Case in Point Sialorrhea in an Adult Taking Aripiprazole

Teja S. Shigemitsu, PharmD, Jennifer A. Boyd, PharmD, BCPP, and Albert Sattin, MD

After five months of treatment with aripiprazole, this patient developed excessive sialorrhea, an extremely uncommon adverse effect.

DA approved in 2002, aripip- initial exam AND PATIENT tions included: mirtazapine 15 mg per razole is the newest atypi- HISTORY day, simvastatin 20 mg per day, met- cal antipsychotic drug on the A 58-year-old man was admitted to a formin 850 mg twice a day, and benaz- Fmarket. Compared to other VA hospital following acute onset of epril 40 mg per day. antipsychotics, aripiprazole has the depressive symptoms (including tear- Further review of the patient’s rec- advantages of a minimal effect on fulness, decreased motivation, lack ords revealed that he had undergone weight gain, no cardiac effects, and of energy, and insomnia) that had cognitive testing approximately six a low risk of extrapyramidal adverse progressed gradually to encompass months prior to admission, the re- effects. prominent psychotic features. Spe- sults of which had revealed substan- The drug does have adverse ef- cifically, the patient was experienc- tial cognitive deficits in language and fects, however, the most common of ing delusional guilt and ruminations visuospatial ability but average mem- which are headache, nausea, vomit- about past transgressions, which he ory and attentional abilities. Clinicians ing, akathisia, tremor, and constipa- said had resulted in several individu- detected a hint of psychotic thinking, tion. As with any new medication, als persecuting him and speaking to though the patient was guarded in postmarketing experience plays a key him in his sleep and in person. He general. role in uncovering other possible ad- was convinced that a horrible fate Several months later, he was re- verse effects. was going to befall him. Fearing this ferred to geriatric psychiatry, where Thus far, there has been one case event, and because he said that his he scored 29 out of 30 on the Folstein report in the medical literature of persecutors had told him to sit with- Mini-Mental Status Exam and did not sialorrhea, or drooling, associated out moving, he had stopped taking appear overtly depressed. When his with aripiprazole use.1 It describes a medications and eating, instead con- depressive symptoms escalated, how- six-year-old child who received two fining himself to his room, huddled ever, he was prescribed citalopram doses of the drug and subsequently by the air conditioner—the only 10 mg. This was followed one month developed lethargy, sialorrhea, and place that he felt somewhat safe. later by trazodone 50 to 100 mg at flaccid facial muscles. These symp- The patient had a medical history bedtime as needed to aid in sleep and toms improved with administration of hypertension; diabetes; hyperlipi- alprazolam 0.25 mg twice daily to of diphenhydramine. In this article, demia; anemia; sleep apnea, requiring augment treatment of agitation. Two we present what we believe to be bilevel positive airway pressure; and a months later, citalopram, trazodone, the first case report of aripiprazole- cerebrovascular accident that had oc- and alprazolam were discontinued— induced sialorrhea in an adult. curred several years ago and resulted in due to treatment failure and poor ap- residual right-sided hemiplegia. Prior petite with citalopram. The patient

At the time of this writing, Dr. Shigemitsu was a to his stroke, he had no history of psy- was switched to mirtazapine 7.5 mg pharmacy resident at the VA Greater Los Angeles chiatric illness other than alcohol de- nightly. Healthcare System (VAGLAHS), Los Angeles, CA. pendence, which was in remission for Mirtazapine therapy had been se- He is now a pharmacist at VAGLAHS. Dr. Boyd is a clinical pharmacist in psychiatry and Dr. Sattin almost 40 years. Upon hospital admis- lected because it was thought that it is an attending psychiatrist, both at VAGLAHS. sion, the patient’s prescribed medica- would help the patient sleep, improve

JANUARY 2007 • FEDERAL PRACTITIONER • 11 CASE IN POINT

his appetite, and decrease his depres- vastatin, metformin, benazepril, and Saliva secretion is induced largely sive symptoms, which were very mild aspirin-dipyridamole). by the parasympathetic nervous sys- at the time. The mirtazapine dose During this time, the patient began tem. To a lesser extent, the sympa- eventually was increased from 7.5 to to drool excessively. The aripiprazole thetic nervous system induces saliva 15 mg nightly with some signs of im- dose was decreased to 5 mg, and then secretion by increasing its protein provement. He worsened, however, the drug was stopped completely. content. All antipsychotic drugs have and subsequently was admitted to the Following discontinuation of aripip- the potential to induce drooling— VA hospital following his caregiver’s razole, the drooling subsided. due to the fact that they can cause reports that he no longer was eating The patient has experienced no a decrease in swallowing, which re- or leaving his room. further drooling since the discontin- sults from pseudoparkinsonian bra- Given the patient’s symptoms and uation of aripiprazole. Currently, his dykinesia. The typical antipsychotics, his medical and psychological history, only treatment for his psychiatric such as haloperidol, are more likely he was diagnosed with severe psy- symptoms is maintenance ECT. The to cause these symptoms, however. chotic depression. This condition was patient’s mental health status, how- The blockade of alpha-2 adrener- believed to be related both to his stroke ever, is contingent on his agreeing gic receptors additionally may cause and to his feelings regarding his moth- to continue routine ECT to control his drooling. Furthermore, there has er’s death from a stroke three months symptoms. been one case report of sialorrhea prior to the hospital admission. in a patient who was being treated About the condition with olanzapine but showed no clini- Treatment course Aripiprazole’s mechanism of action is cal signs of parkinsonism. Olanza- Upon admission, his mirtazapine mixed dopamine-serotonin agonist- pine, like clozapine, is a direct agonist dose was increased to 22.5 mg at bed- antagonist activity. It binds to D2 re- at the M4 receptor, suggesting yet a time. Oral quetiapine 25 mg was ceptors and is a partial agonist at the third mechanism for antipsychotic- added at bedtime to target his psy- 5HT1a receptor, but it is an antago- induced sialorrhea.4 ● chotic depression. This drug was then nist to the 5HT2a, H1, and alpha 1 titrated up to 100 mg. The patient adrenergic receptors. Although the The opinions expressed herein are those continued to resist taking his medica- drug may cause an increase in saliva- of the authors and do not necessarily tions, however, principally because of tion in approximately 2% of patients,2 reflect those of Federal Practitioner, his fear of being sedated and thereby the reaction was surprising in this Quadrant HealthCom Inc., the U.S. “losing his protective vigilance.” patient after such a long duration of government, or any of its agencies. After the patient had been receiv- treatment with the drug. Sialorrhea is This article may discuss unlabeled or ing mirtazapine for two months, a observed more commonly in patients investigational use of certain drugs. decision was made to discontinue taking clozapine, as a result of mus- Please review complete prescribing in- mirtazapine and quetiapine and carinic receptor agonism. formation for specific drugs or drug switch to aripiprazole. The latter Saliva is produced and secreted combinations—including indications, medication was chosen in the hopes by the six major salivary glands. contraindications, warnings, and ad- that it would be less sedating while Together, they secrete approximately verse effects—before administering still targeting his psychotic depres- 1.5 L of saliva per day. Saliva functions pharmacologic therapy to patients. sion. His response was not optimal, to keep the mouth clean and to aid however, despite titration from 5 to in food digestion. references 1. Lofton AL, Klein-Schwartz W. Atypical experience: 10 mg daily. When saliva flow becomes too A case series of pediatric aripiprazole exposures. Shortly thereafter, treatment with high, though, it can have negative ef- Clin Toxicol (Phila). 2005;43:151–153. 2. Abilify [prescribing information]. Rockville, MD: electroconvulsive therapy (ECT) was fects. For example, people with sial- Otsuka America Pharmaceutical, Inc.; October begun. With the ECT, the patient orrhea may develop chapped or dry 2006. Available at: www.bms.com/cgi-bin/anybin. pl?sql=select%20PPI%20from%20TB_PRODUCT_ became more adherent to his medi- skin around the mouth and lips— PPI%20where%20PPI_SEQ=101&key=PPI. Ac- cations and improved clinically. He which puts them at risk for infection. cessed January 2, 2007. 3. Hockstein NG, Samadi DS, Gendron K, Handler continued taking oral aripiprazole In addition, sialorrhea during sleep SD. Sialorrhea: A management challenge. Am Fam monotherapy (10 mg daily) for the may increase a patient’s risk of aspira- Physician. 2004;69:2628–2634. 4. Perkins DO, McClure RK. Hypersalivation coinci- next five months, along with his tion. There also is a negative social dent with olanzapine treatment. Am J Psychiatry. other medications (including sim- stigma associated with sialorrhea.3 1998;155:993–994.

12 • FEDERAL PRACTITIONER • JANUARY 2007