Is low-dose naltrexone (LDN) effective for treating lichen planus?

Low-Dose Naltrexone for Lichen Planus

Low-dose naltrexone (LDN) at 3 mg daily is an emerging off-label treatment option for lichen planus, particularly for nail and scalp variants (lichen planopilaris), but it should not replace high-potency topical corticosteroids as first-line therapy for standard cutaneous or oral lichen planus.

First-Line Treatment Remains Topical Corticosteroids

• High-potency topical corticosteroids, specifically clobetasol propionate 0.05%, are the established first-line treatment for all forms of lichen planus including cutaneous, oral, and genital lesions 1, 2.
• For oral lichen planus, apply clobetasol propionate 0.05% or fluocinonide 0.05% gel to dried mucosa twice daily for 2-3 months, then taper gradually 1, 2.
• Gel formulations are strongly preferred over creams or ointments for mucosal disease 1, 2.

Evidence for Low-Dose Naltrexone in Lichen Planus

Nail Lichen Planus

• The most compelling evidence exists for nail lichen planus: A 2024 case series of 7 patients with biopsy-proven nail lichen planus treated with LDN 3 mg daily showed clinical response in 4 of 7 patients (57%), with an overall 35% reduction in nail lichen planus severity index 3.
• Two patients with severe nail disease achieved reduction to mild severity after 2-11 months of treatment 3.
• Importantly, most patients (6 of 7) had failed at least one prior treatment (median 2.5 prior treatments), suggesting LDN may be useful for refractory cases 3.
• No adverse events were reported and no patients discontinued treatment due to side effects 3.

Lichen Planopilaris (Scalp Variant)

• A 2023 prospective study of 26 patients with frontal fibrosing alopecia and lichen planopilaris treated with LDN 3 mg daily for one year showed significant reduction in erythema (mean decrease of 0.93 on a 0-3 scale, p<0.0001) 4.
• Scale also decreased but did not reach statistical significance at 12 months 4.
• A 2017 case series of 4 patients with lichen planopilaris showed reduction in pruritus, clinical inflammation, and disease progression with LDN 3 mg daily 5.

Mechanism of Action

• LDN acts as an opioid antagonist at μ-opioid and κ-opioid receptors, and antagonizes toll-like receptor 4, reducing pro-inflammatory cytokine release and modulating microglial activity 6.
• At low doses (1-5 mg), naltrexone demonstrates immunomodulatory effects including decreased release of TNF, IL-6, and IL-12, inhibition of T lymphocyte proliferation, and down-regulation of chemokine receptors 7, 8.

Clinical Algorithm for Using LDN in Lichen Planus

When to Consider LDN:

1. Nail lichen planus that has failed topical corticosteroids and intralesional triamcinolone (5-10 mg/cc) 6, 3
2. Lichen planopilaris with prominent erythema that is refractory to standard treatments 4
3. Refractory cases where systemic immunomodulators would otherwise be considered but are contraindicated 3, 5

Dosing Protocol:

• Start LDN at 1.5 mg at bedtime, increase by 1.5 mg every 2 weeks to a target dose of 3-4.5 mg at bedtime 6, 3, 5.
• Treat for a minimum of 2-3 months before assessing response 3.
• Continue treatment for up to 12 months if beneficial response is observed 4.

Expected Outcomes:

• For nail disease: Expect 35-57% reduction in severity over 2-11 months 3.
• For scalp disease: Expect reduction in erythema and possibly scale over 12 months 4.
• Symptom improvement (pruritus, burning) may occur but is less predictable 4, 5.

Important Caveats and Pitfalls

• LDN is not a replacement for first-line topical corticosteroids - it should be reserved for refractory cases or specific variants (nail, scalp) 1, 2, 3.
• Common side effects include headache, tachycardia, and vivid dreams, though these were not reported in the lichen planus studies 6.
• LDN must be compounded as the FDA-approved dose is 50 mg for addiction treatment; 3 mg is off-label 3, 5.
• Evidence is limited to small case series and uncontrolled studies - no randomized controlled trials exist for lichen planus specifically 4, 3, 5.
• The medication is cost-effective and well-tolerated, making it an attractive option when other treatments have failed 5, 8.
• For oral lichen planus, topical calcineurin inhibitors (tacrolimus 0.1%) remain the preferred alternative to corticosteroids before considering systemic options like LDN 1, 2.

Monitoring Requirements

• Assess clinical response at 3 months with attention to erythema, scale, and patient-reported symptoms 4, 3.
• At higher doses (50-100 mg), liver function monitoring is recommended, though this is less relevant at the 3 mg dose used for lichen planus 8.
• Continue follow-up to monitor for disease progression and adverse effects 2, 3.