What medications should be avoided in patients with Parkinson's disease?

Medications to Avoid in Parkinson's Disease

Most antipsychotics must be avoided in Parkinson's disease due to dopamine receptor blockade that worsens parkinsonian symptoms, with only three exceptions: quetiapine, clozapine, and pimavanserin. 1, 2

High-Priority Medications to Completely Avoid

Antipsychotics (Most Types)

• All typical antipsychotics (haloperidol, chlorpromazine, etc.) are contraindicated as they cause severe dopamine D2 receptor blockade that dramatically worsens motor symptoms 1, 2, 3
• Most atypical antipsychotics (risperidone, olanzapine, ziprasidone, aripiprazole) should be avoided despite being "atypical," as they still worsen parkinsonism 1, 4
• The only three acceptable antipsychotics are quetiapine, clozapine, and pimavanserin - all others must be avoided 1, 2

Antiemetics with Dopamine Blockade

• Metoclopramide is particularly dangerous and causes extrapyramidal signs including acute dystonic reactions, drug-induced parkinsonism, akathisia, and tardive dyskinesia 2, 5
• The FDA label explicitly warns that metoclopramide causes parkinsonian-like symptoms (bradykinesia, tremor, cogwheel rigidity, mask-like facies) and states "patients with pre-existing Parkinson's disease should be given metoclopramide cautiously, if at all, since such patients may experience exacerbation of parkinsonian symptoms" 5
• Prochlorperazine should also be avoided as it causes similar extrapyramidal effects 3

Anesthetic Agents

• Pethidine (meperidine) must be completely avoided due to high risk of delirium and adverse CNS effects 2
• Benzodiazepines should be avoided as they increase risk of delirium, falls, fractures, cognitive impairment, and dependence in older adults 1, 2

Medications Requiring Extreme Caution

Sedatives and Hypnotics

• Sedative hypnotics can precipitate delirium and should be avoided when possible 2
• Corticosteroids can precipitate delirium and require careful consideration 2

Analgesics

• Morphine, fentanyl, and oxycodone are not specifically contraindicated but require careful titration to minimal effective doses 2
• Paracetamol (acetaminophen) should be prioritized as first-line therapy for postoperative pain 2
• Gabapentinoids should be used with caution, carefully weighing risks versus benefits 2

Critical Management Principles

Levodopa Timing and Interactions

• Administer levodopa at least 30 minutes before meals to optimize absorption and avoid competition with dietary large neutral amino acids 1, 2
• Separate levodopa from iron and calcium supplements by at least 2 hours 2
• Consider protein redistribution diet (low-protein breakfast and lunch, protein at dinner only) for patients experiencing motor fluctuations 1

Antiparkinsonian Drug Withdrawal

• Never discontinue levodopa, dopamine agonists, or amantadine abruptly as this can lead to severe life-threatening withdrawal symptoms 6
• Abrupt dopamine agonist withdrawal can cause dopamine agonist withdrawal syndrome (DAWS) with severe psychiatric and autonomic symptoms 6

Common Pitfalls to Avoid

Misdiagnosis of Drug-Induced Symptoms

• Drug-induced parkinsonism from metoclopramide or antipsychotics should not be confused with disease progression - these medications cause acute worsening that is reversible upon discontinuation 2, 5
• Distinguish between parkinsonian tremor and other movement disorders (myoclonus, akathisia, restless legs syndrome) before attributing symptoms to disease progression 2

Emergency Psychosis Management

• In acute psychotic emergencies requiring parenteral administration, no safe parenteral antipsychotic option exists for PD patients - olanzapine and ziprasidone are available parenterally but lack evidence for safety in PD 7
• Clozapine is the only antipsychotic proven effective without worsening motor function, but it requires agranulocytosis monitoring and is not available parenterally 4, 7

Nausea and Vomiting Management

• Domperidone is preferred over metoclopramide for nausea/vomiting as minimal amounts cross the blood-brain barrier, resulting in minimal extrapyramidal effects 7
• Ondansetron (5-HT3 antagonist) can be considered as it lacks dopamine-blocking properties 4

Hiccup Management

• Chlorpromazine is contraindicated for hiccups in PD despite being first-line in general population 7
• Baclofen should be considered as first-line alternative for intractable hiccups 7