schizophrenia negative type
Schizophrenia trials have been revitalized by the approval of muscarinic receptor agonists (xanomeline-trospium/KarXT) — the first non-dopaminergic antipsychotic approved in decades — validating a long-hypothesized cholinergic mechanism and opening new mechanistic territory. Negative symptom treatment and cognitive impairment associated with schizophrenia (CIAS) remain critical unmet needs with no approved therapies.
Active trials investigate M1/M4 muscarinic agonists, trace amine-associated receptor 1 (TAAR1) agonists (ulotaront), glycine transporter inhibitors, cognitive remediation combined with pharmacotherapy, and long-acting injectable formulations to improve adherence. PANSS total score and negative symptom subscales are standard primary endpoints.