Antidepressants have significant benefits only for some patients, study finds

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The use of antidepressants represented a significant and long-term improvement in about 15% of patients with depression when compared to the use of placebos. For the other 85%, there is also improvement, but the benefits were close to those seen in participants who used the placebo.

The conclusion is from a study published in early August in the medical journal BMJ. With this result, the authors point out that antidepressants represent a considerable benefit in the treatment of depression in a specific portion of patients. Therefore, in their assessment, it would be necessary to investigate factors associated with those people who have better responses to medications.

For Marcelo Feijó, professor at the Department of Psychiatry at EMA (Paulista School of Medicine) at UNIFESP (Federal University of São Paulo), the study shows that antidepressants work, but also indicates the need to understand why he has a significant result in certain group.

“This is important data because it shows that we need to improve the types of treatment for depression”, he says.

The article consisted of a review of clinical studies on the effectiveness of antidepressants. All of these peer-reviewed studies were done between 1979 and 2016 and had been submitted to the US Food and Drug Administration (FDA) as clinical studies to review the drug’s effectiveness. Some authors of the new research are linked to the agency, while others are researchers from North American universities, such as Harvard and Johns Hopkins.

In total, the new research reviewed 232 clinical studies. Adding up participants from all these studies, the review looked at the effect of antidepressants and placebos on more than 73,000 people.

Scientists considered the Hamilton Rating Scale for Depression (HAMD17). This scale is composed of 17 questions and, with the answers, a calculation is made to indicate whether or not the person has depression. The new research used this model to look at the effects that drugs and placebos had on participants.

The result was that antidepressants had about 1.7 more positive change on the participants’ HAMD17 scale compared to placebos. That is, the benefit of antidepressants in relation to placebos is small, at least in most cases.

Christian Dunker, psychoanalyst and professor at the Institute of Psychology at USP (University of São Paulo), states that the confusion of the effects between placebo and antidepressant is known, but still unexplained. “Deep down, no one can say exactly why this happens.”

The improvement effect by using a placebo is not unique to clinical studies with antidepressants. “In depressions, in the first weeks of treatment, the placebo effect explains up to 40% of the improvement. Therefore, to be considered effective, any new antidepressant has to result in an improvement above placebo,” says Wagner Gattaz, full professor at the Institute of Psychiatry, Hospital das Clínicas, USP.

Gattaz explains that one of the hypotheses to explain the placebo effect is the suggestion to the research participant that he was actually using the drug. “This psychological suggestion can lead the organism, controlled by the brain, to develop biological mechanisms that explain the placebo effect.”

Significant improvement

In addition to the small change provided by antidepressants, there are situations in which the drugs cause a greater improvement compared to people using a placebo. These cases, however, are rarer: according to the new study, about 15% of patients are in this scenario.

For the authors, this data is an indication that antidepressants bring a possibility of greater reduction in symptoms in the short term, in addition to reducing more severe cases of depression in the long term. Even so, considerable improvement would not be a reality for most patients with depression.

“The drug has a greater effect on a group of patients. This is interesting and relatively expected because we see that there are many patients who do not respond or respond partially to treatment”, says Feijó, a professor at Unifesp.

The point opens the debate on which patients and clinical factors are on the list in which the use of antidepressants brings the best benefits. In the study itself, the issue is pointed out as one that needs to be further investigated.

Feijó believes that this point is an indication that treatment with antidepressants is already positive for patients, but that it needs to improve. “It’s better to have the treatment than not because it already helps a lot, but it still has a lot to evolve”, he says.

Scientists also write that it is necessary to look more carefully at the relationship between benefits and risks arising from the use of antidepressants. Since a minority share of drug users would have a significant gain, the research suggests that the analysis of risks associated with drugs need to be better explored by patients and doctors.

For Dunker, this is related to a trend in medicine to seek greater precision in treatments. In addition, the idea that the response to medication differs depending on the patient concerns the perspective that depression is a disease with different causes and presentations. Consequently, the clinical picture would also have different ways of being treated.

“This idea that [o cérebro] it would be an organ like another that reacts more or less the same to the same substance”, says the professor.

Gattaz says that it is common for patients to benefit more from antidepressants compared to others. He explains that studies are already looking for biomarkers that can predict what the response of patients to drugs would be like in order to have greater accuracy in the treatment.

“There is no doubt of antidepressants’ effectiveness in treating depression, as well as preventing new relapses. This study confirms this effectiveness, which is naturally not for all patients. A subgroup of patients does not respond adequately to conventional treatments,” he says .

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