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Urinary retention following repeated high-dose quetiapine

Associate Adjunct Professor III Chief, Mood Disorders Clinic Department of Psychiatry Veterans Affairs Long Beach Healthcare System 5901 East 7th Street (06/116a) Long Beach, California 90822-5201 fax 562/826-5088 Kenneth.Sokolski{at}med.va.gov

Brenda J Brown, MA

Clinical Research Coordinator Veterans Affairs Long Beach Healthcare System

Mark Melden, MD

Resident in Psychiatry University of California, Irvine Orange, California

Published Online, March 23, 2004. www.theannals.com, DOI 10.1345/aph.1D502

Case Report. A 48-year-old white woman with chronic paranoid schizophrenia and no prior history of urinary retention had been stabilized on quetiapine 900 mg/day, lorazepam 1 mg 4 times a day, and diphenhydramine 25 mg at bedtime for several months. No other medications were taken. Due to agitation, the patient increased the diphenhydramine dose to 100 mg/day for 2 weeks, with no adverse effects. Continued nervousness and paranoid delusions then prompted her to double her dose of quetiapine to 1800 mg/day. Ten days later, she reported urinary hesitancy. She next self-prescribed another increase in quetiapine to 2400 mg/day.

Several days later, the patient presented to the emergency department (ED), unable to void. She denied misuse of diphenhydramine and had no history of anticholinergic abuse. Except for warm, dry skin and tachycardia, urologic and gynecologic examinations, electrocardiogram, complete blood cell count, serum chemistry, urinalysis, and toxicology screen were normal. Vital signs were T 36.5 °C, HR 98 beats/min, RR 20 breaths/min, and BP 120/80 mm Hg. Post-void catheterization removed 1200 mL of urine. The patient was discharged, but returned to the ED the following morning with worsening urinary retention, at which time she revealed having increased her quetiapine dosage to 2400 mg/day. Catheterization again drained 1200 mL of urine. At this time, vital signs were T 36.3°C, HR 110 beats/min, RR 20 breaths/min, and BP 142/74 mm Hg. Ultrasound showed no signs of urinary obstruction, and lumbar magnetic resonance imaging indicated no spinal cord impingement.

A urinary catheter was placed, and the patient was admitted for observation. To prevent decompensation, she was maintained on quetiapine 900 mg/day, lorazepam as needed, and diphenhydramine 75 mg at bedtime. Over the next 48 hours, the patient's urinary retention resolved. Two months later, she again developed urinary hesitancy after increasing her quetiapine dosage to 1800 mg/day, while taking diphenhydramine 75 mg/day, which resolved on lowering the quetiapine dose to 900 mg/day.

Discussion. Quetiapine has not been associated with urinary retention at therapeutic doses.³ Pharmacologic studies have suggested, however, that quetiapine could cause voiding difficulties if plasma concentrations became elevated.⁴ Although medication concentrations were not measured in this patient, repeated high doses of quetiapine in combination with diphenhydramine apparently caused dose-related cholinergic block-ade. Based on the results of the Naranjo probability scale, a probable relationship existed between the urinary retention and increasing doses of quetiapine to >900 mg/day.⁵ The anticholinergic effects reported here could have been mediated via direct antagonism of muscarinic receptors or through antihistaminergic mechanisms common to both agents.¹

References

1. Goldstein JM, Brecher M. Clarification of anticholinergic effects of quetiapine (letter). J Clin Psychiatry 2000;61:9.
2. Watts D, Wax P. Physostigmine administration for quetiapine toxicity (abstract 1-265). Presented at: North American Congress of Clinical Toxicology Annual Meeting, Chicago, September 4–9,2003 : 641.
3. Garver DL. Review of quetiapine side effects. J Clin Psychiatry 2000; 61(suppl 8):31 -3.
4. Richelson E. Receptor pharmacology of neuroleptics: relation to clinical effects. J Clin Psychiatry 1999;60(suppl 10):5 -14.
5. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions.Clin Pharmacol Ther 1981;30:239-45.[Medline]

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