How would you decide between escalation to clozapine vs xanomeline-tropsium (Cobenfy) for treatment-resistant schizophrenia?

Clozapine is the only agent FDA approved for treatment-resistant schizophrenia (TRS) as well as suicidality associated with schizophrenia or schizoaffective disorder. Clozapine has also robust anti-hostility and anti-aggressive effects as established in double-blind randomized clinical trials, inclu...

For treatment-resistant schizophrenia, Cobenfy would be a logical step. Cobenfy does not have potent and few persistent side effects, so a trial is not as difficult to use in TRS as a clozapine trial, with all the serious side effects of clozapine. But, one would have to move systematically into suc...

Clozaril is a miracle for TRS.

This is a tricky one since clozapine is very anticholinergic.

I would need more information to see if titration is necessary, or if it is, then how to proceed forward.

Recent feedback for Xanomeline-trospium use supports improvement of positive, negative, and cognitive domains with fewer side effects. Add Xanomeline-trospium, begin slow taper of clozapine, and closely monitor signs and symptoms.