Disease: treatment-resistant depression (TRD)

Molecular Mechanisms of Emerging Antidepressant Strategies: From Ketamine to Neuromodulation

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Depression is a serious mental health condition affecting over 300 million people worldwide, with many patients not responding well to standard antidepressants. This review examines both traditional antidepressants like SSRIs and exciting new treatments including ketamine and psilocybin, as well as brain stimulation techniques. The key finding is that different treatments work through similar mechanisms—all ultimately enhancing brain cell connections and reducing inflammation—suggesting that combining different approaches might work better than single therapies.

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Antidepressant Switching as a Proxy Phenotype for Drug Nonresponse: Investigating Clinical, Demographic, and Genetic Characteristics

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This study examined why some people don’t respond well to common antidepressant medications called SSRIs. Researchers used prescription records from over 38,000 people to identify those who switched to different antidepressants as a sign of poor response. They found that people with higher education and income were less likely to switch medications, and that genetic factors influenced who responded poorly to treatment. The research demonstrates that switching medications can serve as a reliable marker for identifying nonresponders, potentially helping doctors personalize antidepressant prescribing in the future.

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How to account for hallucinations in the interpretation of the antidepressant effects of psychedelics: a translational framework

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Psychedelic drugs like LSD and psilocybin show promise in treating depression with effects lasting months after single doses. However, scientists debate whether the hallucinations and mystical experiences these drugs produce are necessary for their healing effects. This review proposes a framework to test whether lower doses without hallucinations might still provide antidepressant benefits, similar to how anesthesia-administered ketamine works without the patient’s awareness.

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Synthesis and bioactivity of psilocybin analogues containing a stable carbon–phosphorus bond

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Researchers created new chemical versions of psilocybin (the active compound in magic mushrooms) that cannot be broken down by the body’s natural enzymes in the same way. They tested these new compounds to see if they could help with depression and anxiety by targeting specific brain receptors. The best compound worked well on the intended brain receptors but importantly showed less activity on a heart-related receptor, potentially making it safer than natural psilocybin.

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Attitudes toward psychedelics and psychedelic-assisted psychotherapy among Australian mental healthcare providers

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Australian doctors and mental health professionals have positive views about using psychedelics like psilocybin and MDMA to treat depression and trauma, which were recently approved by regulators. However, many still have safety concerns and gaps in their knowledge, particularly psychiatrists. Most doctors learn about psychedelics from podcasts and websites rather than formal training. The study recommends that professional organizations provide better education to prepare healthcare workers for this new treatment approach.

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A Review of the Food and Drug Administration Pipeline and Proposed California Legislation on Medicinal Psychedelics

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Psychedelic compounds like psilocybin and ketamine show promise in treating serious mental health conditions including PTSD and depression. The FDA carefully evaluates these drugs through multi-phase clinical trials to ensure they are safe and effective. While California has proposed making psychedelics more widely available through legislation, the FDA’s thorough approval process provides important protections by identifying potential risks and ensuring proper medical oversight.

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The association between diverse psychological protocols and the efficacy of psilocybin-assisted therapy for clinical depressive symptoms: a Bayesian meta-analysis

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This research examined how different types of psychological support during psilocybin treatment affect depression outcomes. Researchers analyzed 10 clinical trials involving 515 patients with depression. They found that whether therapists used structured manuals or flexible approaches, or whether therapy was directive or non-directive, the depression improvement from psilocybin treatment was similar across all approaches.

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