Oral analgesic studies: Pentazocine hydrochloride, codeine, aspirin, and placebo and their influence on response to placebo

In an analgesic study of 244 patients with postsurgical pain, doses of placebo, 600 mg. aspirin, 60 mg. codeine, and 35 and 50 mg. of pentazocine were compared. Two drug presentations were used, the second one always placebo, in this “double unknowns” design. Pentazocine, 50 mg., was found to be equivalent to 60 mg. of codeine in analgesic potency; 600 mg. aspirin was superior to the 35 mg. dose of pentazocine. The analgesic potency of placebo as a second dose was functionally dependent on the preceding medication. When placebo followed placebo, responses were identical. This finding is interpreted to be a serious drawback to crossover designs in clinical trials of analgesics.