12.4 Dementia, Parkinson Disease, Migraine, Insomnia & Restless Legs Syndrome
Key Takeaways
Cholinesterase inhibitors can cause bradycardia and syncope, so use them cautiously in conduction disease, and avoid anticholinergics that cancel their effect.
In Parkinson disease, avoid metoclopramide, prochlorperazine, haloperidol and risperidone; domperidone (maximum 30 mg/day) is preferred for nausea and quetiapine or clozapine for psychosis.
Medication-overuse headache occurs with triptans, opioids or combination analgesics on 10 or more days a month, or simple analgesics on 15 or more days.
CBT-I is first-line for insomnia, and sedating antihistamines and benzodiazepines are avoided in older adults.
Restless legs syndrome is managed first by checking ferritin, removing aggravating drugs such as diphenhydramine, and non-drug measures.
Dementia, Parkinson Disease, Migraine, Insomnia & Restless Legs Syndrome
These neurological conditions are common in community practice. Each has a characteristic medication-safety trap: anticholinergic burden in dementia, dopamine blockers in Parkinson disease, medication overuse in migraine, sedative hypnotics in older adults, and drug-induced restless legs. PEBC sample items have tested several of these (cholinesterase inhibitor cautions, drugs that worsen Parkinson disease, and first steps for restless legs).
1. Dementia (Alzheimer Disease and Related Dementias)
- Cholinesterase inhibitors (ChEIs):
- Agents: donepezil, rivastigmine (oral or patch), galantamine, for mild to moderate Alzheimer disease. They also help dementia with Lewy bodies and Parkinson disease dementia (rivastigmine).
- Benefit: modest; assess cognition and function after about 3 to 6 months.
- Adverse effects: nausea, vomiting, diarrhea, weight loss, vivid dreams (dose donepezil in the morning if this occurs), and vagotonic effects: bradycardia, heart block and syncope. Use them cautiously in conduction disease (for example, left bundle branch block or sick sinus syndrome) and with other rate-slowing drugs such as beta-blockers.
- Memantine (an NMDA antagonist) is used in moderate to severe disease, alone or with a ChEI. Reduce the dose in severe renal impairment. It can cause dizziness and confusion.
- Avoid anticholinergics: oxybutynin, diphenhydramine, tricyclics and paroxetine worsen cognition and cancel out ChEI effects. Combining a ChEI with an anticholinergic bladder drug is a classic prescribing cascade.
- Behavioural and psychological symptoms: treat non-drug causes first (pain, constipation, infection, environment). Antipsychotics are reserved for severe aggression or psychosis with risk of harm, at the lowest dose for the shortest time. In Canada, risperidone is indicated for short-term management of severe aggression in Alzheimer dementia. All antipsychotics carry a boxed warning for increased mortality and stroke in dementia (section 13.3).
2. Parkinson Disease
| Drug class | Examples | Key points |
|---|---|---|
| Levodopa/carbidopa | Immediate- and controlled-release | Most effective symptomatic therapy. Dietary protein competes for absorption. Long-term use brings wearing-off and dyskinesias |
| Dopamine agonists | Pramipexole, ropinirole, rotigotine patch | Used in younger patients. Impulse-control disorders (gambling, shopping, hypersexuality), sudden sleep attacks, hallucinations and edema |
| MAO-B inhibitors | Rasagiline, selegiline | Mild benefit. Serotonergic and sympathomimetic interactions (meperidine, dextromethorphan, some antidepressants) |
| COMT inhibitor | Entacapone | Extends each levodopa dose; colours the urine orange |
| Amantadine | Reduces levodopa-induced dyskinesia. Livedo reticularis; renal dose adjustment |
Caution
Avoid central dopamine (D2) blockers in Parkinson disease:
- Never use: metoclopramide, prochlorperazine, haloperidol, and most other antipsychotics, including risperidone. They worsen motor symptoms and can trigger severe rigidity.
- Nausea: domperidone does not cross the blood-brain barrier and is preferred for nausea (watch the QT interval: maximum 30 mg/day in Canada).
- Psychosis: quetiapine or clozapine are preferred.
- Never stop levodopa abruptly. Withdrawal can cause a syndrome resembling neuroleptic malignant syndrome.
3. Migraine
- Acute treatment:
- First line: NSAIDs (ibuprofen, naproxen, ASA) or acetaminophen, taken early in the attack.
- Triptans (sumatriptan, rizatriptan, zolmitriptan, almotriptan, eletriptan) for moderate to severe attacks. They are contraindicated in coronary or cerebrovascular disease and uncontrolled hypertension, and serotonin syndrome is a theoretical concern with SSRIs. A second dose may be taken after 2 hours if the headache returns.
- Antiemetics: metoclopramide or domperidone help nausea and absorption.
- Avoid opioids and butalbital combinations.
- Medication-overuse headache: risk rises when triptans, opioids or combination analgesics are used on 10 or more days a month, or simple analgesics on 15 or more days a month. Patients reaching these thresholds need preventive therapy and withdrawal of the overused drug.
- Prevention: consider it when attacks are frequent (for example, 4 or more headache days a month) or disabling.
- Beta-blockers: propranolol, metoprolol.
- Amitriptyline.
- Topiramate: teratogenic; reduces hormonal contraceptive efficacy at higher doses; cognitive slowing and paresthesias.
- Candesartan.
- CGRP monoclonal antibodies: erenumab, galcanezumab, fremanezumab, eptinezumab.
- OnabotulinumtoxinA for chronic migraine.
- Allow 2 to 3 months at an adequate dose before judging a preventive.
- Pregnancy: acetaminophen is preferred, and sumatriptan has the most pregnancy data. Valproate is avoided in anyone who could become pregnant.
4. Insomnia
- First-line: cognitive behavioural therapy for insomnia (CBT-I). It includes sleep restriction, stimulus control and cognitive techniques, and is more durable than drugs.
- When drugs are used: use the lowest dose for the shortest time, and screen for causes (pain, depression, sleep apnea, caffeine, diuretics, stimulants).
- Zopiclone: 3.75 mg in older adults (maximum 7.5 mg). Bitter taste and next-morning impairment.
- Zolpidem sublingual: lower doses for women.
- Low-dose doxepin (3 to 6 mg) for sleep maintenance.
- Lemborexant, an orexin receptor antagonist.
- Benzodiazepines are generally avoided in older adults: falls, fractures, cognitive impairment and motor vehicle crashes (Beers Criteria).
- Avoid sedating antihistamines (diphenhydramine, doxylamine) in older adults because of anticholinergic effects and tolerance within days.
- Melatonin is a natural health product. It is most useful for circadian rhythm problems such as jet lag and delayed sleep phase.
5. Restless Legs Syndrome (RLS)
RLS is an urge to move the legs, usually with uncomfortable sensations. It starts or worsens at rest and in the evening, and is relieved by movement.
- Look for causes and aggravating drugs:
- Check ferritin and iron studies. Supplement iron if ferritin is below about 75 µg/L.
- Aggravating drugs: sedating antihistamines (diphenhydramine), antidepressants (SSRIs, SNRIs, mirtazapine), antipsychotics, metoclopramide, and alcohol or caffeine.
- Non-drug first steps:
- moderate exercise, stretching, massage and a warm bath before bed;
- regular sleep habits;
- reducing caffeine and alcohol.
- Drug therapy for persistent symptoms: current guidelines favour alpha-2-delta ligands (gabapentin, pregabalin) first. Dopamine agonists (pramipexole, ropinirole) are now used more cautiously because of augmentation: symptoms that start earlier in the day, become more intense, and spread to the arms.
A 74-year-old man with Parkinson disease, taking levodopa/carbidopa, develops nausea after a new medication was started. The prescriber asks for an antiemetic recommendation. Which option is most appropriate?
Metoclopramide 10 mg three times daily, 30 minutes before meals.
Haloperidol 0.5 mg twice daily.
Prochlorperazine 10 mg every 6 hours as needed.
Domperidone 10 mg up to three times daily.
A 41-year-old woman with migraine uses sumatriptan 50 mg on about 12 days each month and an ibuprofen-codeine combination on several other days. Her headaches are becoming more frequent. What is the most important assessment?
Medication-overuse headache: start prevention and withdraw the overused drugs.
Her sumatriptan dose is too low, so it should be increased to 100 mg on each headache day.
She should replace sumatriptan with daily codeine to control the frequency of attacks.
Her headache frequency is unrelated to her medications, so no change is needed.
A 59-year-old woman reports an uncomfortable urge to move her legs in the evenings that is relieved by walking, and it is disturbing her sleep. Diphenhydramine 25 mg at bedtime has not helped. What is the most appropriate initial recommendation?
Increase the diphenhydramine to 50 mg at bedtime, because 25 mg is too low.
Recommend sleeping in a cold room and avoiding all exercise.
Exercise, stretching and a warm bath, stop diphenhydramine, and check ferritin.
Start pramipexole immediately, because dopamine agonists are the only effective therapy for this condition.
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