What medications can be used for comfort in a patient with multisystem atrophy (MSA) nearing end stages?

From the Guidelines

For patients with end-stage multisystem atrophy (MSA), opioids such as morphine (starting at 2.5-5mg orally every 4 hours as needed) or hydromorphone (0.5-1mg orally every 4 hours as needed) are effective for pain and dyspnea, and should be considered as the primary medication for comfort. According to the most recent and highest quality study available 1, opioids are recommended for shortness of breath and pain. Benzodiazepines like lorazepam (0.5-1mg orally or sublingually every 4-6 hours) can help with anxiety, restlessness, and respiratory distress. Anticholinergics such as glycopyrrolate (0.2mg subcutaneously every 4-6 hours) or atropine drops (1% solution, 1-2 drops sublingually every 4 hours) are useful for managing excessive secretions. For nausea, haloperidol (0.5-1mg orally or subcutaneously every 6-8 hours) or ondansetron (4-8mg orally every 8 hours) can provide relief. Midazolam (2.5-5mg subcutaneously as needed) may be appropriate for terminal agitation.

Some key points to consider when using these medications include:

• Dosing should be individualized based on the patient's weight, kidney and liver function, prior opioid exposure, and symptom severity.
• Regular reassessment is essential to balance symptom control with side effects.
• The route of administration may need to be adjusted as swallowing difficulties progress.
• All medications should include oral/intravenous/subcutaneous routes of administration where possible, as recommended by 1.
• The use of opioids for dyspnea is also supported by other studies, such as 1, which recommends opioids for patients with severe and unrelieved dyspnea.

It's worth noting that while other studies, such as 1, 1, and 1, provide additional information on palliative care, the most recent and highest quality study available 1 provides the most relevant guidance for medication use in end-stage MSA.

From the FDA Drug Label

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use

In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response

If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response.

For a patient with Multisystem Atrophy (MSA) nearing end stages, morphine can be used for comfort. However, it is crucial to:

• Prescribe the lowest effective dosage and minimum duration of concomitant use with other CNS depressants.
• Titrate the dose based on clinical response.
• Monitor patients closely for signs and symptoms of respiratory depression and sedation.
• Advise patients and caregivers about the risks of respiratory depression and sedation.
• Consider using short-acting analgesics as needed until analgesic efficacy is attained.
• Be aware of the potential for adrenal insufficiency and withdrawal symptoms when discontinuing the medication. It is essential to exercise caution and carefully manage the patient's medication regimen to ensure their comfort and safety 2.

From the Research

Medications for Comfort in MSA Patients

When a patient with multisystem atrophy (MSA) is nearing the end stages, various medications can be used to improve comfort. The primary focus is on managing symptoms such as orthostatic hypotension, parkinsonian features, and other related issues.

• Levodopa Therapy: Studies have shown that levodopa can be effective in about 40-60% of patients with MSA and predominant parkinsonian features 3.
• Dopamine Agonists and Amantadine: These can also be employed to manage parkinsonian symptoms, although they are not more effective than levodopa 3.
• Orthostatic Hypotension Management: Several pharmacological agents have been used to reduce orthostatic hypotension (OH) in MSA patients, including fludrocortisone and midodrine 4. Octreotide has also been found to be beneficial in treating severe symptomatic postprandial orthostatic hypotension 4.
• Symptomatic Treatment: Since no causal therapy is available for MSA, symptomatic treatment plays a crucial role in patient care. This includes managing various symptoms such as dystonia, myoclonus, spasticity, depression, and cognitive dysfunction 5.

Non-Pharmacological Strategies

In addition to medications, non-pharmacological strategies can also be used to alleviate symptoms and improve patient comfort.

• Avoiding Aggravating Factors: Avoiding factors that exacerbate orthostatic hypotension, such as the effects of food, micturition, exposure to a warm environment, and physiological diurnal changes, can help manage OH 3.
• Self-Care Protocols: Utilization of self-care protocols can assist in planning more effective care regimens and improving patient comfort 6.