What medications can cause Parkinson's symptoms?

Medications That Cause Parkinson's Symptoms

Antipsychotic medications and antiemetic agents that block dopamine receptors are the primary culprits causing drug-induced parkinsonism, with high-potency typical antipsychotics like haloperidol and antiemetics like metoclopramide posing the greatest risk. 1

Primary Offending Drug Classes

Antipsychotic Medications (Highest Risk)

Typical (First-Generation) Antipsychotics:

• High-potency agents carry the greatest risk and include haloperidol, perphenazine, pimozide, fluphenazine, and trifluoperazine 1
• Low-potency agents like chlorpromazine and thioridazine cause fewer extrapyramidal symptoms but still pose risk 1, 2
• These medications induce bradykinesia, tremors, and rigidity that can be difficult to distinguish from idiopathic Parkinson's disease 1

Atypical (Second-Generation) Antipsychotics:

• Lower risk than typical antipsychotics but can still cause parkinsonism 3
• Include olanzapine, asenapine, clozapine, and lurasidone 1

Antiemetic Agents (Very Common Cause)

"Hidden Neuroleptics":

• Metoclopramide is a frequent offender used for nausea and gastroparesis 4, 5, 6
• Other benzamide derivatives including domperidone 6
• Prochlorperazine, metopimazine, and triethylperazine 6
• These agents block dopamine receptors peripherally and centrally, causing the same parkinsonian symptoms as antipsychotics 5, 6

Calcium Channel Blockers

• Flunarizine and cinnarizine account for approximately 30% of drug-induced parkinsonism cases 6
• These medications tend to cause symptoms with delayed onset, typically appearing 9-12 months after initiation 6

Other Dopamine-Depleting or Blocking Agents

• Reserpine and tetrabenazine deplete dopamine stores 5
• Alpha-methyldopa blocks dopamine synthesis 5, 6
• Veralipride (used for menopausal symptoms) 6

Miscellaneous Agents (Lower Risk)

• Selective serotonin reuptake inhibitors, particularly fluoxetine 5, 6
• Lithium 5
• Amiodarone 5
• Valproic acid and other anticonvulsants 1

Clinical Presentation and Timing

Onset Patterns:

• Antidopaminergic drugs (antipsychotics and antiemetics) typically cause symptoms within 0-6 months of initiation 6
• Calcium channel blockers show a delayed pattern with peak onset at 9-12 months 6
• Average time to symptom development is 473 days (range: 1 day to 15 years) 6

Distinguishing Features from Idiopathic Parkinson's Disease:

• Drug-induced parkinsonism more commonly presents with bilateral symptoms (77% of cases) 6
• Resting tremor is often absent in drug-induced cases 5
• May be accompanied by tardive dyskinesia 5
• The complete triad of tremor, akinesia, and rigidity occurs in only 25% of drug-induced cases 6

Risk Factors

Patient Demographics:

• Women are affected more frequently (63% of cases) 6
• Elderly patients are at higher risk, with mean age of 65 years in reported cases 6
• Children and adolescents may have higher risk for extrapyramidal symptoms than adults 1

Management Approach

Immediate Actions:

1. Discontinue the offending medication if clinically feasible 1, 2
2. Symptoms completely resolve in 74% of patients after drug withdrawal 6
3. In 15% of cases, drug-induced symptoms unmask underlying idiopathic Parkinson's disease 6

Pharmacologic Treatment if Discontinuation Not Possible:

• Anticholinergic agents (benztropine, trihexyphenidyl) are first-line for younger patients 1, 7
• Amantadine is better tolerated in elderly patients with similar efficacy 1, 7
• Prophylactic anticholinergics are contraindicated in elderly patients 7

Alternative Strategies:

• Reduce the antipsychotic dose to the minimum effective level 1, 7
• Switch to atypical antipsychotics with lower extrapyramidal symptom risk 3, 7
• For patients with Parkinson's disease requiring antipsychotics, use quetiapine, clozapine, or pimavanserin 1

Critical Pitfalls to Avoid

• Do not mistake drug-induced parkinsonism for worsening of underlying psychiatric illness or negative symptoms of schizophrenia 1
• Do not use levodopa for antipsychotic-induced pseudo-parkinsonism as it is ineffective 2
• Avoid epinephrine for hypotension in patients on antipsychotics as it may paradoxically lower blood pressure further; use norepinephrine or phenylephrine instead 2
• Do not routinely prescribe prophylactic antiparkinsonian agents except in high-risk patients (young males on high-potency agents with history of dystonic reactions) 1
• Monitor frequently during the first 3 months of antipsychotic treatment when extrapyramidal symptoms most commonly emerge 7