SynthesisThe journal of headache and pain2014
Use of a fixed combination of acetylsalicylic acid, acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized, double-blind, placebo-controlled, crossover studies.
Synthesis in The journal of headache and pain, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 4 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- Paracetamol Combination Therapy for Back Pain and Osteoarthritis: A Systematic Review and Meta-Analyses.Drugs · 2024Pooled it
- Headaches in adults in supplementary health: management.Revista da Associacao Medica Brasileira (1992) · 2024Guideline
- Paracetamol versus ibuprofen in treating episodic tension-type headache: a systematic review and network meta-analysis.Scientific reports · 2023Pooled it
- Paracetamol (acetaminophen) for acute treatment of episodic tension-type headache in adults.The Cochrane database of systematic reviews · 2016Pooled it
- Combination vs. single-drug nonprescription analgesics for acute pain management: A narrative review.British journal of clinical pharmacology · 2025Review
- Hallmarks of primary headache: part 2- Tension-type headache.The journal of headache and pain · 2025Review
- Impact of Headache and Over-the-Counter Treatment on Pain and Functional and Cognitive Parameters: A Real-World Study across Three Geographies.Pain and therapy · 2025Article
- Chronic Stress and Headaches: The Role of the HPA Axis and Autonomic Nervous System.Biomedicines · 2025Review
- Debate: differences and similarities between tension-type headache and migraine.The journal of headache and pain · 2023Review
- Review
- The Effect of Coffee in the Prevention of Oral Mucositis Associated with Head and Neck Radiotherapy.Florence Nightingale journal of nursing · 2023Article
- Current Understanding of the Pathophysiology and Approach to Tension-Type Headache.Current neurology and neuroscience reports · 2021Review
- Why is the therapeutic effect of acute antimigraine drugs delayed? A review of controlled trials and hypotheses about the delay of effect.British journal of clinical pharmacology · 2019Review
- Administration of Micronized Caffeine Using a Novel Oral Delivery Film Results in Rapid Absorption and Electroencephalogram Suppression.Frontiers in pharmacology · 2019Article
- Commentary: Acute Tension-Type Headaches Are Associated with Impaired Cognitive Function and More Negative Mood.Frontiers in neurology · 2016Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMost patients with episodic tension-type headache treat headache episodes with over-the-counter medication. Combination analgesics containing caffeine may be more effective and as well tolerated as monotherapy. The aim of this study was to evaluate the efficacy of the combination of acetylsalicylic acid, acetaminophen (paracetamol) and caffeine in episodic tension-type headache using recently recommended endpoints.
methodsFour randomized, controlled trials of identical design in 1,900 patients with episodic tension-type headache comparing acetylsalicylic acid, acetaminophen and caffeine vs. acetaminophen or placebo were pooled. Analysis populations were 'all headache episodes' and those with 'severe pain at baseline'. Post-hoc defined primary endpoint: headache episodes pain-free at 2 h. Secondary endpoints: headache episodes pain-free at 1 h, headache response at 2 h (mild or no pain), degree of interference with daily activities.
results6,861 headache episodes were treated, including 2,215 severe headache episodes. The proportion of headache episodes pain-free at 2 h was significantly higher with the triple combination (28.5%) vs. acetaminophen (21.0%) and placebo (18.0%) (p < 0.0001), and similarly for those severe at baseline (20.2% vs. 12.1% and 10.8%; p ≤ 0.0003). A similar pattern of superiority was observed for secondary endpoints. The triple combination was generally well tolerated.
conclusionsThe combination of acetylsalicylic acid, acetaminophen and caffeine is effective and well tolerated in episodic tension-type headache, and significantly superior to acetaminophen with regard to being pain-free at 2 h, headache response at 2 h and ability to return to daily activities, even in those with pain rated severe at baseline.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.