Aspirin in episodic tension-type headache: placebo-controlled dose-ranging comparison with paracetamol

Most people with episodic tension-type headache (TTH) treat themselves with over-the-counter analgesics. In the absence of clear evidence of dose-related efficacy of the two most commonly used analgesics, aspirin (acetylsalicylic acid) and paracetamol (acetaminophen), this study compared two doses of each with placebo. In a double-blind, double-dummy, randomized parallel-groups comparative trial, 638 consenting subjects aged 16-65 years with episodic TTH (but not migraine) by IHS criteria were recruited from the UK general population by advertisement. They treated one episode of moderate or severe TTH with a single dose of 500 or 1000 mg aspirin, 500 or 1000 mg paracetamol or placebo. The primary objective was to compare aspirin 1000 mg with placebo, and the primary end-point was subjective pain relief (total or worthwhile) 2 h after treatment ('response'). Additionally, pain intensity on a 100-mm visual analogue scale and functional impairment were monitored regularly for 4 h and at 24 h, although rescue medication was allowed after 2 h. The analysis was of the intention-to-treat population of 542 who took treatment (all providing outcome data). Treatment groups were matched at baseline. Aspirin 1000 mg (75.7% response rate; P=0.0009) and to a lesser extent aspirin 500 mg (70.3%; P=0.011) and paracetamol 1000 mg (71.2%; P=0.007), but not paracetamol 500 mg (63.8%; P=0.104), were statistically more effective than placebo despite a high placebo-response rate (54.5%). Outcome was not affected by headache intensity at baseline. Secondary end-points including functional recovery (by median times of 4.0-13.5 h) were consistent with these findings, although a minority of subjects recorded long-duration functional impairment (37-54 h). Adverse events reported by 13.4-18.9% of subjects were mild or moderate, and transient. No safety concerns arose.