Riluzole

Riluzole is a drug used to treat amyotrophic lateral sclerosis. It delays the onset of ventilator-dependence in selected patients and may increase survival by approximately two months. A Cochrane Library review states a 9% gain in the probability of surviving one year. In secondary analyses of survival at separate time points, there was a significant survival advantage with Riluzole 100 mg at six, nine, 12 and 15 months, but not at three or 18 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. There were no data on quality of life, but patients treated with riluzole remained in a more moderately affected health state significantly longer than placebo-treated patients (weighted mean difference 35.5 days, 95% confidence interval 5.9 to 65.0).

Mechanism

Riluzole has several actions:

• Sodium channel blockade
• High-voltage calcium channel blockade
• N-methyl-D-aspartate (NMDA)/glutamate receptor blockade

Riluzole preferentially blocks TTX-S sodium channels, which are associated with damaged neurons. This reduces influx of calcium ions and indirectly prevents stimulation of glutamate receptors. Together with direct glutamate receptor blockade, the effect of the inhibitory neurotransmitter glutamate on motor neurons is greatly reduced.

Clinical Use

Whilst Riluzole has been proven to slow down ALS, patients do not report any subjective improvement. Approximately 10% of patients experience side effects such as nausea and fatigue which lead them to discontinue treatment. Safety monitoring includes regular liver function tests and people with liver disease such as hepatitis should be monitored carefully.

In the UK Riluzole has been available through the NHS since 1997 at a standard dosage of 50mg twice daily. There has been some evidence to show that higher doses might produce more significant improvements in ALS patients but at £5 a tablet it is at risk of being prohibitively expensive. One study in the Netherlands found that Riluzole is metabolised differently by males and females, and its levels in plasma are decreased in patients that smoke cigarettes.

A number of recent case studies have also indicated Riluzole as an antidepressant of last resort for intractable depression or OCD which have been unresponsive to other pharmacological therapies.