Dosage Range for Low Dose Naltrexone (LDN)
The recommended dosage range for low dose naltrexone (LDN) is 1.5 mg to 4.5 mg daily, typically administered at bedtime. 1
Dosing Protocol
- Starting dose: 1.5 mg at bedtime
- Titration schedule: Increase by 1.5 mg every two weeks
- Target dose: 4.5 mg at bedtime
- Maximum dose: 4.5 mg daily
Evidence Base
Low dose naltrexone (LDN) represents a significant departure from standard naltrexone dosing, which typically ranges from 50-100 mg daily for alcohol and opioid use disorders. At low doses (1-5 mg), naltrexone exhibits different pharmacodynamic properties that make it useful for pain management and other conditions 2.
The Ophthalmology journal guidelines (2017) specifically recommend LDN for neuropathic corneal pain, starting at 1.5 mg at bedtime with gradual bi-weekly increases of 1.5 mg to a maximum dose of 4.5 mg at bedtime 1. This dosing protocol has shown efficacy in managing neuropathic pain conditions.
Mechanism of Action at Low Doses
At low doses, naltrexone functions differently than at standard doses:
- Acts as an antagonist to toll-like receptor 4, reducing pro-inflammatory cytokines
- Modulates microglial activity
- Transiently blocks opioid receptors, leading to upregulation of endogenous opioid signaling
- Creates an anti-inflammatory effect rather than primarily blocking opioid receptors 2
Clinical Applications
LDN has shown promise in treating various conditions:
- Neuropathic pain conditions
- Fibromyalgia
- Complex regional pain syndrome
- Multiple sclerosis
- Crohn's disease
- Chronic fatigue syndrome 2, 3
A medication use evaluation in veterans found that LDN therapy (at 4.5 mg daily) resulted in a small decrease in pain scores, with an average treatment duration of 123 days 4. The FDA has recently granted orphan drug designation for LDN in the treatment of complex regional pain syndrome 5.
Side Effects
LDN is generally well-tolerated with minimal adverse effects:
- Headache
- Vivid dreams
- Insomnia
- Nausea
- Dizziness 4
Approximately 32% of patients report some adverse effects, but these are typically mild and transient 4.
Important Considerations
- LDN is an off-label use of naltrexone
- It has minimal drug-drug interactions
- It is relatively inexpensive compared to other chronic pain treatments
- It avoids the adverse effects associated with NSAIDs and opioids 6
- It should not be used concurrently with opioid medications due to antagonistic effects
Conclusion
For patients requiring low dose naltrexone therapy, the evidence supports starting at 1.5 mg at bedtime and gradually increasing to 4.5 mg as tolerated. This dosing strategy maximizes therapeutic benefit while minimizing potential side effects.