To the Editor: We read with interest the recent article by Kiernan.1 Many patients with motor neurone disease (MND) are also taking complementary therapies, with the potential for drug interaction with riluzole. A recent patient highlighted this.

A man in his 50s with progressive MND commenced riluzole at the time of diagnosis. Initial liver function tests performed after starting the drug gave normal results. Eight months later, with disease progression, he began taking low-dose naltrexone 50 mg dissolved in 50 mL of water, of which he took 4 mL a day.

Three months later, he began to feel nauseous, with debilitating lethargy, and developed jaundice. Liver function tests showed: alanine aminotransferase level, 3030 U/L; and asparate aminotransferase level, 2074 U/L. On stopping taking both drugs, his symptoms resolved and the liver function test results gradually became normal. No other contributing cause for the hepatotoxicity was found.

From the temporal profile, the hepatotoxicity in our patient was possibly due to the combination of riluzole and naltrexone, although either drug alone could be implicated, or there may have been another mechanism. Riluzole is predominantly metabolised by cytochrome P450 enzymes (CYP1A2), but there is considerable patient variability, and the hepatotoxicity mechanism is largely unknown2 (see also MIMS Online: http://www.mims.hcn.net.au).

In recent months, low-dose naltrexone has become popular with patients who have MND, although there are no published data of efficacy. Hepatotoxicity caused by naltrexone is dose-dependent and uncommon.3 Naltrexone is metabolised by glucuronidation in the liver to an active metabolite, but a direct interaction with riluzole through cytochrome P450 enzymes appears unlikely.4 There have been no clinical studies to evaluate interactions with other drugs of either riluzole or naltrexone (apart from opiates).3

This case highlighted for us that patients may be taking other therapies for MND, and that clinicians should be aware of the possibility of serious drug interactions when riluzole is prescribed.

In reply: Henderson and McCombe describe a patient to highlight an issue raised in a recent editorial:1 that patients with motor neurone disease (MND) may develop abnormal liver function tests for reasons other than riluzole therapy. In their patient, riluzole was prescribed for a year and liver function test results remained stable. Deterioration in liver function coincided with the introduction of naltrexone. Ultimately, riluzole, an established MND therapy, had to be ceased.

Naltrexone is an authority medication, prescribed in the setting of alcohol or opioid dependence. MEDLINE searches failed to find any study or indication for naltrexone in the treatment of MND. An internet search, however, revealed a number of personal anecdotes, with a curiously Australian emphasis, suggesting an immuno-modulatory role for naltrexone in MND. A few further clicks of the mouse and the naltrexone ordering site with costings appeared.

Patients with incurable diseases commonly seek “alternative” treatments2 at great personal financial cost, calculated at thousands of dollars per patient with MND.3 Often there is insufficient, or, as with naltrexone, no evidence that these treatments are effective.4 Most patients with MND will consider alternative therapy, irrespective of their educational background5 or understanding of disease pathophysiology. How each physician approaches the use of complementary and alternative therapies by their patients may develop into an important issue in the therapeutic relationship. Certainly, being aware of the possibility may prove critical. In the patient described by Henderson and McCombe, an unfortunate outcome of irreversible liver failure in a patient with NMD was averted through conventional monitoring of liver function.