Title : What Caffein brings to Paracetamol (Acetaminophen) in pain Management
Abstract:
Background: Paracetamol is effective and safe in mild to moderate migraine attacks and episodes of tension-type headache (TTH). Few data are available on the use of paracetamol combined with caffeine, the aim of which is to achieve a higher analgesic efficacy of paracetamol while lowering its dose and thus reducing the risk of side effects.
Objective: The aim of this work is to provide an overview of data on the cumulative analgesic effects of this combination and to clarify the mechanisms underlying the potentiation by caffeine of the antinociceptive effect of paracetamol in migraine and TTH.
Methods: A search was conducted in PubMed, MEDLINE, ClinicalTrials.gov and Cochrane Database from inception to March 2024 with a focus on paracetamol 1000 mg in combination with caffeine 130 mg.
Results: In preclinical studies caffeine has been shown to increase the antinociceptive effects of paracetamol with various mechanisms: inhibition of microglial COX2 via antagonism of adenosine A2A receptors or activation of glycinergic transmission. Two pharmacokinetic studies in healthy subject have shown that caffeine increases paracetamol absorption rate and decreases paracetamol clearance. Two randomized double blind clinical studies have both demonstrated that in patients suffering from TTH, the combination offers a significant higher pain relief compared to paracetamol alone. Two other TTH clinical trials have shown that the efficacy and safety of combination was comparable to Naproxen 550 mg and Ibuprofen 400 mg. One randomized, cross-over trial has shown a comparable efficacy/safety profile of the combination vs sumatriptan 50 mg in treatment of migraine attack. No data are available on the risk of medication overuse with the combination compared to paracetamol alone.
Conclusions: Caffeine accelerates and prolongs the analgesic effect of paracetamol over time with a significant improvement of pain relief in patients with primary headaches without added safety issues.
