Skip to main content Accessibility help
×
Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-24T16:24:14.583Z Has data issue: false hasContentIssue false

9 - Managing Sialorrhea

Published online by Cambridge University Press:  19 October 2021

Jonathan M. Meyer
Affiliation:
University of California, San Diego
Stephen M. Stahl
Affiliation:
University of California, San Diego
Get access

Summary

Sialorrhea may be the most common adverse effect of clozapine treatment, with prevalence estimates ranging from 30% to 90%, yet it is often underreported, underrecognized, and undertreated, leading to treatment dissatisfaction and discontinuation, social consequences, and possible medical morbidity in the form of aspiration events. Recent data indicate that the prevalence is likely closer to the 90% figure based on a detailed 2016 study of 98 clozapine-treated patients who were assessed for hypersalivation using two rating scales: the Nocturnal Hypersalivation Rating Scale and the Drooling Severity and Frequency Scale. Sialorrhea was experienced by 92% of subjects overall, more commonly at night (85% of subjects) than in the daytime (48%). Daytime symptoms were severe in 18%, and sialorrhea was considered frequent or occurring on a constant basis in 20%. Importantly, sialorrhea had at least a moderate impact on the quality of life in 15% of study subjects. While many studies of clozapine discontinuation focus on physician determined medical concerns, sialorrhea emerges as the third most common adverse drug reaction cited by patients as a reason for discontinuing treatment, behind sedation and nausea. Importantly, sialorrhea during clozapine therapy has been associated with reports of aspiration pneumonia. The extent of pneumonia risk from clozapine treatment has been quantified in three studies, with rates 1.99–3.18 times higher in clozapine-treated patients compared with other antipsychotics. Supporting this concept is the finding that pulmonary illness was the most common cause (32%) of medically related hospital admissions for clozapine-treated patients at one major US medical center, of which 58% were for pneumonia. Lastly, parotitis has also been reported and associated with hypersalivation.

Type
Chapter
Information
The Clozapine Handbook
Stahl's Handbooks
, pp. 172 - 189
Publisher: Cambridge University Press
Print publication year: 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Maher, S., Cunningham, A., O’Callaghan, N., et al. (2016). Clozapine-induced hypersalivation: An estimate of prevalence, severity and impact on quality of life. Therapeutic Advances in Psychopharmacology, 6, 178184.CrossRefGoogle ScholarPubMed
Legge, S. E., Hamshere, M., Hayes, R. D., et al. (2016). Reasons for discontinuing clozapine: A cohort study of patients commencing treatment. Schizophrenia Research, 174, 113119.CrossRefGoogle ScholarPubMed
Kaplan, J., Schwartz, A. C. and Ward, M. C. (2018). Clozapine-associated aspiration pneumonia: Case series and review of the literature. Psychosomatics, 59, 199203.CrossRefGoogle ScholarPubMed
Leung, J. G., Hasassri, M. E., Barreto, J. N., et al. (2017). Characterization of admission types in medically hospitalized patients prescribed clozapine. Psychosomatics, 58, 164172.CrossRefGoogle ScholarPubMed
De Fazio, P., Gaetano, R., Caroleo, M., et al. (2015). Rare and very rare adverse effects of clozapine. Neuropsychiatric Disease and Treatment, 11, 19952003.CrossRefGoogle ScholarPubMed
Syed, R., Au, K., Cahill, C., et al. (2008). Pharmacological interventions for clozapine-induced hypersalivation. Cochrane Database of Systematic Reviews, 3, Cd005579.CrossRefGoogle Scholar
Freudenreich, O. (2005). Drug-induced sialorrhea. Drugs Today (Barcelona), 41, 411418.CrossRefGoogle ScholarPubMed
Restivo, D. A., Panebianco, M., Casabona, A., et al. (2018). Botulinum toxin A for sialorrhoea associated with neurological disorders: Evaluation of the relationship between effect of treatment and the number of glands treated. Toxins (Basel), 10, E5563.Google Scholar
Dashtipour, K., Bhidayasiri, R., Chen, J. J., et al. (2017). RimabotulinumtoxinB in sialorrhea: Systematic review of clinical trials. Journal of Clinical Movement Disorders, 4, 917.CrossRefGoogle ScholarPubMed
Proctor, G. B. and Carpenter, G. H. (2014). Salivary secretion: mechanism and neural regulation. Monographs in Oral Sciences, 24, 1429.Google Scholar
Ryberg, A. T., Warfvinge, G., Axelsson, L., et al. (2008). Expression of muscarinic receptor subtypes in salivary glands of rats, sheep and man. Archives of Oral Biology, 53, 6674.CrossRefGoogle ScholarPubMed
Sugawara, Y., Kikuchi, Y., Yoneda, M., et al. (2016). Electrophysiological evidence showing muscarinic agonist-antagonist activities of N-desmethylclozapine using hippocampal excitatory and inhibitory neurons. Brain Research, 1642, 255262.Google Scholar
Schneider, B., Weigmann, H., Hiemke, C., et al. (2004). Reduction of clozapine-induced hypersalivation by pirenzepine is safe. Pharmacopsychiatry, 37, 4345.Google Scholar
Subramanian, S., Vollm, B. A. and Huband, N. (2017). Clozapine dose for schizophrenia. Cochrane Database of Systematic Reviews, 6, Cd009555.Google Scholar
Solismaa, A., Kampman, O., Seppälä, N., et al. (2014). Polymorphism in alpha 2A adrenergic receptor gene is associated with sialorrhea in schizophrenia patients on clozapine treatment. Human Psychopharmacology Clinical and Experimental, 29, 336341.CrossRefGoogle ScholarPubMed
Evatt, M. L., Chaudhuri, K. R., Chou, K. L., et al. (2009). Dysautonomia rating scales in Parkinson’s disease: Sialorrhea, dysphagia, and constipation – Critique and recommendations by movement disorders task force on rating scales for Parkinson’s disease. Movement Disorders, 24, 635646.CrossRefGoogle ScholarPubMed
Thomas-Stonell, N. and Greenberg, J. (1988). Three treatment approaches and clinical factors in the reduction of drooling. Dysphagia, 3, 7378.CrossRefGoogle ScholarPubMed
Spivak, B., Adlersberg, S., Rosen, L., et al. (1997). Trihexyphenidyl treatment of clozapine-induced hypersalivation. International Clinical Psychopharmacology, 12, 213215.Google Scholar
Sockalingam, S., Shammi, C. and Remington, G. (2007). Clozapine-induced hypersalivation: A review of treatment strategies. Canadian Journal of Psychiatry, 52, 377384.CrossRefGoogle ScholarPubMed
Barr, J. R., Moura, H., Boyer, A. E., et al. (2005). Botulinum neurotoxin detection and differentiation by mass spectrometry. Emerging Infectious Diseases, 11, 15781583.CrossRefGoogle ScholarPubMed
Bushara, K. O. and Park, D. M. (1994). Botulinum toxin and sweating. Journal of Neurology, Neurosurgery, and Psychiatry, 57, 14371438.CrossRefGoogle ScholarPubMed
Petracca, M., Guidubaldi, A., Ricciardi, L., et al. (2015). Botulinum Toxin A and B in sialorrhea: Long-term data and literature overview. Toxicon, 107, 129140.Google Scholar
Guidubaldi, A., Fasano, A., Ialongo, T., et al. (2011). Botulinum toxin A versus B in sialorrhea: A prospective, randomized, double-blind, crossover pilot study in patients with amyotrophic lateral sclerosis or Parkinson’s disease. Movement Disorders, 26, 313319.CrossRefGoogle ScholarPubMed
Kahl, K. G., Hagenah, J., Zapf, S., et al. (2004). Botulinum toxin as an effective treatment of clozapine-induced hypersalivation. Psychopharmacology (Berlin), 173, 229230.CrossRefGoogle ScholarPubMed
Bird, A. M., Smith, T. L. and Walton, A. E. (2011). Current treatment strategies for clozapine-induced sialorrhea. Annals of Pharmacotherapy, 45, 667675.Google Scholar
Verma, R. and Anand, K. S. (2018). Botulinum toxin: A novel therapy for clozapine-induced sialorrhoea. Psychopharmacology (Berlin), 235, 369371.Google Scholar
Reinstein, M., Sirotovskya, L. and Chasonov, M. (1999). Comparative efficacy and tolerability of benzatropine and terazosin in the treatment of hypersalivation secondary to clozapine. Clinical Drug Investigation, 17, 97102.CrossRefGoogle Scholar
Kreinin, A., Miodownik, C., Sokolik, S., et al. (2011). Amisulpride versus moclobemide in treatment of clozapine-induced hypersalivation. World Journal of Biological Psychiatry, 12, 620626.Google Scholar
Loy, F., Isola, M., Isola, R., et al. (2014). The antipsychotic amisulpride: Ultrastructural evidence of its secretory activity in salivary glands. Oral Diseases, 20, 796802.CrossRefGoogle ScholarPubMed
Kulkarni, R. R. (2015). Low-dose amisulpride for debilitating clozapine-induced sialorrhea: Case series and review of literature. Indian Journal of Psychological Medicine, 37, 446448.Google Scholar
Barnes, T. R., Leeson, V. C., Paton, C., et al. (2017). Amisulpride augmentation in clozapine-unresponsive schizophrenia (AMICUS): A double-blind, placebo-controlled, randomised trial of clinical effectiveness and cost-effectiveness. Health Technology Assessment, 21, 156.CrossRefGoogle ScholarPubMed
Liang, C. S., Ho, P. S., Shen, L. J., et al. (2010). Comparison of the efficacy and impact on cognition of glycopyrrolate and biperiden for clozapine-induced sialorrhea in schizophrenic patients: A randomized, double-blind, crossover study. Schizophrenia Research, 119, 138144.CrossRefGoogle ScholarPubMed
Man, W. H., Colen-de Koning, J. C., Schulte, P. F., et al. (2017). The effect of glycopyrrolate on nocturnal sialorrhea in patients using clozapine: A randomized, crossover, double-blind, placebo-controlled trial. Journal of Clinical Psychopharmacology, 37, 155161.CrossRefGoogle ScholarPubMed
Weiner, D. M., Meltzer, H. Y., Veinbergs, I., et al. (2004). The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine. Psychopharmacology, 177, 207216.CrossRefGoogle ScholarPubMed
Doran, A., Obach, R. S., Smith, B. J., et al. (2005). The impact of P-glycoprotein on the disposition of drugs targeted for indications of the central nervous system: Evaluation using the MDR1A/1B knockout mouse model. Drug Metabolism and Disposition, 33, 165174.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×