What medications are used to treat itching?

Medications for Itching

For generalized pruritus, start with emollients and non-sedating second-generation antihistamines like loratadine 10 mg daily or fexofenadine 180 mg daily during the day, reserving first-generation sedating antihistamines (diphenhydramine 25-50 mg or hydroxyzine 25-50 mg) for nighttime use only. 1

Stepwise Treatment Algorithm

Step 1: Universal Foundation - Topical Therapy

• Apply emollients at least once daily regardless of the cause of itching - this is the cornerstone of all pruritus management 1, 2
• For localized inflammatory pruritus (eczema, dermatitis), use moderate-to-high potency topical corticosteroids:
  • Hydrocortisone 2.5%, mometasone furoate 0.1%, or betamethasone valerate 0.1% applied 3-4 times daily for maximum 7 days 1, 3
  • Do not exceed 7 days to avoid skin atrophy 3
• For generalized pruritus of unknown origin, topical doxepin is the most evidence-based option but must be strictly limited to 8 days maximum, 10% body surface area maximum, and 12 grams daily maximum due to contact dermatitis risk 1, 2
• Menthol 0.5% can provide symptomatic counter-irritant relief 1, 3

Step 2: First-Line Systemic Therapy - Antihistamines

• For daytime pruritus: Use non-sedating second-generation antihistamines 4, 1
  • Loratadine 10 mg daily 4, 1
  • Fexofenadine 180 mg daily 1
  • These are preferred because they avoid sedation and cognitive impairment 1
• For nighttime pruritus: Use first-generation sedating antihistamines 4, 1
  • Diphenhydramine 25-50 mg at bedtime 4, 1
  • Hydroxyzine 25-50 mg at bedtime 4, 1
  • Caution: Long-term use of sedating antihistamines may increase dementia risk in elderly patients 1

Important caveat: Antihistamines have limited efficacy when histamine is not the primary mediator of itch. They work well for urticaria but show minimal benefit for eczema-related pruritus, where the itch-scratch cycle benefits more from the sedative effect than histamine blockade 5, 6

Step 3: Second-Line Systemic Therapy - Neuropathic Agents

• Reserve these for patients who fail antihistamines and topical therapy 4, 1
• Gabapentin 900-3600 mg daily 4, 1, 3
• Pregabalin 25-150 mg daily 4, 1, 3
• These work by reducing peripheral release of itch mediators and modulating central opioid receptors 4

Step 4: Third-Line Options for Refractory Cases

• Doxepin (oral): 10 mg twice daily - functions as both tricyclic antidepressant and potent H1/H2 histamine antagonist 4, 1
  • Particularly effective for uremic pruritus (58% complete resolution vs 8% with placebo) 1
  • Drowsiness occurs in 50% but typically resolves within 2 days 1
• SSRIs (paroxetine or sertraline) for refractory cases 1
• Aprepitant (NK-1 receptor antagonist) has shown benefit for drug-induced pruritus from targeted cancer therapies 4
• Systemic corticosteroids 0.5-2 mg/kg daily for temporary relief of severe, widespread pruritus 4

Disease-Specific Modifications

Hepatic Pruritus

• First-line: Rifampicin 1, 2
• Second-line: Cholestyramine 1
• Third-line: Sertraline 1
• Critical: Do NOT use gabapentin for hepatic pruritus despite its efficacy in other forms 1, 2

Uremic Pruritus (Dialysis Patients)

• Optimize dialysis adequacy and normalize calcium-phosphate balance first 1, 2
• Topical capsaicin cream or calcipotriol 1
• Oral gabapentin 1
• Oral doxepin 10 mg twice daily (87.5% overall improvement rate) 1

Opioid-Induced Pruritus

• First-line: Naltrexone when opioid cessation is impossible 1, 2
• Alternatives: methylnaltrexone, ondansetron, droperidol, mirtazapine, or gabapentin 1

Vulvar Pruritus

• Most commonly caused by candidiasis - treat with 7 days of topical azole therapy (80-90% cure rate) 3, 2
• Symptomatic relief with topical corticosteroids (hydrocortisone 2.5%, mometasone 0.1%, or betamethasone 0.1%) for maximum 7 days 3
• If topical therapy fails, advance to systemic antihistamines, then neuropathic agents 3

Critical Pitfalls to Avoid

• Never use topical corticosteroids for more than 7 days - this causes skin atrophy and increases trauma risk 3
• Avoid long-term sedating antihistamines in elderly patients except in palliative care due to dementia risk 1
• Do not use gabapentin for hepatic pruritus - it is contraindicated despite efficacy elsewhere 1, 2
• Limit topical doxepin strictly to 8 days, 10% body surface area, and 12 grams daily 1, 2
• Avoid capsaicin for vulvar pruritus - it lacks efficacy in this location 3
• Do not use crotamiton cream, topical capsaicin, or calamine lotion for generalized pruritus of unknown origin - no evidence of efficacy 2

Mandatory Reassessment

• Reevaluate after 2 weeks if no improvement or worsening occurs to advance treatment or investigate underlying systemic disease 3, 2