Tolerability and efficacy of a combination of paracetamol and caffeine in the treatment of tension-type headache: a randomised, double-blind, double-dummy, cross-over study versus placebo and naproxen sodium

Abstract

The main aim of this study was to confirm in an Italian population affected by tension-type headache (TTH) the good profile of safety and tolerability of the combination paracetamol 1,000 mg–caffeine 130 mg (PCF) observed in previous studies, by a comparison with naproxen sodium 550 mg (NAP) and placebo (PLA). A secondary objective was to assess the efficacy of PCF in the acute treatment of TTH. This was a multicentre, randomised, double-blind, double-dummy, crossover, placebo-controlled trial. Tolerability was assessed by recording adverse events by the patient in the 4-h post-dose treatment. To assess the efficacy, the sum of pain intensity differences (SPID) and the total pain relief (TOTPAR) were calculated. Comparing PCF and NAP and PCF and PLA for tolerability, the difference was nonsignificant but the result regarding noninferiority was inconclusive, whilst NAP was noninferior to PLA. As regards SPID and TOTPAR, both PCF and NAP were better than placebo (P < 0.05), but not significantly different from each other. In conclusion, PCF was well-tolerated and effective in the treatment of acute TTH.

Evidence for efficacy of acute treatment of episodic tension-type headache: Methodological critique of randomised trials for oral treatments

“…There were 40 included reports [6,8,11,[17][18][19][20][21][22][23][24][25]30,[35][36][37]39,[44][45][46][47]53,[55][56][57][59][60][61]64,[66][67][68][69][74][75][76][77]79,82,83]. Four reports included more than 1 trial.…”

Efficacy of fixed combinations of acetylsalicyclic acid, acetaminophen and caffeine in the treatment of idiopathic headache: a review

“…This held true as well for the post‐hoc analysis of patients with menstruation‐associated migraine [28]. A shortly publicized study compared the combination of 1000 mg acetaminophen in combination with 130 mg caffeine to naproxen and placebo [29]. End‐points were the sum of pain intensity differences and total pain relief.…”

“…End‐points were the sum of pain intensity differences and total pain relief. The combination and naproxen were better than placebo, but no difference between the two vera were found [29].…”

A Risk-Benefit Assessment of Paracetamol (Acetaminophen) Combined with Caffeine

“…In an experimental pain model, paracetamol (1,000 mg) when combined with caffeine (130 mg) had a sustained antinociception‐enhancing effect [30]. Moreover, the combination of paracetamol and caffeine has been shown to be as efficacious as ibuprofen after periodontal surgery [31] and naproxen sodium in tension‐type headache [32]. However, few studies have evaluated the efficacy of a caffeine‐analgesic combination vs the same analgesic alone.…”