Case Presentation: This report describes a 70-year-old female with a history of major depressive disorder, breast cancer, anxiety, hypothyroidism, hypertension, and type 2 diabetes mellitus, who developed serotonin syndrome (SS) after starting venlafaxine while on chronic trazodone. She presented to the ED with new-onset confusion, agitation, intractable nausea, vomiting, diaphoresis, fever (39.1°C), tremors, muscle rigidity, and mild diarrhea. Vitals: T 39.1°C, HR 184 bpm with EKG showing atrial fibrillation, BP 204/130 mmHg, RR 24, O2 sat 96% RA. Exam showed disorientation, hyperreflexia, inducible clonus, mydriasis, agitation, and rigors. Labs showed elevated lactic acid (3.9), otherwise normal counts, electrolytes, thyroid function, and negative tox screen. CXR showed left lower lobe infiltrate consistent with pneumonia.SS was diagnosed clinically via Hunter Criteria. Management included IV fluids, external cooling, IV lorazepam for agitation/neuromuscular symptoms, and cyproheptadine. She improved within 24–48 hours with resolution of fever, clonus, agitation, and rigidity, and was discharged after 5 days with outpatient psychiatry follow-up and a revised antidepressant regimen to low-dose mirtazapine, a non-serotonergic agent.
Discussion: Serotonin Syndrome (SS) is a potentially life-threatening condition resulting from excess serotonergic activity, most commonly due to drug interactions or overdose. It is characterized by a triad of altered mental status, autonomic instability, and neuromuscular abnormalities. In this case, the diagnosis was supported by the Hunter Criteria, which remains the most reliable diagnostic tool. Common causative agents include SSRIs, SNRIs, MAOIs, TCAs, linezolid, and recreational drugs. Even seemingly mild interactions—for example, SSRIs combined with over-the-counter medications like dextromethorphan—can precipitate SS. Early recognition is critical, as symptoms can escalate rapidly.Management involves immediate discontinuation of serotonergic agents, supportive care, and administration of benzodiazepines for agitation or tremors. In moderate to severe cases, cyproheptadine, a serotonin receptor antagonist, may be used.This case underscores the importance of thorough medication reconciliation and heightened clinician awareness. With the increasing prevalence of antidepressant use and polypharmacy, serotonin syndrome must remain a key differential diagnosis in patients presenting with altered mental status and neuromuscular symptoms, particularly after recent medication changes.In this instance, serotonin syndrome was triggered by the combination of trazodone and venlafaxine. Elderly patients are especially vulnerable due to age-related changes in drug metabolism and clearance, as well as a higher likelihood of polypharmacy. While trazodone is often considered relatively safe, it should be used with caution—or avoided—when prescribed alongside other serotonergic agents.Ultimately, prompt identification, cessation of offending medications, and appropriate supportive measures typically lead to full recovery.
Conclusions: Serotonin Syndrome should be considered in elderly patients presenting with altered mental status, autonomic instability, and neuromuscular abnormalities, especially when on serotonergic medications. Vigilant medication reconciliation and early intervention can reduce morbidity and improve outcomes.