depression

Individualised dosing of a synthetic inhalable formulation of mebufotenine, a psychedelic substance, led to improvements in depressive symptoms compared with placebo and was well tolerated. These are the results of a phase 2 clinical trial published in the journal JAMA Psychiatry, which includes Spanish participation. According to the authors, this supports its potential as a novel, fast-acting treatment for treatment-resistant depression.

A meta-analysis published in the journal JAMA Psychiatry showed that psychedelic-assisted therapy is no more effective against depression than traditional antidepressants in clinical trials. The research found differences in the use of double-blind methods—that is, when neither the participants nor the researchers know which treatment each group is receiving—which minimises subjective influences on the results. Double-blinding made a difference in the case of traditional drugs, but not in the case of psychedelics, confirming that these trials are, in practice, always open-label.

The study of psychedelic drugs in pharmacological treatments had its eureka moment with chemist Albert Hofmann's famous bike ride under the influence of LSD in 1938 and then developed over decades, but with Richard Nixon it was shelved. In recent years, it has resurfaced in hospitals and laboratories around the world. Last week, the Congress of Deputies hosted a conference on these substances. We explain what they are, what they are used for, the current state of research, and their risks, with the help of expert sources.

Dimethyltryptamine (DMT) is responsible for the psychedelic effects of ayahuasca. According to the results of a phase IIa clinical trial published in Nature Medicine, this molecule improved depressive symptoms in adults with depression after one dose. The trial included 34 people, 17 of whom received intravenous DMT. This second group showed greater improvements in depressive symptoms than the control group. After two weeks, in the second part of the trial, DMT was administered to all participants and the antidepressant effects lasted for three months. Adverse effects were mainly pain at the injection site, nausea and transient anxiety.

High academic pressure during adolescence is linked to increased rates of depressive symptoms and self-harm, which can persist into early adulthood. This finding, published in The Lancet Child & Adolescent Health, was observed in a sample of nearly 5,000 young people born in England (UK) in 1991 and 1992. Academic pressure was measured when participants were 15 years old, mental health was assessed repeatedly between ages 16 and 22, and self-harm was tracked up to age 24. While the association with depressive symptoms was observed up to age 22, it was strongest at 16. Regarding self-harm, each one-point increase in academic pressure was associated with an 8 % higher likelihood of engaging in self-injurious behavior.

Physical exercise of any kind shows similar benefits to psychological therapy for the treatment of depression in adults. This is one of the conclusions of a new systematic review by the Cochrane Collaboration based on data from almost 5,000 people, which is the latest update of a review first published in 2008. With regard to antidepressants, the research shows a similar effect, but the evidence is somewhat more limited. The authors point to the lack of robustness in terms of long-term treatment with physical exercise. 

A meta-analysis published in The Lancet Psychiatry journal concludes that the most effective way to discontinue antidepressant treatment in people with remitting depression is to gradually reduce the dose in combination with psychological therapy. Furthermore, this strategy proved to be just as effective in preventing relapses into depression as continuing medication. The study was based on data from more than 17,000 adults with depression and anxiety in remission, although the evidence for the latter disorder was not as robust. 

A new article published in eClinicalMedicine measures mental health problems in the Gaza Strip among the population over 40 years of age before and after the genocide committed by Israel. The study indicates that the proportion of these adults experiencing high levels of distress has tripled in the last five years, with a peak following the escalation of the massacre since October 2023. It was already known that chronic stress factors affecting victims pose a serious threat to mental health, but no longitudinal study had yet been conducted comparing distress in the same individuals before and after the genocide.  

Different antidepressant drugs cause different side effects in the body, in parameters such as heart rate, blood pressure or body weight, according to a meta-analysis published by The Lancet. For example, agomelatine administration is associated with weight loss, while other molecules such as maprotiline are associated with weight gain. The research brings together 151 studies and 17 reports from the US Food and Drug Administration (FDA), including more than 58,000 people and comparing 30 antidepressant drugs with a placebo.

Large language models—artificial intelligence systems based on deep learning—could be useful in detecting mental health risks such as depression and suicide risk in narrative tests of patients undergoing psychiatric treatment. This is one of the conclusions of research published in JAMA Network Open, which also shows the potential of embeddings — a natural language processing technique that converts human language into mathematical vectors — to achieve the same end.