Classic conditioning and placebo effects in crossover studies.
OBJECTIVE
To find evidence of classically conditioned placebo effects in a placebo-controlled crossover drug study. Specifically, we tested a prediction of the conditioning model that the placebo response will be greater after drug exposure than before.


METHODS
Twenty-four patients with mild to moderate essential hypertension and no contraindications to atenolol participated in the study. The study design required randomized assignment to one of three groups: placebo followed by 50 mg atenolol daily, followed by no treatment, each for 1 week; atenolol followed by placebo; and atenolol followed by nothing (to show residual drug effects). Twice-daily blood pressure measurements were made by patients at home; once-weekly measurements of blood pressure and heart rate were made by a research nurse.


RESULTS
Before drug treatment, there were no differences in the antihypertensive responses of patients taking placebo and patients taking nothing (difference, 0.98 mm Hg; 95% confidence interval, -0.98 to 2.93). After atenolol treatment, placebo treatment produced a significantly greater antihypertensive response than no treatment (difference, -6.09 mm Hg; 95% confidence interval, -11.81 to -0.38). Thus the placebo response after atenolol administration was more than a residual drug effect. Similar patterns were observed for heart rate but not for blood pressure readings taken in the office.


CONCLUSIONS
These observations are consistent with a conditioning model of placebo effects. These findings warrant further investigation in larger studies and in other disease models.
Suchman
A L
AL
Department of Medicine, Highland Hospital, Rochester, NY 14620.
Ader
R
R
D000328:Adult; D000368:Aged; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003214:Conditioning, Classical / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect
D001262:Atenolol