Via Research Recognition Day Program VCOM-Carolinas 2025

Case Reports

Drugs, Drugs, and More Drugs: A Case of Avoidable Serotonin Syndrome Grant H. Hagglund, OMS-III, M.A. 1,2 , Alyssa Rojas, OMS-III 1,2 , Kristopher Coontz, MD, MPH 2 1. Edward Via College of Osteopathic Medicine – Carolinas, Spartanburg, SC 2. Cleveland Clinic Indian River Hospital, Vero Beach, FL

Figures

Introduction

Discussion

● Treatment of SS: Discontinuation of offending agents & monitor washout period, as patients can experience antidepressant discontinuation syndrome in 15% of cases. Symptoms include dizziness, nausea, headache, insomnia, and irritability [4]. Cyproheptadine is used in severe cases. ● Recognition of polypharmacy is a powerful diagnostic tool to adjust your differential diagnosis. ● A recent study showed half of patients had at least 1 medication discrepancy between hospital discharge and patient self-reported medication lists [5]. ● Kanaan et al reported adverse drug events occurred in approximately 1 in 5 hospital discharges; >50% within the first 14 days of discharge [6]. ● Annual healthcare costs attributed to polypharmacy: $76.6 billion [7] ● Four screening tools allow for closer monitoring of drug use in the elderly: Beers Criteria, Screening Tool of Older Person’s Prescriptions, Medication Appropriate Index, and the Hyper-pharmacotherapy Assessment Tool ● The Swiss Cheese Model retroactively pinpoints numerous multidisciplinary systems failures in prescribing, communication, and medication reconciliation that delayed diagnosis in this case, led to increased healthcare encounters (which compounded the polypharmacy), and could have resulted in severe harm. ● Our patient received medications from three different pharmacy systems whose EMRs did not effectively communicate. Ultimately, only two medications in total overlapped with what he was taking. Conclusions Serotonin syndrome presents variably, often resulting in missed or delayed diagnosis, resulting in harm and increased healthcare costs. It is critical to perform a thorough medication reconciliation to identify harmful or overlapping medications, utilizing collateral. This unusual presentation of recurrent orthostatic syncope with polypharmacy reminds us that serotonin syndrome may not always present with its textbook definition, and that “complete” medication reconciliations should be interrogated.

Serotonin syndrome (SS) is a rare, but potentially life-threatening complication of drugs that increase serotonin levels in the central and peripheral nervous systems [1]. ● Inciting drugs: SSRIs, SNRIs, MAOIs, TCAs, fentanyl/tramadol, olanzapine ● Variable presentations include autonomic dysfunction, neuromuscular excitability, and/or altered mental status [1] ● Underdiagnosed and often missed on initial presentation.

Before

After

Sertraline HCl 50mg Escitalopram 10mg Venlafaxine 37.5mg Duloxetine 60mg Duloxetine 30mg

Sertraline HCl 50mg Duloxetine 60mg Midodrine 5mg Alprazolam 1mg Gabapentin 300mg

Is the patient current on a serotonergic drug or within a washout period?

Losartan potassium 25mg Salcubitril-Valsartan 24-26mg Midodrine 5mg Percocet 5-325mg Alprazolam 1mg

No

Yes

Table 1. List of patient’s medications possibly contributing to orthostatic hypotension and falls. ● Italicized : increased before falls began. ● Underlined: added during previous hospital encounters. ● 2023 Beer’s Criteria medications specific for falls [2].

Not serotonin syndrome

Is a minimum of 1+ conditions below present? 1. Spontaneous clonus

2. Inducible clonus + agitation/diaphoresis 3. Ocular clonus + agitation/diaphoresis 4. Tremor + hyperreflexia 5. Inducible or ocular clonus + hypertonia and hyperthermia

Figure 1. The Hunter Toxicity Criteria Decision Rules are the most accurate way to diagnose SS, with 84% sensitivity and 97% specificity [1].

Gabapentin 300mg Oxybutynin 10mg ER Empagliflozin 10mg

No

Yes

Serotonin syndrome

Not serotonin syndrome

Non-Neurogenic - Intravascular volume loss - Excessive venous pooling - Endocrine disorders - Cardiovascular Disease - Multiple myeloma - Paraneoplastic syndromes - Multiple sclerosis - Renal failure

Case Description

● An 80-year-old male with a past medical history of heart failure with mid-range ejection fraction, type 2 diabetes mellitus with peripheral neuropathy, peripheral vascular disease, and paroxysmal atrial fibrillation presented to the emergency room after a pre-syncopal fall. Four similar episodes in the prior 4 months resulted in prolonged hospital stays and medication adjustments. A correct medication reconciliation was not made until his 4th encounter. ● Physical exam demonstrated profound orthostatic hypotension, irregular rate and rhythm, grossly normal cognition, intact motor function, an asymmetric resting tremor, and absent signs of Parkinsonism. Lab testing revealed an acute kidney injury with creatinine of 1.32. Morning cortisol was normal at 8.8 (4.8 19.5). CT of the brain was unremarkable. ECG revealed sinus tachycardia. ● The patient and partner were unable to list his medications, which were obtained via mailed “bubble packs”. Comprehensive medication reconciliations with pharmacist and partner with all pills revealed he was taking four serotonergic drugs (Table 1) coupled with multiple central and peripheral-acting drugs with known autonomic side effects from multiple prescribers. Sertraline was added, and duloxetine increased, prior to the first fall. Repeat physical exam elicited marked ankle clonus. A clinical diagnosis of serotonin syndrome was made. ● Treatment included discontinuation of escitalopram, venlafaxine, opiates, and oxybutynin. Diuretics and blood pressure medications were held. Acute rehab with medical titration was declined by the patient, and he was discharged with home health. He returned 4 days later with continued orthostasis, and medications were adjusted further. Two months following the most recent discharge, the patient has not had similar episodes.

Neurogenic - Primary autonomic dysregulation - Parkinsonism Disorders - Diabetes mellitus - Amyloidosis - Excessive alcohol use - Vitamin deficiencies (B 1 , B 12 ) - Autoimmune autonomic ganglionopathy - Infectious disease - Chemotherapy agents - Spinal cord injuries - Autoimmune diseases

Medications - Tricyclic antidepressants - α 1 -adrenergic antagonists - Central Sympatholytics (Clonidine, Methyldopa) - Direct Vasodilators - Serotonin antagonists - Monoamine oxidase inhibitors

Orthostatic Hypotension Differential Diagnosis [3]

- Diuretics - Nitrates

Medical Mimics - Vasovagal syncope - Postural Tachycardia Syndrome (POTS) - Afferent Baroreflex Failure

References

Figure 2. Differential Diagnosis of orthostatic hypotension. On 1 st presentation, volume and meds likely. Neurogenic and adrenal etiologies considered in this case.

2025 Research Recognition Day

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