title: [Caffeine plus analgesics-a significant combination.].
abstract: Since the ban of phenacetin and barbiturates in analgesics, caffeine as a constituent of analgesics has recently more often been blamed for promoting the abuse of analgesics. The available relevant literature was reviewed to perform a benefit/risk analysis. The results were as follows. The capability of caffeine to potentiate analgesia was demonstrated in controlled clinical trials involving approximately 12000 patients. This effect does not mean that there is a stronger analgesic effect, but that the addition of caffeine allows to reduce the dose of analgesics significantly, while maintaining the same analgesic efficacy. A minimum single dose of 50 mg caffeine is required to achieve this potentiation. Furthermore, it was demonstrated in controlled clinical trials in about 2000 patients that the maximum analgesic effect is achieved after 30-45 min with caffeine-containing analgesics, but only after 60-90 min with monotherapy. This must be regarded as a great advantage in terms of cumulative toxicity, because additional or higher doses due to insufficienttimeliness of efficacy are thus avoided. Thus, the analgesic benefit of caffeine as a constituant of analgesic drugs can no longer be denied, even though some studies leave room for criticism. (It should be added that this beneficial effect was investigated only for acute treatment with acetylsalicylic acid plus caffeine or with paracetamol plus caffeine). Toxicity studies with combination drugs indicate that there are no risks beyond the known risks of the individual components. On the contrary, the studies suggest that there is a tendency towards underadditivity; with an equal analgesic efficacy, therefore, the toxicological risk of an analgesic plus caffeine tends to be lower than with the respective analgesic alone. With respect to the frequently postulated promotion of analgesic abuse by caffeine, the results of this review are best summarized by citing the statement of the Federal Drug Review Committee "Neurology/Psychiatry" at the Bundesgesundheitsamt (BGA): "There is no evidence showing that a possible potential for dependence in the case of analgesics, such as acetylsalicylic acid or paracetamol, is increased by caffeine. Even though this could be assumed in theory, based on the available data there is no proof of an additional abuse potential for caffeine in combination with analgesics" [11]. The question of whether combination analgesics containing caffeine ought to be sold only on prescription might better be answered in the negative; in Germany, the percentage of self-medication (i.e., without consulting the doctor) in the consumption of prescription analgesics reaches up to 40% (1). Furthermore one could even argue that by introducing prescription schedule for analgesics containing caffeine a higher consumption of analgesic substance might be induced (to achieve an analgesic efficacy equal to that of combination drugs). This however might cause a higher and unpredictable risk (e.g., gastrointestinal bleeding) with proper use in exchange for of a reduction in the predictable risk with misuse or abuse. This would raise major ethical and legal issues. Minimizing one special risk does not automatically reduce the overall risk.
authors.affiliation: Fachbereich 3 (Theoretische Medizin) der Universität des Saarlandes, Köln, Deutschland.
authors.forename: J M
authors.initials: JM
authors.lastname: Fox