are cyp2d6 poor metabolizers 5-10% of people of european ancestry?
“poor metabolizers make up roughly 5-10% of people of European ancestry,”
a host, a psychiatry resident said on PsychEd: Educational Psychiatry Podcast, 2026-09-01, at 05:28. hear it in context →
the episode: PsychEd Shorts 16: CYP Metabolism (at 05:28). we link the show's own page; we do not re-host audio.
first, the part that holds
the band is right. the primary record puts cyp2d6 poor metabolizers in european-ancestry populations squarely inside 5-10%, and fda labels print that exact range.
what we found when we went and looked
we went and looked. two fda-approved labels we read (amitriptyline, perphenazine) say "about 7 to 10% of caucasians" have little or no cyp2d6 activity, and the atomoxetine label says "approximately 7% of a caucasian population are pms". a genotyped us clinical cohort of 104,509 people found 5,987 poor metabolizers, 5.7%, across all ancestries. a 2021 meta-analysis of more than 336,000 subjects in 318 reports lists several european groups above the top of the band: british 12.1%, danish 10.6%, basque 9.7%. so 5-10% holds as a rough aggregate, with the caveat that there is no single european number — loss-of-function alleles are graded across europe, higher in the north and centre, lower in the south.
assertion by assertion
| assertion | verdict | what the record says |
|---|---|---|
| cyp2d6 poor metabolizers make up roughly 5-10% of people of european ancestry | confirmed | fda labels for amitriptyline and perphenazine state "about 7 to 10% of caucasians" are poor metabolizers; the atomoxetine label states "approximately 7% of a caucasian population are pms"; a genotyped cohort of 104,509 us patients found 5.7% poor metabolizers, though that cohort is all-ancestry, not european-specific, and the labels carry no methodology or citation [1][4][5] |
| 10% is the ceiling for european-ancestry populations | undersold | a meta-analysis of >336,000 subjects across 318 reports found "high percentages of cyp2d6 pm ... in the british (12.1%), the danish (10.6%), and basque (french) people (9.7%)" — pooled from individual country studies with differing genotyping panels, so the high values are not a single uniform estimate [2] |
| one 5-10% band describes european ancestry as a whole | overstated | a systematic analysis of 82,791 healthy individuals from 79 publications across 31 european countries found the no-function alleles cyp2d6*4 and *5 graded geographically, pivoting around 20-25% in northern and central europe and running lower in the south; allele frequency is one step removed from phenotype, so the gradient in predicted poor metabolizers is inferred, not directly reported [2][3] |
| the percentage describes people who measurably metabolize these drugs poorly | unverifiable | the large cohort number is a genotype-predicted phenotype — an activity score assigned from star alleles, not a measured clearance — and the translation tables have been revised over time, so the same genotypes can be binned differently in different years; the label percentages give no method at all [1][4] |
both directions
for the speaker: the range appears verbatim in current fda-approved labeling: "about 7 to 10% of caucasians are so called 'poor metabolizers'" on an amitriptyline label, "7% to 10% of caucasians and a low percentage of asians have little or no activity" on a perphenazine label, and "approximately 7% of a caucasian population are pms" on the atomoxetine label. the largest genotyped cohort we could read, 104,509 us patients, landed at 5.7% poor metabolizers — the bottom of the band. the meta-analysis country estimates for northwestern europe sit at or above the top of it. a reader repeating 5-10% is repeating what the regulator prints.
against: nothing contradicts the band, but two things complicate it. the frequency is graded within europe rather than flat, so a southern european population and a faroese or danish one are not the same draw, and a listener who hears "people of european ancestry" as one bin will be wrong in both directions. and the band's provenance is thin: the label sentences cite no study, and the figures that do come from large datasets are genotype-predicted phenotypes, so the number depends on which activity-score table was in force when the study was run. the 5-10% framing also carries no information about intermediate metabolizers, who are far more common — 10.7% in the 104,509-person cohort — and who are the group most often collapsed into "normal" in casual retellings.
what this cannot say
genotype-predicted phenotype is not measured enzyme activity; star-allele panels miss rare and structural variants, and activity-score cut-offs have been revised, so the same person can be binned differently across studies and years. "european ancestry" is a crude container, and us clinical cohorts record self-reported race, not ancestry. the meta-analysis country figures are pooled from studies with different genotyping panels and sampling frames, which inflates spread. drug interactions can convert a genotypic normal metabolizer into a functional poor one, which no prevalence figure captures. our own limit: two of the sources we most wanted — the cpic-based worldwide genotype-to-phenotype paper and a nature-hosted analysis — would not open to automated fetching, so this check rests on what we could actually read, and we did not find a european-ancestry-specific pooled genotype estimate in a source we could open.
sources, each one fetched and read
- Del Tredici AL, Malhotra A, Dedek M, Espin F, Roach D, Zhu G, Voland J, Moreno TA. Frequency of CYP2D6 alleles including structural variants in the United States. Frontiers in Pharmacology, 2018. doi:10.3389/fphar.2018.00305 What we read there: "Among the 104,509 patients, 2,329 (2.2%) were predicted to be ultrarapid metabolizers (UMs), 85,021 (81.4%) normal metabolizers (NMs), 11,172 (10.7%) intermediate metabolizers (IMs), and 5,987 (5.7%) poor metabolizers (PMs)" Fetched 2026-10-12 (HTTP 200). https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00305/full
- Koopmans AB, Braakman MH, Vinkers DJ, Hoek HW, van Harten PN. Meta-analysis of probability estimates of worldwide variation of CYP2D6 and CYP2C19. Translational Psychiatry, 2021. PMC7904867 What we read there: "High percentages of CYP2D6 PM were found in Europeans, for example, in the British (12.1%), the Danish (10.6%), and Basque (French) people (9.7%)"; the meta-analysis covers ">336,000 subjects, 318 reports" Fetched 2026-10-12 (HTTP 200). https://pmc.ncbi.nlm.nih.gov/articles/PMC7904867/
- Petrović J, Pešić V, Lauschke VM. Frequencies of clinically important CYP2C19 and CYP2D6 alleles are graded across Europe. European Journal of Human Genetics, 2019. PMC6906321 What we read there: "we systematically analyzed the frequency distribution of clinically relevant CYP2C19 and CYP2D6 alleles across Europe based on data from 82,791 healthy individuals extracted from 79 original publications"; the no-function alleles CYP2D6*4 and *5 show highest frequencies in northern and central europe, pivoting around 20-25%, and substantially lower frequencies in southern europe Fetched 2026-10-12 (HTTP 200). https://pmc.ncbi.nlm.nih.gov/articles/PMC6906321/
- FDA-approved label, amitriptyline hydrochloride tablet, film coated (Accord Healthcare Inc.), PRECAUTIONS, "Drugs Metabolized by P450 2D6", via DailyMed What we read there: "about 7 to 10% of Caucasians are so called 'poor metabolizers'" Fetched 2026-10-12 (HTTP 200). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e6d2c80-fbc8-444e-bdd3-6a91fe1b95bd
- FDA-approved label, atomoxetine, laboratory tests section, retrieved via the openFDA drug label API, 2026 What we read there: "Approximately 7% of a Caucasian population are PMs." Fetched 2026-10-12 (HTTP 200). https://api.fda.gov/drug/label.json?search=openfda.generic_name:"atomoxetine"+AND+clinical_pharmacology:"poor metabolizers"&limit=1
speakers are described by role, not named. one sentence is quoted under fair use, with attribution and a link to the original at the timestamp; we do not re-host audio or video. nothing on this page is a reason to start, stop or change a medication. if you have the file behind anything marked unverifiable, the research board is where people can answer. adam