Riluzole is typically dosed at 50 mg by mouth twice a day, although 200-mg/d doses have also been examined in clinical trials.20,55 Generally, the drug is well tolerated, with common adverse effects including asthenia, nausea, gastrointestinal upset, and abnormal liver test results. Liver function should be monitored regularly during riluzole therapy, with elevations in serum alanine transferase of particular concern.55
Additional agents have been used to reduce muscle spasticity, muscle cramping and fasciculations, and the associated pain some patients experience, attributable in part to lack of activity and/or inflammation.56 For spasticity, tizanidine or baclofen (orally, a maximum of 20 mg in divided doses; or lower doses administered intrathecally, for patients who experience sedation and fatigue with high oral doses56,57) are often used. Carbamazepine and phenytoin are most commonly used to relieve muscle cramps.56 For some patients, NSAIDs may be adequate to control moderate to severe pain, but others may require opioids.2,56,58
Depressive disorders must be identified accurately, using appropriate clinical tools, before SSRIs (eg, citalopram) or other medications (eg, amitriptyline) are prescribed3; these agents should not be used presumptively,37 as estimates of prevalence of depression among ALS patients range from 2% to 75%.2,37,38,54 Estimates of anxiety prevalence in these patients range from 0% to 30%, reflecting the importance of accurate diagnosis before lorazepam or other agents are prescribed.3,38
Promising results have been reported in the use of modafinil to manage fatigue in patients with ALS.59 For patients with pseudobulbar affect, dextromethorphan 20 mg/quinidine sulfate 10 mg is an FDA-approved treatment.35
Vitamins and other supplements, including creatine, vitamin E, coenzyme Q10, and acetylcysteine, have not been shown to improve survival in this patient population.3
Nonpharmacologic Interventions
Supportive measures for ALS include physical and occupational therapy. In speech and language therapy, breathing and relaxation patterns can be used to correct ineffective compensatory behaviors and help patients “economize” their speaking efforts.60
Nutritional support is also important in patients who have difficulty swallowing, although this can be alleviated somewhat by changes in posture (eg, lowering the chin before attempting to swallow) and by use of thickened fluids; those with immobility of the tongue may find swallowing easier with the head tilted back.60 Once oral alimentation is no longer possible, enteral tube feeding is an option that may prolong survival.60,61
As ALS progresses, dysphagia may be aggravated as the ability to cough, reflexively or voluntarily, is reduced.60 As breathing becomes increasingly difficult, patients may require respiratory support. Noninvasive ventilation, using either continuous or bilevel positive airway pressure, may be implemented early in patients with respiratory-onset ALS, and later in the disease process for other patients, to prevent apnea and hypoventilation.28,62 Mechanical ventilation via tracheostomy is the most invasive method to address respiratory dysfunction in patients with ALS; however, like noninvasive ventilation, nocturnal mechanical ventilation has been shown to extend survival in these patients.28,63,64
Diaphragm pacing stimulation (DPS) has emerged as a possible alternative to mechanical ventilation for ALS patients. The pacing system consists of a battery-operated external pulse generator with electrodes placed after laparoscopic mapping on the diaphragm.65 Natural respiration is mimicked as stimulation from the external pulse generator prompts the diaphragm to contract. Researchers have shown that the minimally invasive surgery (including use of general anesthesia) required to install the DPS system can be safely performed on patients with ALS, and its use can delay the need for a ventilator by 24 months.65,66 Use of the DPS device was granted FDA approval in 2011, under the Humanitarian Device Exemption program.67
Addressing Quality of Life
For the patient with ALS, quality of life is an important consideration throughout disease management. According to numerous research teams, quality of life for these patients depends less on physical function and strength and more on social relationships, existential issues, and spirituality.2,37,54 A high level of quality of life can be sustained in patients with ALS, despite the decline they experience in physical function.
Addressing depression and anxiety by nonpharmacologic means may be needed. Loss of physical strength and mobility and difficulties with speech, swallowing, and breathing can challenge even the strongest patient’s coping skills; even more difficult can be the increased dependence on caregivers, the loss of income, and the financial burdens incurred in health care–related expenses. In some patients, the severity of disease, the lack of effective treatments, and the loss of independence may trigger thoughts of suicide or the wish to “hasten death.”37,39 The importance of counseling, support groups, spirituality or religion, and palliative care, from early in the disease process, cannot be overstated.3,37
Some of these considerations may also be of benefit to spouses and other nonpaid caregivers of the patient with ALS, at least half of whom report feeling physically or psychologically unwell.37,68 Even when professional nursing services or hospice support are available, caregivers often devote 12 hours or more per day to nonprofessional patient care.69 Strategies that support the caregiver can reduce the patient’s perception of burden in that individual.37
