Correctly identifying patients who do not respond to antidepressant drugs – about 30% of the total – and finding effective treatment strategies: this is the goal of the new guidelines on depression published in recent days on Molecular Psychiatry. “An important step to arrive at a definition based on homogeneous and comparable clinical data, and to give hope to these patients”, explains Luca Sforzini, psychiatrist and young researcher at King’s College London, first signatory of the article. “Especially in psychiatry many definitions have so far been taken by convention, today the focus is on precision medicine”.
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The initiative is part of the EU-PEARL European project, “born to validate new research methods, the so-called platform trials, the method used for COVID vaccines, which allows you to simultaneously compare different drugs and obtain results in shorter times “, remember Carmine Pariante, a professor of psychiatry at King’s College, who led the study. “In this case, the goal is to give a univocal definition of patients resistant or partially resistant to treatments, which helps researchers to identify the biological markers underlying these resistances, and the specialists to define an effective therapeutic strategy”.
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The new guidelines
The new guidelines propose to define resistant to therapy those patients who have not obtained results with at least two treatments – possibly carried out at different times and with active ingredients with different mechanisms of action – and partially responsive when they have obtained a modest but unsatisfactory improvement with at least one drug. Noting that these results should be quantified with objective methods, such as evaluation scales still little used today, not only at the clinical level: the study shows that only one third of the researches examined used the criteria required to select homogeneous patients, and not always the difference between non-responding and partially responding patients, who may require different therapeutic strategies, is highlighted.
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What the patients say
Sometimes the criteria for defining non-compliance with drugs are not solid, they are based on vague indications – “I took that drug and it did nothing to me” – “without considering clinical evidence that clarifies the duration of treatment, dosages and adherence to therapy, or even the fact that perhaps the patient paid less attention to the symptoms on which the drug had an effect ”, notes Pariante. And not to mention that patients and doctors can evaluate the symptoms and their severity differently, also considering that antidepressants are not easy to manage drugs, “because they take at least fifteen days to take effect, while the side effects can manifest themselves earlier” , observes Sforzini.
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The Delphi method
The Delphi method was used to define the new guidelines, “used to reach a consensus when there is no clear scientific data,” explains Sforzini. In this case, more than sixty experts from different countries, doctors, researchers, representatives of regulatory bodies and pharmaceutical companies were involved, also involving a patient who would report her experience, “precisely because it is important to understand, beyond the clinical scales , how people really feel, ”observes the researcher.
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The new guidelines could help identify the biological causes of drug resistance, working on a homogeneous group of patients, and give a scientific basis to the algorithms that design the therapeutic path. Today we generally start with an SSRI, a serotonin reuptake inhibitor, “if the drugs of this family do not work, a tricyclic is used, while the monoxidase inhibitors are now little used because they are difficult to manage”, explains Pariante, “But there are also other drugs, anxiolytics or low-dose antipsychotics, lithium and other active ingredients such as ketamine, while at an experimental level we are beginning to study the effectiveness of anti-inflammatories”. “Without forgetting psychotherapy, whose effectiveness is recognized today especially in the less severe forms, and transcranial magnetic stimulation”, concludes Sforzini.
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