Are antidepressants really effective? If the majority of studies on the subject show a slight improvement in symptoms, do all patients really benefit? This is the question that Marc Stone, deputy director of the center for the evaluation of drugs of the FDA and researchers specializing in the placebo effect, wanted to answer. In meta-analysis in which the researchers used data from 232 trials conducted in the United States on anti-depressants given as monotherapy between 1979 and 2016. In total, 73,388 people – adults and children – were counted.
And their results published in the British Medical Journal on August 2, 2022 show that only 15% of clinical trial participants really benefit from antidepressants compared to placebo. That is 85% of cases where the drug does no better than a placebo.
For the study, the severity of depression was assessed using thehamilton scale. And on average, the difference between the effect of antidepressants and placebos was small, just 1.8 points on the Hamilton scale (9.8 points in the antidepressant group and 8.0 in the placebo group).
The more severe the depression, the more effective the antidepressant and the placebo are, according to the researchers, but the effect of the drug compared to the placebo increases with the starting severity of the depression, which “proves that there is an active phenomenon on the treatment side, even weak”says psychiatrist Guillaume Fond.
What kinds of responses do drugs offer?
According to the researchers, three types of response were possible among study participants: strong response, non-specific response, and minimal response, with moderate improvement at the end of treatment. Patients taking an antidepressant were more likely to experience a significant response, 24.5% in the antidepressant group versus 9.6% in the placebo group
But then, why do we observe a response with the placebo? “The heterogeneity of depression is such that some patients respond to nothing, and others to everything, including placebo.“, continues Dr. Fond.
“We’re going to prescribe an antidepressant with a certain mode of action. If we get it right, there will be a good response, which also explains why tricyclics that have a broader action at the receptor level are considered the most effective in this study.“, he explains. “But there can also be minimal response or no response with significant side effects“, he continues.
An increasingly discussed treatment
This is not the first time that the effectiveness of antidepressants has been questioned. In July 2022, a meta-analysis showed that serotonin – a neuromodulator involved in mood regulation and the basis of treatments known as selective serotonin reuptake inhibitors (the most common: Prozac, Zoloft, etc.) – would in fact be ineffective in the treatment of depression.
“The idea that depression is the result of abnormalities in brain chemicals, particularly serotonin (5-hydroxytryptamine or 5-HT), has been influential for decades and provides important rationale for the use of antidepressants”, said psychiatrist Johanna Moncrieff, responsible for this study. But they say no evidence that low serotonin causes depression, and these might work”through placebo effect“.
Discoveries that are not without reacting within the medical class. Recently, psychiatrists at the Royal College of Psychiatrists even asked patients to do not stop their treatment without discussing it with a healthcare professional first.
Sources:
- Response to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration: individual participant data analysis, British Medical JournalAugust 2, 2022
- How many patients are really good responders to antidepressants?, UnivadisSeptember 8, 2022
