What is the preferred pain medication in stroke patients, comparing paracetamol (acetaminophen) to other options like Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and opioids?

Pain Management in Stroke Patients: Paracetamol vs Other Analgesics

For general pain management in stroke patients, paracetamol (acetaminophen) should be the first-line analgesic, with NSAIDs generally avoided due to cardiovascular and bleeding risks, and opioids reserved only for severe refractory pain. 1

First-Line Treatment: Paracetamol

Paracetamol up to 3-4 grams daily is the preferred initial analgesic for stroke patients due to its superior safety profile compared to NSAIDs and opioids. 1, 2 This recommendation is based on:

• Absence of cardiovascular toxicity, which is critical given stroke patients' underlying vascular disease 1
• No increased bleeding risk, unlike NSAIDs which can cause gastrointestinal bleeding and platelet dysfunction 1
• No renal toxicity at standard doses, though long-term high-dose use requires monitoring 1
• Effectiveness in multimodal analgesia when combined with other non-opioid approaches 1

The most commonly prescribed pain medication in stroke rehabilitation is acetaminophen, followed by narcotic analgesics and NSAIDs. 3

NSAIDs: Generally Contraindicated

NSAIDs should be avoided in stroke patients due to multiple safety concerns:

• Diclofenac significantly increases ischemic stroke risk (OR 1.53), particularly at high doses (OR 1.62), with long-term use (OR 2.39), and in patients with high cardiovascular risk (OR 1.78) 4
• Aceclofenac also increases stroke risk at high doses (OR 1.67) and with prolonged treatment (OR 2.00) 4
• All NSAIDs carry dose-dependent risks including cardiovascular events, gastrointestinal bleeding, and renal dysfunction 1
• Swiss stroke guidelines explicitly recommend avoiding NSAIDs for headache management in acute stroke, favoring paracetamol instead 1

The only potential exceptions are ibuprofen (OR 0.94) and naproxen (OR 0.68), which did not show increased stroke risk in population studies, but should still be used cautiously given other NSAID-class effects. 4

Opioids: Reserved for Severe Pain

Opioid analgesics should be minimized and used only when paracetamol is insufficient for moderate to severe pain. 1, 2

• Tramadol is the preferred opioid if escalation is needed, starting at 12.5-25 mg every 4-6 hours, due to lower respiratory depression risk compared to traditional opioids 5, 2
• Hydrocodone with acetaminophen is the most commonly prescribed narcotic analgesic in stroke rehabilitation when opioids are necessary 3
• Short-acting opioids like oxycodone (5 mg every 4-6 hours) may be considered for severe breakthrough pain, limited to the shortest reasonable course 5

Central Post-Stroke Pain: Different Approach

For the specific syndrome of central post-stroke pain (affecting 7-8% of stroke patients), the treatment algorithm differs entirely:

• Amitriptyline 75 mg at bedtime and lamotrigine are first-line pharmacological treatments (Class IIa, Level B) 1
• Pregabalin, gabapentin, carbamazepine, or phenytoin are second-line options (Class IIb, Level B) 1
• Standard analgesics like paracetamol and NSAIDs are ineffective for neuropathic central pain 1

The most frequently prescribed anticonvulsant for post-stroke pain is gabapentin, and the most common tricyclic antidepressant is amitriptyline. 3

Critical Caveats

Prophylactic paracetamol use in normothermic acute stroke patients without pain or fever may worsen outcomes. A retrospective analysis of 6,015 patients found that paracetamol started within 3 days in patients without pain/fever and baseline temperature <37°C was associated with worse functional outcomes (OR 0.58). 6 This suggests paracetamol should be used for specific indications (pain or fever control), not routinely.

Antiplatelet agents should be held if craniectomy is likely, though their use does not constitute an absolute contraindication for surgery. 1 If craniectomy is ruled out, aspirin 100-300 mg should be administered. 1

Practical Treatment Algorithm

1. Assess pain type: Nociceptive vs. neuropathic (central post-stroke pain)
2. For nociceptive pain: Start paracetamol 650-1000 mg every 6 hours (maximum 4 g/24 hours) 1
3. If inadequate response: Add tramadol 12.5-25 mg every 4-6 hours as needed 5, 2
4. For severe refractory pain: Consider short-acting opioids for limited duration 5
5. For central post-stroke pain: Initiate amitriptyline or lamotrigine, not standard analgesics 1
6. Avoid NSAIDs unless absolutely necessary and only after careful cardiovascular risk assessment 1, 4

Monitor renal function with chronic paracetamol use, particularly in elderly patients or those with pre-existing kidney disease. 1, 2