What is a rational approach to the first line pharmacotherapeutic management of pruritus?

First-Line Pharmacotherapeutic Management of Pruritus

For mild to moderate pruritus, the first-line pharmacotherapeutic approach should be non-sedating, second-generation antihistamines (such as loratadine 10 mg daily) during daytime, and first-generation antihistamines (such as diphenhydramine 25-50 mg or hydroxyzine 25-50 mg) for nighttime use when sedation is beneficial. 1

Assessment and Classification

• Pruritus can be categorized by etiology into inflammatory (60% of cases), neuropathic (25% of cases), or mixed causes (15% of cases) 2
• Consider underlying causes including dermatological conditions, systemic diseases, medication-induced pruritus, and psychogenic factors 1, 2
• Evaluate for xerosis (dry skin), which is a common contributor to pruritus that requires specific management 1

Stepwise Approach to Management

Step 1: Topical Therapies

• Apply emollients regularly to prevent and treat skin dryness 1
• For mild localized pruritus, use:
  • Topical antipruritic agents containing menthol 0.5% 1, 2
  • Moderate-potency topical corticosteroids (mometasone furoate 0.1% or betamethasone valerate 0.1% ointment) 1
  • Lotions containing urea or polidocanol for soothing effect 1

Step 2: Systemic Antihistamines

• For daytime use: Non-sedating second-generation antihistamines (loratadine 10 mg daily, fexofenadine 180 mg) 1
• For nighttime use: First-generation antihistamines with sedative properties (diphenhydramine 25-50 mg, hydroxyzine 25-50 mg) 1, 3
• Consider combination of H1 and H2 antagonists in refractory cases 1

Step 3: For Refractory Cases

• Antiepileptic agents as second-line treatment:
  • Gabapentin (900-3600 mg daily) 1
  • Pregabalin (25-150 mg daily) 1
• Other systemic options:
  • Tricyclic antidepressant doxepin (potent histamine antagonist) 1
  • SSRIs such as paroxetine or sertraline 1
  • Mirtazapine for refractory cases 1

Special Considerations for Specific Causes

Opioid-Induced Pruritus

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

Hepatic Pruritus

• First-line: Rifampicin 1
• Second-line: Cholestyramine 1
• Third-line: Sertraline 1
• Avoid gabapentin in hepatic pruritus 1

Uremic Pruritus

• Ensure adequate dialysis and normalize calcium-phosphate balance 1
• Consider capsaicin cream, topical calcipotriol, or oral gabapentin 1
• Avoid long-term sedative antihistamines except in palliative care 1

Pruritus of Unknown Origin

• Start with emollients and self-care advice 1
• Consider non-sedative antihistamines (fexofenadine 180 mg or loratadine 10 mg) 1
• Topical options include clobetasone butyrate or menthol 1
• Avoid crotamiton cream, topical capsaicin, or calamine lotion 1

Common Pitfalls and Caveats

• Sedative antihistamines should be used with caution, especially in elderly patients, as long-term use may predispose to dementia 1
• Antihistamines have limited efficacy in non-histaminergic pruritus (such as atopic dermatitis and psoriasis) 4
• Always address underlying causes rather than just treating the symptom 2, 5
• Gabapentin should not be used in hepatic pruritus despite its efficacy in other forms of pruritus 1
• Topical doxepin treatment should be limited to 8 days, 10% of body surface area, and 12 g daily due to risk of allergic contact dermatitis 1