Impact of experimentally-induced expectancy on the analgesic efficacy of tramadol in chronic pain patients: A 2 x 2 factorial, randomized, placebo-controlled, double-blind trial

Variations in treatment effects between drug trials are usually attributed to different patient characteristics, variations in outcome assessment, and random error. We have previously hypothesized that part of the variation i n treatment effects between drug trials might be caused by differences in n onspecific factors. In a randomized clinical trial, we aimed to investigate whether experimentally induced expectancy can modify the analgesic effect of tramadol relative to placebo in chronic pain patients. In a 2 x 2 factor ial, randomized, placebo-controlled, double-blind trial, chronic pain patie nts attending a chronic pain outpatient clinic were randomized to receive a single oral dose of 50 mg tramadol or placebo, and they were further rando mized to receive positive or neutral information, verbally expressed by the physician, regarding the expected analgesic effect of the drug: Pain inten sity was measured using a 10 centimeter visual analogue scale at baseline, and 0.5, 1, 2, 4 6, and 8 hours after. baseline. The one-hour pain intensit y difference, calculated as the sum of pain intensity differences between b aseline and 0.5 and 1 hour was taken as main outcome measure. The one-hour sum of pain intensity differences of 28 patients treated after positive exp ectation and randomized to tramadol was 1.4 cm, while in 27 patients random ized to placebo, if was 0.8 cm. This corresponds with an analgesic effect o f tramadol relative to placebo of 0.6 cm (95% confidence interval [CI], -0. 5 cm to 1.8 cm). The 28 patients in the neutral expectancy group who were r andomized to tramadol reported a 1.4 cm decrease on the sum of pain intensi ty differences, while 28 patients in the placebo group reported a 0.9 cm de crease. This corresponds with an analgesic effect of tramadol relative to p lacebo of 0.5 cm (95% CI, -0.9 cm to 1.8 cm). The 0.1 cm difference (0.6 cm - 0.5 cm) in analgesic effect between positive and neutral expectancy grou p, was not statistically significant (95% CI, -0.7 nn to 1.0 cm). This tria l did not discern a significant difference in the analgesic effect of trama dol between a positive and neutral expectancy group. This means that the ph enomenon either does not exist, or we had an inappropriate model to demonst rate it. Regardless, this study demonstrates the type of quality trial that should be done to find out which non-specific factors, such as information regarding the expected effect, can modify treatment effects. J Pain Sympto m Manage 2001; 21:210-217. (C) U.S. Cancer Pain Relief Committee, 2001.