What first‑line medication is recommended for a typical tension‑type headache, and how should it be adjusted in patients with liver disease, peptic ulcer disease, renal impairment, or cardiovascular risk?

First-Line Medication for Tension-Type Headache

Paracetamol (acetaminophen) 1000 mg is the recommended first-line medication for acute episodic tension-type headache, with dose adjustments required for liver disease and consideration of NSAIDs as alternatives in patients with renal impairment, peptic ulcer disease, or cardiovascular risk. 1, 2, 3

Standard First-Line Treatment

• Paracetamol 1000 mg provides a statistically significant benefit for tension-type headache, achieving pain-free status at 2 hours with a number-needed-to-treat (NNT) of 22 compared to placebo. 3
• Lower doses of paracetamol (500–650 mg) have not demonstrated statistically significant superiority over placebo, making the full 1000 mg dose essential for therapeutic effect. 3
• Ibuprofen 400–800 mg is an alternative first-line option, showing slightly better efficacy than paracetamol for pain-free status at 2 hours (NNT 1.73 vs 1.62), though the difference is not statistically significant. 2
• Combination therapy with acetylsalicylic acid 250 mg + paracetamol 250 mg + caffeine 65 mg is superior to paracetamol alone, achieving pain-free status at 2 hours in 28.5% vs 21.0% of episodes (p < 0.0001). 4

Adjustments for Liver Disease

• Paracetamol is contraindicated in patients with significant hepatic impairment or active liver disease due to risk of hepatotoxicity. 1
• Switch to ibuprofen 400–800 mg as the first-line agent in patients with liver disease, provided renal function and cardiovascular status are normal. 1, 2
• If NSAIDs are also contraindicated, consider parenteral metoclopramide 10 mg IV (NNT 2 for acute pain relief) or metamizole where available (NNT 4). 5

Adjustments for Peptic Ulcer Disease

• Avoid all NSAIDs (ibuprofen, naproxen, aspirin) in patients with active peptic ulcer disease or history of gastrointestinal bleeding. 1, 2
• Use paracetamol 1000 mg as the sole first-line option, as it does not increase gastrointestinal bleeding risk. 2, 3
• If paracetamol fails after 2–3 episodes, escalate to parenteral metoclopramide 10 mg IV rather than introducing NSAIDs. 5

Adjustments for Renal Impairment

• Paracetamol 1000 mg remains the safest option in renal impairment, as it does not affect renal function or blood pressure. 1, 2
• NSAIDs are contraindicated when creatinine clearance is <30 mL/min due to risk of acute kidney injury and fluid retention. 1
• For moderate renal impairment (CrCl 30–60 mL/min), reduce NSAID dose by 50% and limit duration to 3 consecutive days maximum. 1

Adjustments for Cardiovascular Risk

• Paracetamol 1000 mg is the preferred agent in patients with uncontrolled hypertension, coronary artery disease, or heart failure, as it does not raise blood pressure or increase cardiovascular events. 1, 2
• NSAIDs are relatively contraindicated in uncontrolled hypertension because they can further elevate blood pressure and increase cardiovascular risk. 1
• Once blood pressure is controlled, NSAIDs may be reconsidered because they demonstrate superior efficacy to paracetamol for most headache types. 1

Critical Frequency Limitation

• Limit all acute tension-type headache medications to ≤2 days per week (≤10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 6, 1
• If headaches occur more than twice weekly despite acute treatment, initiate preventive therapy rather than increasing acute medication frequency. 6, 1

Parenteral Options for Refractory Cases

• Metoclopramide 10 mg IV is the most effective parenteral agent for tension-type headache unresponsive to oral analgesics (NNT 2). 5
• Chlorpromazine IV (NNT 4) and metamizole IV (NNT 4) are alternative parenteral options where available. 5
• Avoid opioids (meperidine, hydromorphone, codeine) for tension-type headache, as they provide no proven benefit and carry high risk of dependence and medication-overuse headache. 1, 5

Common Pitfalls to Avoid

• Do not prescribe paracetamol doses below 1000 mg for moderate-to-severe tension-type headache, as lower doses lack proven efficacy. 3
• Do not combine NSAIDs with paracetamol in patients with peptic ulcer disease or renal impairment, as the NSAID component negates the safety advantage. 1, 2
• Do not allow patients to escalate acute medication frequency beyond 2 days per week; instead, transition to preventive therapy. 6, 1