Clinical Geriatrics

CASE PRESENTATION
Mrs. M is a 77-year-old married woman who was brought to the emergency room after her husband found her to be confused and diaphoretic. She has a prior history of a right middle cerebral artery stroke, with left hemiplegia 3 months ago. Mrs. M was diagnosed with depression while undergoing rehabilitation. She was able to regain ambulation with a walker and was discharged home 1 month ago. She has a history of hypertension, atrial fibrillation, osteoporosis, and gastroesophageal reflux disease (GERD). Her current medications include venlafaxine extended-release 150 mg daily for depression, citalopram 20 mg daily for anxiety, metoprolol 25 mg twice daily for hypertension, digoxin 0.125 mg daily for atrial fibrillation, warfarin 2 mg daily for atrial fibrillation, and omeprazole 20 mg daily for GERD. One week ago she went to her primary care physician for follow-up with complaints of insomnia and restlessness. Trazodone 50 mg at bedtime was prescribed. She slept better but developed difficulty walking after 3 days, and complained of nausea. Four days later her husband found her breathing rapidly and unable to answer questions, and he called an ambulance.

In the emergency room the patient appeared alert but disoriented. She was febrile with a temperature of 103 degrees F, her pulse was 100, respiratory rate was 24, and blood pressure was 180/80. Generalized rigidity was noted with tremors in her left hand and arm. A head computed tomography (CT) scan was performed due to concerns that the patient was experiencing a new stroke, but only the previous old right cerebrovascular accident was found. She was admitted to the hospital due to concerns of sepsis with delirium, and was empirically started on intravenous fluids and levofloxacin. Oxygen was administered via nasal canula. All of her current medications, including venlafaxine, citalopram, and trazodone, were continued.

A chest x-ray was negative for any infiltrates or signs of pneumonia. Mrs. M became increasingly confused, and her muscular rigidity more pronounced. Her blood cultures were negative, and her complete blood count and chemistry panel were within normal limits. Her oral intake was poor. A Neurology consultation suggested neuroleptic malignant syndrome (NMS) as a possible diagnosis. On the 5th hospital day, a Psychiatry consult was requested due to “worsening confusion and to rule out catatonia.”

DISCUSSION
Serotonin syndrome is a clinical condition that results from central and peripheral serotonergic hyperstimulation.1 The incidence of this syndrome appears to be increasing, and correlates with the widespread use of selective serotonin reuptake inhibitors (SSRIs) and other medications that increase serotonergic tone.2 In 2002, there were 7349 reports of toxicity and 93 deaths associated with toxic effects of SSRIs among 26,733 treated outpatients.3 Among elderly patients, the mortality rate has been as high as 11%. The major clinical presentation of serotonin syndrome includes confusion, mental status changes, motor restlessness, tremor, gastrointestinal disturbances, fever, and autonomic instability (Table I).2-4 Unfortunately, despite the frequent use of medications that cause serotonin syndrome and the increasing practice of polypharmacy with these agents (Table II),1-3,5,6 the majority of clinicians do not recognize this clinical diagnosis.2,3

Older adults are particularly vulnerable to this syndrome, and are often treated with multiple serotonergic medications, which put them at high risk for development of the serotonin syndrome. Serotonin syndrome is an adverse drug reaction, and is commonly associated with polypharmacy with two or more medications.7 The increase in dose or recent addition of a medication that raises serotonin availability should alert the clinician to the possibility of the disorder.