Emerging Treatments in Schizophrenia

Although antipsychotics have been available for almost 70 years and greatly improved outcomes individuals with schizophrenia, all currently options derive their efficacy from blockade of dopaminergic receptors. However, this mechanism action leaves many symptoms unresolved is associated a significant side effect burden. The mechanisms underlying which were initially thought to be related excessive presynaptic dopamine in specific areas the brain, are now understood much more complex involve structural molecular changes throughout brain circuits. Consequently, drug discovery efforts sought new targets search safer effective medications that can improve schizophrenia psychosis, including trace amine–associated receptors (TAARs), muscarinic receptors, serotonergic Positive phase 2 trial results indicating safety TAAR1 agonist ulotaront (SEP-363856) M1/M4 KarXT (xanomeline plus trospium) total, positive, negative patients acute exacerbation serotonin 5-HT2A agonist/antagonist pimavanserin predominant symptom control encouraging. Taken together, these data indicate context ongoing 3 programs may soon access first non–D2 blocking medication, could drastically change treatment landscape who do not fully respond or cannot tolerate antipsychotic agents act via postsynaptic D2 receptor blockade.