Drugs for Motor Neuron Disease

Drugs for motor neuron disease slow progression modestly; the largest benefits come from non-invasive ventilation, nutrition and symptom control by a multidisciplinary team. Riluzole is the established disease-modifying drug.

Classification. Riluzole (glutamate release inhibitor), edaravone (free radical scavenger), tofersen (antisense oligonucleotide for SOD1 disease), and symptomatic drugs.

Pharmacokinetics. Riluzole is metabolised by CYP1A2 and glucuronidated.

• Riluzole 50 mg twice daily, 1 hour before or 2 hours after meals.
• Edaravone 60 mg intravenously daily for 14 days, then 10 of 14 days in later cycles; oral 105 mg daily on the same schedule.
• Tofersen 100 mg intrathecally, 3 doses 14 days apart, then every 28 days, for SOD1 mutations.

Differences. Riluzole extends median survival by about 2 to 3 months. Edaravone and tofersen have limited availability and high cost.

• Riluzole: start early after diagnosis; continue until severe disease or intolerance.
• Sialorrhoea: glycopyrronium 1 mg three times daily, amitriptyline 10 to 25 mg at night, hyoscine patch; botulinum toxin to salivary glands.
• Pseudobulbar affect: amitriptyline 10 to 25 mg at night or dextromethorphan with quinidine.
• Cramps and spasticity: baclofen 5 to 10 mg three times daily.
• Breathlessness: non-invasive ventilation when forced vital capacity falls under 50 percent, or with orthopnoea, morning headache or daytime sleepiness; low-dose oral morphine 2.5 mg for dyspnoea.
• Nutrition: early gastrostomy when weight falls or swallowing declines.
• Exclude mimics: HIV, HTLV-1, cervical spondylotic myelopathy, thyrotoxicosis, vitamin B12 deficiency and heavy metal exposure.

Selection. Early palliative care alongside disease-modifying treatment.

Contraindications. Riluzole in severe liver impairment and pregnancy.

Adverse effects. Riluzole: nausea, fatigue, dizziness, liver enzyme rise (stop if ALT is more than 5 times the upper limit of normal), neutropenia, interstitial lung disease. Edaravone: bruising, gait disturbance, allergic reactions. Tofersen: myelitis, radiculitis, raised cerebrospinal fluid protein.

Interactions. Smoking induces CYP1A2 and lowers riluzole levels; ciprofloxacin and fluvoxamine raise them.

Special groups.

• Pregnancy: avoid riluzole.
• Breastfeeding: avoid.
• Older adults: monitor liver enzymes closely.
• Kidney impairment: caution with riluzole.
• Liver impairment: avoid in severe disease.

Monitoring. Liver enzymes monthly for 3 months, then every 3 months; full blood count if fever or infection; weight and forced vital capacity every 3 months.

Referral and escalation. All patients need specialist and multidisciplinary care. Fever with a low neutrophil count on riluzole needs urgent assessment.