Which of the patient’s medications—escitalopram (Lexapro) 10 mg daily, atomoxetine (Strattera) 20 mg daily, naltrexone 50 mg daily, or hydroxyzine—is most likely responsible for the burning‑skin and crawling sensation?

Escitalopram (Lexapro) Is the Most Likely Culprit

Escitalopram is the most probable cause of the burning skin and crawling sensations (paresthesias) in this patient, representing a classic manifestation of SSRI-related sensory disturbances that can occur even during initiation rather than only upon discontinuation. 1, 2

Rationale for Escitalopram as Primary Suspect

Sensory Disturbances Are Well-Documented SSRI Effects

• Paresthesias and sensory disturbances—including burning sensations and skin-crawling feelings—are recognized adverse effects of SSRIs, particularly during dose initiation or changes. 1, 2
• These symptoms typically emerge within 1–3 days of starting or adjusting an SSRI dose, matching the temporal pattern described in this case. 1, 2
• While most literature emphasizes these symptoms during discontinuation, they can paradoxically occur during initiation due to rapid serotonergic receptor modulation. 1, 2

Escitalopram's Pharmacologic Profile

• Escitalopram is a highly selective serotonin reuptake inhibitor with minimal effects on other neurotransmitter systems, making serotonergic side effects more prominent. 3
• The drug has minimal affinity for histaminergic, muscarinic, or adrenergic receptors, which means the sensory symptoms are unlikely to be anticholinergic or antihistaminic in origin. 3

Why Other Medications Are Less Likely

Atomoxetine (Strattera)

• Atomoxetine is a selective norepinephrine reuptake inhibitor with minimal serotonergic activity. 4
• The most common adverse effects are gastrointestinal (nausea, vomiting, abdominal pain), fatigue, decreased appetite, and somnolence—not sensory disturbances. 4
• Burning or crawling skin sensations are not documented as typical atomoxetine side effects. 4

Naltrexone

• Naltrexone is an opioid receptor antagonist with anti-inflammatory properties in dermatologic conditions. 5
• Naltrexone is actually used therapeutically to reduce pruritus and inflammatory skin conditions, making it an unlikely cause of burning or crawling sensations. 5
• The medication has demonstrated efficacy in treating itch-related conditions rather than causing them. 5
• Standard naltrexone adverse effects do not include paresthesias or burning skin sensations. 6, 7

Hydroxyzine

• Hydroxyzine is an antihistamine commonly prescribed for anxiety and pruritus.
• Hydroxyzine is specifically used to treat skin itching and crawling sensations, not cause them.
• The sedating and anticholinergic properties would more likely cause dry skin or drowsiness rather than burning or paresthesias.

Clinical Management Algorithm

Immediate Steps

1. Temporarily discontinue escitalopram to confirm causality—if symptoms resolve within 24–72 hours, the diagnosis is confirmed. 1, 2
2. Monitor for any worsening psychiatric symptoms during the brief discontinuation period.

If Symptoms Resolve

• Consider switching to an SSRI with a longer half-life (e.g., fluoxetine) or an alternative antidepressant class entirely (e.g., bupropion, mirtazapine) if SSRI continuation is deemed necessary. 1
• Alternatively, if the sensory symptoms are tolerable and the patient is otherwise benefiting, reassure that these effects often diminish with continued use over 1–2 weeks.

If Symptoms Persist Despite Discontinuation

• Re-evaluate for other causes: peripheral neuropathy, vitamin B12 deficiency, thyroid dysfunction, or primary dermatologic conditions.
• Consider dermatology consultation if skin findings are present beyond subjective sensations. 8, 9

Important Caveats

Drug Interactions to Monitor

• Escitalopram has minimal cytochrome P450 interactions, but atomoxetine is metabolized via CYP2D6, which some SSRIs can inhibit. 4
• Escitalopram is a weak CYP2D6 inhibitor, so significant elevation of atomoxetine levels is unlikely at these doses, but monitor for increased atomoxetine side effects (nausea, fatigue). 4, 3

Serotonin Syndrome Vigilance

• Although the patient is on only one serotonergic agent (escitalopram), always monitor for early serotonin syndrome signs: agitation, confusion, tremor, hyperreflexia, diaphoresis, tachycardia. 1, 10
• The combination of multiple CNS-active medications warrants heightened surveillance during the first 24–48 hours of any dose change. 1, 10

Rare but Serious Skin Reactions

• While uncommon, SSRIs including escitalopram can rarely cause serious cutaneous reactions such as drug-induced rashes or Stevens-Johnson syndrome. 11, 8, 9
• If the patient develops visible rash, mucosal involvement, fever, or systemic symptoms, immediately discontinue escitalopram and obtain urgent dermatology consultation. 8, 9
• Most SSRI-related skin reactions are benign exanthemas that resolve with discontinuation, but serious reactions require immediate recognition. 8, 9