Caffeine as an analgesic adjuvant in tension headache

Abstract

Six randomized, double-blind, two-period crossover studies, conducted under similar protocols, compared the efficacy of two analgesic combinations containing caffeine with an acetaminophen 1000 mg control and with a placebo in outpatients with episodic tension-type headaches. In four studies, comprising 1900 patients, the caffeine-containing analgesic consisted of a combination of 500 mg acetaminophen, 500 mg aspirin, and 130 mg caffeine (APAP/ASA/CAF). In two studies, comprising 911 patients, the caffeine-containing analgesic consisted of a combination of 1000 mg acetaminophen and 130 mg caffeine (APAP/CAF). Patients self-medicated for moderate or severe headache pain, and with a self-rating record they rated their pain and its relief hourly for 4 hours. In all six studies, the caffeine-containing analgesics were significantly superior both to placebo and to 1000 mg acetaminophen, and acetaminophen was significantly superior to placebo. The significant analgesic adjuvant effect of caffeine was independent of patients' usual caffeine use or their caffeine consumption in the 4 hours before medication. For each treatment, the pooled analgesic responses for the four studies of APAP/ASA/CAF were virtually superimposable on the responses in the two APAP/CAF studies. The combinations produced more stomach discomfort, nervousness, and dizziness than acetaminophen or placebo.

Drug therapy in headache

“…[9][10][11][12] Paracetamol has not been shown to be effective at doses below 1,000 mg and some studies have shown it to be less effective than NSAIDs. Combination analgesics containing caffeine may be more effective still, 13 but are likely to carry a greater propensity to induce medication overuse headache -though it is unlikely that patients with TTH alone, without a personal or family history of migraine, are susceptible to this condition. 14 …”

Safety of opioid patch initiation in Australian residential aged care

“…Psychological, physical and environmental factors are important in TTH and should be addressed during assessment and treatment (Holroyd, 2002). The addition of caffeine to paracetamol, aspirin (Migliardi et al, 1994 Level I) or ibuprofen (Diamond et al, 2000 Level II) significantly improved analgesia and a paracetamol-aspirin-caffeine combination was more effective than placebo and all three component drugs alone, in terms of analgesia outcomes and time to effect (Diener et al, 2005 Level II). IV magnesium was ineffective in treating acute TTH in the emergency department (Frank et al, 2004 Level II).…”

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

“…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). Key objectives of these studies were to compare the efficacy and speed of pain relief with these two new rapid-acting paracetamol-plus-caffeine formulations versus placebo and ibuprofen in ETTH.…”

“…In a pooled analysis of four randomized, double-blind, double-dummy, two-period crossover trials in adults with ETTH, 500 mg paracetamol-500 mg aspirin-130 mg caffeine also showed significantly better efficacy on SPID, maximum PID, TOT-PAR, maximum pain relief, and duration of time with pain at least half gone compared with both placebo and 1,000 mg paracetamol alone (all P<0.001). 12 A second analysis of the same four studies reported that the triple combination was also associated with a significantly (P<0.0001) greater percentage of pain-free subjects at 2 hours (28.5%) compared with acetaminophen alone (21%) or placebo (18%); this was also true in the subset of subjects with severe pain at baseline (percentage pain-free at 2 hours 20.2% vs 12.1% [P<0.0001] and 10.8% [P=0.0003], respectively). 22 In addition, a randomized, double-blind, placebo-controlled trial also supported a more rapid onset and greater pain relief with paracetamolaspirin-caffeine compared with aspirin, paracetamol, caffeine, and placebo alone in the treatment of a variety of headache types.…”

“…For example, in a pooled analysis of two randomized, double-blind, double-dummy, two-period crossover trials in adults with ETTH, 1,000 mg paracetamol plus 130 mg caffeine showed significantly better efficacy on SPID, maximum PID, TOTPAR, maximum pain relief, and duration of time with pain at least half gone compared with both placebo and 1,000 mg paracetamol alone (all P<0.001). 12 An Italian randomized, double-blind, double-dummy, crossover trial in patients with TTH found that 1,000 mg paracetamol plus 130 mg caffeine was as effective as 550 mg naproxen sodium and more effective than placebo with regard to PID, TOTPAR, and proportion of subjects requiring rescue medication. 18 Another randomized, double-blind, crossover trial in adults with nonmigraine headaches found that 65 or 130 mg caffeine alone, 648 mg paracetamol alone, or 648 mg paracetamol plus either 65 or 130 mg caffeine all significantly reduced pain (as reported on 100 mm visual analogue scale) compared with placebo at 120 minutes, whereas 130 mg caffeine with or without paracetamol also produced significant pain reduction versus placebo at 30 and 60 minutes postdose (all P<0.05).…”