Consider metabolic risk first when you choose an antipsychotic: a weight-gaining drug, especially in a young person, puts them on a highway to diabetes, high cholesterol and heart disease. The pines (olanzapine, clozapine, quetiapine) are the worst, and even the lighter drugs like aripiprazole can still cause weight gain.
Why it comes first
Please consider metabolic side effects first when you pick an antipsychotic, rather than only what works. Try to spare patients the weight gain, cholesterol problems and diabetes.
“So what I would say is that please, please consider first the metabolic side effects when you pick your antipsychotics. Rather than what works or what doesn't, try to spare your patients the weight gain, cholesterol problems, diabetes”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 A metabolically heavy antipsychotic, especially in a young person, puts them on a highway to diabetes, high cholesterol, heart disease and over-sedation, all with long-term morbidity and mortality. Do not keep someone on one without thinking about and trying other options.
“if you use an antipsychotic that causes a lot of metabolic side effects, especially in a young person, you are putting them on a metabolic highway to eventually develop all kinds of morbidity and mortality risk from diabetes and high cholesterol”
4:55Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 Also said in 1 more episode
“If you keep your patients on a weight gain, second generation or first generation, without thinking and trying other things, at least you are putting them on a highway to heart disease, diabetes, and over sedation in the long term”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 Pick weight-sparing medications when possible. That often trades for a risk of akathisia, or sometimes tardive dyskinesia with a first-generation drug.
“I think it's super important to pick weight sparing medications when possible. Yes, that trades often for risk of akathisia. or maybe sometimes even risk of tardive dyskinesia if you're picking a first generation”
31:29Detecting Subtle Signs of Psychosis: Assessment of Voices, Delusions, and PsychosisFeb 2026
Compared with others
The pines (olanzapine, clozapine, quetiapine) are by far the most metabolic medications we have. The dones vary more, with risperidone in the middle.
“the pines are, which they were thinking, olanzapine, clozapine, quetiapine, by far the most metabolic medications we have. Then the dones have more variants. Risperidone in the middle”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 Clozapine and olanzapine are probably the two worst for weight gain and metabolic risk, and it is more significant in non-white patients. It is very reasonable to start metformin from day one.
“clozapine and olanzapine are probably the two worst drugs we have in regards to metabolic risk in terms of weight gain. It's more significant in non-white patients. It's very reasonable to start metformin from day one”
30:03Top 10 Things to Know About ClozapineDec 2025 We draw the line at aripiprazole: it still causes some weight gain, but less than most, and we do not want to try anything heavier unless we really have to.
“So you can see there, I kind of draw the line starting with Abilify. Abilify, while still having his weight gain, reasonably less of the proportion than most people. But you can see I'm pretty aggressive. I do not want to try anything above Abilify unless I really have to”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025
Talking to patients
Do not tell a patient starting aripiprazole they will not gain weight because it is on the lower end. You will run into problems, and they will stop trusting you.
“And don't tell patients if you're starting Abilify that they're not going to have weight gain because it's on the lower end. You will run into problems. Your patient will not trust you”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025
It also comes up on
- HaloperidolThe trade-off is plain: sleepy, heavier and full of metabolic syndrome on other drugs, or more tardive dyskinesia and akathisia on this one.
- AkathisiaChoosing an antipsychotic is often a trade: sleepy, heavier and full of metabolic syndrome, or more tardive dyskinesia and more akathisia.
- Tardive dyskinesiaChoosing an antipsychotic is often a trade: sleepy, heavier and full of metabolic syndrome, or more tardive dyskinesia and more akathisia.
From these episodes
- Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 · 1 point
- Detecting Subtle Signs of Psychosis: Assessment of Voices, Delusions, and PsychosisFeb 2026 · 1 point
- Top 10 Things to Know About ClozapineDec 2025 · 1 point
- Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 · 5 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.