Sjögren's syndrome is a chronic autoimmune rheumatic disorder characterized primarily by dry mouth (xerostomia) and dry eyes (xerophthalmia). Hypofunction of the salivary and lacrimal glands causes discomfort and serious side effects, including increased susceptibility to infection. Over-the-counter saliva and tear substitutes provide only short-term relief and often fail to prevent long-term complications. Pilocarpine has been used successfully to treat the signs and symptoms of radiation-induced dry mouth, but not the dryness symptoms associated with Sjögren's syndrome. Vivino and associates evaluated the safety and effectiveness of pilocarpine tablets in treating dry mouth and eyes in patients with Sjögren's syndrome.
Patients eligible for the study had a primary or secondary diagnosis of Sjögren's syndrome, with significant dry mouth and eyes. Before entry into the study, patients were required to stop using any electric device to produce saliva and to discontinue using any medications that caused dry mouth. Patients with clinically significant cardiac, renal or gastrointestinal conditions, diabetes mellitus or multiple sclerosis were excluded from the study. Those who met the study criteria were randomized to receive either 2.5 mg or 5 mg of pilocarpine, or placebo tablets four times daily for 12 weeks. Efficacy was measured by response to questionnaires and measurements of salivary flow obtained at follow-up visits six and 12 weeks after initiation of the study. Safety was evaluated based on results of laboratory and diagnostic studies.
Of the 373 predominantly female patients enrolled in the study, 121 were in the 2.5-mg group, 127 were in the 5-mg group and 125 were in the placebo group. Demographic characteristics were similar across groups. Within six to 12 weeks after pilocarpine therapy was initiated, patients in the 5-mg group reported significant overall improvements in the symptoms of eye and mouth dryness compared with the other groups. These patients also slept better and reported improvements in dry skin and nasal dryness. Salivary flow also increased significantly in this group compared with the other groups. No serious drug-related adverse effects were reported, although some patients reported mild or moderate sweating, flushing and urinary frequency.
The authors conclude that treatment with the higher dosage of pilocarpine significantly improved the dryness associated with Sjögren's syndrome and that these benefits clearly outweighed the mild to moderate adverse cholinergic activity. Almost any patient with some degree of exocrine gland dysfunction in association with Sjögren's syndrome could potentially benefit from this treatment.