The first new schizophrenia drug target in 70 years

That approach controls hallucinations and delusions for many patients but does little for the flattened emotion and withdrawal that also define the illness, and it causes stiffness and weight gain. KarXT combines two older drugs to act on a different class of receptor entirely, avoiding dopamine blockade altogether.

In the EMERGENT-2 trial, 252 adults with schizophrenia took KarXT or placebo for five weeks. Psychosis symptom scores fell significantly more on the drug, with meaningful improvement in negative symptoms like social withdrawal as well, an effect coming from the muscarinic receptors it targets rather than dopamine.

KarXT pairs xanomeline, a muscarinic agonist developed decades ago, with trospium, an older drug that blocks xanomeline's side effects outside the brain, letting a higher dose reach the brain safely. The result, approved by the FDA in 2024 under the name Cobenfy, is the first new mechanism for treating psychosis since the 1950s, though long-term data on how it compares with dopamine blockers over years is still being gathered.

A new way to quiet psychosis.