Am J Psychiatry 1991; 148:193-196
Copyright © 1991 by American Psychiatric Association
Heterogeneity of clinical response during placebo treatment
FM Quitkin, JG Rabkin, JW Stewart, PJ McGrath, W Harrison, DC Ross, E Tricamo, J Fleiss, J Markowitz and DF Klein
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY.
OBJECTIVE: The authors attempted to identify different patterns of
improvement among patients receiving placebo during clinical trials. It was
hypothesized that patients who improved abruptly would differ from patients
whose improvement was gradual in that they would tend to improve earlier
and would tend to have less persistent improvement. METHOD: The subjects
were 144 patients who met the DSM-III criteria for depressive illness and
were randomly assigned to placebo medication in four double-blind
antidepressant drug trials. All studies lasted 6 weeks. Mood change was
rated each week on a 7-point scale; a rating of 1 or 2 was considered an
indication of improvement. Improvement was judged to be abrupt if the first
score of 1 or 2 was immediately preceded by a score of 4 or worse, and it
was classified as gradual if the first score of 1 or 2 was preceded by a
score of 3 in at least 1 week. Improvement was considered persistent if a
score of 1 or 2 was not followed by a score of 3 or worse in any subsequent
week. RESULTS: Of the 144 patients, 72 showed clinical improvement during
at least one weekly visit; 33 improved abruptly and 39 improved gradually.
The abrupt improvements occurred significantly earlier in the trial and
were less likely to persist than the gradual improvements regardless of
when they occurred. CONCLUSIONS: These data suggest that among patients
receiving placebo abrupt improvements are a form of placebo response and
gradual responses may be the result of spontaneous remission. These
preliminary observations require validation.
