Caffeine as an analgesic adjuvant for acute pain in adults

Derry, Christopher J; Derry, Sheena; Moore, R Andrew

doi:10.1002/14651858.cd009281.pub2

Cited by 56 publications

(53 citation statements)

References 39 publications

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“…The NNT for the pain-free at 2 hours outcome with paracetamol-sodium bicarbonate-caffeine in study 1 was 12, which is similar to NNTs reported in meta-analyses for paracetamol (NNT 22), 7 ibuprofen (NNT 14), 11 and ketoprofen (NNT 9). 17 The NNT for paracetamol with Optizorbcaffeine in study 2 could not be calculated, because the absolute risk difference from placebo was <1%.…”

supporting

confidence: 76%

“…Adding caffeine as an adjuvant to common analgesics, including paracetamol, has been shown to provide a small but significant increase in relief from various types of acute pain. 11 More specifically, randomized double-blind studies have found that caffeine enhances the analgesic efficacy of paracetamol in patients with ETTH. 12 Here, we report results from two multicenter, randomized, placebo-controlled studies of patients with ETTH to evaluate the efficacy of a combination of paracetamol and caffeine using two different formulations designed to enable faster absorption of paracetamol in combination with caffeine: one that included sodium bicarbonate (study 1) and one that used paracetamol with Optizorb (study 2).…”

Section: Introductionmentioning

confidence: 99%

“…16 It is difficult to compare NNTs from our results with the existing literature, because the Cochrane meta-analyses for ibuprofen and paracetamol did not calculate NNTs for painfree at 1 hour (the risk difference from placebo was <1%), and no data on this outcome were available for ketoprofen. 7,11,17 Ours are the first published studies to combine rapidacting paracetamol formulations with caffeine in the treatment of ETTH. Previous studies have reported enhanced efficacy when caffeine was added to standard paracetamol or ibuprofen.…”

mentioning

confidence: 99%

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Efficacy and safety of two fast-absorbing formulations of paracetamol in combination with caffeine for episodic tension-type headache: results from two randomized placebo- and active-controlled trials

Yue¹,

Reed²,

Shneyer³

et al. 2017

OAJCT

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Objectives: Two randomized placebo-controlled trials evaluated whether combining rapidacting paracetamol formulations with caffeine resulted in faster/greater relief of episodic tension-type headache (ETTH) compared with placebo and over-the-counter (OTC) analgesics. Both studies were prematurely terminated. Materials and methods:In the single-blind crossover study 1, adults with ETTH (n=66) received three of the following in random sequence: paracetamol 1,000 mg with sodium bicarbonate 650 mg and caffeine 130 mg; paracetamol 1,000 mg; ibuprofen 400 mg; and placebo. In the double-blind parallel-group study 2, adults with ETTH (n=157) were randomly assigned 2:2:1 to treat up to three headaches with paracetamol with Optizorb technology 1,000 mg plus caffeine 130 mg; ibuprofen 400 mg; and placebo. Results: In study 1, the primary outcome -mean time to perceptible pain relief -was 36.7, 38, 48.9, and 42.7 minutes in the paracetamol-sodium bicarbonate-caffeine, ibuprofen, paracetamol, and placebo groups, respectively; differences were not statistically significant. In study 2, the weighted sum of pain intensity (scale of 0 [no pain] to 4 [severe pain]) difference from the time of treatment to hour 4, the primary outcome, showed numerically favorable differences for paracetamol with Optizorb-caffeine compared with ibuprofen (difference in least square means −0.3, 95% confidence interval −1.05 to 0.45) and placebo (−0.47, 95% confidence interval −1.36 to 0.42). In both studies, secondary outcomes suggested faster and greater relief with rapid paracetamol-caffeine compared with placebo and paracetamol; a few of these outcomes achieved statistical significance at ~45-90 minutes in study 1. Adverse events were mostly mild and consistent with known safety profiles of OTC analgesics and caffeine. Conclusion: Firm conclusions regarding the speed and efficacy of rapid-acting paracetamol formulations plus caffeine compared with placebo and traditional OTC analgesics for ETTH cannot be drawn, because the studies were terminated early. Some encouraging trends seen suggest this combination deserves further investigation.

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supporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Efficacy and safety of two fast-absorbing formulations of paracetamol in combination with caffeine for episodic tension-type headache: results from two randomized placebo- and active-controlled trials

Yue¹,

Reed²,

Shneyer³

et al. 2017

OAJCT

View full text Add to dashboard Cite

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“…To this end, two drugs often found in combination in commercial medicines in are paracetamol (acetaminophen) and caffeine. Paracetamol is effective at relieving mild to moderate pain and fever, and caffeine is a mild stimulant that helps reduce fatigue, and it is also thought to enhance the painkilling effect of paracetamol 18 .…”

Section: Introductionmentioning

confidence: 99%

3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics

et al. 2015

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Citation: Goyanes A, Wang J, Buanz A, Martinez-Pacheco R, Telford R, Gaisford S and Basit AW (2015) 3D printing of medicines: Engineering novel oral devices with unique design and drug release characteristics. Molecular Pharmaceutics. 12(11): 3783-4174. Key wordsThree dimensional printing; controlled-release; fused deposition modelling; PVA; paracetamol; acetaminophen; caffeine; hot melt extrusion; Raman mapping 2 AbstractThree dimensional printing (3DP) was used to engineer novel oral drug delivery devices, with specialised design configurations loaded with multiple actives, with applications in personalised medicine. A filament extruder was used to obtain drug-loaded -paracetamol (acetaminophen) or caffeine -filaments of polyvinyl alcohol with characteristics suitable for use in fused-deposition modelling 3D printing. A multi-nozzle 3D printer enabled fabrication of capsule-shaped solid devices, containing paracetamol and caffeine, with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different from the drug in the adjacent layers; and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least squares component matching to produce false colour representations of distribution of the drugs showed clearly the areas that contain paracetamol and caffeine, and that there is a definitive separation between the drug layers.Drug release tests in biorelevant media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both drugs was simultaneous and independent of drug solubility. With the DuoCaplet design it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device, and the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design configurations and unique drug release characteristics, which would not otherwise be possible using conventional manufacturing methods.3

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“…Besides, acetaminophen as a non-opioid analgesic with antipyretic properties has been shown to be effective in relieving mild to moderate postoperative pain (10)(11)(12). Moreover, caffeine has been added to common analgesics such as acetaminophen or NSAIDs in the belief that it enhances analgesic efficacy, however, evidence to support this belief is limited and often based on invalid comparisons (13). Tramadol is a synthetic analogue of codeine and prevents norepinephrine and serotonin reuptake (14).…”

Section: Introductionmentioning

confidence: 99%

Clinical Trial of Combination of Acetaminophen, Ibuprofen and Caffeine on Pain Relief and Analgesic Use After Impacted Lower Third Molar Surgery

2017

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Objectives: Relieving a very painful procedure such as impacted lower third molar surgery by combining analgesics into a single product using their synergistic effects is favorable. We designed a prospective, randomized, double-blind clinical trial to study the beneficial effect of the combination of acetaminophen, ibuprofen, and caffeine on reducing the severity of postoperative pain after impacted lower third molars surgery. Methods:This was a double-blinded clinical trial on 108 patients scheduled for impacted third molar surgery. The patients were randomly assigned into 2 groups. Two hours before the procedure the intervention group received combination therapy of acetaminophen (600 mg), ibuprofen (400 mg), and caffeine (15 mg) as pre-emptive analgesia, and the control group received placebo. All patients received gelofen capsules (400 mg) uniformly after the intervention as PRN. Postoperative assessment of pain severity [using a 10-point visual analog scale (VAS)] and analgesic consumption was performed at 2, 4, 6, and 8 hours after the operation. All statistical analyses were performed using SPSS software (version 19.0, SPSS Inc., Chicago, Illinois), with chi-square test or Fisher's and Mann-Whitney U test. Results:The severity of preoperative pain did not differ before receiving the first dose of study drugs. However, at any time points after the surgery, the mean pain score was significantly lower in the group who received combination regimen than the control group (P < 0.001). In a general linear model, using a repeated-measures analysis, concerning the analgesic dose administered after the surgery, the mean number of doses in 8 hours was 0.96 for the combination therapy group and 1.8 for the control group, with a significant difference (P = 0.022). Conclusions:The pre-emptive combination therapy including acetaminophen, ibuprofen, and caffeine can be used efficiently to control postoperative pain after impacted third molar surgery.

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Caffeine as an analgesic adjuvant for acute pain in adults

Cited by 56 publications

References 39 publications

Efficacy and safety of two fast-absorbing formulations of paracetamol in combination with caffeine for episodic tension-type headache: results from two randomized placebo- and active-controlled trials

Efficacy and safety of two fast-absorbing formulations of paracetamol in combination with caffeine for episodic tension-type headache: results from two randomized placebo- and active-controlled trials

3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics

Clinical Trial of Combination of Acetaminophen, Ibuprofen and Caffeine on Pain Relief and Analgesic Use After Impacted Lower Third Molar Surgery

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