We rank ziprasidone C tier: it works and is light on weight, but it is flattening and does little for mood. The QTc worry is overblown; the real drawback is that it must be taken with a 500 calorie meal, sometimes twice a day.
Our take
C tier. Quite flattening, lots of dopamine blockade and not much help for mood, but not a bad choice. The QTc prolongation should not scare you: it is basically clinically insignificant.
“Quite flattening. Lots of dopamine blockade. Not much help for mood. But it's not a bad choice. The QTC prolongation should not scare you. It's basically clinically insignificant”
48:38Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026
When we reach for it
Along with lurasidone, it is probably one of the best second-generation choices for avoiding weight gain.
“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 There are studies showing IM ziprasidone works for acute agitation, and some say it is underused there. It seems to calm the patient without flattening them.
“There are studies that it works for acute agitation. And some people say it's underused for acute agitation. So I guess IM suprazodone helps calm the patient without like flattening them”
49:43Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026
Dosing and titration
You really need to take it with food: the main drawback is the 500 calorie absorption requirement, which not everyone can meet routinely. The antipsychotics that need food tend to end in "-done".
“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 At a high enough dose you will not absorb enough with one meal, so you may have to split it twice a day.
“Geodon, if you need a high enough dose, you're not going to absorb enough. in one meal, so you might have to go to BID”
50:06Insomnia and Sleep Medications in PsychiatryDec 2024
From these episodes
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.