We rank chlorpromazine D tier. Its side-effect profile is genuinely awful (histamine, alpha-1 and muscarinic effects plus EPS and a high risk of tardive dyskinesia), and it gives little D2 blockade until doses that are intolerable, so outpatients do not stay on it.
Our take
It is genuinely an awful medication in terms of side effects, and you do not get much D2 blockade until higher doses, where the side effects are intolerable. Having been tested in children is no reason to be comfortable giving it to them.
“I hate that child psychiatrists are so comfortable around here giving this to children because it's been tested because it's genuinely an awful medication in terms of side profile. Okay. And you don't even get that much D2 blockade until you get to higher doses where it has intolerable side effects”
1:05:41Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026
Side effects and safety
It hits the HAM receptors, so it brings histamine, alpha-1 and muscarinic problems. It counts as first generation because it also causes EPS, and it carries a high risk of tardive dyskinesia.
“because chlorpromazine does hit the ham receptors. So it does have histaminergic alpha-1 and muscarinic problems. The reason why we call it first-gen is because it does also cause EPS. It does cause high risk of tardive dyskinesia”
1:07:36Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 We cannot recall keeping anyone on it as an outpatient, or any patient keeping themselves on it. It is just so poorly tolerated.
“I don't think I've ever kept anyone on chlorpromazine as outpatient, to be honest with you. And I don't think any of my patients have ever kept themselves on chlorpromazine as outpatient either. It's just so poorly tolerated”
1:07:00Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026
It also comes up on
- AntipsychoticsHaloperidol and risperidone are one-to-one in chlorpromazine equivalents, yet risperidone stops at 8 mg while haloperidol gets pushed to very high heights. Dosed like risperidone, haloperidol is much better tolerated, though some people do need high doses.
- HaloperidolHaloperidol and risperidone are one to one in chlorpromazine equivalents for D2 blockade. Nobody starts risperidone at 5 mg or takes it past 8, yet haloperidol is routinely started at 5 mg and pushed to very high doses.
- RisperidoneRisperidone and haloperidol are roughly one to one in chlorpromazine equivalents for D2 blockade. No one starts risperidone at 5 mg, and we dose it only up to 8 mg, yet haloperidol is routinely started at 5 mg and pushed to very high doses.
- Treatment-resistant schizophreniaIt means two failed antipsychotic trials, each for an adequate time (typically about six weeks) and at an adequate dose (600 chlorpromazine, or Thorazine, equivalents).
- AntipsychoticsTo switch, start the new agent first to test tolerability, then slowly come down on the old one by chlorpromazine equivalents.
- ClozapineTreatment-resistant schizophrenia means two failed antipsychotic trials, each for an adequate time (typically about six weeks) at an adequate dose (about 600 chlorpromazine equivalents).
From these episodes
- Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 · 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.