title: Immediate-release oxybutynin for the treatment of clozapine-induced sialorrhea.
abstract: OBJECTIVE
  To describe a case of clozapine-induced sialorrhea alleviated by immediate-release oxybutynin.
  
  
  METHODS
  A 53-year-old female with schizoaffective disorder-bipolar type was admitted to a psychiatric unit and initiated on clozapine. During titration to a dose of 300 mg daily and despite taking concomitant oral benztropine 1 mg twice daily, the patient began to experience mild sialorrhea. The sialorrhea became profuse when the clozapine dose reached 400 mg daily, and the patient was routinely seen with a saliva-soaked shirt. Additionally, she had become self-conscious and wanted to stop clozapine therapy. Immediate-release oxybutynin 5 mg daily was started, resulting in significant reduction of the sialorrhea within 24 hours. The patient was discharged on clozapine 300 mg daily, risperidone 6 mg at bedtime, immediate-release oxybutynin 5 mg twice daily, and oral benztropine 1.5 mg daily, with only mild sialorrhea.
  
  
  CONCLUSIONS
  It is unknown why clozapine induces sialorrhea. One speculation is that clozapine interrupts muscarinic receptor homeostasis. Immediate-release oxybutynin is an anticholinergic agent with high affinity for salivary gland M₃ receptors that may have restored muscarinic receptor imbalance in our patient. N-Desethyl-oxybutynin, an active metabolite of oxybutynin, is largely responsible for oxybutynin's anticholinergic activity. The activity of oxybutynin and its metabolite may result in dry mouth in over 80% of patients taking the immediate-release formulation, while producing dry mouth in only 40% and 7.5% of patients taking the extended-release and topical formulations, respectively.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report of immediate-release oxybutynin successfully reducing clozapine-induced sialorrhea. If oxybutynin is considered for this indication, use of the immediate-release formulation seems prudent. Additional data, including randomized controlled trials, are needed to confirm whether immediate-release oxybutynin has a significant role in the management of this stigmatizing adverse effect.
authors.affiliation: Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. leungjg@upmc.edu
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Leung
authors.forename: Neil V
authors.initials: NV
authors.lastname: Puri
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Jacobson
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008333:Mandelic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D011618:Psychotic Disorders / Q000188:drug therapy; D012798:Sialorrhea / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D003024:Clozapine; C005419:oxybutynin