Lurasidone is S tier for us: metabolically clean, covering every phase of bipolar disorder, and by its action it should work in mania even though it was never tested there. Its costs are probably the highest akathisia risk of any antipsychotic and a 350-calorie food requirement, which rules it out for patients whose appetite swings with their illness.
When we reach for it
In bipolar disorder we want an antipsychotic that works for every phase, so lurasidone is the natural choice.
“if I'm going to give you an antipsychotic, I want it to work for every phase of the bipolar disorder. So naturally, that's Latuda. Unfortunately, Latuda has The most akathisia risk, that's the restlessness of every antipsychotic, probably”
37:01The Best Bipolar Medication Review From The Best Bipolar ExpertJan 2025 It is a really great medication, especially in bipolar. It was only studied in bipolar depression and never tested in acute mania, likely because it was sold as the bipolar depression drug; given how it acts, it makes no sense that it would work in acute schizophrenia but not acute mania.
“The truth is, it's a really great medication, especially in bipolar. It just was never tested in acute mania”
46:37Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 Also said in 1 more episode
“it does not make any sense that based on the drug action that Latuda would work on acute schizophrenia, but not acute mania. Okay. I think they wanted to sell Latuda as the bipolar depression med. And so they only studied it on bipolar depression”
45:50The Best Bipolar Medication Review From The Best Bipolar ExpertJan 2025 Our acute mania combination is lithium, lurasidone and gabapentin. Lurasidone works quickly and at low doses; lithium is the most effective long term.
“It's lithium. Okay. And... It's latuda, and then it's gabapentin. And why? Because I find latuda to be effective quickly and at low doses. Lithium is most effective long-term”
44:48The Best Bipolar Medication Review From The Best Bipolar ExpertJan 2025
Dosing and titration
Food, food, food, and dinnertime. It does not absorb without at least 350 calories, or the patient gets half the dose, and it seems better tolerated once at night. You do need to talk to patients about this.
“needs to be taken with 350 calories or else the patient will get half the dose. It is something you actually do need to talk to patients about”
46:53Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 Also said in 1 more episode
“Latuda. Food, food, food. And dinnertime, dinnertime, dinnertime, okay? uh it's not going to absorb without that at least 350 calories and it seems to be based on the research and clinical experience uh better tolerate if you take it once at night”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 The antipsychotics you need to take with food tend to end in -done, and ziprasidone is another one. The main drawback is the 500-calorie absorption requirement, which not everyone can routinely meet, up to twice a day.
“And the main drawback is actually the 500 calorie absorption requirement that not everyone can routinely do that up to twice a day, which you might need on zaprazodone compared to the trazodone”
48:58Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 Also said in 1 more episode
“The ones you need to take with food tend to end with Doan. So Ziprasidone is another one you really need to take with food”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025
Side effects and safety
It has the highest akathisia risk of the antipsychotics, with aripiprazole also up there. The drugs that cause less weight gain tend to be the bad ones for akathisia.
“The medications I do favor that cause less weight gain do tend to be pretty bad for akathisia, and that is Latuda and Abilify. Latuda is definitely number one and Abilify is up there in terms of akathisia risk”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 It is metabolically pretty clean: minimal weight gain, minimal QTc prolongation and low prolactin. Along with ziprasidone, it is probably the best second-generation choice for avoiding weight gain.
“It is metabolically pretty clean. I have had patients who have been on it and have had minimal weight gain. Minimal QTC prolongation, low prolactin”
47:00Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 Also said in 1 more episode
“After that, Latuda, Geodon are probably the best ones to go to in terms of not having much weight gain. and second generation. Vraylar, relatively new. I have not seen much weight gain on that either”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 It seems to cause less of the cognitive dulling we see with a lot of other antipsychotics.
“But I do see it does have less of that cognitive dulling that I see with a lot of the other antipsychotics”
47:49Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 At least one study shows relative safety in pregnancy. Other antipsychotics generally accepted in pregnancy include haloperidol, olanzapine and quetiapine.
“there's at least one study showing relative safety in pregnancy. So that's a nice thing to have with trazodone. While we're on it, I believe other ones that are generally accepted in pregnancy that you can see here on the board include Haldol, Olanzapine, and Quetiapine”
47:56Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026
Compared with others
It has the highest risk of akathisia, but if it does not cause horrible akathisia, it is a great medication.
“if it doesn't cause you horrible akathisia, and it is the highest risk for that, if it doesn't cause that, then it's a great medication”
45:04Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026
Pitfalls
It is a no-go for anyone whose appetite fluctuates with their mood disorder or psychosis: they will intermittently decompensate whenever they start eating less dinner.
“if you have anybody who gets fluctuating appetite because of their mood disorder or psychosis, then it becomes a no go because they're just going to intermittently decompensate if they start eating less dinner”
45:59Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026
From these episodes
- Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 · 8 points
- Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 · 4 points
- The Best Bipolar Medication Review From The Best Bipolar ExpertJan 2025 · 3 points
Every point above is something said on the Psychofarm podcast, with the words as spoken and a link to the moment in the episode. It is education, not medical advice, and an episode reflects what we thought when we recorded it.