Residents’ Corner

The Lowdown on Low-Dose Naltrexone

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Low-dose naltrexone (LDN) has become a hot topic in many fields of medicine, including dermatology. It has gained popularity as an alternative, off-label treatment that works by targeting inflammation. Patients may ask you about LDN as a treatment option for a variety of inflammatory skin conditions, specifically in comparison to more traditional systemic treatments. It is important for dermatologists to know what LDN is, how it works, how to prescribe it, and what side effects should be monitored.

Resident Pearl

  • Low-dose naltrexone is an alternative antiinflammatory treatment to consider in patients with inflammatory skin diseases, with a minimal side-effect profile.


 

References

Low-dose naltrexone (LDN) has shown efficacy in off-label treatment of a variety of inflammatory diseases ranging from Crohn disease to multiple sclerosis.1 There are limited data about the use of LDN in dermatology, but reports regarding how it works as an anti-inflammatory agent have been published.1,2

Naltrexone is an opioid receptor antagonist that originally was approved by the US Food and Drug Administration to treat addiction to alcohol, opiates, and heroin.2 The dose of naltrexone to treat addiction ranges from 50 to 100 mg/d, and at these levels the effects of opioids are blocked for 24 hours; however, the dosing for LDN is much lower, ranging from 1.5 to 4.5 mg/d.3 At this low dose, naltrexone partially binds to various opioid receptors, leading to a temporary blockade.4 One of the downstream effects of this opioid receptor blockade is a paradoxical increase in endogenous endorphins.3

In addition to opioid blockage, lower doses of naltrexone have anti-inflammatory effects by inhibiting nonopioid receptors. Naltrexone blocks toll-like receptor 4, which is found on keratinocytes and also on macrophages such as microglia.5 These macrophages also contain inflammatory compounds such as tumor necrosis factor α and IL-6. Low-dose naltrexone can suppress levels of these inflammatory markers. It is important to note that these anti-inflammatory effects have not been observed at the standard higher doses of naltrexone.1

When to Use

Low-dose naltrexone is a treatment option for inflammatory dermatologic conditions. A recent review of the literature outlined the use of LDN in a variety of inflammatory skin conditions. Improvement was noted in patients with Hailey-Hailey disease, lichen planopilaris, and various types of pruritus (ie, aquagenic, cholestatic, uremic, atopic dermatitis related).3 A case report of LDN successfully treating a patient with psoriasis also has been published.6 We often use LDN at the University of Wisconsin (Madison, Wisconsin) to treat patients with psoriasis. Ekelem et al3 also discussed patients with skin conditions that either had no response or worsened with naltrexone treatment, including various types of pruritus (ie, uremic, mycosis fungoides related, other causes of pruritus). Importantly, in the majority of cases without an improved response, the dose used was 50 mg/d.3 Higher doses of naltrexone are not known to have anti-inflammatory effects.

Low-dose naltrexone can be considered as a treatment option in patients with contraindications to other systemic anti-inflammatory treatments; for example, patients with a history of malignancy may prefer to avoid treatment with biologic agents. Low-dose naltrexone also can be considered as a treatment option in patients who are uncomfortable with the side-effect profiles of other systemic anti-inflammatory treatments, such as the risk for leukemias and lymphomas associated with biologic agents, the risk for liver toxicity with methotrexate, or the risk for hyperlipidemia with acitretin.

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