flow rate, modified Radboud Oral Motor Inventory for PD drooling scores, global impression of change scale, and Drooling Severity and Frequency Scale with every cycle. There was no difference between the ultrasound-guided versus blinded injections using anatomical landmarks. Similarly, statistically significant improvement was observed with rimabotulinum toxin (botulinum toxin B) at 4 weeks in another randomized controlled trial.^[20]
  
  
  
  • E. Deep brain stimulation: Bilateral subthalamic nucleus deep brain stimulation has been shown to reduce sialorrhea; therefore, it demonstrates a modest level of benefit.^[21],[22]
  
  
  
  • F. Nonpharmacological approaches: Speech and behavioral therapy under the guidance of otolaryngologists and neuropsychologists, respectively, can be helpful. Behavioral modifications such as chewing gum or hard candy may serve as a tactile clue to swallow more frequently. In addition, in certain scenarios it may serve as a time-locked reminder to the patient to swallow saliva at regular intervals of 30 minutes each day.^[23]
  
  
  
  • G. Other therapies: The other treatments mentioned in the literature include radiotherapy and surgical options such as sectioning of the chorda tympani nerves known as neurectomy, ligation or relocation of the salivary duct, and excision of the gland itself. These are more invasive procedures that can lead to the potential complications of aspiration pneumonia, loss of taste, dry mouth, and dental caries. Postma et al.^[24] studied the long-term efficacy and safety of radiotherapy to major salivary glands in 28 patients with parkinsonism (22 with PD). A total dose of 12 Gy was administered to the parotid gland and a part of the submandibular gland bilaterally. There was remarkable improvement in sialorrhea at 1 month, and this effect was persistent at 1 year. In their study, 75% of the patients experienced transient side effects in the form of loss of taste and dry mouth. In addition, the efficacy and safety of irradiation to the parotid and submandibular glands have been demonstrated in recent randomized clinical trials.^[25]
  
  
  

Figure 1: Anatomical landmarks for botulinum toxin injection for the parotid (A) and submandibular glands (B) (adapted from Srivanitchapoom et al.[4]) Click here to view

Conclusion

Table 1: Summary of major studies focusing on various interventions used for sialorrhea in Parkinson's disease Click here to view

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