Additional Treatments for ALS Beyond Riluzole
For adults with ALS, add sodium phenylbutyrate/taurursodiol (PB/TURSO) and edaravone as disease-modifying therapies alongside riluzole, while implementing comprehensive symptomatic management to improve quality of life and functional outcomes.
Disease-Modifying Therapies
FDA-Approved Options Beyond Riluzole
Sodium phenylbutyrate/taurursodiol (RELYVRIO) is FDA-approved for treatment of ALS in adults and should be considered as an additional disease-modifying agent 1.
Edaravone is FDA-approved to slow ALS progression and represents the second disease-modifying treatment option after riluzole 2.
These agents can be used in combination with riluzole, as they target different pathophysiologic mechanisms 3.
Riluzole Formulation Considerations
When dysphagia develops (which occurs in nearly all ALS patients), switch from riluzole tablets to riluzole oral suspension (ROS) or oral film (ROF) rather than crushing tablets, which causes drug loss and aspiration risk 4.
ROF requires minimal swallowing capacity and maintains efficacy when tablets become inadequate 4.
ROS can be administered via percutaneous endoscopic gastrostomy (PEG) tube in severe dysphagia 4.
Symptomatic Management Algorithm
Bulbar Symptoms
Pseudobulbar affect (emotional lability): Use dextromethorphan/quinidine as first-line treatment 3.
Excessive salivation (sialorrhea): Treat with anticholinergic agents or botulinum toxin injections to salivary glands 3.
Dysphagia management: Screen for malnutrition (BMI, weight loss) at diagnosis and every 3 months; consider early PEG placement as weight loss is detrimental to survival 5.
Neuromuscular Symptoms
Muscle cramps and spasms: Use mexiletine, gabapentin, or baclofen 3.
Spasticity: Treat with baclofen (oral or intrathecal), tizanidine, or dantrolene 3.
Fasciculations: Consider gabapentin or carbamazepine if bothersome 3.
Pain Management
Musculoskeletal pain from immobility: Use NSAIDs, acetaminophen, or opioids as needed 3.
Neuropathic pain: Treat with gabapentin, pregabalin, or duloxetine 3.
Neuropsychiatric Symptoms
Depression: Use SSRIs or SNRIs; avoid tricyclic antidepressants due to anticholinergic effects that worsen sialorrhea 3.
Anxiety: Consider SSRIs, SNRIs, or benzodiazepines for acute episodes 3.
Insomnia: Use trazodone, zolpidem, or melatonin 3.
Other Common Symptoms
Fatigue: Trial modafinil or amantadine, though evidence is limited 3.
Constipation: Use stool softeners, osmotic laxatives (polyethylene glycol), or stimulant laxatives 3.
Urinary urgency: Consider anticholinergic agents if not contraindicated by sialorrhea 3.
Multidisciplinary Care Approach
Multidisciplinary ALS clinics prolong survival and improve quality of life through coordinated management of respiratory function, nutrition, physical therapy, occupational therapy, speech therapy, and psychosocial support 2.
Regular monitoring of respiratory function (forced vital capacity) is essential, with early consideration of non-invasive ventilation when FVC falls below 50% predicted 2.
Emerging Therapies Under Investigation
Tofersen (antisense oligonucleotide for SOD1 mutations) has received accelerated FDA approval contingent upon confirmatory trials 3.
Other investigational approaches include tyrosine kinase inhibitors, RIPK1 inhibition, mesenchymal stem cells, and novel trial designs testing sequential experimental treatments 3.
Critical Pitfalls to Avoid
Do not crush riluzole tablets when dysphagia develops; this reduces drug intake and increases aspiration risk—switch to oral suspension or film formulations instead 4.
Do not delay nutritional support; weight loss significantly worsens survival, so screen regularly and consider early PEG placement 5.
Do not rely solely on disease-modifying therapies; symptomatic management is essential for quality of life even though evidence for many symptomatic treatments is limited 3.
Do not overlook respiratory monitoring; early non-invasive ventilation improves survival and quality of life 2.