Quetiapine-Induced Hypersalivation

Abstract

Sir: Quetiapine fumarate is a dibenzothiazepine-derivative antipsychotic with combined antagonism at dopamine (D1, D2) and serotonin type 1 and type 2 (5-HT1A, 5-HT2A, 5-HT2C) receptors. Additionally, quetiapine antagonizes α1- and α2-adrenergic and histamine H1 receptors. Protean binding at the above receptors explains the common side effects, which include hypersomnolence, hypotension, headache, weight gain, and gastrointestinal disturbance. However, to our knowledge, there have been no case reports of quetiapine-induced hypersalivation. We report the case of a patient with schizoaffective disorder taking low-dose quetiapine who developed hypersalivation, which remitted after discontinuation of the drug. We suggest that quetiapine antagonism at the α2 receptor contributes to the phenomenon of hypersalivation. Case report. Ms. A, a 36-year-old woman of Korean descent with a 16-year history of schizoaffective disorder, was admitted to the adult psychiatric medical care unit with a relapse of mania with psychosis. The patient's symptoms included elated mood, grandiose delusions of being a Power Ranger, disorganized behavior, and decreased need for sleep. The patient had been previously stabilized on clozapine with the only noted side effect being increased sedation. During this hospitalization, the patient refused administration of clozapine and instead was started on risperidone. Within a few days of commencement, the patient developed extrapyramidal symptoms with rigidity, dystonia, and slurring of speech, which prompted discontinuation of the risperidone. After a drug-free period of 3 days, the patient was started on quetiapine 25 mg b.i.d., and within a day, she developed increased salivation. When the dosage was increased to 50 mg b.i.d., the salivation worsened; the patient was drooling most of the day, and all of her clothing was wet. Benztropine (1 mg p.o. b.i.d.) and atropine eye drops (0.1%) sublingually did not reduce the hypersalivation. The quetiapine was stopped, and 1 day later, the hypersalivation resolved. Based on the temporal relationship between the administration and discontinuation of quetiapine and the onset and cessation of the patient's hypersalivation, it is possible that the hypersalivation was induced by the quetiapine. Hypersalivation is a common and distressing side effect seen with many psychotropic medications. However, no previous reports have associated increased salivation with the use of quetiapine. We attempt to explain the mechanism behind this event using the drug's known receptor affinities and the resultant binding effects observed in a closely related antipsychotic agent. Among the antipsychotics, clozapine is well recognized for inducing increased, voluminous salivation early in the course of treatment in up to 54% of patients.1 Clozapine is structurally similar to quetiapine and possesses a comparably broad receptor profile, which includes antagonistic activity at dopamine (D1, D2, D3, D4) receptors, adrenergic blockade activity at the α1 and α2 receptors, and antagonism at serotonin 5-HT2 receptors and histamine H1 receptors. However, unlike quetiapine, clozapine possesses both agonistic and antagonistic properties at muscarinic receptors. Specifically, clozapine has antagonist activity at M1, M2, M3, and M5 receptors, but exhibits agonist effects on the M4 receptor. One proposed mechanism for clozapine-induced hypersalivation focuses on its antagonism of α2-adrenergic receptors.2 Through blockade of sympathetic stimulation, parasympathetic stimulation is left unopposed to cause high salivary flow rates. Direct parasympathetic stimulation through its agonist effects at the M4 receptor has also been suggested to explain clozapine-induced hypersalivation.3 Quetiapine and clozapine both share blocking affinity at α2-adrenergic receptors, whereas only clozapine has agonist properties at the M4 receptor. We thus propose that α2-adrenergic blockade is the mechanism for quetiapine-induced hypersalivation. Further study is needed to draw definite conclusions regarding this proposed relationship.