By: Elsa Thomas, PharmD Candidate c/o 2013
Atropine is an anticholinergic used to treat various conditions, such as bradycardia, neuromuscular blockade, mydriasis, nerve agent poisoning, and salivary hypersecretion.1,2 Pharmacologically, it inhibits smooth muscle and glands innervated by postganglionic cholinergic nerves.1,2 It also has functions in the central nervous system (CNS); it could stimulate or depress it based on the administered dose.1,2 Its utility for treating salivary hypersecretion (i.e. sialorrhea) is a result of muscarinic antagonism of acetylcholine, resulting in dry mouth and reduction of salivary, bronchial, gastric, and sweat gland secretions.1,2 For adults, to reduce salivation and bronchial secretions, an oral dose of 0.4 mg is suggested, which may be repeated every 4 to 6 hours as needed.1,2 In the form of an injection, 0.4 to 0.6 mg may be administered intramuscularly (IM), intravenously (IV), or subcutaneously (SC) over 30 to 60 minutes, and repeated every 4 to 6 hours as needed.1,2 Interestingly a 1% ophthalmic solution of atropine has also been widely used, sublingually, for the treatment of the same.1,2
Sublingual atropine sulfate appears to have several advantages over the conventional IM route, including better bioavailability, rapid onset of action, and early “atropinization.”3 It is a relatively safe and effective procedure (with the aim of substituting conventional IM injections), and is readily available in the form of ophthalmic drops.1-3 Yet, there are very few clinical studies on the safety and efficacy of sublingually delivered atropine for the treatment of sialorrhea.3-7
A single randomized controlled trial investigated the efficacy of atropine to reduce salivary hypersecretion with 2 drops of 0.5% SL atropine (0.5 mg total dose).4 In the 22 adults who were receiving palliative care in the trial, the drug failed to show any benefit versus placebo.3 The authors of this study suggested that their findings might have been a result of inadequate dosing.4 In contrast, sublingual atropine was a simple and inexpensive treatment for sialorrhea, as reported by an open-label pilot study of sublingual atropine drops for the treatment of sialorrhea in seven patients (six with Parkinson’s disease, one with progressive supranuclear palsy).5 Participants demonstrated statistically significant declines in saliva production, both objectively and subjectively, and the majority of patients did not experience any anticholinergic side effects.5
In 2000, there was a case report of a 44 year old female with chronic schizophrenia with hypersalivation secondary to clozapine.6 It cited resolution of persistent symptoms after administration of atropine 1% eye drops, 1 to 2 drops (0.5 to 1 mg) administered sublingually in the morning.6 The patient also reported no adverse effects from the treatment, which appeared to be the benefit of local administration of atropine versus systemic use (e.g. IM, IV).6 An updated report on the benefit of atropine drops for the treatment of sialorrhea induced by clozapine described that several patients experienced rebound sialorrhea due to the short duration of atropine, which necessitated repeat dosing.7
Although atropine does not require any specialized skill for use, unlike surgical removal, and has reversible effects, it is still contraindicated in patients with cognitive impairment, dementia, or hallucinations.1,2,4 These patients are at higher risks for overdose due to mishandled dropper bottles.1,2,4 Some patients reported difficulty in manipulating the dropper to ensure proper dosing.6 In addition, dropper sizes are not standardized; ideally, 1 drop of 1% atropine solution should contain 500 micrograms of atropine (if 20 drops are in 1 mL of solution).1,2 The potential for accidental overdose with drops is therefore, worrisome.6
Drug-related adverse effects caused by atropine include dry mouth, blurred vision, urinary hesitancy and retention, tachycardia, palpitation, and constipation.1,2 It may also produce CNS disturbances, ataxia, hallucinations, and delirium, but these effects are more common with systemic doses of atropine (exceeding 10 mg) and are rare with local administration.1,2 Therefore, it is necessary that a patient’s heart rate, blood pressure, and mental status be monitored closely while on extended and high daily dose therapy with this drug.1
Hence, even with limited trial data, it seems that 1-2 drops (0.5 to 1 mg) of 1% ophthalmic atropine sulfate every 4 to 6 hours (not exceeding 10 mg daily) may be both effective and safe in the treatment of sialorrhea.1-7
- Lexi-Comp OnlineTM. Atropine (Lexi Drugs). Bethesda, Maryland: American Society of Health-System Pharmacists, Inc.; Accessed May 19, 2012.
- Drug Facts and Comparisons. Facts & Comparisons [database online]. Atropine Sulfate. St. Louis, MO: Wolters Kluwer Health, Inc.; April 2011. Accessed May 19, 2012.
- Rajpal S, Ali R, Bhatnagar A, Bhandari SK, et. al. Clinical and bioavailability studies of sublingually administered atropine sulfate. Am J Emerg Med. 2010 Feb;28(2):143-50.
- De Simone GG, Eisenchlas JH, Junin M, et al. Atropine drops for drooling: a randomized controlled trial. Palliat Med 2006; 20: 665-71.
- Hyson HC, Johnson AM, Jog MS. Sublingual atropine for sialorrhea secondary to parkinsonism: a pilot study. Mov Disord. 2002 Nov;17(6):1318-20.
- Comley C, Galletly C, Ash D. Use of atropine eye drops for clozapine induced hypersalivation. Aust N Z J Psychiatry. 2000 Dec;34(6):1033-4.
- Tessier P, Antonello C. Clozapine and sialorrhea: update. J Psychiatry Neurosci. 2001 May;26(3):253.