How do you approach treatment-refractory schizophrenia which has not responded to multiple antipsychotic trials including clozapine?  

I would also add that there are now case reports and case series of the ketogenic diet having significant benefits for the treatment of refractory schizophrenia, including some cases of those who had not benefitted from clozapine. The mechanisms of action by which a ketogenic diet improves brain hea...

I have had success using a combination of Clozaril with Invega Sustenna or Abilify Maintena, in the treatment of refractory schizophrenia.

I see a lot of treatment-resistant schizophrenia patients as I work in specialized residential facilities, so basically step-downs from State Hospital. I use a lot of clozapine and Sustenna combo, making sure the clozapine level is not toxic and that the QTC and heart are within normal limits with g...

In desperate cases, lithium, ECT.

A difficult situation. In these cases, I have worked hard to establish a trusting relationship with the patients. It can be fraught, especially due to the inherent paranoia. However, by being respectful of the patient, a cooperative partnership can be forged.

A 3-month trial of a gluten-free diet can help a subset of patients with schizophrenia.

There’s also some evidence for using memantine in combination with clozapine to treat positive symptoms. I’ve seen some clinical benefits from this combination as well.

Sometimes we can't call it treatment refractory unless we max out on clozapine dose. I have seen some patients' levels pushed to 1,200 to see the benefit. If sedation is an issue we can always add fluvoxamine as a CYP1A2 inhibitor and keep the clozapine dose low to accomplish the same benefit. I ha...

While I have no personal experience with this strategy, it's come up a time or two in my reading:Shrestha et al., PMID 33654602

To the extent a certain amount of "refractoriness to treatment" in patients with schizophrenia has to do with failure to comply with treatment, I would most strongly recommend to both psychiatrists and their patients' loved ones the book "I AM NOT SICK - I Don't Need Help! How to Help Someone with M...

There are two possible ways. The one with the most evidence is for an ECT series and the new evidence, particularly for hallucinations in TMS.

Cobenfy is a definite must!