Akathisia is a big reason people cannot stay on an antipsychotic, and the weight-sparing drugs, lurasidone above all and aripiprazole close behind, carry the most risk. Outpatients often hide it, so ask; plan ahead with PRN benztropine and use propranolol for the long term.
Which drugs cause it
The antipsychotics that cause less weight gain tend to be pretty bad for akathisia. Lurasidone is definitely number one and aripiprazole is up there. If lurasidone 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 Also said in 1 more episode
“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 Newer, mood-helping, weight-light antipsychotics still need watching for akathisia. It is very uncomfortable and a big reason people cannot take the medication.
“Just because your medication is newer, helps with mood, and doesn't cause so much weight gain, well, watch out for akathisia. It's a big reason why people can't take the med well. It's very uncomfortable”
1:03:14Psychosis: History, Delusions, Diagnosis, Theories, and Modern CareNov 2024 Choosing an antipsychotic is often a trade: sleepy, heavier and full of metabolic syndrome, or more tardive dyskinesia and more akathisia.
“You ask yourself, Do I want to be sleepy, fat, and full of metabolic syndrome? Or do I want to be developing more targeted dyskinesia and having more akathisia”
7:05Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026
Spotting it
Outpatient akathisia is largely subjective, something the patient feels, and they can suppress it, especially in the visit with you.
“Largely, in my experience, outpatient akathisia is subjective. It's something that the patient feels. They can suppress it, especially in the encounter with you”
32:17Detecting Subtle Signs of Psychosis: Assessment of Voices, Delusions, and PsychosisFeb 2026
Treating it
Plan ahead. If a patient has a history of akathisia, even on the less akathisia-prone drugs, or is worried about it, give PRN benztropine: take this if you become restless.
“When patients have told me about history of akathisia, even from the less akathetic medications, or just if the patient is concerned about it, I will give some benztropine, for example, as a PRN. Take this if you become restless”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 Start benztropine at 0.5 mg, one or up to two at a time, and ask the patient to call if they need more than 1 mg a day. Dispense 30 or 60.
“I like to start with a half milligram dose, and I say take one or up to two at a time. Call me if you need more than one milligram of the day and I give 30 or 60, whatever I kind of feel like”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 For the long term, propranolol twice a day is preferred, with effect from as little as 10 mg twice a day. If it is mild, restless-legs-like and only at night, nighttime gabapentin can be quite effective.
“Long term, I do prefer to put people on propranolol. twice a day. You can get effect from as little as 10 milligrams twice a day for akathisia. If the akathisia is more like a restless legs thing that's mild and only at night, gabapentin can be quite effective, nighttime gabapentin”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025
Pitfalls and myths
The same doctors who say never prescribe benztropine will give olanzapine and quetiapine without blinking, and those are already anticholinergic.
“The same doctors who say never prescribe the Benzterpene are also the same ones who will not blink and give Zyprexa and Seroquel, which are themselves already anticholinergic”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025
It also comes up on
- Negative symptomsPerphenazine is surprisingly decent at negative symptoms, with less EPS and akathisia than haloperidol or fluphenazine, a cleaner metabolic profile and minimal weight gain, though still a moderate EPS risk.
- AntipsychoticsIf you give an antipsychotic in bipolar disorder, choose one that works for every phase, such as lurasidone, though it carries the most akathisia.
- AnxietyPropranolol needs some evidence of an upregulated fight-or-flight system. It is used for trauma disorders and for akathisia, being low risk and effective.
- Bipolar depressionIf you are giving an antipsychotic, you want one that works for every phase of bipolar disorder, which naturally points to lurasidone. Unfortunately it probably carries the most akathisia risk of any antipsychotic.
- Metabolic side effectsPick weight-sparing medications when possible. That often trades for a risk of akathisia, or sometimes tardive dyskinesia with a first-generation drug.
- PerphenazineCompared with haloperidol or fluphenazine, the high-potency first-generation drugs, you get less EPS and akathisia, though still a moderate EPS risk. It is a little cleaner metabolically with minimal weight gain, and surprisingly decent for negative symptoms.
- PropranololFor anxiety, look for evidence that the fight-or-flight system is upregulated before using it. We do use it for trauma disorders, and certainly for akathisia, because it is low risk and effective.
From these episodes
- Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 · 2 points
- Detecting Subtle Signs of Psychosis: Assessment of Voices, Delusions, and PsychosisFeb 2026 · 1 point
- Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 · 5 points
- Psychosis: History, Delusions, Diagnosis, Theories, and Modern CareNov 2024 · 1 point
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.