Solifenacin-Induced Delirium and Hallucinations☆

General Hospital Psychiatry 35 (2013) 682.e3–682.e4

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General Hospital Psychiatry

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Case Report Solifenacin-induced delirium and hallucinations☆

Matej Štuhec, Pharm.D. ⁎ Ormoz Psychiatric Hospital, Department for Clinical Pharmacy, Slovenia, Ptujska Cesta 33, Ormoz, Slovenia article info abstract

Article history: Solifenacin-induced cognitive adverse effects have not been reported frequently, but solifenacin-induced Received 11 April 2013 delirium and hallucinations with successful switching to darifenacin, without additional drug, have not been Revised 5 June 2013 reported in the literature. In this case report, we present an 80-year-old Caucasian male with insomnia and Accepted 5 June 2013 anxiety symptoms and overactive bladder who developed delirium and hallucinations when treated with Keywords: solifenacin and trazodone. After solifenacin discontinuation and switching to darifenacin, symptoms signiﬁcantly improved immediately. Such a case has not yet been described in literature; however, an Solifenacin Delirium adverse effect associated with solifenacin can occur, as this report clearly demonstrates. Hallucinations © 2013 Elsevier Inc. All rights reserved. Darifenacin Antimuscarinic adverse effect Case report

1. Introduction tion of Diseases, 10th Revision (ICD-10)], and depression with psychotic features was ruled out with differential diagnosis. Patient reported Solifenacin is a competitive muscarinic receptor antagonist, which insomnia, fear, fatigue, nausea, chest pain, shortness of breath and is used for overactive bladder (OAB) treatment. It acts as an headache. Solifenacin (Vesicare) 5 mg daily in morning dose was antimuscarinic agent, showing the highest affinity for the muscarinic prescribed to him 1 week earlier by his physicians because of OAB. M(3) receptor, which mediates urinary bladder contraction. In Laboratory results collected on admission included a normal complete preclinical studies, solifenacin exhibited a highly bladder-selective blood cell, normal electrolytes, normal liver enzymes and liver profile compared with other antimuscarinic agents. Solifenacin was functions tests. His medications previous to hospitalization included also shown to increase bladder capacity without affecting residual zolpidem 5 mg daily, enalapril 10 mg daily and solifenacin 5 mg daily. urine in an OAB model of rats. Clinically, solifenacin ameliorates all He had no known childhood health problems and reported no previous symptoms in OAB patients, and in particular, it produces a significant delirium, hallucinations or seizures. His score on the Mini-Mental State decrease in urgency episodes, which is the principal symptom of OAB. Exam was 28/30, and the patient had no history of dementia. After The pharmacological profile of solifenacin is therefore considered to hospital admission, trazodone 50 mg was introduced and titrated up to contribute to its beneficial effects of high efficacy against OAB 100 mg on the second day and 150 mg daily at bedtime on the third symptoms with good tolerability [1]. day. In 10 days of this treatment, his mental status normalized. In this paper, delirium and hallucinations induced in an 80-year- Insomnia, fear, fatigue and nausea stopped. On the 11th day in the old Slovenian male with OAB and insomnia and anxiety symptoms by afternoon, delirium, uncontrolled behavior and hallucinations were solifenacin are presented. reported, and patient reported disorientation. Disturbance of con- sciousness, change in cognition, slow thinking and mood lability were also reported, and the patient was diagnosed with delirium (ICD-10). 2. Case description Laboratory results were normal, and patient was afebrile with no findings and signs of infection. The clinical pharmacist advised An 80-year-old Slovenian male was admitted in 2013 to a immediate discontinuation of solifenacin and switching to darifenacin psychiatric department because of insomnia and anxiety symptoms. 7.5 mg daily. Day after discontinuation, the patient recovered. The patient had no previous history of psychiatric illness. He was Symptoms of OAB were treated with 7.5 mg darifenacin daily. diagnosed with anxiety unspecified disorder [International Classifica- 3. Discussion ☆ Conflict of interests: The authors have no personal affiliations, financial relationship or any commercial interest to disclose relative to this article. The submitted report or A randomised, double-blind, triple-crossover trial in 26 elderly any essential part of it is not published or simultaneously submitted to other volunteers (≥75 years) with OAB treatment was described in 2013. publications prior to its appearance in this Journal. fi ⁎ Corresponding author. Tel.: +38 641239414. Solifenacin was not associated with signi cant changes from baseline E-mail address: [email protected]. in any of the five standard, composite outcomes of cognitive function

[2]. In a retrospective analysis of pooled data from four studies ment was observed. Daily dose of trazodone was not changed in published in 2006, solifenacin 5 mg and 10 mg once daily were switching time, which suggests that delirium was probably induced efficacious and well tolerated in the treatment of elderly patients by the anticholinergic effect of solifenacin. Delirium was not induced (aged ≥65 years) with OAB [3]. In a single-center, randomised, by trazodone itself, but pharmacodynamic drug–drug interaction double-blind, placebo-controlled study in 12 healthy elderly volun- between solifenacin and trazodone could occur, which led to small teers, with three crossover periods separated by two 14-day washout additive anticholinergic overstimulation. An adverse event was periods, a single 10-mg dose of solifenacin did not impair cognitive observed also in the afternoon. The concentration of solifenacin function in a healthy elderly population compared with placebo and reaches its peak 6 hours after morning dose, which also indicates a oxybutynin immediate-release 10 mg [4]. link between these factors. Adverse effect was determined by a In a pharmacological study reported in 2012, brain penetration clinical pharmacist with the Naranjo probability scale and was was low for antimuscarinics that are P-gp substrates (5-HMT, probably associated with solifenacin use (6 points) and possibly darifenacin and trospium) and significant for those that are not associated with trazodone use (4 points) [11]. P-gp substrates (oxybutynin, solifenacin and tolterodine) [5]. Five In conclusion, it is known that trazodone itself has considerably randomized, double-blind, multiple-dose studies of cognitive func- fewer prominent anticholinergic effects. Possibly, the addition of tion were identified by Kay and Ebinger in 2008. Oxybutynin was trazodone, which is generally safe in patients with OAB, to solifenacin consistently associated with cognitive deficit (four studies), whereas may have resulted in not only additive but synergistic CNS darifenacin did not impair cognition (three studies). For solifenacin anticholinergic burden, thus exacerbating the already present and trospium, there were no human studies evaluating memory, the preadmission mild CNS effects. Substitution of solifenacin with cognitive function most vulnerable to central nervous system (CNS) darifenacin reversed this interaction and reduced the intensity of or anticholinergics [6]. Adverse effects described in this case are eliminated the CNS disturbances. probably associated to muscarinic receptor subtype selectivity and the ability of the agent to cross the blood–brain barrier, where P-gp plays a role in limiting permeability. 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