Clozapine+'3rd-gen' antipsychotic augmentation refractory conditions, with positive and negative symptoms, definitely require a lot of provider guidance and contact. Optimization of doses and time on medication, review of the situation/ outside consults.
I mean the newer ones include cariprazine (as you mentioned), brexpiprazole, (lurasidone 2010). Efficacy is not as high as clozapine generally but tolerability is better.
Still could be an antipsychotic trial-and-error of agents she hasn't been on. Amisulpride. Paliperidone or asenapine, olanzapine, etc...
Lumateperone got approved in December in the USA and should be available later this year. Vaguely new class with some changes on typical targets. 5-ht2a antagonist, d2 mixed agonist/antagonist on pre vs postsynaptic, d1 aff, SRI.
Sometimes clozapine can exacerbate OCD, so that can be a factor for providers to evaluate with your friend.
That's getting to be (or at) the stage you start to consider ECT, depending on severity and lack of response to pharmacological agents and outpatient therapy. (I had evals for ECT and was set up for it, but ended up doing rTMS. rTMS doesn't have the evidence base or efficacy of ECT.)
Multiple other augments, depends on what she has tried. Memantine for negative symptoms. Valproic acid/ sodium valproate. Lithium. ADs.
More experimental you have minocycline (which disappointed in some trials), glycine supplementation (not new, which may interfere with clozapine), sarcosine (glycine transporter inhibitor), sodium benzoate (food preservative and now d-amino acid oxidase inhibitor), NAC, others. But any of that would require close contact and monitoring for potential interference, from her treatment team.
Pimavanserin for some hallucinations. 5-ht2a inverse agonist.
It can be tough, man, when you see someone you care about suffering and you can't seem to help them or see them get worse. Keep up with your friend but give some space for yourself in terms of what you can actually do. Advocate respectfully if possible.
Best of luck .
