There is a long tradition of combining drugs with different mechanisms of action. As early as the beginning of the 20th century, the pharmacologist Emil Bürgi published papers on the targeted combination of active substances and in 1938 he wrote the German book “Medicinal Drug Combinations”. Even at that time, painkillers containing the co-analgesic caffeine in addition to an analgesic were already on the market.
A review by the Cochrane Collaboration compared the analgesic effect of a common analgesic with a combination of the analgesic and caffeine . The authors assessed 25 studies with a total of 4262 participants. In all pain conditions investigated, the addition of caffeine significantly increased the proportion of patients who experienced effective pain relief (see Figure 1):
Figure 1: In all pain conditions investigated, the addition of caffeine significantly increased the proportion of patients who experienced effective pain relief
The positive effect on pain reduction was even greater when headache pain (migraine and tension-type headache) was considered:
There was also a clear difference in postoperative pain, where the positive effect on pain relief was 60% versus 51%.
Figure 2: Caffeine-containing analgesics also showed greatly improved pain relief in relation to headache.
In the studies considered, caffeine was added as co-analgesic in doses of 50 to 260 mg. Most studies used a caffeine addition of 100 to 200 mg per dose. Only one study investigated a variable amount of caffeine added to a 200 mg dose of ibuprofen. This study showed the same results as were also noted in the others: caffeine doses of 65 mg or less appeared not to improve the analgesic effect, whereas doses of 100 to 200 mg produced markedly improved pain relief. This observation is also reflected in the dosage of current standard combination preparations, most of which contain 100 mg caffeine.
The authors of this Cochrane Review of 25 studies found no reports of serious adverse events related to the analgesic or to caffeine. They therefore came to the same conclusion as the European Food Safety Authority (EFSA) whose assessment regarded a harmful effect through the addition of caffeine to an analgesic as improbable – provided the recommended dosage is observed.
Analgesics with caffeine are superior to analgesics without caffeine for acute pain, without displaying a relevant increased risk of side effects!
Conflict of interest: T. Weiser is an employee of Sanofi.
Disclosure: Medical writing and publication funded by Sanofi Aventis Deutschland GmbH.