What is the typical dosing schedule for low dose naltrexone (LDN)?

Low Dose Naltrexone (LDN) Dosing Schedule

The typical dosing schedule for low dose naltrexone (LDN) starts at 1.5 mg once daily at bedtime, with gradual bi-weekly increases of 1.5 mg to a final maximum dose of 4.5 mg taken at bedtime. 1

Starting Dose and Titration

• Initial dose: 1.5 mg once daily at bedtime
• Titration: Increase by 1.5 mg every two weeks
• Target dose: 4.5 mg once daily at bedtime
• Administration time: Bedtime is preferred to minimize side effects

Dosing Considerations

Dose Range

• The effective dose range for LDN is typically between 1-5 mg daily 2
• Recent research suggests that effective doses can vary widely between patients, from as low as 0.1 mg to 4.5 mg per day 3
• Some conditions may require personalized titration to find the optimal dose for each patient 3

Condition-Specific Dosing

For gastrointestinal disorders, different dosing has been used 4:

• Diarrhea-predominant conditions: 2.5 mg once daily
• Constipation-predominant conditions: 2.5 mg twice daily
• Inflammatory bowel disease: 4.5 mg once daily

Mechanism of Action

LDN works through multiple mechanisms:

• Antagonism of μ-opioid and κ-opioid receptors
• Antagonism of toll-like receptor 4, reducing pro-inflammatory cytokines
• Modulation of microglial activity
• Transient opioid-receptor blockade leading to upregulation of endogenous opioid signaling 2

Side Effects and Monitoring

Common side effects include:

• Headache
• Vivid dreams
• Tachycardia
• Insomnia or sleep disturbances
• Gastrointestinal symptoms

Most side effects are mild and transient. In one study, 38.8% of patients had no side effects, while 61.2% experienced some side effects, with 32.4% of those reporting that symptoms were short-lived 4.

Important Precautions

Contraindications

• Concurrent opioid use: LDN cannot be used with opioids due to reduced efficacy and potential for withdrawal 5
• Procedures requiring opioids: LDN must be discontinued before procedures requiring opioid analgesia 1

Drug Interactions

• May reduce efficacy of opioid analgesics
• May precipitate withdrawal in opioid-dependent patients

Clinical Pearls

1. Bedtime administration helps minimize side effects
2. Personalized titration may be necessary to find the optimal dose
3. Allow 2-4 weeks at each dose to properly assess response
4. If side effects occur, consider slowing the titration schedule
5. LDN is typically compounded as standard naltrexone is only available in 50 mg tablets

By following this dosing schedule and monitoring for side effects, LDN can be effectively used for various conditions including neuropathic pain, fibromyalgia, and certain inflammatory conditions.