Researchers from the University of Gothenburg found the assertion of ineffectiveness is at least partly based on a misinterpretation of the outcome of the clinical trials once conducted to demonstrate their efficacy.
In recent years, many observers have argued that the most commonly used antidepressant medications, the selective serotonin reuptake inhibitors (SSRIs), are ineffective. This criticism has caused authorities in many countries to become increasingly cautious in recommending these medications.
One reason for questioning of the SSRIs efficacy stems from a retrospective review of the clinical trials conducted by the pharmaceutical companies as they were developing the drugs. The studies, conducted years ago, showed that less than half of the trials reported a statistically significant difference between the tested SSRI and placebo.
In order to shed further light on this controversial issue, researchers analyzed the data from all major company-sponsored placebo-controlled studies addressing the effect of any of three SSRIs — citalopram (Celexa), sertraline (Zoloft) and paroxetine (Paxil) — for major depression in adults.
The analyses was conducted by Ph.D. student Fredrik Hieronymus and others in a research team led by pharmacologist Elias Eriksson, M.D., Ph.D.
The researchers discovered a reason for the less than stellar outcomes may be traced to an outdated rating scale used decades ago.
“In order to measure the antidepressant effect, the pharmaceutical companies have unwisely assessed the reduction in the sum score for a large number of symptoms listed on a rating scale.
“However, the sensitivity of this instrument is markedly marred by the fact that many of these symptoms occur also in subjects without depression, while others are absent also in many depressed patients. For this and other reasons, the usefulness of this rating scale, which was constructed already during the 1950s, has since long been questioned.”
To overcome this bias, researchers analyzed the effect of the treatment on a key item on the the scale — depressed mood.
According to Eriksson, the results are noteworthy: Using the conventional (old) measure of efficacy, only 44 percent of the 32 comparisons reveal a significant superiority of the SSRIs over placebo.
When the Gothenburg researchers instead examined the efficacy on depressed mood, 29 of the 32 comparisons (91 percent) showed a significant difference favoring the active drug.
“Our conclusion is that the questioning of the antidepressant efficacy of SSRIs is to a large extent based on an unfortunate misinterpretation of the available data. The truth is that the scientific support for these drugs exerting an antidepressant impact is very robust across studies,” said Eriksson.