Home
May 20, 2024
ALS (Amyotrophic Lateral Sclerosis), also known as Lou Gehrig’s disease, is an incurable progressive neurodegenerative disorder that leads to weakness, spasticity, and incoordination of the muscles involved in speaking, swallowing, breathing, and ambulation.
Background1-4
Its onset most often occurs between the ages of 40 and 70, with a median survival time of 30 months, but progression can vary. It’s a highly symptomatic condition that reveals itself with early symptoms like mild muscle weakness, twitching, cramps, and / or stiffness which progress to more severe symptoms over time. There are two ALS variants; the more common spinal variant (~80% of cases) and the bulbar variant (~20% of cases). The spinal variant is characterized by early, often asymmetric limb weakness and late onset deficits in cranial nerve functioning, while the bulbar variant presents with deficits in speech and swallowing, followed by progressive muscle weakness.
Symptom Management Pearls1-4
Since ALS is currently incurable, patient care primarily focusses on symptom management and improving quality of life. Symptoms commonly experienced by those with ALS and considerations for managing them are described in Table 1. Dysphagia will invariably occur, which can lead to nutritional deficiencies and challenges with medication administration. As such, it’s common to encounter alternate feeding methods, like enteral tubes, and non-oral routes of medication administration employed in this population. Best practices for medication administration via enteral tubes are discussed here.
Table 1. Common ALS Symptoms and Pearls for Management
| Symptom | Comments |
|---|---|
| Dyspnea 2,5,6,8 | • Impacts up to 85% of ALS patients • Opioids (morphine is the most studied) are effective treatments and can be safely used to palliate dyspnea and reduce symptoms of breathlessness, even in patients prone to respiratory depression • Titration of the opioid against the clinical effect almost never leads to life-threatening respiratory depression • Lorazepam can be used to treat anxiety due to respiratory insufficiency |
| Muscle spasm / spasticity2,7 | • Caused by damage to upper motor neurons and may be associated with cramps and uncoordinated movement • Excess spasticity negatively impacts comfort and physical function • For spasticity, an antispastic medication should be used, such as baclofen, tizanidine, diazepam, or less commonly dantrolene • Muscle relaxants (e.g., cyclobenzaprine and methocarbamol) are less likely to be effective for spasticity |
| Pain1,7,8 | • Primary causes of pain are disease-related and include spasticity, cramping, and neuropathy • Secondary causes are due to immobility (e.g., musculoskeletal pain, pressure ulcers, soft tissue injury) • Treatment with non-opioid and adjuvant analgesics should be optimized • Opioids are effective for managing pain in ALS, although fear of fatal respiratory depression may be a barrier to use |
| Respiratory failure 1,6,9 | • Most patients will succumb to respiratory failure within 2 to 5 years of diagnosis • As respiratory muscles weaken, patients may experience breathing difficulty, requiring the use of non-invasive ventilation (NIV) or mechanical ventilation to support breathing • NIV has demonstrated survival benefit and increased quality of life • Symptoms often managed with opioids or benzodiazepines |
| Sialorrhea1,9,10 | • Symptoms arise from the inability to properly handle saliva • Antisecretory medications (e.g., scopolamine, hyoscyamine) are effective in ~70% of patients • Consider medications with anticholinergic properties in situations where multi-symptom benefit could be provided (e.g., tricyclic antidepressants if depression, neuropathy, and sialorrhea) |
| Thick Mucus1,9,10 | • Muscle weakness causes inability to clear sputum with a forceful cough • Treatment includes mucolytics (e.g., guaifenesin, nebulized acetylcysteine) or nebulized saline • Anticholinergic drugs used to treat sialorrhea or other conditions can thicken mucus |
Pseudobulbar Affect (PBA)11-14
Along with a number of cognitive and behavioral changes, those with ALS may experience pseudobulbar affect (PBA) – a generally under-recognized, misdiagnosed, and undertreated / mistreated neurologic syndrome of emotional affect disinhibition. It’s characterized by frequent short periods of uncontrollable emotional outbursts of crying and / or laughing that are usually exaggerated, inappropriate to the stimulus or situation, and not consistent with the individual’s emotional state. PBA’s cause isn’t completely understood, but it’s strongly associated with neurological diseases or injuries that affect the frontal lobes and descending pathways to the brain stem, basis pontis, and cerebellum like ALS, dementia, multiple sclerosis (MS), stroke, and traumatic brain injury. These inappropriate laughing / crying episodes may cause distress, embarrassment, frustration, and lead to social withdrawal and isolation.
Management primarily consists of using Nuedexta (dextromethorphan/quinidine) – the only FDA approved treatment for PBA. Dextromethorphan is useful for PBA management (its antitussive metabolite dextrorphan isn’t), so it’s coadministered with quinidine (a strong CYP2D6 inhibitor) to reduce dextromethorphan metabolism. In other words, quinidine’s role in this capacity is to increase and prolong systemic exposure to dextromethorphan. We’ve previously described a potential solution for overcoming barriers to Nuedexta use in hospice. Other off-label PBA treatments with reported clinical efficacy include SSRIs and certain TCAs, like amitriptyline and nortriptyline.
Disease Modifying Drugs8,15,16
There is no known cure for ALS and only a few medications have demonstrated efficacy for slowing decline and / or improving function. The three disease modifying drugs and considerations for their use are listed in Table 2. In April 2024, Relyvrio, another ALS drug, was voluntarily removed from the market after it failed to demonstrate clinically significant improvements in quality of life, survival, or respiratory function in a clinical trial. ALS disease modifying drugs are typically expensive and, with the exception of riluzole tablets, distribution is often limited to specialty pharmacies or infusion centers. Lastly, the benefits of these drugs are modest and more evident when used in early stages of disease, making their utility in terminally ill hospice patients questionable.
Table 2. ALS Disease Modifying Drugs
| Drug | Comments |
|---|---|
| Edaravone8,15,17-19 (Radicava) | • May slow rate of functional decline by reducing oxidative stress and restricting death of motor nerve cells • May increase quality of life (benefits limited to 1-2 years) • Adverse effects include gait disturbance, headache, and injection-site reactions. • Requires cyclic dosing: initial cycle is 14 days on / 14 days off; subsequent cycles 10 days on / 14 days off • Oral formulation needs to be given in the morning on an empty stomach; food shouldn’t be consumed for 1 hour after administration |
| Riluzole8,15,17 (Rilutek, Exservan, Tiglutik) | • Thought to reduce glutamate-induced excitotoxicity by various mechanisms • Can prolong survival and time to tracheostomy by ~2-3 months • Not known to improve symptoms or quality of life • Significant adverse effects can warrant discontinuation including fatigue, somnolence, weakness, and nausea • Needs to be taken on an empty stomach 1 hour before or 2 hours after a meal |
| Tofersen8,15,17,20,21 (Qalsody) | • Indicated for a small subset of ALS patients with the SOD1 gene mutation (~2% of patients) • Associated with reduced production of neurofilament (a marker of axonal injury and neurodegeneration) • May slow decline in clinical / respiratory function, strength, and quality of life • After first 3 doses / cycles, dosing interval is once every 28 days • Administered at designated treatment center or under direction of a provider experienced in performing lumbar punctures |
Written by: OnePoint Patient Care Clinical Team
Joseph Solien, PharmD, BCGP, BCPP – Vice President of Clinical Services
Melissa Corak, PharmD, BCGP – Senior Clinical Pharmacist
John Corrigan, PharmD, BCGP – Clinical Pharmacist
References