Skip to main content
MyDeficiencies

Thiothixene

Thioxanthene antipsychotic

Also sold as Navane.

Analyze another medication Medication directory

Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Thiothixene has no classical depletion machinery of the kind seen with diuretics, anticonvulsant enzyme inducers, or acid-suppressing drugs. It is rapidly and well absorbed with no documented food, mineral, or antacid interaction; it is extensively metabolized hepatically and eliminated mainly in feces via biliary excretion rather than renally; and it is a substrate, not an inducer or inhibitor, of hepatic drug-metabolizing enzymes (the one named enzyme-induction interaction on the label runs in the opposite direction, with carbamazepine increasing thiothixene's own clearance). The classical nutrient mechanism screen (absorption interference, enzyme induction, renal wasting, cofactor antagonism, dilutional/hormonal disturbance, changed intake, increased utilization) returns no evidenced, drug-specific classical vitamin or mineral finding beyond a labeled increase in appetite and weight, which does not by itself point to any single nutrient and is not graded here.

Thioxanthene antipsychotic · ATC N05AF04 · also sold as Navane (discontinued; generic available) · reviewed 2026-10-02. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Thiothixene in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low
Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden, Complex I inhibition (in vitro, mechanistic)

Yellow — Low

See study details

Thiothixene directly inhibits Complex I of the mitochondrial electron transport chain in isolated rat brain mitochondria; a second, independent in vitro study separately found thiothixene disrupts normal respiratory control in isolated mitochondria. Both are drug-specific, both are preclinical, and neither has been replicated in a human clinical sample.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key negative/null findings: No human clinical study was located measuring mitochondrial function directly in thiothixene-treated patients; the Burkhardt platelet-activity finding is described at the neuroleptic-class level, not confirmed as thiothixene-specific in the retrievable abstract.
  • At-risk subgroups: None established clinically; theoretical concern would be greatest with high cumulative dose/duration, by analogy to the extrapyramidal-symptom literature these in vitro findings were originally proposed to explain.
  • Counter-evidence on record: None located suggesting thiothixene spares Complex I or mitochondrial respiration; both available drug-specific studies point the same direction.

Regulatory status

Not mentioned in the FDA label or DailyMed labeling; this is not a labeled adverse effect.

Population evidence

Burkhardt et al. 1993 (Ann Neurol): in vitro rat brain mitochondria; haloperidol, chlorpromazine, and thiothixene inhibited Complex I; clozapine inhibited at higher concentrations. A companion observation reported reduced platelet Complex I activity in neuroleptic-treated patients comparable to idiopathic Parkinson's disease, though the drug-level breakdown of that patient-platelet arm is not specified in the available abstract. Soberón et al. 1976 (Rev Esp Fisiol): isolated mitochondria exposed to thiothixene and thioridazine; both drugs stimulated state 3 and state 4 respiration and produced a complete loss of respiratory control, with only minor change to oxidative phosphorylation.

Mechanism

Direct inhibition of NADH:ubiquinone oxidoreductase (Complex I); separately, uncoupling-type loss of respiratory control in isolated mitochondria. Named and drug-specific, not inferred from class.

Counter-evidence held on record

This is preclinical, in vitro evidence from isolated animal mitochondria, not a measured clinical deficiency or a validated functional marker in patients. It does not establish that thiothixene causes clinically meaningful mitochondrial disease in humans, and it is not a basis for any supplement or antioxidant recommendation.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress, mechanistic inference from Complex I inhibition (not directly measured)

Yellow — Low

See study details

No study has directly measured an oxidative-stress biomarker (malondialdehyde, superoxide dismutase, glutathione, or similar) in thiothixene-exposed tissue or patients. This entry is graded yellow on mechanistic inference only: Complex I inhibition is a well-established site of electron leak and reactive-oxygen-species generation in mitochondrial biochemistry generally, and thiothixene is independently documented to inhibit Complex I (see Mitochondrial burden).

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key negative/null findings: None available; this is the category's central evidence gap, not a null result. No drug-specific or confirmed thioxanthene-class oxidative-marker study was successfully opened during this review.
  • At-risk subgroups: None established clinically.
  • Counter-evidence on record: None located; also none confirming the inference, since the one potentially relevant drug-specific record could not be verified.

Regulatory status

Not mentioned in the FDA label or DailyMed labeling.

Population evidence

No direct oxidative-stress biomarker study for thiothixene was located. A title-matching record, "The Effect of Thiothixene Antipsychotic Drug on Serum Lipid Peroxidation Level in Rat," was found via web search but could not be opened for cohort or methods verification after repeated attempts (ResearchGate returned HTTP 429 on two direct fetches; Semantic Scholar's paper-search API and the Crossref bibliographic-search API each returned HTTP 429/proxy rate-limit rejections on separate attempts). Per this protocol's rule against citing a source that was not opened, that record is disclosed here but is not used to support this grade.

Mechanism

Inferred, not measured: inhibition of Complex I is a canonical driver of electron leak to oxygen, generating superoxide, in general mitochondrial biochemistry. The inference chain (thiothixene inhibits Complex I → Complex I inhibition is linked to increased ROS generation in general) is explicit and is not presented as a direct finding.

Counter-evidence held on record

This is the weakest-evidenced yellow entry in this dossier: an inference from a drug-specific mitochondrial finding to a downstream redox effect that has not itself been measured for thiothixene. It should not be read as equivalent in strength to a directly measured oxidative marker, and it is not a basis for antioxidant supplementation.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Copper

Not graded — disclosed evidence gap

See study details

No evidence at any tier was located linking thiothixene, or a defensible thioxanthene-class member, to copper status, and no circulating consumer claim exists to rebut.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B/C evidence located, and no circulating claim found to grade white instead. Channels tried: web search for "thiothixene copper ceruloplasmin" and related phrasings (clean zero result, generic copper-biology pages only, nothing drug-related); web search for phenothiazine/thioxanthene class plus serum copper/zinc in schizophrenia (blocked before completion by this session's web-search quota, not a content result); the FDA label and DailyMed labeling (no mention of copper); OpenAlex works-search API for antipsychotic/phenothiazine/copper phrasings (HTTP 429 rate-limit block on repeated attempts); Europe PMC REST search API (HTTP 429/proxy rate-limit block); Crossref works-search API (HTTP 429/proxy rate-limit block). The rate-limit pattern matches this project's documented org-level network restriction on these channels. This should be read as an unresolved gap, genuinely searched but not fully tooling-clear, and flagged for re-check in a future revision rather than a confirmed absence of literature.

Iron

Not graded — disclosed evidence gap

See study details

No evidence at any tier was located linking thiothixene, or a defensible thioxanthene-class member, to iron status, hemoglobin, or ferritin, and no circulating consumer claim exists to rebut.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B/C evidence located, and no circulating claim found to grade white instead. Channels tried: web search for "thiothixene iron OR anemia OR hematologic" (clean zero result; the only hematologic label finding, leukopenia/leukocytosis, is a white-cell effect, not iron/red-cell related, and "hemolytic anemia" on the label is explicitly attributed to "other antipsychotic drugs," not thiothixene, so it does not support a thiothixene-specific grade); a planned web search on antipsychotic-induced akathisia and iron deficiency/ferritin could not be run because this session's web-search quota was exhausted before reaching it; OpenAlex works-search API for the same query (HTTP 429 rate-limit block); Europe PMC REST search API (HTTP 429/proxy rate-limit block). As with Copper, this is an unresolved gap with a genuine search attempt behind it, not a confirmed absence of literature, and should be re-checked when these channels are reachable.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk, thioxanthene-class antibacterial activity (class extrapolation)

Yellow — Low

Evidence: class extrapolation

Thiothixene itself has not been tested for antimicrobial or gut-dysbiotic effects. Two other thioxanthene-class antipsychotics, flupentixol and zuclopenthixol/clopenthixol, show measurable antibacterial activity against Gram-positive, Gram-negative, and in one case mycobacterial organisms in a 2025 systematic review, passing the cohort test for class extrapolation because the cited cohort includes defensible thioxanthene-class members, not merely "typical antipsychotics" in general.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow, class extrapolation

Limits on what this shows

  • Key negative/null findings: No data located, positive or negative, for thiothixene itself; this is the explicit gap this extrapolation is substituting for.
  • At-risk subgroups: None established for thiothixene specifically.
  • Counter-evidence on record: None located for thiothixene; no study reports thiothixene as microbiome-neutral either.

Regulatory status

Not mentioned in the FDA label.

Population evidence

McDonagh, Murray, Hallahan, Miliotis, 2025, Journal of Psychiatric Research: systematic review of off-target antimicrobial/microbiome-disrupting effects of antipsychotics. Thioxanthene members named: clopenthixol/zuclopenthixol (high antibacterial activity against Gram-positive, Gram-negative organisms and M. tuberculosis), flupentixol (broad antibacterial activity; synergy with colistin against A. baumannii). Phenothiazine members (chlorpromazine, thioridazine, fluphenazine, trifluoperazine, perphenazine, levomepromazine) and the butyrophenone haloperidol are also named in the same review but are chemically more distant from the thioxanthene scaffold and are not the basis for this extrapolation.

Mechanism

Lipophilic, cationic amphiphilic tricyclic/tricyclic-adjacent structure disrupting bacterial membranes, proposed as a shared mechanism across phenothiazine and thioxanthene antipsychotics generally; not confirmed for thiothixene specifically.

Counter-evidence held on record

This is class-level evidence from other thioxanthenes, not a thiothixene-specific finding, and is labeled as such per Hard Rule 6. It does not establish that thiothixene itself disrupts the gut microbiome, and it is not a basis for probiotic supplementation. This source is very likely shared with sibling phenothiazine dossiers in this same project batch (see Overlap map) and should not be double-counted as independent confirmation across drugs.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

ATP production, Complex I-linked synthesis capacity (in vitro, mechanistic)

Yellow — Low

See study details

The same two thiothixene-specific in vitro mitochondrial studies that support the Mitochondrial burden entry bear directly on ATP synthesis capacity: Complex I inhibition constrains the proton-motive force that drives ATP synthase, and the Soberón finding of lost respiratory control describes mitochondria consuming oxygen inefficiently relative to ATP yield (a classic uncoupling signature).

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key negative/null findings: Soberón et al. explicitly reported only "minor changes" to oxidative phosphorylation itself, a genuine partial-null result that bounds how large this effect is, and no study has measured cellular ATP concentration directly in thiothixene-exposed tissue.
  • At-risk subgroups: None established clinically.
  • Counter-evidence on record: The "only minor changes to oxidative phosphorylation" finding itself is a partial counter-weight against assuming a large functional ATP deficit; it is reported here rather than omitted.

Regulatory status

Not mentioned in the FDA label or DailyMed labeling.

Population evidence

Burkhardt et al. 1993 (Ann Neurol): thiothixene-induced Complex I inhibition in isolated rat brain mitochondria. Soberón et al. 1976 (Rev Esp Fisiol): thiothixene-stimulated state 3/4 respiration with loss of respiratory control and only minor change in oxidative phosphorylation, an uncoupling-type pattern in which oxygen consumption rises without a matched ATP yield.

Mechanism

Complex I is the entry point of the electron transport chain feeding oxidative phosphorylation; its inhibition, combined with loss of respiratory control, is mechanistically consistent with reduced ATP-synthesis efficiency per unit of oxygen consumed.

Counter-evidence held on record

This entry shares its underlying studies with Mitochondrial burden and with Oxygen delivery/utilization below (see Overlap map); it is not three independent confirmations of the same effect, and it is not a basis for CoQ10, creatine, or other energy-support supplementation.

Oxygen delivery/utilization, cellular oxygen-consumption efficiency (in vitro, mechanistic)

Yellow — Low

See study details

In isolated mitochondria, thiothixene increases oxygen consumption (state 3 and state 4 respiration both rise) while respiratory control is lost, meaning oxygen is consumed less efficiently relative to ATP output. This is a cellular oxygen-utilization finding, separate from hemoglobin, hematocrit, or blood pressure.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key negative/null findings: No change in arterial oxygenation, hemoglobin, or hematocrit is documented for thiothixene anywhere in the label or the literature located for this review.
  • At-risk subgroups: None established clinically.
  • Counter-evidence on record: None located.

Regulatory status

Not mentioned in the FDA label as an oxygen-utilization effect.

Population evidence

Soberón et al. 1976 (Rev Esp Fisiol): isolated mitochondria, thiothixene and thioridazine, increased state 3/4 oxygen consumption with loss of respiratory control.

Mechanism

Mitochondrial uncoupling-type effect on oxygen utilization at the cellular respiration level, named and drug-specific.

Counter-evidence held on record

Mechanism clarification, not a graded finding: thiothixene's labeled cardiovascular effects (tachycardia, hypotension, lightheadedness, syncope) reflect alpha-1 adrenergic blockade, the drug's own incidental pharmacology, and are not an oxygen-delivery nutrient deficiency under Hard Rule 2 of this protocol. Only the mitochondrial oxygen-utilization finding above is graded. This entry shares its source with Mitochondrial burden and ATP production (see Overlap map) and is not independent confirmation of either.

How the body handles this medication

Absorption
Rapidly and well absorbed from the GI tract; peak plasma concentration at 1-3 hours after an oral dose. No food, mineral, or antacid interaction is documented.Drugs.com professional monograph; DailyMed label, setid 81c40311-7dc4-4332-8920-a39a8466aea6
Protein binding
Greater than 99% bound to plasma proteins.Drugs.com professional monograph
Metabolism
Extensive hepatic oxidative first-pass metabolism to thiothixene sulfoxide and N-desmethylthiothixene. No specific CYP450 isoform is named in the current FDA label or the professional monograph; the 2009 FDA label contains no formal Clinical Pharmacology/CYP section, a genuine PK-documentation gap for this older drug, not a tooling failure of this review.Drugs.com professional monograph; FDA label 016584s059, accessdata.fda.gov
Elimination
Eliminated mainly in feces via biliary excretion, as unchanged drug and demethylated/hydroxylated metabolites; not primarily renal. Terminal half-life approximately 34-35 hours; clearance is reduced in women and in patients over 50. Not expected to be removed by hemodialysis or peritoneal dialysis.Drugs.com professional monograph
Enzyme induction, direction of effect
Thiothixene is a substrate, not a documented inducer or inhibitor, of hepatic microsomal enzymes. Hepatic enzyme inducers such as carbamazepine significantly increase thiothixene's own clearance; this is the nutrient-irrelevant drug-affecting-drug direction and is not filed as a depletion.DailyMed label, setid 81c40311-7dc4-4332-8920-a39a8466aea6
Renal/hepatic impairment
No dosage-adjustment guidance for renal or hepatic impairment appears in the current label; no accumulation data are published. Transient, infrequent elevations of serum transaminase and alkaline phosphatase are reported, with no confirmed case of thiothixene-attributable jaundice.DailyMed label, setid 81c40311-7dc4-4332-8920-a39a8466aea6

What the research says is worth watching

General information from the medication label and the studies above. It is not personal medical advice, and any change belongs with your prescriber.

  • Hematology

    Baseline and periodic CBC

    Per the FDA label, patients with a pre-existing low white blood cell count or a history of clinically significant leukopenia/neutropenia should have frequent CBC monitoring during the first months of therapy. This is a labeled safety measure, not a nutrient-deficiency check.

  • Ophthalmologic

    Periodic eye exam with long-term use

    Fine lenticular pigmentation and pigmentary retinopathy have been noted with prolonged thiothixene therapy; periodic ophthalmologic observation is reasonable with extended treatment.

  • Hepatic

    Periodic liver enzymes

    Transient, infrequent elevations in serum transaminase and alkaline phosphatase are documented; periodic monitoring is a reasonable, routine safety measure.

  • Metabolic

    Weight, glucose, lipids

    Increased appetite and weight gain are labeled effects. Routine metabolic monitoring (weight, fasting glucose, lipid panel) follows standard antipsychotic-monitoring practice; this is not a nutrient-deficiency finding.

  • Cardiovascular

    Blood pressure, especially orthostatic

    Tachycardia, hypotension, lightheadedness, and syncope are labeled effects of thiothixene's own alpha-1 adrenergic blockade, more likely when combined with other hypotensive agents. Monitor blood pressure, particularly on standing; this is a pharmacologic effect, not an oxygen-delivery nutrient deficiency.

  • Trace minerals

    No thiothixene-specific protocol

    No evidence base currently supports a thiothixene-specific iron or copper monitoring protocol beyond what standard CBC/anemia workup would already catch if clinically indicated for unrelated reasons.

Overlap map, to prevent double counting

Cross-references where two or more entries in this dossier, or in sibling dossiers in the same project batch, rest on the same underlying source.

  • Mitochondrial burden

    Shares evidence with: ATP production; Oxidative stress; Oxygen delivery/utilization

    Note: All four entries draw on Burkhardt et al. 1993 and/or Soberón et al. 1976. Within this dossier, these are two studies supporting up to four category entries, not four independent lines of confirmation.

  • ATP production

    Shares evidence with: Oxygen delivery/utilization

    Note: Both rest specifically on the Soberón 1976 state 3/4 respiration and respiratory-control-loss finding.

  • Mitochondrial burden (Burkhardt et al. 1993)

    Shares evidence with: Sibling dossiers for chlorpromazine and haloperidol in this project batch

    Note: Burkhardt et al. 1993 tested haloperidol, chlorpromazine, thiothixene, and clozapine in the same in vitro experiment. A reader comparing this dossier to a chlorpromazine or haloperidol dossier in the same series should treat this as one shared source across drugs, not independent confirmation for each.

  • Gut microbiome risk (McDonagh et al. 2025)

    Shares evidence with: Sibling phenothiazine dossiers in this project batch (chlorpromazine, thioridazine, fluphenazine, trifluoperazine, perphenazine, levomepromazine) and haloperidol

    Note: McDonagh et al. 2025 is a systematic review covering many antipsychotics in one paper, including phenothiazine-class drugs in this same batch. The same citation is very likely to recur in those sibling dossiers; it should not be counted as separate confirmation for each drug.

All references used above
  1. Thiothixene Capsules, USP, full prescribing information (DailyMed) — Regulatory label. National Library of Medicine DailyMed, setid 81c40311-7dc4-4332-8920-a39a8466aea6.
  2. NAVANE (thiothixene) Capsules, FDA prescribing information, label 016584s059 — Regulatory label, accessdata.fda.gov. Contains no formal Clinical Pharmacology/CYP section; confirmed gap, not a tooling failure.
  3. Thiothixene, professional monograph — Pharmacokinetic reference (AHFS-derived): absorption, protein binding, metabolism, elimination half-life, route of elimination.
  4. Burkhardt C, Kelly JP, Lim YH, Filley CM, Parker WD Jr. Neuroleptic medications inhibit complex I of the electron transport chain. Ann Neurol. 1993;33(5):512-517. PMID 8098932. — Tier B, in vitro, rat brain mitochondria. Cohort (compounds tested): haloperidol, chlorpromazine, thiothixene, clozapine (at higher concentration). Thiothixene explicitly named; passes the cohort test for this drug directly, no class extrapolation needed for this source.PubMed's own article page for this PMID could not be opened directly; blocked by a bot-verification/CAPTCHA challenge page on repeated attempts. Retrieved instead via OpenAlex's single-record PMID lookup endpoint, which returned title, authors, journal, year, and abstract.
  5. Soberón R, López-Alarcón L, García-Cañero R, López-Martínez M, Gosálvez M. Action of the antipsychotic drugs thiotixene and thioridazine on isolated mitochondria. Rev Esp Fisiol. 1976;32(4):275-279. PMID 1005886. — Tier B, in vitro, isolated mitochondria. Cohort: thiotixene (thiothixene) and thioridazine, named directly. Found stimulated state 3/4 respiration, complete loss of respiratory control, minor change to oxidative phosphorylation.Europe PMC REST lookup for this PMID returned an HTTP 429 rate-limit rejection and was not used; OpenAlex's single-record lookup succeeded instead.
  6. McDonagh F, Murray EK, Hallahan BP, Miliotis G. Systematic examination of off-target effects of antipsychotic medications associated with microbiome disruption and heightened bacterial infection risks. J Psychiatr Res. 2025. PMID 40499249. DOI 10.1016/j.jpsychires.2025.05.046. — Tier C for thiothixene (not in the reviewed cohort). Cohort includes thioxanthene-class members clopenthixol/zuclopenthixol and flupentixol, plus multiple phenothiazines, haloperidol, and several second-generation antipsychotics. Used here strictly as class extrapolation for Gut microbiome risk, labeled as such.
  7. Tiotixene. Wikipedia. — Background/orientation only (structure class, major metabolite name, approximate bioavailability and half-life range); not relied on for any graded claim. Used to cross-check, not substitute for, the professional monograph and FDA label.
  8. WHO Collaborating Centre for Drug Statistics Methodology, ATC/DDD Index, code N05AF — ATC code confirmation: N05AF04 = tiotixene (thiothixene), thioxanthene derivatives.
  9. "The Effect of Thiothixene Antipsychotic Drug on Serum Lipid Peroxidation Level in Rat" (title located, record not opened) — Indexed on ResearchGate under publication id 233799520. Direct relevance to Oxidative stress if verified, but cohort, dose, direction of effect, and full citation could not be confirmed.Not opened and not used to support any grade in this dossier. Two direct WebFetch attempts to the ResearchGate page returned HTTP 429. A Semantic Scholar paper-search API attempt for the same title returned HTTP 429. A Crossref bibliographic-search API attempt returned an HTTP 429/proxy rate-limit rejection. Flagged for re-attempt in a future revision when these channels are reachable.