What medications are used to treat itching?

Medications for Itching

For general pruritus, start with non-sedating second-generation antihistamines (loratadine 10 mg daily or fexofenadine 180 mg daily) during the day, combined with regular emollient application; reserve first-generation antihistamines (diphenhydramine 25-50 mg or hydroxyzine 25-50 mg) for nighttime use only when sleep is disrupted. 1, 2

Stepwise Treatment Algorithm

First-Line: Topical Therapies + Non-Sedating Antihistamines

Topical Management:

• Apply emollients regularly throughout the day to maintain skin barrier function and prevent xerosis, which commonly contributes to pruritus 1, 3
• For localized itching, use moderate-potency topical corticosteroids: mometasone furoate 0.1% or betamethasone valerate 0.1% ointment applied 2-4 times daily 4, 1, 3
• Over-the-counter hydrocortisone 1% cream can be applied 3-4 times daily for minor skin irritations, though evidence shows low-potency corticosteroids (0.2%-2.5% hydrocortisone) are not effective for significant pruritus 4, 5
• Consider lotions containing urea or polidocanol for additional soothing effect 1, 2
• Menthol-containing preparations may provide supplemental relief through cooling mechanisms 2, 3

Systemic Antihistamines:

• Daytime: Use non-sedating second-generation antihistamines as first choice: loratadine 10 mg daily, fexofenadine 180 mg daily, or cetirizine 10 mg daily 4, 1, 2
• Nighttime: First-generation antihistamines with sedative properties can be used specifically for sleep disruption: diphenhydramine 25-50 mg or hydroxyzine 25-50 mg at bedtime only 4, 1, 2
• Important caveat: Avoid long-term use of sedating antihistamines in elderly patients due to increased dementia risk; use second-generation agents instead 1, 2, 3

Second-Line: Antiepileptic Agents

When antihistamines fail after 2 weeks, escalate to:

• Gabapentin 900-3600 mg daily, particularly effective for neuropathic itching 4, 1, 2
• Pregabalin 25-150 mg daily as an alternative with similar mechanism of action 4, 1, 2
• Critical pitfall: Do NOT use gabapentin for hepatic pruritus despite its efficacy in other forms—it should be avoided in this specific context 1, 2

Third-Line: Antidepressants

For refractory cases:

• Doxepin (tricyclic antidepressant with potent H1/H2 histamine antagonist properties): 10 mg orally twice daily 1, 2
  • Achieves complete resolution in 58% of uremic pruritus cases versus 8% with placebo 1
  • Drowsiness occurs in 50% but typically resolves within 2 days 1
  • Topical doxepin warning: Limit to maximum 8 days duration, 10% body surface area, and 12 grams daily due to allergic contact dermatitis risk 1, 2
• SSRIs (paroxetine or sertraline) for certain pruritus types 1, 2

Cause-Specific Treatments

Opioid-Induced Pruritus

• First choice: Naltrexone if opioid cessation is impossible 1
• Alternatives: Methylnaltrexone, ondansetron, droperidol, mirtazapine, or gabapentin 1

Hepatic Pruritus

• First-line: Rifampicin 1, 2
• Second-line: Cholestyramine 1
• Third-line: Sertraline 1
• Avoid: Gabapentin specifically in this context 1, 2

Uremic Pruritus (Dialysis Patients)

• Ensure adequate dialysis and normalize calcium-phosphate balance first 1
• Doxepin 10 mg twice daily is highly effective (87.5% overall improvement rate) 1
• Alternatives: Capsaicin cream, topical calcipotriol, or oral gabapentin 1, 2
• Avoid: Long-term sedative antihistamines except in palliative care 1

Cholestatic Pruritus

• Ursodeoxycholic acid (UDCA) 10-15 mg/kg per day 2

Cancer Therapy-Induced Pruritus

• For EGFR inhibitor-related itching: Start with diphenhydramine 25 mg IV/PO every 6 hours PRN or hydroxyzine 10 mg PO every 6 hours PRN 4
• Apply Aveeno or Lubriderm lotion three times daily 4
• If persistent/severe despite above measures, consult dermatology and consider topical steroid agents 4

Common Pitfalls to Avoid

• Do not use topical corticosteroids long-term (>2-4 weeks) due to skin atrophy and tachyphylaxis risk 3
• Avoid sedating antihistamines in elderly patients for chronic use due to cognitive impairment and dementia risk; use second-generation agents instead 1, 2, 3
• Hydroxyzine is contraindicated in early pregnancy; second-generation antihistamines are safer alternatives 2
• Reassess diagnosis if no improvement after 2 weeks of appropriate therapy and consider dermatology referral 3
• Evidence shows oral antihistamines have uncertain efficacy for contact dermatitis from poison ivy/oak/sumac, though they may help with nighttime sleep 4
• Dose adjustments required for many antihistamines in renal impairment 2