Antipsychotics and related add-ons, judged on overall efficacy in schizophrenia and bipolar disorders (not as augmenting agents), accounting for adverse effects. From the Psychofarm podcast, October 2026: 29 ranked, each with the reason and the moment it was said.
It works well and carries almost no metabolic burden. The tradeoff is more movement side effects, which is accepted when the aim is to prevent a seriously bad outcome in severe illness.
The other host said S tier does not mean first line and he would not think of haloperidol before a different medication. The first host does not use it first line either.
“I've selected the first med, and I think it's because it's going to be controversial and there's something to talk about. It's Haldolp. Haldol goes into the S tier. This is really controversial”
Efficacy is closer to B or A, especially for non-schizophrenia conditions, but the weight gain, appetite, diabetes risk and sedation outweigh the benefit. Similar results can be had with other combinations.
The other host sees a real role in bipolar 2 and says it should be considered. The first host still says the benefit is not worth the side effects.
“Let's put it in C tier. Quetiapine goes into C tier. And it is a bit of a shame because I would say that its efficacy is at B or even A tier”
Placed in S as the king of antipsychotics, though weight gain and the monitoring and titration demands would otherwise make it an A. It is also called probably the best antipsychotic and badly underused.
Placed in S by convention. The first host personally rates it A.
“And politically, I have to put Closarill in S tier. I think the world would riot if I didn't do so. Okay. It's really, to me, more of an A tier, and that is because of its weight gain and the monitoring requirements”
Perhaps the most effective antipsychotic of the class and seen as the second best after clozapine, held back only by having the most weight gain. Patients tend to like it and stay on it.
“And this one goes into A tier. If it was not for the fact that it has the most weight gain out of all the antipsychotics in the studies, way more than clozapine”
The weight benefit over olanzapine looks small and still leaves plenty of weight gain. It would sit above olanzapine, but it is on patent and too expensive for the benefit.
“we should go ahead and throw olanzapine samidorphan into B tier. Okay, I am not very impressed with Libalvi. That's the brand name”
It works very well and comes in many forms, with side effects of weight gain, sedation, orthostasis, sexual effects and raised prolactin. Seen as a middle-ground first-line choice.
“we have to rank Risperdal. And Risperdal is solidly A tier. Okay. It works great. It works really, really, really well. And comes in a lot of different forms, right”
As an oral alone it would be B, but the range of formulations, including injectables out to six months, earns it A. It is slightly less potent than risperidone but more predictable between patients.
Placed A because of its injectable forms. As an oral alone it would be B.
“I think I would put it at B tier otherwise, but because it comes in so many different forms and has so much utility, it has to sit up there in A tier with their speridone”
Well tolerated, but not efficacious enough for serious mental illness. It is the top low-dose augmenting agent for depression and can be pushed to higher doses in patients who skip doses.
“Aripiprazole probably has to go in B tier. I probably would have put it into A tier when I was younger, but having tried to use it a lot because of its favorable side effect profile, it's simply not efficacious enough”
Essentially aripiprazole, harder to dose and much more expensive, so there is no practical use case until the price changes.
The other host agreed and said he might feel differently once it is generic.
“Yeah, yeah. Brexpiprazole or Rexulti is essentially Abilify, but harder to dose because it comes in smaller milligram increments, in my opinion, and way more expensive. So I'm going to put it into D tier. Until the price changes, it is in D tier”
Well tolerated with efficacy for bipolar depression, but expensive and on patent, and not very effective for mania and psychosis. It would not rank much higher even if it were cheap.
Named as Periprazine in the transcript.
“Where do you put Periprazine? Give it a B. Give it a B. That's nice. I kind of like Vraylar, Curvies”
An underrated medication that is not as effective as haloperidol or clozapine but works well when akathisia is avoided, with few side effects. It fails in people with erratic eating.
The first host considered S minus because it needs a steady dinner with enough calories. The other host agreed with S.
“Yeah. So let's put Latuda on the board. I'm putting it into S-Class. This, I think, is a very underrated medication. Is it as effective as Haldol and claspine? No”
It works but does little for mood, flattens patients, and the 500 calorie meal requirement is hard to meet. The QTc worry is called clinically insignificant.
Named as Zaprazodone and Giadon in the transcript.
“Zaprazodone. This is Geodon. It works, but doesn't really work for mood. And it has much greater calorie requirement. I'd put it in C tier”
Not an antipsychotic, but it has some D2 blockade at high doses. Placed in D rather than F because it can be a good augmenting agent in schizophrenia spectrum and bipolar disorders.
“Since this is the antipsychotic tier list, I would put it in D tier, but not F tier. I'll explain why in a second. I'll explain why in a second”
A Japanese azapirone derived from buspirone that is effective in schizophrenia. The hosts have not used it, so it was not ranked.
“And then, so for that note, we should add something that I barely know about because it helps us think more about buspirone and maybe someday we'll get it. It's called perospirone. That we're going to put in need more experience”
Underrated, with efficacy between B and A, but many cannot tolerate the taste and numbing of the sublingual form, and its weight gain and sedation make risperidone the usual pick.
Named as Acentipine in the transcript. The other host has not used it.
“Going back to things that work and we have access to. Acentipine. Where should I put that? Probably B-class. Acentipine. B-class”
Single fixed dose, expensive and on patent, and the serotonin reuptake activity is thought to cause agitation and cycling in true bipolar illness. Not seen as very effective for psychosis.
The other host has never used it.
“Let's talk about Kapilida. The manufacturer is going to hate me for this. Put it in the F tier. Oh, boy. This is Lumeteperone”
Presumed to work like the other done drugs. Limited access and no long-acting injectable, and no reason seen to use it over risperidone or paliperidone.
“Now for Eloperidone Fanapt, this unfortunately goes into needs more experience. I have no doubt it works. I have not had really much opportunity to use it because it's not really on formulary in my area”
It works somewhat and has a niche for people who cannot tolerate D2 blockade, but remission was never seen and it is expensive. It probably will not work for most people with psychosis.
“I would throw this one into D class, D as in dog, because it kind of works, but it doesn't work a whole lot”
Would be S except for patients with no bipolar features. Worth adding in a schizophrenia spectrum disorder with any hint of mood problems, before a second antipsychotic.
“Okay. Now for sort of more random stuff. We've done all the big dogs. Let's talk about add a mood stabilizer. This is A class. This is A class”
It works, but is poorly tolerated, and if it works something else will too. Neither host keeps outpatients on it.
Started as C tier, moved to D after the other host argued for it.
“I guess it's almost D tier. Okay, fine. You've talked me into it. Put it in D tier. It's just because I've been reserving D and below for stuff that actually doesn't work”
Seems to work, perhaps at about 60 percent of clozapine's efficacy without the blood draws, but with too many side effects including urinary incontinence and retention.
“So loxapine, loxapine, let's put it in C tier. I feel like there's just some nerds in psychiatry who get super excited by loxapine because the receptor profile is supposedly very similar to clozapine”
One of the forgotten first-generation drugs that are more atypical than people think and worth using more.
Placed together with perphenazine, thioridazine and trifluoperazine as a group.
“These go into A tier, B tier, B tier, sorry, B tier. I'm putting these in the B tier and that's actually because I kind of think we should encourage them to be used a little bit more”
One of the forgotten first-generation drugs that are more atypical than people think and worth using more.
Placed together with perphenazine, thioridazine and trifluoperazine as a group.
“These go into A tier, B tier, B tier, sorry, B tier. I'm putting these in the B tier and that's actually because I kind of think we should encourage them to be used a little bit more”
One of the forgotten first-generation drugs that are more atypical than people think and worth using more.
Placed together with perphenazine, thioridazine and trifluoperazine as a group.
“These go into A tier, B tier, B tier, sorry, B tier. I'm putting these in the B tier and that's actually because I kind of think we should encourage them to be used a little bit more”
Popular and available internationally but not in the United States, so the hosts cannot comment.
“And similarly, AmiSoulPride goes into needs more experience. I believe this is really popular and good and available internationally, but not available in the United States again”
These rankings are the hosts’ and guests’ opinions from one episode, for clinicians and the curious. They are education, not medical advice, and not a guide to choosing a treatment for any one person.
Educational content only. These resources are for education. They are not medical advice and not a substitute for clinical judgment, current guidelines, or individualized patient care.