On clozapine, constipation is the start of a progression that can end in ileus and bowel obstruction, and obstruction kills more patients than neutropenia does. Start a bowel regimen with the drug and ask every patient about their bowel movements.
Why it matters on clozapine
Deaths from bowel obstruction outnumber deaths from neutropenia, yet the whole REMS infrastructure was built to protect against neutropenia. Bowel obstruction is a real risk.
“there's deaths from bowel obstructions. And there's more deaths in the bowel obstruction than there is from neutropenia. So the whole REM infrastructure was built out to protect patients from neutropenia. But the bowel obstruction is a real thing”
24:00Top 10 Things to Know About ClozapineDec 2025 Constipation, ileus and small bowel obstruction are the same thing: a progression of worsening constipation and its consequences.
“the constipation... the ileus, the small bowel risk, those are all the same thing, just kind of progression of the worsening constipation and having sequelae”
20:15Top 10 Things to Know About ClozapineDec 2025 Clozapine slows transit a lot: a normal time is about 24 hours, and on clozapine it stretches to about 110.
“a normal time for a person is 24 hours. You could feel free to run the experiments yourself. but if you take clozapine it slows things down to 110 hours which is pretty significant”
21:30Top 10 Things to Know About ClozapineDec 2025
Prevention
Start docusate in pretty much every patient you start on clozapine. Some guidelines suggest starting with an osmotic laxative such as polyethylene glycol (Miralax).
“So docusate should pretty much be started on every single patient that you start clozapine. Some guidelines suggest starting with an osmotic laxative like polyethylene glycol, which is Miralax”
22:22Top 10 Things to Know About ClozapineDec 2025 Consider starting a bowel regimen prophylactically, and ask patients whether they are pooping.
“Only other one I'll add is make sure, you know, consider starting a bowel regimen prophylactically and ask the patients if they're pooping”
21:17Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026
It also comes up on
- AmitriptylineA tricyclic is worth it when there is another indication and it is safe for that particular patient (for example, for cardiac reasons, or no constipation): it will help the sleep and you can treat the primary disorder too.
- InsomniaTricyclics help sleep when there is another indication and the patient can safely take one (cardiac status, no constipation), so you treat the primary disorder too. Pregabalin dosed at night is a nice fit when there is genuine neuropathic pain disturbing sleep.
- Tricyclic antidepressantsFor sleep: if you have another indication and the patient can take one safely (cardiac status, no constipation), a TCA will help the sleep while treating the primary disorder.
From these episodes
- Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 · 1 point
- Top 10 Things to Know About ClozapineDec 2025 · 4 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.