Prion disease
- Overview
- Theory
- Diagnosis
- Management
- Follow up
- Resources
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
all patients
supportive care
Treatment is focused on symptom management and quality of life for both patient and caregivers.
Constipation, bowel obstruction, immobility, thromboses, pneumonia, decubitus ulcers, pulmonary emboli, and other conditions found in less ambulatory patients should be considered.
benzodiazepine or antidepressant
Treatment recommended for ALL patients in selected patient group
Clonazepam is a long-acting benzodiazepine and avoids the potential rebound anxiety/agitation associated with lorazepam. Lorazepam can also be used to treat agitation.
Trazodone may be prescribed as a mild sedative during the day.
Selective serotonin reuptake inhibitors (SSRIs) such as citalopram can be tried, increasing dose quickly to effect.
Doses should be started low and increased gradually according to response.
Primary options
clonazepam: 0.25 to 0.5 mg orally three times daily initially, increase according to response, maximum 4 mg/day
OR
lorazepam: 1-2 mg orally two to three times daily initially, increase according to response, maximum 10 mg/day
OR
trazodone: 50 mg orally three times daily initially, increase by 50 mg/day increments every 3-4 days according to response, maximum 400 mg/day
OR
citalopram: 10-40 mg orally once daily
antipsychotic
Treatment recommended for ALL patients in selected patient group
Useful second-generation (atypical) antipsychotics include risperidone, olanzapine, quetiapine, and ziprasidone.
The practitioner may wish to avoid aripiprazole, which can be mildly stimulating.
If the patient is unable to take oral medication, haloperidol (a typical antipsychotic), olanzapine, or ziprasidone injections can be considered.
Doses should be started low and increased gradually according to response.
Primary options
risperidone: 1-4 mg/day orally given in 1-2 divided doses
OR
olanzapine: 2.5 to 10 mg intramuscularly every 2-4 hours when required, maximum 30 mg/day; 2.5 to 20 mg orally once daily
OR
quetiapine: 50-800 mg/day orally given in 2-3 divided doses
OR
ziprasidone: 10 mg intramuscularly every 2 hours when required or 20 mg intramuscularly every 4 hours when required, maximum 40 mg/day; 20-80 mg orally twice daily
Secondary options
haloperidol lactate: 2-5 mg intramuscularly every 4-8 hours when required
benzodiazepine or anticonvulsant
Treatment recommended for ALL patients in selected patient group
It is recommended that patients experiencing myoclonus should only be treated if it is distressing to them and/or if it is disturbing their caregiver's ability to care for the patient. Myoclonus may also exacerbate existing pain conditions such as osteoarthritis.
Clonazepam is useful in treating bothersome myoclonus, as it possesses anticonvulsant activity. Lorazepam can also be used to treat myoclonus.
Other anticonvulsants such as levetiracetam and zonisamide have been used successfully to treat myoclonus in other conditions.
Valproic acid is often effective for the treatment of myoclonus; however, it is usually avoided when possible in early Creutzfeldt-Jakob disease or in patients undergoing experimental treatments, as one paper showed worse prion activity in vitro; whether valproic acid worsens prion disease in humans is not known.[141]Shaked GM, Engelstein R, Avraham I, et al. Valproic acid treatment results in increased accumulation of prion proteins. Ann Neurol. 2002 Oct;52(4):416-20. http://www.ncbi.nlm.nih.gov/pubmed/12325069?tool=bestpractice.com [142]Sander JW, Duncan JS. Valproic acid and prion proteins. Ann Neurol. 2003 May;53(5):688-9. http://www.ncbi.nlm.nih.gov/pubmed/12731011?tool=bestpractice.com
Doses should be started low and increased gradually according to response.
Primary options
clonazepam: 0.25 to 0.5 mg orally three times daily initially, increase according to response, maximum 20 mg/day
OR
lorazepam: 1-2 mg orally two to three times daily initially, increase according to response, maximum 10 mg/day
OR
levetiracetam: consult specialist for guidance on dose
OR
zonisamide: consult specialist for guidance on dose
selective serotonin reuptake inhibitor (SSRI)
Treatment recommended for ALL patients in selected patient group
SSRIs can be helpful in treating depression in patients with prion disease. They may also be helpful in reducing anxiety, aggressive behavior, obsessive compulsive behavior, and poor impulse control.
Fluoxetine has a very long half-life and numerous drug interactions, so practitioners may want to avoid its use.
Doses should be started low and increased gradually according to response.
Primary options
citalopram: 10-40 mg orally once daily
OR
sertraline: 25-200 mg orally once daily
OR
escitalopram: 5-20 mg orally once daily
OR
paroxetine: 20-50 mg orally once daily
hypnotic
Treatment recommended for ALL patients in selected patient group
Trazodone may be prescribed as a mild sedative during the day or at night as a sleep medication and is preferred in Creutzfeldt-Jacob disease.
Clonazepam or lorazepam might also be helpful. If a benzodiazepine is currently being prescribed, the last dose is administered at or near bedtime.
Zolpidem and eszopiclone are third-line alternatives. The US Food and Drug Administration (FDA) recommends that bedtime doses of zolpidem be lowered as data show that blood levels in some patients may be high enough the morning after use to impair activities that require alertness, including driving.[143]US Food and Drug Administration. Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist). 2018 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/questions-and-answers-risk-next-morning-impairment-after-use-insomnia-drugs-fda-requires-lower The data show the risk to be highest in patients taking the extended-release formulation, and that women appear to be more susceptible to this risk because they eliminate zolpidem more slowly from their bodies compared to men. The FDA also warns that eszopiclone can cause next-day impairment of driving and other activities that require alertness. As a result, the recommended starting dose has been lowered as higher doses are more likely to result in next-day impairment. The risk of next-morning drowsiness also applies to all drugs taken for insomnia, and the lowest dose that treats the patient's symptoms should be prescribed.
Primary options
trazodone: 25-50 mg orally once daily at bedtime when required
Secondary options
clonazepam: 0.25 to 0.5 mg orally three times daily initially when required, increase according to response, maximum 4 mg/day
OR
lorazepam: 1-2 mg orally two to three times daily initially when required, increase according to response, maximum 10 mg/day
Tertiary options
zolpidem: 5 mg orally (immediate-release) once daily at bedtime when required; 6.25 mg orally (extended-release) once daily at bedtime when required; higher doses may cause next-morning drowsiness and are not recommended, especially in women
OR
eszopiclone: 1 mg orally once daily at bedtime when required initially, dose may be increased to 2-3 mg once daily at bedtime
analgesics
Treatment recommended for ALL patients in selected patient group
Pain is not a common symptom in sporadic Creutzfeldt-Jakob disease (CJD), and the etiology should be evaluated. Constipation, bowel obstruction, immobility, thromboses, pneumonia, decubitus ulcers, pulmonary emboli, and other conditions found in less ambulatory patients should be considered.
Pain is treated with acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), or opioids, in that order of preference.
Pain may be expressed as agitation in CJD patients who have impaired communication. Pain may be treated in CJD on a regular dosing schedule, and not as needed, due to the inability to communicate effectively.
In certain forms of CJD, such as variant CJD and rare sporadic CJD, pain may occur in regions of the body and may migrate. These syndromes are difficult to treat but would be treated in the same manner as neuropathic pain.[144]Spencer MD, Knight RS, Will RG. First hundred cases of variant Creutzfeldt-Jakob disease: retrospective case note review of early psychiatric and neurological features. BMJ. 2002 Jun 22;324(7352):1479-82. http://www.bmj.com/cgi/content/full/324/7352/1479 http://www.ncbi.nlm.nih.gov/pubmed/12077031?tool=bestpractice.com
Primary options
acetaminophen: 325-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day
Secondary options
ibuprofen: 400-800 mg orally every 6-8 hours when required, maximum 2400 mg/day
OR
naproxen: 250-500 mg orally every 12 hours when required, maximum 1250 mg/day
Tertiary options
codeine sulfate: 15-60 mg orally every 4-6 hours when required, maximum 360 mg/day
OR
oxycodone: 5-10 mg orally (immediate-release) every 6 hours when required
Choose a patient group to see our recommendations
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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