Table 3.

Topical neuromodulatory anti-pruritic therapies

Therapy	Mechanism of action	Pruritic disorders with reported benefit	Comments
Topical anesthetics
Lidocaine 2.5–5%,	Blocks voltage gated Na channels	neuropathic pruritus, pruritus ani, postburn pruritus, notalgia paresthetica (NP)	*Prilocaine associated with methemoglobinemia in pediatric patients
Prilocaine 2.5%
Pramoxine 1%	Stabilizes neuronal membrane by uncertain mechanism	xerosis, uremic pruritus (UP), psoriasis
Polidocanol 3%	Non-ionic surfactant	atopic dermatitis (AD), contact dermatitis, psoriasis, idiopathic pruritus	*Formulated with urea
Capsaicin	Activates TRPV1 on sensory fibers, depleting substance P over time and prevents neural transmission	AD, UP, brachioradial pruritus, pruritus ani, prurigo nodularis (PN), aquagenic pruritus	*Burning sensation with initial use may limit patient compliance
Menthol	Activates TRPM8 on sensory fibers triggering a cooling sensation	lichen amyloidosis, as well as hydroxyethyl starch-induced, histamine-induced, and mustard gas-induced pruritus	*May be useful in patients who report cooling alleviates symptoms
N-palmitoylethanolamine cream	Cannabinoid receptor CB2 agonist	AD, PN, lichen simplex chronicus, uremic pruritus	*Efficacy demonstrated in pilot studies only
			*Not FDA approved for itch
Naltrexone 1% cream	µ-opioid receptor antagonist	AD	*Not FDA approved for itch
Aprepitant	Neurokinin 1 receptor antagonist	PN, nephrogenic pruritus, Sézary syndrome, paraneoplastic and drug-induced pruritus	*Efficacy demonstrated in pilot studies only
			*Not FDA approved for itch