Will New Antipsychotics for Schizophrenia Be Game Changers?

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  • While ulotaront performed poorly in recent Phase 3 trials, KarXT is expected to receive FDA approval.

However, while clozapine itself is also strongly anticholinergic, one of its major metabolites is an M1 muscarinic agonist, so it’s possible that clozapine’s superior efficacy could be related to cholinergic stimulation.

A Game Changer?

With ulotaront “stalled in the water” at the moment, it’s anticipated that KarXT will be the first antipsychotic medication approved by the FDA that finally breaks the “5-HT2, D2, me too” mold. It’s impossible to predict just how much of a game changer KarXT will be, but its novel mechanism of action and its demonstrated efficacy across all symptom domains of schizophrenia (positive, negative, and cognitive) is certainly reason for at least cautious enthusiasm.

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I’m waiting to see whether the two studies will be replicated in which autoantibodies to NRXN1 (study) and NCAM1 (study) were found in patients with schizophrenia, in 2% and in 5% of patients respectively. If they are replicated, an opportunity will open to find non-antipsychotic therapies acting to suppress these autoantibodies.

That would be just great. That means possible precision treatment for about 7% of patients (take or leave some % points, because the studies were small).

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Karxt has tons of side effects as well, dry mouth is like 8 vs 4% I think

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The side effect profile of KarXT is much better than that of conventional ones. I prefer to have a dry mouth than a disproportionate increase in weight and cholesterol, blood sugar, etc.
And if it is confirmed that KarXT does not produce demotivation and apathy like current antipsychotics, it will be a true revolution.

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