Evaluation of analgesic agents in recurring headache compared with other clinical pain models.

The efficacy of three preparations (placebo, analgesic agent, and analgesic plus antihistaminic agent) were compared in a double-blind crossover study in subjects with recurring headaches. It was confirmed that headache as a pain model does not show the usual return of pain with as the effects of a single analgesic dose wear off. Consequently, there is no "peak effect," and the rationale for comparing treatments by "area under the curve" calculations is weakened. Greater efficacy was demonstrated for the analgesic over the placebo and for the analgesic and antihistaminic combined over the analgesic alone in several parameters. Slopes of straight lines derived as a quadratic function of pain versus time data proved to be a more effective discriminator between treatments than area under the curve calculations from the same data.