3 ms·

This data isn't terribly surprising to me in itself. The promise always seemed much greater for anxiety disorders than for depression, and I honestly believe we

This data isn't terribly surprising to me in itself. The promise always seemed much greater for anxiety disorders than for depression, and I honestly believe we'll never find a pharmacological treatment that significantly outperforms SSRIs when depression is defined as broadly as it is in this trial. Depression is really a wide family of disorders that we don't have very good ways of telling apart yet, but likely work quite differently, along with a very fat tail of somatic conditions that are very commonly misdiagnosed as MDD or some other depression diagnosis. This seriously confuses any attempts at comparing efficacies like this. Anxiety disorders are much better understood and more clearly delineated. And what we see in anxiety land is huge strides being made even just in new forms of therapy. Metacognitive therapy is starting to show real improvement over CBT. Pilot studies with a new form of intensive exposure therapy have shown staggering remission rates of over 70% in severe anxiety disorders like panic disorder(look up the Bergen 4 day treatment). MDMA-assisted therapy for PTSD looks very promising as well. For depression, dissociatives have looked much more promising than psychedelics for a while now.

jdietrich 3y ago
Anxiety disorders do seem to be much more tractable than depressive disorders even with traditional treatment approaches and we seem to be making meaningful progress from many directions. The Bergen papers are absolutely wild - I don't think I've ever seen d > 4 in a real psychiatry paper, nor have I seen people continuing to improve post-treatment at anywhere near that rate; obvious caveats apply regarding generalisability and healthcare economics. https://pubmed.ncbi.nlm.nih.gov/37127598/ https://pubmed.ncbi.nlm.nih.gov/37127598/ https://pubmed.ncbi.nlm.nih.gov/36418989/ https://pubmed.ncbi.nlm.nih.gov/36418989/ https://pubmed.ncbi.nlm.nih.gov/29774005/ https://pubmed.ncbi.nlm.nih.gov/29774005/ I think you're probably right about multiple depressive subtypes that are inadequately differentiated; I think there's a particularly acute problem with the failure to differentiate between short, self-limiting episodes induced by specific life stressors and more durable illness characterised by chronicity and treatment-resistance. The data we've seen regarding elevated inflammatory markers and the associations with severity and chronicity might point towards a meaningful subtype that would benefit from a novel treatment approach, but it's still quite early to say; minocycline has fizzled out as a potential treatment, but the inflammatory pathways are at least worth investigating. https://pubmed.ncbi.nlm.nih.gov/36103181/ https://pubmed.ncbi.nlm.nih.gov/36103181/ PTSD is a bit of a strange one at the moment, because of the active debate about diagnostic criteria and thresholds; I'm somewhat concerned that an increasingly heterogeneous patient group might muddy the waters in research. I'll elide over the debate regarding cPTSD, because there seems to be far more heat than light. I'm not especially excited about MDMA-assisted psychotherapy for PTSD, but only because we've been seeing comparable effect sizes for specialised psychotherapy without MDMA; again, probably not a breakthrough, but potentially beneficial for a subset of patients. (Es)ketamine is clearly very useful in the management of acute depressive crises, although I'm somewhat more sceptical about the general applicability for less acute and less severe depressive illness. If I had to wager, I'd say that the next meaningful advance will probably be novel NMDAR antagonists.

jdietrich 3y ago

Anxiety disorders do seem to be much more tractable than depressive disorders even with traditional treatment approaches and we seem to be making meaningful progress from many directions. The Bergen papers are absolutely wild - I don't think I've ever seen d > 4 in a real psychiatry paper, nor have I seen people continuing to improve post-treatment at anywhere near that rate; obvious caveats apply regarding generalisability and healthcare economics. https://pubmed.ncbi.nlm.nih.gov/37127598/ https://pubmed.ncbi.nlm.nih.gov/37127598/ https://pubmed.ncbi.nlm.nih.gov/36418989/ https://pubmed.ncbi.nlm.nih.gov/36418989/ https://pubmed.ncbi.nlm.nih.gov/29774005/ https://pubmed.ncbi.nlm.nih.gov/29774005/ I think you're probably right about multiple depressive subtypes that are inadequately differentiated; I think there's a particularly acute problem with the failure to differentiate between short, self-limiting episodes induced by specific life stressors and more durable illness characterised by chronicity and treatment-resistance. The data we've seen regarding elevated inflammatory markers and the associations with severity and chronicity might point towards a meaningful subtype that would benefit from a novel treatment approach, but it's still quite early to say; minocycline has fizzled out as a potential treatment, but the inflammatory pathways are at least worth investigating. https://pubmed.ncbi.nlm.nih.gov/36103181/ https://pubmed.ncbi.nlm.nih.gov/36103181/ PTSD is a bit of a strange one at the moment, because of the active debate about diagnostic criteria and thresholds; I'm somewhat concerned that an increasingly heterogeneous patient group might muddy the waters in research. I'll elide over the debate regarding cPTSD, because there seems to be far more heat than light. I'm not especially excited about MDMA-assisted psychotherapy for PTSD, but only because we've been seeing comparable effect sizes for specialised psychotherapy without MDMA; again, probably not a breakthrough, but potentially beneficial for a subset of patients. (Es)ketamine is clearly very useful in the management of acute depressive crises, although I'm somewhat more sceptical about the general applicability for less acute and less severe depressive illness. If I had to wager, I'd say that the next meaningful advance will probably be novel NMDAR antagonists.