New Drugs, New Mechanisms, and New Uses-View Presentation

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Video Summary

The video features two expert psychiatrists discussing recent advances in pharmacologic treatments for schizophrenia, depression, PTSD, and related disorders. Dr. Steven Marder focuses on novel antipsychotics for schizophrenia, highlighting the advent of drugs that do not primarily block dopamine D2 receptors, thus reducing common side effects like weight gain, neurological issues, and diminished reward experience. He emphasizes xenomaline traspium, a first muscarinic receptor-targeting antipsychotic now available, which shows promise for both positive and negative symptoms but carries initial gastrointestinal side effects. Other emerging drugs discussed include ulodurant (TAR1 agonist), roluperidone (targeting serotonin and sigma receptors), brilaroxazine (partial dopamine agonist), and N-methyl amisulpride, all of which may offer improvements over traditional treatments. For treatment-resistant schizophrenia, evenamide, targeting glutamate regulation, is highlighted as a promising adjunct.<br /><br />Dr. Kristol discusses breakthroughs in antidepressant therapies, emphasizing glutamate synaptic abnormalities in depression, such as reduced synaptic density and impaired glutamate homeostasis. He details ketamine and esketamine as rapid-acting antidepressants capable of promoting synaptic regrowth and shows that their effects surpass traditional SSRIs in speed and efficacy, including reducing relapse and mortality rates. Coverage includes psychedelics like psilocybin, their neuroplastic effects, and efforts to develop non-hallucinogenic 'neuroplastogens.' He mentions ongoing studies on drugs targeting synaptic homeostasis and anti-anhedonic agents like kappa-opioid receptor antagonists and anti-inflammatory treatments. Integration of pharmacologic and psychotherapeutic approaches is stressed for optimized outcomes.<br /><br />Overall, the presentations underscore a paradigm shift toward targeting diverse neurobiological mechanisms beyond classic monoamine systems, offering hope for improved efficacy, tolerability, and symptom domains in serious mental illnesses.

Keywords

schizophrenia pharmacologic treatments

novel antipsychotics

dopamine D2 receptor

xenomaline traspium

ulodurant TAR1 agonist

roluperidone serotonin sigma receptors

brilaroxazine partial dopamine agonist

N-methyl amisulpride

evenamide glutamate regulation

ketamine esketamine antidepressants

psilocybin neuroplasticity

kappa-opioid receptor antagonists