What causes legs to feel feverish after starting Lexapro (escitalopram)?

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Feverish Sensation in Legs After Starting Escitalopram (Lexapro)

The feverish sensation in your legs after starting Lexapro is most likely due to mild serotonin syndrome, which requires discontinuation of the medication and consultation with your healthcare provider immediately.

Understanding the Cause

Escitalopram (Lexapro) is a selective serotonin reuptake inhibitor (SSRI) that can cause several neurological and autonomic symptoms through its effects on serotonin levels:

  • SSRIs like escitalopram can cause mild to moderate serotonin syndrome, characterized by neuromuscular abnormalities including increased muscle tone (particularly in the lower extremities), tremors, and sensations of heat or feverishness 1

  • The onset of serotonin syndrome symptoms typically occurs within hours to days after starting an SSRI or increasing the dose 1

  • Serotonin syndrome presents with a triad of symptoms: mental status changes, autonomic hyperactivity (including fever or sensations of heat), and neuromuscular abnormalities 1

Clinical Manifestations

The feverish sensation in your legs may be part of a constellation of symptoms:

  • Increased muscle tone in the lower extremities is a characteristic feature of serotonin syndrome, which can manifest as a sensation of heat or feverishness 1

  • Drug-induced fever typically develops after starting a medication, with an average lag time of 21 days (median 8 days) 2

  • Other symptoms that may accompany this sensation include tremors, hyperreflexia, clonus, restlessness, and autonomic instability 1

Severity Assessment

Serotonin syndrome exists on a spectrum of severity:

  • Mild cases may present with subtle symptoms like tremor, hyperreflexia, or feverish sensations 1

  • Moderate cases involve more pronounced symptoms including elevated temperature, tachycardia, diaphoresis, and hyperactive bowel sounds 1

  • Severe cases can be life-threatening with hyperthermia, metabolic acidosis, rhabdomyolysis, seizures, and renal failure 1

Management Approach

The appropriate management depends on symptom severity:

  • For mild symptoms: Discontinue escitalopram and contact your healthcare provider immediately 1, 2

  • Symptoms typically resolve within 1-3 days after discontinuation of the offending agent, but may take up to 7 days 2, 3

  • For moderate to severe symptoms, immediate medical attention is required as this can be a medical emergency 1

  • Benzodiazepines may be used for agitation and muscle symptoms 1

  • In severe cases, serotonin2A antagonists like cyproheptadine may be considered under medical supervision 1

Risk Factors and Prevention

Several factors can increase the risk of developing serotonin syndrome:

  • Combining escitalopram with other serotonergic medications significantly increases risk 1, 4

  • Higher doses of escitalopram may increase the likelihood of adverse effects 1

  • Starting at a lower dose and gradually increasing can reduce the risk of adverse effects 1

  • Patients with certain genetic variations may metabolize SSRIs differently, affecting their susceptibility 1

Important Warnings

  • Do not stop escitalopram abruptly without medical guidance, as this can cause withdrawal symptoms including anxiety, irritability, dizziness, electric shock-like sensations, and confusion 5

  • Never combine escitalopram with monoamine oxidase inhibitors (MAOIs) as this can cause severe or life-threatening serotonin syndrome 5

  • Avoid combining escitalopram with other serotonergic medications without medical supervision 1, 4

  • Report any new or worsening symptoms to your healthcare provider immediately 5

Alternative Considerations

Other possible explanations for feverish sensations in the legs include:

  • Restless legs syndrome (RLS), which has been reported with escitalopram use 6

  • Simple drug-induced hypersensitivity fever, which typically resolves after discontinuation 2

  • Anticholinergic effects, though these are less common with escitalopram compared to other antidepressants 2

Remember that prompt recognition and management of these symptoms is essential to prevent progression to more severe manifestations of serotonin syndrome.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Drug-Induced Fever

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Management of Fever Induced by Amisulpride

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Serotonin syndrome in a patient taking Lexapro and Flexeril: a case report.

The American journal of emergency medicine, 2008

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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