How to manage D-amphetamine (dextroamphetamine) induced pruritus?

Management of D-Amphetamine Induced Pruritus

Discontinue dextroamphetamine immediately if medically feasible, as drug cessation is the primary treatment for drug-induced pruritus. 1, 2

Initial Assessment and Drug Discontinuation

• First-line action: Stop the offending medication when the risk-benefit ratio is acceptable, as this is the fundamental principle for managing drug-induced itch 1, 3
• If dextroamphetamine cannot be discontinued (e.g., essential for ADHD management), proceed with aggressive symptomatic antipruritic therapy 3
• Rule out other causes of pruritus including concomitant medications, systemic diseases, or dermatological conditions before attributing symptoms solely to dextroamphetamine 1

Symptomatic Treatment While Awaiting Resolution

Topical Therapies (First-Line Symptomatic Treatment)

• Apply emollients liberally to the entire body at least once daily to prevent xerosis, which can worsen pruritus 2, 4
• Use moderate-to-high potency topical corticosteroids (mometasone furoate 0.1% ointment or betamethasone valerate 0.1% ointment) for localized or mild pruritus 1, 2, 4
• Consider topical menthol 0.5% preparations or lotions containing urea or polidocanol for additional symptomatic relief 1, 2
• Topical doxepin can be used but limit to 8 days, 10% body surface area, and 12g daily maximum 2, 4

Oral Antihistamines (Second-Line)

• Start with non-sedating second-generation antihistamines such as fexofenadine 180 mg daily or loratadine 10 mg daily for daytime pruritus 1, 2, 4
• Use first-generation sedating antihistamines (diphenhydramine 25-50 mg or hydroxyzine 25-50 mg) specifically for nighttime pruritus to aid sleep 1
• Important caveat: Antihistamines have limited efficacy in non-histamine-mediated pruritus, which may include amphetamine-induced itch 5

GABA Agonists (Third-Line)

• Gabapentin 900-3600 mg daily or pregabalin 25-150 mg daily if antihistamines fail to provide adequate relief 1, 2, 4
• These agents work peripherally by reducing calcitonin gene-related peptide release and centrally by modulating mu-opioid receptors 1

Antidepressants (Alternative Third-Line)

• Consider mirtazapine, paroxetine, or fluvoxamine as alternative third-line agents 2, 4
• These may be particularly useful if there is concurrent anxiety or depression related to chronic pruritus 1

Monitoring and Escalation

• Reassess severity after 2 weeks of any intervention 1
• If pruritus persists despite topical therapy and oral antihistamines, escalate to GABA agonists or antidepressants 1, 2
• For severe, constant pruritus limiting self-care or sleep (Grade ≥3), consider temporary interruption of dextroamphetamine if medically possible 1, 4

Critical Clinical Pitfalls

• Do not use crotamiton cream or topical capsaicin as they are ineffective for generalized pruritus 1
• Avoid long-term use of sedating antihistamines except in palliative settings due to dementia risk 2
• Do not assume all pruritus is amphetamine-related; amphetamine toxicity typically presents with hyperactivity, hyperthermia, tachycardia, and mydriasis rather than isolated pruritus 6

Special Consideration

• One case report paradoxically describes improvement of chronic eczema with dextroamphetamine treatment 7, suggesting the relationship between amphetamines and pruritus may be complex and patient-specific
• If pruritus develops early in amphetamine therapy, it may resolve spontaneously with continued use, similar to opioid-induced pruritus patterns 1