Olanzapine-Associated Chronic Urinary Retention and Ciliochoroidal Effusion: Rare Adverse Effects of a Commonly Prescribed Antipsychotic

Dear Editor,

Olanzapine, a second-generation antipsychotic, is used for a wide range of psychiatric disorders. Although relatively safe and well-tolerated compared to first-generation antipsychotics, rare adverse effects have been reported. We report a rare case of ciliochoroidal effusion with angle-closure glaucoma and chronic urinary retention with urethral spasm associated with olanzapine, which resolved on discontinuation of the drug.

Case Report

Mr A, a 51-year-old single male from urban, middle socioeconomic background of southern India, presented with gradual onset of psychiatric illness since the age of 25. It was characterized by irritability, suspiciousness, aggression, and sleep disturbance. Mental status examination revealed delusions of persecution and reference and thought broadcasting. The patient had been diagnosed with paranoid schizophrenia. He had comorbid hypertension for seven years and was on 10 mg of cilnidipine. There was history of ischemic heart disease in his father and a second- degree relative, Addison’s disease in his mother, leukemia in his elder brother, psychotic illness in a maternal third- degree relative, and alcohol use disorder in a second-degree relative. He has been on 22.5 mg of olanzapine for the past four years. There was a worsening of psychotic symptoms, difficulty in urination, and blurring of vision, and he was referred to our tertiary center for further evaluation. Physical and systemic examinations were within normal limits, with normal blood pressure measurements. Computed tomography of the brain was normal.

Urological Evaluation

The patient had gradual onset of lower urinary tract symptoms, with a poor stream of urine and incomplete sense of voiding for more than a year. Ultrasonography of the abdomen and pelvis revealed a distended urinary bladder with a normal prostate gland volume. Uroflowmetry showed a post-void residual volume of 340 ml, with a peak urine flow rate of <15 mL/s. The possibility of olanzapine-associated chronic urinary retention with urethral spasm was considered. Olanzapine was cross-tapered with aripiprazole, which was gradually increased up to 20 mg/day, with concomitant improvement in psychotic symptoms. Treatment with 8 mg of silodosin and 25 mg of bethanechol was started. Uroflowmetry after one month revealed a post-void residual volume of 200 ml, with an improved peak urine flow rate of 19 mL/s. Application of the Naranjo probability scale indicated a score of 5, which indicates “probable” association between the use of olanzapine and chronic urinary retention and urethral spasm. ¹

Ophthalmological Evaluation

A detailed evaluation revealed an elevated intraocular pressure (IOP) of 40 mmHg. The anterior chamber was shallow in both eyes, and gonioscopy revealed an oppositional angle closure (Figure S1). Ultrasound biomicroscopy showed closed angles with prominent anteriorly displaced ciliary bodies in both eyes. Ultrasound B-scan showed shallow choroidal detachment in the posterior segment. The possibility of olanzapine-associated angle closure due to ciliochoroidal effusion was considered. Timolol 0.5% eye drops were initiated, given raised IOP, and topical homatropine to relieve the ciliary body spasm. Two weeks after starting treatment and stopping olanzapine, the depth of the anterior chamber increased (Figure S1) and the IOP was 10 mmHg in both eyes. Ultrasound bio-microscopy also showed deepening of the anterior chamber with posterior rotation of the ciliary body. After four months, the IOP was 12 mmHg in both eyes, with a deep anterior chamber. Application of the Naranjo probability scale gave a score of 5, which indicates a “probable” association between the use of olanzapine and angle-closure due to ciliochoroidal effusion. ¹

Discussion

We have described a rare association of chronic urinary retention and ciliochoroidal effusion with olanzapine in a patient who did not have other risk factors. Among atypical antipsychotics, clozapine, olanzapine, and quetiapine have a significant affinity for muscarinic receptors compared to dopamine D2 receptors, leading to significant peripheral and central anticholinergic effects. ² Urinary incontinence and retention have been commonly reported with nearly all typical antipsychotics but have been rare with atypical antipsychotics. The impacts of olanzapine on several voiding parameters and external urethral sphincter have been demonstrated in an earlier animal model, emphasizing both the central and the peripheral anti-muscarinic activity of the drug. ³ The risk of urinary retention with olanzapine is higher in older adults with comorbid prostate hyperplasia and concomitant medications that can impair micturition.^4,5

Drugs can precipitate acute angle- closure either by pupillary block mechanism or non-pupillary block mechanisms such as ciliary body or ciliochoroidal effusion. ⁶ Typical antipsychotics can precipitate acute angle-closure due to muscarinic blockade mediating the pupillary block mechanism.^7,8 Our report contrasts with the earlier report where olanzapine precipitated an acute angle- closure crisis through pupillary block mechanism without evidence of ciliochoroidal effusion. ⁹ Although there are earlier reports of acetazolamide, topiramate, and other sulfa derivatives precipitating acute angle-closure through similar non-pupillary mechanisms, there has been no report of olanzapine mediating acute angle-closure through ciliary and choroidal effusion. ¹⁰ The management of acute angle-closure in the pupillary block and non-pupillary block mechanisms varies significantly. Proper identification and high suspicion are essential in patients with narrow angles who are on antipsychotic medications with concomitant use of antiparkinsonian agents.