Quetiapine

Limits on what this shows

• Key negative/null findings: None located specific to quetiapine and mitochondrial Complex I; no counter-study was found reporting no change.
• At-risk subgroups: Not established in humans; cannot be extrapolated from a single rodent brain-tissue study.
• Counter-evidence on record: None found directly contradicting this specific finding; the broader oxidative-stress literature below (protective direction) is a related but distinct measurement.

Regulatory status

Not a labeled effect; the FDA label does not mention mitochondrial function.

Population evidence

Ji et al. 2009 (J Proteome Res, PMID 19441803): rat cerebral cortex and hippocampal mitochondria were profiled by quantitative proteomics after treatment with chlorpromazine, clozapine, or quetiapine versus control. Fourteen proteins changed significantly; six belonged to the respiratory electron transport chain, including the Complex I (NADH dehydrogenase) subunits Ndufa10, Ndufv2, and Ndufs3. Findings were confirmed by quantitative real-time PCR and Western blot. This is animal data only; no quetiapine-specific human mitochondrial-function study was located.

Mechanism

Direct alteration of Complex I subunit protein expression in brain mitochondria (Step 2 mechanism D/E: cofactor antagonism / mitochondrial interference). The abstract retrieved did not specify the direction (up- or down-regulation) of each subunit change, so this is reported as "altered," not as a confirmed decrease.

Framing caution

Single animal study, brain tissue only, direction of change not fully resolved. Should not be read as evidence of clinically meaningful mitochondrial toxicity in patients.

Counter-evidence held on record

Shares its underlying source with the ATP production entry below; see the overlap map.

Limits on what this shows

• Key negative/null findings: Han et al. 2015 explicitly found the protective effect in brain tissue did not extend to liver tissue in the same ethanol model, an important boundary: the antioxidant signal is tissue- and insult-specific, not systemic.
• At-risk subgroups: Not established; all evidence is animal/cell-model, under superimposed toxic or disease stress, not baseline healthy physiology.
• Counter-evidence on record: No quetiapine-specific study was found showing it increases oxidative stress. This review could not complete a search for human oxidative-stress biomarker data in quetiapine-treated patients before the literature-database tools became rate-limited; that is a genuine gap in this pass, not a claim that no such human data could exist.

Regulatory status

Not a labeled effect either direction.

Population evidence

Multiple quetiapine-specific animal/cell studies, identified by title and confirmed as quetiapine-administered from the PubMed listing itself (full abstracts not individually re-verified beyond title/journal/PMID due to a mid-session rate-limit, disclosed below): quetiapine attenuated cadmium neurotoxicity via reduced oxidative stress (Althagafy et al. 2024, Mol Biol Rep, PMID 38750264); moderated doxorubicin-induced cognitive deficits via oxidative-stress reduction (Mani & Alshammeri 2023, Int J Mol Sci, PMID 37511284); improved oxidative balance in chronically stressed rats (Grolli et al. 2023, Naunyn Schmiedebergs Arch Pharmacol, PMID 36735044); mitigated ethanol-induced brain (not liver) oxidative stress (Han et al. 2015, Neuropsychiatr Dis Treat, PMID 26109862); showed an anti-oxidative-stress mechanism relevant to Alzheimer's disease models (Xu et al. 2008, FEBS J, PMID 18554300); and reduced hippocampal oxidative stress in phencyclidine (He et al. 2018, Neuroreport, PMID 30036204) and transgenic Alzheimer's mouse models (Luo et al. 2014, Neuroreport, PMID 24642954).

Mechanism

Not a single named biochemical mechanism; across these studies quetiapine consistently lowers markers of oxidative damage (e.g., malondialdehyde, reactive oxygen species) in tissue already under toxic or pathological stress, consistent with described antioxidant/free-radical-scavenging chemistry attributed to quetiapine and its metabolites in some of this literature.

Framing caution

This is a reverse-direction, apparently protective finding, not a depletion risk. It should never be read as license to skip antioxidant-relevant monitoring, and it does not establish that quetiapine raises systemic antioxidant capacity in humans at baseline; every supporting study used quetiapine against a specific toxic or pathological insult.

Limits on what this shows

• Why no grade: Both conditions for ungraded were met: no Tier B or Tier C evidence supports even a yellow grade, and no circulating consumer claim was found to rebut as white.

Channels tried

PubMed search-listing page for "quetiapine copper" (10 results reviewed by title); Drugs.com quetiapine side-effects page checked directly for any nutrient-depletion mention.

What happened

All ten PubMed hits were either (a) studies using cuprizone, a copper-chelating neurotoxin used purely as an experimental demyelination-model reagent, in which quetiapine was tested as a potential protective agent against cuprizone's own toxicity, not as a cause of copper depletion in patients; or (b) case reports and reviews of Wilson's disease (a genetic copper-overload disorder) in which quetiapine was used to manage the patient's neuropsychiatric symptoms, not evidence that quetiapine itself alters copper metabolism. Drugs.com's side-effects listing contained no nutrient-depletion mentions of any kind for quetiapine.

Assessment

Genuine literature gap, not a tooling failure. The searches returned real, relevant-looking results that on inspection do not support a copper claim; this is a clean negative, not a blocked or empty query.

Limits on what this shows

• Why no grade: Both conditions for ungraded were met: no Tier B or Tier C evidence supports even a yellow grade, and no circulating consumer claim was found to rebut as white.

Channels tried

PubMed search-listing pages for "quetiapine iron status" (zero results) and "quetiapine AND iron" (9 results, reviewed by title/journal/PMID); Drugs.com side-effects page checked directly.

What happened

The nine results were dominated by the reverse relationship: baseline iron deficiency as a risk factor that worsens antipsychotic-induced extrapyramidal symptoms and restless-legs-type movement effects (case reports specifically involving amisulpride, ziprasidone, and olanzapine, not quetiapine, plus a class-level review), which per this project's rules is a nutrient-affecting-drug-response interaction, not a drug-caused depletion, and is largely not even quetiapine-specific. One additional result, Altschuler & Kast 2005 (Med Hypotheses, PMID 15893120), is a hypothesis-only paper proposing that H1-antihistamine antipsychotics (quetiapine named as an example) might improve anemia of chronic disease via interleukin-6 suppression; it proposes no primary quetiapine data and does not meet the Tier B bar (mechanistic study using this medication) or Tier C bar (class-level study) as written, since it tests nothing empirically. No study measuring quetiapine's effect on serum iron, ferritin, or transferrin saturation was located.

Assessment

Genuine literature gap for a depletion claim, not a tooling failure; the searches completed cleanly. The one hypothesis-level, reverse-direction, protective idea found is noted for completeness but does not clear the bar for any color grade.

Limits on what this shows

• Key negative/null findings: Not established; the baseline butyrate-producer deficit is a disease-vs-control finding, not a quetiapine-specific null result, and no contradicting sub-finding was located in the text retrieved.
• At-risk subgroups: Not established.
• Counter-evidence on record: None retrieved.

Regulatory status

Not addressed in the FDA label.

Population evidence

Hu et al. 2019 (PMID 31380217): a human cohort study explicitly stated, per its own PubMed listing description, to "characterize the gut microbiota in depressed patients with bipolar disorder compared with healthy controls, to examine the effects of quetiapine treatment on the microbiota." Lai et al. 2022 (Psychiatry Research, PMID 34896845): a metagenomic follow-on analysis in the same disease area, involving 62 patients receiving one month of quetiapine treatment, examining gut bacterial signatures for diagnosis and treatment-outcome prediction. Both confirm quetiapine specifically as the studied exposure in a human cohort, which is what was verifiable from the search-listing record retrieved.

Mechanism

Partially confirmed on follow-up (Step 2 category G, microbiome disruption): an OpenAlex per-PMID lookup for Hu et al. 2019 (PMID 31380217) recovered a partial abstract stating that untreated bipolar-depression patients had lower levels of butyrate-producing bacteria than healthy controls, and that "following quetiapine monotherapy, microbial markers changed notably," with a random-forest model reaching AUC 0.81 (untreated vs. control) and 0.93 (treatment responders vs. nonresponders). The genus-level direction of the quetiapine-associated changes was not stated in the retrieved text. The Lai et al. 2022 (PMID 34896845) abstract still could not be retrieved (OpenAlex returned no stored abstract for this record).

Framing caution

Graded yellow on the strength of confirmed study existence, drug-specific human cohort, and now a partial abstract, still not a confirmed effect size. Tooling disclosure: PubMed's individual abstract pages and the Europe PMC REST API remained unreachable for these two PMIDs on this follow-up pass (empty content and HTTP 429 respectively), but OpenAlex's per-PMID endpoint (https://api.openalex.org/works/pmid/{id}) returned a usable partial abstract for Hu et al. 2019, illustrating why this channel is worth trying first under sustained rate-limiting. Because the quetiapine-associated taxa-level direction is still not stated for either study, and the Lai et al. 2022 abstract remains unretrieved, this entry stays yellow rather than advancing to orange; a future pass should try OpenAlex, Europe PMC, or the publisher page directly for PMID 34896845, and, for PMID 31380217, look for the genus-level table in the full text rather than the abstract alone.

Limits on what this shows

• Key negative/null findings: None located specific to quetiapine and ATP synthase.
• At-risk subgroups: Not established in humans.
• Counter-evidence on record: None found; no human ATP-production or cellular-energy study in quetiapine-treated patients was located this session.

Regulatory status

Not a labeled effect.

Population evidence

Ji et al. 2009 (J Proteome Res, PMID 19441803), the same rat brain mitochondrial proteomics study described under Mitochondrial burden, identified the mitochondrial F1F0 ATP synthase beta subunit (Atp5b) among the proteins with significantly changed expression after quetiapine treatment, alongside vacuolar ATPase subunits Atp6v1b2 and Atp6v1a1 (the latter two are not mitochondrial ATP synthase and are noted here for completeness, not counted as ATP-production evidence). Animal, brain-tissue-only data; no human ATP-production study was located.

Mechanism

Direct alteration of ATP synthase subunit protein expression in brain mitochondria; direction of change not specified in the retrieved abstract text.

Framing caution

Single animal study, brain tissue only, direction not confirmed. Reported as a distinct entry from Mitochondrial burden per the project's rule against merging them, but they rest on the same single source; see the overlap map.

Limits on what this shows

• Key negative/null findings: None located; no cohort, pharmacovigilance, or clinical-trial study quantifying hemoglobin or hematocrit change across a quetiapine-treated population was found, only individual case reports.
• At-risk subgroups: A pediatric patient in one report; not otherwise established beyond the individual cases described.
• Counter-evidence on record: None directly rebutting these reports. The FDA label's silence on anemia is not counter-evidence; it reflects that these are rare, idiosyncratic case reports rather than a labeled adverse-reaction frequency category.

Regulatory status

Not a labeled effect. The DailyMed SPL was re-checked specifically for anemia, hemolytic anemia, hemoglobin, and hematocrit language this session; none was found. The label documents leukopenia, neutropenia, and agranulocytosis, which are white-cell/immune findings and are tracked in the monitoring panel, not this category.

Population evidence

Three quetiapine-specific case reports, located via dedicated PubMed search-listing queries for "quetiapine hemoglobin," "quetiapine hematocrit," "quetiapine anemia," and "quetiapine red blood cell," with abstract text recovered through OpenAlex's per-PMID lookup endpoint after PubMed's individual abstract pages and the Europe PMC REST API both remained blocked (bot-check and HTTP 429 respectively). Arıcı et al. 2018 (PMID 30466224) report what they describe as the first documented pediatric case of quetiapine-induced autoimmune hemolytic anemia, with quetiapine as the sole implicated antipsychotic. Nair & Lippmann 2005 (Psychosomatics, PMID 15765830) report "Blood Dyscrasia With Quetiapine and Ziprasidone," describing drug-induced macrocytic anemia; two antipsychotics are named, so quetiapine is not isolated in this report. Zhong & Zhou 2026 (PMID 42052532) describe hemolytic anemia emerging 48 hours after a combined quetiapine-and-aripiprazole overdose in a patient with metastatic breast cancer, treated with plasma exchange and washed red-cell transfusion; overdose, drug combination, and underlying malignancy all confound attribution to quetiapine alone in this report.

Mechanism

Not established at a population level. Autoimmune/immune-mediated hemolysis is the mechanism named in the pediatric case; no confirmed marrow mechanism was retrievable for the macrocytic-anemia report, and no dose-response or rechallenge data were located for any of the three.

Framing caution

Three case reports, one combined with another antipsychotic and one occurring in a massive-overdose, drug-combination, and cancer setting, are not proof quetiapine reliably lowers hemoglobin or hematocrit at therapeutic doses. This is a rare, idiosyncratic-hemolysis signal worth clinical awareness, not a general oxygen-delivery-depletion risk, and does not by itself justify CBC monitoring beyond what the monitoring panel already recommends for the drug's labeled white-cell effects.