Neuromodulatory Agents to Treat Pruritus (For Professionals)

They are indicated when conventionale treatment of  itch has failed:  refractory pruritus (chronic itch)

Practical Attitude:

• identify the cause if there is one
• target the right type of itch
• Try many treatments, and stick to the one which works.

Types of itch

• pruriceptive : skin
• neuropathic: central nervous system (CNS) and peripheral nervous (PNS) pathways
• neurogenic: neuromodulators
• psychogenic

There are two types of neuromodulatory treatments:

• treatment which acts on neuromodulatory signals

1. Opioids (Naltrexone, Nalfamene)
2. Noradrenergic and specific serotonin antidepressants (mirtazipine)
3. Anticonvulsants (Gabapentin, Pregabalin)
4. Tahykinines (Aprepitant)

• action on neuromodulatory signals

1. Calcimimetics (Strontium)
2. Tricyclic antidepressants (Doxepin, Ketamine, Amitryptiline)
3. SSRI antidepressants (Paroxetine, Sertraline)

Opioids

• Naltrexone:

1. studies exist in in uremic pruritus, aquagenic pruritus, post burn pain, cholestatic pruritus,  atopic dermatitis (AD).
2. lasts 48 hours (contrarily to naloxone, it has a long half life and does not need subcutaneous or intraveinous administration)
3. oral administration:
   1. Start at 25mg once a day then increase to 50mg. Stop at 25mg if there is an underlying liver condition.
   2. Check LFT (liver function tests) at baseline and 3 months).
   3. Effects are usually seen after 2 to 4 weeks.
   4. Side effects (SE): nausea, Gastrointestinal  cramping, fatigue, insomnia. Do not use in patients with opiod dependance.
4. topical administration: 1% cream twice a day (Indications: lichen Simplex Chronicus (LSC), AD and genital pruritus)

• Nalmafene (Orally):

1. Could be an option if naltrexone works but too many SE.
2. Start at 10mg daily for 2 days and increase up to 120mg daily.
3. SE: drowsiness, dizziness, nausea, hypertension, tachycardia. Do not use in patients with opioid dependance

Noradrenergic and specific serotonin antidepressants

• Mirtazapine (Orally):

1. Studies have been done in cholestatic pruritus, uremic pruritus, CTCL (T-cell lymphoma)
2. The mechanism against itch is unknown
3. Start at 7.5mg bedtime and increase up to 15mg. Maximum daily dose 45mg.
4. Side effects: somnolence, fatigue, weight gain (increased appetite), agitation (especially in the elderly)

Anticonvulsants (decreases pre-synaptic nerve activity):

• Gabapentin (Orally):

1. Studies have been done in uremic pruritus, cholestatic pruritus (not very effective) and post-herpetic neuralgia.
2. Start at 100mg to 300mg at bedtime and increase up to a maximum daily dose of 3600mg
3. Side effects: dizziness, nausea (usually fades after 4 weeks). Avoid using in individuals under 12 because of concentration problems.
4. Beware when using in older patients with renal insufficiency or taking other antidepresssants

Pregabalin (Orally):

1. Studies have been done in aquagenic pruritus and uremic pruritus, post burn pain
2. Side effects similar to gabapentin. Works faster.
3. Start at 50mg to 75mg twice a day for 2 weeks then increase to 150mg to 300 twice a day. Maximum 600mg a day
4. Caution in elderly and if renal insufficiency. Not metabolized by the liver so ok if liver problems.

Tachykinines

• Aprepitant (Orally) (Nk1R receptor antagonist; stops substance P action (Substance P antagonist or SPA)):

1. Used mainly in inpatient

Calcimimetics

1. Topical treatment with Strontium: SrCl2 $% topical hydrogel: studies done in cowhage-induced itch (spicules of tropical legume called Mucuna pruriens)
2. Exact mechnism against itch uncertain
3. No side effects recorded
4. Indications: mild eczema, arthropod bites, mild itch
5. Caveat: more studies are needed to ascertain its efficacy

Tricyclic antidepressants:
Studies have been done in itches of many different origins.

• Doxepin

1. Topical treatment: doxepin 5%
   1. Studies done in atopic dermatitis, LSC, nummular eczema and allergic contact dermatitis
   2. Applied twice daily
   3. Side effects (SE): stinging, burning, drowsiness (dry mouth)
2. oral treatment: studies done in uremic pruritus
   1. Start at 25mg then move to 50mg up to 300mg daily dose. However the limit is often 80mg before side effects stop the benefit of the treatment.

• Ketamine and Amitryptiline:

1. topical amitryptilline 1% combined with ketamine 0.5% in Brachioradial pruritus
2. oral use showed in one study (Yong A): Uremic pruritus at a dosage of 10 to 25mg.
3. Start at 25mg then increase to 50mg for a maximum daily dose of 300mg)

SSRI antidepressants

• Studies have been done in paraneoplastic pruritus, aquagenic pruritus, cholestatic pruritus and psychogenic itch.
• It is not known by what mechanism the itch is improved
• Effects usually are seen after 2 weeks.
• Side effects: nausea-vomiting, sedation, anxiety, fatigue, vertigo, decreased libido (delayed ejaculation). On the skin, eccymoses (increased bleeding with paroxetine – often the patients are taking anticoagulants), alopecia, sun sensitivity
• Paroxetine: start at 10mg up to a maximum daily dose of 40mg.
• Sertraline: start at 25 to 50mg up to a maximum daily dose of 100 to 125mg .

For all oral treatment in the elderly: start at lower doses for oral treatment: 50 to 60% of the starting usual dose.

Contributors:

Dr Christophe Hsu – dermatologist. Geneva, Switzerland

Source of Information: Elmariah S. Novel therapies to treat chronic pruritus. 71st Annual Meeting of the AAD (American Academy of Dermatology) – Miami, Florida, United States of America (USA)