Chronic Itching Management
Treatment Algorithm
For chronic pruritus, begin with emollients and topical therapies, escalating systematically to oral antihistamines, then gabapentin/pregabalin or antidepressants, reserving systemic steroids for severe refractory cases. 1
First-Line: Topical Therapies
Emollients and Barrier Protection
- Apply emollients at least once daily to the entire body to prevent xerosis (dry skin), which commonly triggers pruritus 2, 1
- Use oil-in-water creams or ointments; avoid alcohol-containing lotions 2
- For elderly patients, select moisturizers with high lipid content 1
Topical Anti-Inflammatory Agents
- Moderate-to-high potency topical steroids (mometasone furoate 0.1% ointment, betamethasone valerate 0.1% ointment, or prednicarbate cream 0.02%) for mild-to-moderate pruritus 2
- Hydrocortisone 2.5% significantly decreases pruritus compared to placebo 2, 3
- Topical doxepin: Limit to 8 days, 10% body surface area, and 12g daily maximum 2, 1
Topical Antipruritic Agents
- Menthol 0.5% or clobetasone butyrate provide symptomatic relief 2, 1
- Urea or polidocanol-containing lotions soothe pruritus 2
- Avoid crotamiton cream and capsaicin - evidence does not support their use 2
Second-Line: Oral Antihistamines
Non-Sedating Antihistamines (Daytime Use)
- Fexofenadine 180 mg or loratadine 10 mg daily as first-choice systemic therapy 2, 1
- Cetirizine 10 mg (mildly sedative) can be used as an alternative 2
Sedating Antihistamines (Nighttime Use Only)
- Diphenhydramine 25-50 mg or hydroxyzine 25-50 mg for nocturnal pruritus to break the itch-scratch cycle 2
- Critical caveat: Avoid long-term use of sedating antihistamines except in palliative care settings due to dementia risk 1, 4
Third-Line: Neuromodulatory Agents
GABA Agonists (Antiepileptic Agents)
- Gabapentin 900-3600 mg daily or pregabalin 25-150 mg daily for patients failing antihistamines 2, 1
- These agents reduce peripheral calcitonin gene-related peptide release and modulate central μ-opioid receptors 2
- Important warning: Avoid gabapentin in hepatic pruritus 1, 4
Antidepressants
- Paroxetine, fluvoxamine, or mirtazapine as third-line options 2, 1, 4
- Doxepin (tricyclic antidepressant with potent histamine antagonist properties) available in topical and oral preparations 2
- Sertraline specifically for hepatic pruritus as third-line therapy 1, 4
Opioid Receptor Modulators
- Naltrexone or butorphanol for refractory cases 2, 1
- Naltrexone is first-line for opioid-induced pruritus when cessation is not possible 1, 4
Fourth-Line: Advanced Therapies
Neurokinin-1 Receptor Antagonists
- Aprepitant 80 mg daily reduces pruritus in refractory cases, including EGFR-inhibitor-related and nivolumab-related pruritus 2
Systemic Corticosteroids
- 0.5-2 mg/kg daily for temporary relief of severe, widespread pruritus 2
- Reserve for grade ≥3 pruritus or intolerable grade 2 symptoms 2
Immunosuppressive Therapy
- Consider for intense, widespread pruritus unresponsive to other measures 2
Cause-Specific Management
Hepatic Pruritus
- First-line: Rifampicin 1, 4
- Second-line: Cholestyramine 1, 4
- Third-line: Sertraline 1, 4
- Fourth-line: Naltrexone or nalmefene 4
Uremic Pruritus
- Optimize dialysis parameters, normalize calcium-phosphate balance, control parathyroid hormone levels 1, 4
- BB-UVB phototherapy (Strength of recommendation A) 1, 4
- Avoid cetirizine and long-term sedating antihistamines except in palliative care 4
Drug-Induced Pruritus
- Trial medication cessation when risk-benefit ratio is acceptable 1, 4
- Naltrexone for opioid-induced pruritus; methylnaltrexone as alternative 1
- Diclofenac 100 mg rectally for postoperative pruritus 1
Graded Approach for Cancer Therapy-Related Pruritus
Grade 1 (Mild/Localized)
- Continue anticancer drug at current dose 2
- Topical moderate/high-potency steroids 2
- Reassess after 2 weeks 2
Grade 2 (Intense/Widespread, Intermittent)
- Continue drug at current dose 2
- Topical moderate/high-potency steroid OR oral antihistamines OR GABA agonists (pregabalin/gabapentin) 2
- Reassess after 2 weeks 2
Grade ≥3 (Constant, Limiting Self-Care/Sleep)
- Interrupt treatment until grade 0-1 2
- Continue topical steroids, oral antihistamines, or GABA agonists 2
- Discontinuation may be necessary if no improvement after 2 weeks 2
Common Pitfalls to Avoid
- Do not use crotamiton cream, capsaicin, or calamine lotion - lack of efficacy evidence 2
- Avoid hot showers and excessive soap use - these worsen xerosis 2
- Do not use gabapentin in hepatic pruritus - contraindicated 1, 4
- Limit topical doxepin to prevent systemic absorption and side effects 2
- Avoid long-term sedating antihistamines outside palliative care due to dementia risk 1, 4