Non-smokers had twice the clozapine and olanzapine level per milligram; seven cigarettes a day gave the full effect
In 73 patients in Norwegian nursing homes, the concentration-to-dose ratio of clozapine and olanzapine was twice as high in non-smokers as in smokers. Smoking 7 to 12 cigarettes a day induced metabolism as much as 20 or more.
Weak or heavily disputed. Treat as a question, not an answer. how we score evidence
Caveat on this rating: Small naturalistic sample from nursing homes; the clozapine concentration difference (50%) did not reach conventional significance (p=0.058) although the ratio difference did.
The clozapine label says tobacco smoke lowers the level. This is a measurement of how much, in patients living ordinary lives rather than volunteers.
Significant findings
Haslemo and colleagues (European Journal of Clinical Pharmacology, 2006) recorded smoking habits, doses and serum concentrations in 73 patients with schizophrenia in psychiatric nursing homes: 33 on clozapine and 40 on olanzapine. "Fifty-nine patients (80%) were smokers".
"While the mean ratio was twice as high in non-smokers compared to smokers for both drugs (p<0.01), the C/D ratios of clozapine and olanzapine were not significantly different between the subgroups of smokers (p >0.15). Absolute serum concentrations were also higher in non-smokers compared to smokers: 50% for clozapine (p=0.058) and 67% for olanzapine (p<0.01)."
The practical conclusions: "A daily consumption of 7-12 cigarettes is probably sufficient for maximum induction of clozapine and olanzapine metabolism. A 50% lower starting dose of both drugs in non-smokers seems rational to avoid side effects."
Worth asking
The mechanism is the tar, not the nicotine: the hydrocarbons in smoke induce the liver enzyme CYP1A2, so nicotine patches and gum do not keep the level down when someone quits. That means the interaction runs backwards when a person on clozapine or olanzapine stops smoking, and the level can roughly double over a week or two. If that is you, the question is whether a blood level is booked and whether the dose will be reviewed rather than left where it was when you smoked.
Source
The effect of variable cigarette consumption on the interaction with clozapine and olanzapine — Haslemo T, Eikeseth PH, Tanum L, Molden E, Refsum H (2006)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1007/s00228-006-0209-9
DOI: 10.1007/s00228-006-0209-9
How this was scored
- Study design
- Cross-sectional study / survey
- Funding
- Funding not disclosed
- Published in
- Reputable peer-reviewed journal
- Sample size
- 73
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "contested". Weak or heavily disputed. Treat as a question, not an answer. It scores 39 out of 100 on our published rubric. One caveat travels with that badge: Small naturalistic sample from nursing homes; the clozapine concentration difference (50%) did not reach conventional significance (p=0.058) although the ratio difference did. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
The effect of variable cigarette consumption on the interaction with clozapine and olanzapine — Haslemo T, Eikeseth PH, Tanum L, Molden E, Refsum H (2006). Published in: Reputable peer-reviewed journal. DOI: 10.1007/s00228-006-0209-9. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Cross-sectional study / survey. Funding: Funding not disclosed. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.