The reason that SSRI antidepressants have seemingly not performed better than placebo is because their effects have been measured incorrectly, according to a reanalysis of clinical trial data published in Molecular Psychiatry. A more appropriate way to measure SSRI efficacy, the researchers argued, is to ignore the answers to 16 of the 17 questions about patients’ feelings that were typically asked during the drug trials.
“The recent questioning of the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) is partly based on the observation that approximately half of company-sponsored trials have failed to reveal a significant difference between active drug and placebo,” explained the team of researchers from the University of Gothenburg in Sweden. “Most of these have applied the Hamilton depression rating scale to assess symptom severity, the sum score for its 17 items (HDRS-17-sum) serving as effect parameter.”
The University of Gothenburg researchers chose to focus instead on the answers to just one of the 17 questions from the common depression rating scale. The question they chose was the one in which patients are rated by clinicians on their overall “depressed mood,” or feelings of “sadness, hopeless, helpless, worthless.” According to a copy of the test posted by the National Institute of Health, other questions on the HDRS-17, which the researchers decided to ignore, revolve around topics like suicidal feelings, insomnia and struggles to work.
Answers to the question about “depressed mood” are entered on a scale of 0-4, where 0 is “Absent” and 4 is “Patient reports virtually only these feeling states in his/her spontaneous verbal and non-verbal communication.” Evaluating only the answers to this one question, the researchers found that the SSRIs seemed to have stronger positive effects than placebo in 29 out of the 32 clinical trials they examined. Placebo also produced positive scores on the answers to this question in most of the trials, but by fractions of a point less overall.
“While not claiming that assessing depressed mood only is the optimal way of recording symptom severity, or that other symptoms are irrelevant, we do suggest that a treatment faithfully outperforming placebo in reducing depressed mood can hardly be regarded as ineffective,” wrote the authors. They concluded that the reason SSRIs have seemed to fail to outperform placebo in clinical trials is due to an “insensitive measure of efficacy.”
Hieronymus, F., J. F. Emilsson, S. Nilsson, and E. Eriksson. “Consistent Superiority of Selective Serotonin Reuptake Inhibitors over Placebo in Reducing Depressed Mood in Patients with Major Depression.” Molecular Psychiatry, April 28, 2015. doi:10.1038/mp.2015.53. (Full text)
Hamilton Depression Rating Scale (HDRS) (National Institute of Health)