What is the first line of treatment for Amyotrophic Lateral Sclerosis (ALS)?

First-Line Treatment for Amyotrophic Lateral Sclerosis (ALS)

Riluzole and edaravone are the first-line pharmacological treatments for Amyotrophic Lateral Sclerosis (ALS), with riluzole being the most established option with proven survival benefit.

Pharmacological Management

First-Line Medications

1. Riluzole (100 mg/day)

   • FDA-approved for ALS treatment 1
   • Extends survival by approximately 2-3 months
   • Mechanism: Reduces glutamate excitotoxicity
   • Dosing: 50 mg twice daily
   • Survival benefit primarily observed in stage 4 (late-stage) disease 2
   • Most common side effects:
     • Asthenia (18%)
     • Nausea (15%)
     • Elevated liver enzymes (10-15%) 3
   • Monitoring requirements:
     • Liver function tests before initiation and periodically during treatment
     • Contraindicated in patients with pre-existing elevated transaminases 3

2. Edaravone (60 mg/day)

   • FDA-approved for ALS treatment 4
   • Administered as intravenous infusion over 60 minutes
   • Initial treatment cycle: daily dosing for 14 days followed by 14-day drug-free period
   • Subsequent cycles: daily dosing for 10 days out of 14-day periods, followed by 14-day drug-free periods 4
   • Mechanism: Free radical scavenger that reduces oxidative stress
   • Side effects:
     • Contusion
     • Gait disturbance
     • Headache
     • Hypersensitivity reactions 4

Supportive Care and Symptom Management

Alongside disease-modifying treatment, comprehensive supportive care is essential:

1. Respiratory Management

   • Regular monitoring of respiratory function
   • Non-invasive ventilation when indicated
   • Consideration of tracheostomy for advanced respiratory failure

2. Nutritional Support

   • Enteral nutrition (tube feeding) should be preferred over parenteral nutrition when nutritional support is needed 5
   • Gastrostomy placement before significant weight loss or respiratory compromise
   • Home parenteral nutrition is generally not indicated in ALS patients 5

3. Physical Therapy and Exercise

   • Regular exercise and physical therapy throughout disease course
   • Focus on maintaining mobility and function
   • Both endurance and resistance exercises may slow disease progression and improve quality of life 5

Treatment Algorithm

1. Upon diagnosis of ALS:

   • Start riluzole 50 mg twice daily
   • Monitor liver function tests at baseline, monthly for 3 months, then quarterly
   • Consider adding edaravone IV infusion based on disease progression and patient preference

2. For disease progression despite first-line therapy:

   • Optimize supportive care
   • Consider clinical trial participation if available

3. For patients with liver dysfunction:

   • Edaravone may be considered as primary therapy
   • Monitor for hypersensitivity reactions

Common Pitfalls to Avoid

1. Delayed treatment initiation - Start riluzole as soon as possible after diagnosis, as early intervention may provide greater benefit

2. Inadequate monitoring - Regular liver function monitoring is essential during riluzole treatment, especially in the first 6 months 6

3. Overlooking interstitial pneumonia - This rare but serious adverse effect of riluzole requires vigilant monitoring with chest X-rays as needed 6

4. Neglecting multidisciplinary care - ALS management requires coordinated care from neurologists, pulmonologists, nutritionists, and physical therapists

5. Relying solely on pharmacotherapy - Supportive care measures are equally important for quality of life and survival

While riluzole and edaravone are the only FDA-approved medications for ALS, ongoing research continues to investigate new therapeutic approaches. The current standard of care focuses on these disease-modifying treatments alongside comprehensive symptom management to optimize quality of life and extend survival.