Assess for anxiety exacerbation with somatic features, as the agitation, tachycardia, and diaphoresis are consistent with a severe panic episode or generalized anxiety flare in a patient with known MDD.

Panic does not cause hyperreflexia, diarrhea, or fever. The neuromuscular and autonomic findings point to a pharmacological syndrome, not anxiety.

Order a TSH to evaluate for hyperthyroidism, as the combination of tachycardia, tremor, diaphoresis, and hyperreflexia is consistent with thyrotoxicosis, which can present acutely in middle-aged women.

While hyperthyroidism can cause tachycardia and tremor, the acute onset of the full symptom constellation in the context of two serotonergic medications makes serotonin syndrome the clear priority. Thyroid storm would not explain hyperreflexia with diarrhea in this medication context.

Assess for serotonin syndrome, as duloxetine and tramadol are both serotonergic agents and the presentation of tremor, hyperreflexia, and autonomic instability meets Hunter Criteria.

Duloxetine (SNRI) + tramadol (weak opioid with serotonin reuptake inhibition) is a commonly tested serotonergic drug combination. Tramadol's serotonin reuptake inhibition is often overlooked because it is classified as an opioid. The presentation — agitation, tremor, diarrhea, diaphoresis, hyperreflexia, tachycardia, hypertension, and low-grade fever — is consistent with serotonin syndrome. Hunter Criteria include multiple diagnostic pathways: spontaneous clonus; inducible clonus + agitation or diaphoresis; ocular clonus + agitation or diaphoresis; tremor + hyperreflexia; or hypertonia + temperature >38°C + clonus. This patient meets criteria via tremor + hyperreflexia. Management: discontinue both serotonergic agents, provide supportive care, and assess severity.

Increase duloxetine to 90 mg to better manage the chronic pain, as the agitation and autonomic symptoms likely reflect undertreated pain causing a sympathetic nervous system stress response.

Increasing a serotonergic agent in a patient with possible serotonin syndrome would be dangerous and could precipitate a life-threatening escalation of symptoms.