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MyDeficiencies

Trimipramine

Tricyclic antidepressant, tertiary amine (dibenzazepine)

Also sold as Surmontil.

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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.

Trimipramine's own FDA label is sparse on classical pharmacokinetic detail (it gives no explicit percentage excreted unchanged, no elimination half-life, and does not name the drug's active metabolite), but what it does say rules out the two mechanisms behind most drug-nutrient depletion claims. Trimipramine is extensively hepatically metabolized - the label's Precautions section discusses it through the lens of cytochrome P450 2D6 (debrisoquin hydroxylase), the polymorphic enzyme shared across tricyclic antidepressants, and a tertiary reference (Drugs.com) adds CYP3A4, CYP2C19, and CYP2C9 as contributing pathways with an active metabolite, desmethyltrimipramine. Nothing in the label or in the literature reachable this session documents trimipramine inducing any CYP enzyme - it is a substrate of CYP2D6, and a single case-report-level source (confirmed by title and bibliographic metadata only, not opened in full this session) indicates it may also inhibit CYP2D6-mediated clearance of a co-administered drug. Either way, the enzyme-induction-driven accelerated-catabolism mechanism (Step 2, mechanism B) that drives real depletion claims for drugs like rifampin or carbamazepine is absent here. The label also states trimipramine capsules are "known to be substantially excreted by the kidney" and to be used "with caution" in hepatic impairment, but no renal-wasting or absorption-interference mechanism for any classical vitamin or mineral is documented anywhere this review could reach.

Tricyclic antidepressant, tertiary amine (dibenzazepine) · ATC N06AA06 · also sold as Surmontil · reviewed 2026-10-01. 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 Trimipramine 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.

What the research found

Sodium / water balance - SIADH-mediated dilutional hyponatremia, bounded and not confirmed at the population level

Orange — Moderate

See study details

Trimipramine's label documents SIADH as a neurological adverse reaction. This is a water-retention disorder, not a dietary sodium deficiency, and a large independent surveillance study that broke trimipramine out individually did not attribute hyponatremia to it specifically.

Full detail, limits and 1 references

What the grade means here: 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. Orange

Limits on what this shows

  • Key negative/null findings: Degner et al. 2004 is recorded here as a genuine counter-finding: a large, trimipramine-specific surveillance dataset that discusses hyponatremia/SIADH in detail did not flag it for trimipramine, attributing it instead to SSRIs and venlafaxine. This is the main reason this entry is bounded to orange rather than red.
  • At-risk subgroups: None quantified specifically for trimipramine in any source reached this session. By analogy to the TCA/antidepressant class generally: elderly patients, early weeks of treatment or after a dose increase, concurrent diuretic use, and renal impairment (which the label separately flags as a trimipramine accumulation risk).
  • Counter-evidence on record: See Key negative/null findings. A targeted pharmacovigilance review of antidepressants and hyponatremia (Rochoy et al. 2018, PMID 29773358) was identified via PubMed but could not be opened this session - the WebFetch proxy returned repeated HTTP 429 responses against pubmed.ncbi.nlm.nih.gov for this specific article page across three attempts spaced by 60-100 second waits. Its findings are not cited as evidentiary support here for that reason.

Regulatory status

FDA label (DailyMed): lists "syndrome of inappropriate ADH (antidiuretic hormone) secretion" under Neurological adverse reactions for trimipramine capsules. No incidence figure, susceptible-subgroup detail, or onset-timing language is given beyond its presence on the list.

Population evidence

Tier A, drug-specific (the label itself, naming trimipramine capsules directly). Degner et al. 2004, German AMSP multicenter drug-surveillance program (n=53,042 antidepressant-treated patients, 1993-2000), broke trimipramine out individually at a 0.6% overall severe-adverse-drug-reaction rate (0.3% probable/definite) - comparable to doxepin (also 0.6%/0.3%) and lower than clomipramine (2.1%/1.0%) or amitriptyline (1.0%/0.6%) in the same cohort. The same study's hyponatremia/SIADH discussion is attributed specifically to SSRIs and to venlafaxine, with mirtazapine explicitly noted to show "no case of significant hyponatremia" - trimipramine and doxepin are not named in that specific discussion.

Mechanism

Named in the broader TCA/antidepressant literature: potentiation of antidiuretic hormone (AVP) release or action. Trimipramine's own label does not elaborate a mechanism beyond listing the adverse reaction.

Counter-evidence held on record

This is a water-retention/dilutional disorder, not a dietary sodium deficiency. Do not recommend sodium or fluid supplementation on this basis - that would be the hazard, not the remedy. Management is fluid restriction and dose reassessment by a prescriber; rapid correction of hyponatremia carries its own serious risk (osmotic demyelination) and must only be undertaken clinically.

Vitamin B2

Yellow — Low

See study details

A 1981 study found the tricyclics chlorpromazine, imipramine, and amitriptyline inhibit riboflavin's conversion to its active coenzyme form in rat tissue; trimipramine - imipramine's own alpha-methyl structural analog - was not itself tested, so this is class extrapolation, not drug-specific evidence.

Full detail, limits and 1 references

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: Trimipramine's absence from the tested cohort is itself the key limitation and is stated here rather than glossed over.
  • At-risk subgroups: Speculative extension to trimipramine users rests on its direct structural relationship to imipramine (positive in this study), not on independent data.
  • Counter-evidence on record: No trimipramine-specific riboflavin study of any kind was located via DailyMed, Drugs.com, Crossref, or the partially-reachable PubMed/Europe PMC channels this session.

Regulatory status

Not addressed in trimipramine's own label.

Population evidence

Tier C, class extrapolation. Pinto, Huang & Rivlin 1981, J Clin Invest 68, PMID 6262379, DOI 10.1172/jci110180 (rat liver, brain, and heart): chronic chlorpromazine at clinically comparable doses produced measurable riboflavin-deficiency markers (elevated erythrocyte glutathione reductase activation coefficient, a validated functional riboflavin-status marker) and reduced tissue flavin levels despite adequate dietary intake; imipramine and amitriptyline also inhibited hepatic flavokinase in the same study. Trimipramine was not among the drugs tested - cohort test explicitly fails for this drug (Hard Rule 6). Imipramine is cited as the closest possible class member: trimipramine is imipramine's own alpha-methyl homolog on the identical dibenzazepine tricyclic ring system.

Mechanism

Named: structural mimicry of riboflavin's isoalloxazine ring by the tricyclic nucleus, competitively inhibiting flavokinase (the riboflavin-to-FMN conversion step).

Counter-evidence held on record

Class extrapolation only, with the target drug confirmed absent from the cited cohort. Do not recommend riboflavin supplementation on this basis alone.

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 - class-extrapolated, directionally mixed across TCA class members; trimipramine itself not tested

Yellow — Low

See study details

Trimipramine's direct chemical parent imipramine shows enhanced liver mitochondrial function in two independent rat/mouse studies, while companion tricyclics clomipramine and desipramine show impaired mitochondrial function in their own drug-specific studies; trimipramine itself was not tested by any of them, so this is class extrapolation in a direction that is genuinely unresolved, not drug-specific evidence.

Full detail, limits and 6 references

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: The Bizerra 2023 concentrations (50-300 µM) are one to two orders of magnitude above typical TCA therapeutic plasma levels (commonly sub-micromolar to low single-digit micromolar), an acute toxicology/overdose-relevant model rather than ordinary therapeutic exposure, stated explicitly rather than left implicit. Villa 2017 found no significant bioenergetic change in light synaptic mitochondria, a real null finding within an otherwise mixed result.
  • At-risk subgroups: None established in humans for any TCA including trimipramine; all four class sources are preclinical (rat, mouse, or human cell line).
  • Counter-evidence on record: The direction reversal itself (imipramine enhancing vs. clomipramine/desipramine impairing) is the central counter-finding, recorded explicitly rather than resolved into a single narrative; see Overlap map for shared sourcing with ATP production below. A 2021 paper (Blaess et al., Lipids Health Dis, DOI 10.1186/s12944-021-01552-3, PMID 34743684, open access) was opened in full this session after a PubMed search for "trimipramine" AND "ATP" surfaced it; it names trimipramine specifically as having "lysosomotropic and photosensitizing" properties, but its ATP/NAD(P)H-depletion discussion concerns localized UV-induced skin-cell effects in a dermatologic hypothesis paper, not a systemic mitochondrial or ATP finding for trimipramine, and is therefore not cited as supporting evidence for this entry. Two further leads, Plenge-Tellechea et al. 1999 ( Arch Biochem Biophys, DOI 10.1006/abbi.1999.1375, PMID 10496985) and Soler et al. 2000 ( J Bioenerg Biomembr, DOI 10.1023/a:1005519312463, PMID 11768746), study TCA inhibition of Ca2+-ATPase in plasma membrane and sarcoplasmic reticulum respectively; PubMed's own search index returns both for "trimipramine" AND "ATP," and one OpenAlex summarization pass reported trimipramine as a keyword, but a second, more detailed OpenAlex concepts query for the same two records did not list trimipramine among the tested compounds (only desipramine, clomipramine, and imipramine appeared), and repeated attempts to open the actual abstracts (PubMed, Semantic Scholar, the publisher pages) were all rate-limited or returned no content this session. Given that direct conflict in the two retrieval passes, trimipramine's inclusion in either study is explicitly unconfirmed and neither is cited as evidence here, consistent with the prohibition on citing a source not actually opened; both are flagged for a future revision once those channels are reachable.

Population evidence

Tier C, class extrapolation, directionally mixed. Enhancing: Katyare SS, Rajan RR, "Enhanced oxidative phosphorylation in rat liver mitochondria following prolonged in vivo treatment with imipramine," Br J Pharmacol 1988;95(3):914-922, PMID 3207998 (rat, 1-2 weeks dosing) found state 3 (ADP-stimulated) respiration increased with all substrates tested, with increased cytochrome aa3 and c+c1 content and no change in mitochondrial yield or protein. Liu X et al., "Imipramine activates FAM3A-FOXA2-CPT2 pathway to ameliorate hepatic steatosis," Metabolism 2022, DOI 10.1016/j.metabol.2022.155292, PMID 35995281 (mouse NAFLD model) found imipramine activated a pathway that increases CPT2, a mitochondrial inner-membrane fatty-acid-oxidation enzyme, consistent in direction with Katyare 1988. Impairing: Bizerra PFV et al., "The harmful acute effects of clomipramine in the rat liver: Impairments in mitochondrial bioenergetics," Toxicology Letters 2023, DOI 10.1016/j.toxlet.2023.05.008 (isolated rat liver mitochondria, clomipramine 50-300 µM, supraphysiological) found dose-dependent decreases in oxygen consumption, State III respiration (up to 95% inhibition), membrane potential, and Complex IV activity. Desipramine data are mixed by compartment: Villa et al. 2017, Neuropharmacology 121:30-38 (rat hippocampus, 15 mg/kg × 21 days) found increased cytochrome oxidase activity in non-synaptic mitochondria but decreased electron-transport-chain complex activity in heavy synaptic mitochondria; Lee et al. 2015, Mol Cells 38:732-738 (SH-SY5Y cells, 50-60 µM) found decreased mitochondrial membrane potential. Trimipramine was not tested in any of these four studies - cohort test explicitly fails for this drug (Hard Rule 6); imipramine is cited as the closest class member (direct chemical parent, differing by one methyl branch), with clomipramine and desipramine cited as additional, directionally conflicting class texture.

Mechanism

Named for the impairing direction: direct electron-transport-chain and membrane-potential disruption (Bizerra 2023, Lee 2015). Named for the enhancing direction: altered mitochondrial membrane lipid milieu and fluidity (Katyare 1988) and FAM3A-FOXA2-CPT2 pathway activation (Liu 2022). Both mechanisms are plausible for trimipramine's shared tricyclic cationic-amphiphilic structure, but neither is confirmed for this drug.

Counter-evidence held on record

Class extrapolation only, in a direction that is genuinely contested across TCA class members and concentrations, with trimipramine itself confirmed absent from every cited cohort. Do not present this as trimipramine either damaging or protecting mitochondrial function, and do not use it to justify any mitochondrial-support supplement.

Oxidative Stress

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

Oxidative stress - class-extrapolated from imipramine, trimipramine's direct chemical parent, not itself tested

Yellow — Low

See study details

A drug-specific PubMed search for trimipramine and oxidative stress returned only studies of imipramine - trimipramine's own chemical parent compound, differing by a single methyl branch on the propylamine side chain - showing hepatic oxidative-stress changes with chronic dosing; trimipramine itself was not tested in any study located.

Full detail, limits and 1 references

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: The study's own framing is itself a partial null: imipramine did not worsen oxidative markers beyond the chronic-stress condition in treatment responders; the adverse pattern was specific to the non-responder subgroup.
  • At-risk subgroups: None established in humans; preclinical rat model only, and the adverse signal within that model was itself confined to treatment non-responders.
  • Counter-evidence on record: A PubMed search for "trimipramine" AND "oxidative stress" returns only imipramine-substituted results (10 shown, 123 total for imipramine), underscoring that no trimipramine-specific oxidative-stress study of any kind was located this session across PubMed, Crossref (two phrasings: "trimipramine antioxidant" and "trimipramine oxidative reactive oxygen species", both zero drug-specific hits), and repeatedly-blocked attempts at Europe PMC, Semantic Scholar, and OpenAlex.

Population evidence

Tier C, class extrapolation. Duda W et al. 2016, Neurotoxicity Research 30(2):173-184, PMID 26961706 (male Wistar rats, chronic mild stress [CMS] protocol over 5 weeks with concurrent imipramine administration, split into treatment-responder [CMS-IMI-R, ~80%] and non-responder [CMS-IMI-NR, ~20%] subgroups): CMS-induced hepatic oxidative stress, measured by elevated reactive oxygen species (ROS) and malondialdehyde (MDA), "was not prevented by the IMI administration"; in the treatment-resistant subgroup specifically, MDA was further elevated and glutathione peroxidase/catalase activity further reduced versus imipramine-treated responders. Trimipramine was not among the drugs tested - cohort test explicitly fails for this drug (Hard Rule 6); imipramine is cited as the closest possible class member, being trimipramine's direct synthetic parent compound on the same dibenzazepine ring system.

Mechanism

Not clearly named as a direct pro-oxidant drug effect in the confirmed abstract text - the study frames imipramine as failing to prevent stress-induced oxidative changes in the liver, which is a more modest finding than a drug directly generating oxidative stress. Framed accordingly below.

Counter-evidence held on record

Class extrapolation only, from a chemically adjacent drug that was itself shown to fail to prevent (not directly cause) oxidative changes in one preclinical model. No validated human oxidative-stress biomarker tied to trimipramine dosing exists. Do not use this entry to justify antioxidant or "free radical" supplementation.

Copper and Iron Balance

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

Copper - class-extrapolated from imipramine's own real serum decrease; trimipramine itself not tested

Yellow — Low

See study details

A drug-specific rat study found chronic imipramine - trimipramine's direct chemical parent - significantly lowered serum copper by roughly 14 percent while leaving brain copper unchanged; trimipramine itself was not tested, so this is class extrapolation from a real, directional finding, not drug-specific evidence.

Full detail, limits and 1 references

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: Brain copper was explicitly unchanged with imipramine in the same study, a real null finding disclosed here rather than omitted; only serum copper moved.
  • At-risk subgroups: Cannot be specified; no human data exists for imipramine on this point, let alone for trimipramine.
  • Counter-evidence on record: Crossref searches this session for "trimipramine copper" and "trimipramine ceruloplasmin trace element micronutrient" returned zero trimipramine-specific biological hits (only generic formulary/reference entries), confirming no drug-specific data exists for trimipramine itself at any tier; DailyMed's full label text was also re-checked this session and contains no mention of copper.

Regulatory status

Not addressed in trimipramine's own label.

Population evidence

Tier C, class extrapolation. Schlegel-Zawadzka M, Nowak G, "Alterations in serum and brain trace element levels after antidepressant treatment. Part II. Copper," Biol Trace Elem Res 2000, DOI 10.1385/BTER:73:1:37, PMID 10949967 (rat, chronic imipramine, citalopram, and electroconvulsive shock, confirmed drug-specific to imipramine in its own primary text). Chronic imipramine significantly decreased serum copper by approximately 14 percent; brain copper (hippocampus and cerebellum) was unchanged. Electroconvulsive shock produced the opposite effect on brain copper (a significant increase), a different mechanism from the pharmacological treatment. Trimipramine was not among the drugs tested - cohort test explicitly fails for this drug (Hard Rule 6); imipramine is cited as the closest possible class member on the same basis already established in this dossier's Oxidative stress and Vitamin B2 entries above.

Mechanism

Not established by the source; the authors report the serum decrease without proposing a specific absorption, chelation, or renal-handling mechanism. No such mechanism is documented in trimipramine's own label either.

Counter-evidence held on record

This is a real, drug-specific, statistically significant animal finding for imipramine, not trimipramine; it is a single rat study with no human replication and no confirmed mechanism, and it must not be presented as an established effect for trimipramine. No copper dose is supported by this entry.

Iron - class-extrapolated from imipramine; direction of causality unresolved even in the parent compound

Yellow — Low

See study details

A small human study found imipramine-treated panic disorder patients who developed jitteriness had significantly lower serum iron than those who did not; imipramine is trimipramine's direct chemical parent but was not itself trimipramine, and even within that study the design cannot establish whether low iron preceded or followed the drug effect.

Full detail, limits and 1 references

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 pre-treatment or drug-naive comparator arm is described for the imipramine study; this ambiguity, present even in the class-member source, caps this entry at yellow (Hard Rule 3, Hard Rule 6).
  • At-risk subgroups: Not established for trimipramine; even for imipramine, limited to panic-disorder patients who develop jitteriness, the population actually studied.
  • Counter-evidence on record: Crossref searches this session for "trimipramine iron hemoglobin hematocrit" and "trimipramine hemoglobin anemia erythrocyte" returned zero trimipramine-specific biological hits, confirming the drug-specific gap holds; trimipramine's own label was re-checked this session and is silent on iron, ferritin, and anemia as a nutrient-status issue.

Regulatory status

Not addressed in trimipramine's own label; the label's hematologic caution concerns bone marrow depression, agranulocytosis, eosinophilia, purpura, and thrombocytopenia, a drug-toxicity monitoring point under Hard Rule 2, not an iron-nutrient finding, and is excluded here on that basis.

Population evidence

Tier C, class extrapolation. Yeragani VK, Pohl R, Baton R, Ramesh C, Weinberg P, "Imipramine-induced jitteriness and decreased serum iron levels," Neuropsychobiology 1992, DOI 10.1159/000118801, PMID 1603294 (human, panic disorder patients treated with imipramine). Patients who developed jitteriness on imipramine had significantly lower serum iron than those without jitteriness (p = 0.01); whether iron was measured before treatment or only during the jitteriness episode is not resolved in the available abstract. Trimipramine was not among the drugs tested - cohort test explicitly fails for this drug (Hard Rule 6); imipramine is cited as the closest possible class member, on the same direct-parent basis used elsewhere in this dossier.

Mechanism

Not established. No absorption-interference, chelation, or renal-handling mechanism connecting imipramine, let alone trimipramine, to iron status is documented anywhere located in this review.

Counter-evidence held on record

Do not present this as "trimipramine depletes iron." Even the parent-compound study cannot establish that direction of causality, and it studied a specific side effect (jitteriness) in a specific population, not iron status in TCA users generally. No iron dose is supported by this entry.

Gut Microbiome Risk

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

Gut microbiome risk - class-extrapolated in-vitro antimicrobial activity; trimipramine itself not tested

Yellow — Low

See study details

A 2020 in-vitro screen found desipramine - a different tricyclic antidepressant - directly inhibits growth of 10 of 12 tested gut commensal bacterial strains; trimipramine was not among the six antidepressants tested in that study, so this is class extrapolation on shared tricyclic chemistry, not drug-specific evidence.

Full detail, limits and 2 references

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: Faecalibacterium prausnitzii and Eubacterium rectale were comparatively resistant to desipramine (MIC >800 µg/mL) in the source study - recorded rather than omitted.
  • At-risk subgroups: None established in vivo for any TCA including trimipramine; this is the central evidentiary gap.
  • Counter-evidence on record: In vitro MIC assay only, and in a different TCA. No human or animal in vivo gut-composition data for trimipramine specifically were located via Crossref ("trimipramine gut microbiota antimicrobial" and "trimipramine microbiome gut bacteria", both zero drug-specific hits) or the repeatedly-blocked Europe PMC/PubMed channels this session. Maier et al. 2018 ( Nature 555:623-628), a large non-antibiotic-drug gut-bacteria screen, was checked directly for a trimipramine mention; the accessible portion of the full text did not name trimipramine, desipramine, or any individual tricyclic by name (drug-level results appear to sit in supplementary data not reachable this session), so it is not cited as supporting evidence here (Hard Rule 6 cohort test).

Population evidence

Tier C, class extrapolation. Ait Chait, Mottawea, Tompkins & Hammami 2020, Sci Rep 10:17878, DOI 10.1038/s41598-020-74934-9 (in vitro minimum inhibitory concentration [MIC] assay against 12 ATCC gut commensal/pathogen strains). The six antidepressants tested were phenelzine, venlafaxine, desipramine, bupropion, aripiprazole, and (S)-citalopram - confirmed directly from the paper's own text this session. Desipramine (the one tricyclic in the study) was active against 10/12 strains, MIC 75-800 µg/mL, most sensitive against Akkermansia muciniphila (75 µg/mL) and Escherichia coli (150 µg/mL). Trimipramine was not tested - cohort test explicitly fails for this drug (Hard Rule 6); desipramine is cited as a defensible same-class member sharing the cationic amphiphilic tricyclic structure the authors attribute the antimicrobial action to, though desipramine is a secondary-amine tricyclic and trimipramine a tertiary amine, a structural difference not resolved by this source.

Mechanism

Named for desipramine: direct antimicrobial/membrane action attributed to the cationic amphiphilic tricyclic structure, shared across several TCAs tested in the same paper's broader dataset. Plausibly extends to trimipramine's own tricyclic dibenzazepine structure, but untested.

Counter-evidence held on record

In vitro MIC findings in a different TCA do not by themselves establish an in vivo dysbiosis effect for trimipramine. No probiotic, prebiotic, or supplement-timing recommendation is supported by this entry.

Oxygen and ATP Output

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

Oxygen delivery/utilization - class-extrapolated rare, idiosyncratic immune-mediated anemia in companion tricyclics; not a nutrient-deficiency mechanism, and trimipramine's own label is silent on anemia

Yellow — Low

See study details

Companion tricyclics doxepin and clomipramine each carry a drug-specific, label-documented anemia signal plus an independent case report of immune-mediated red-cell toxicity; trimipramine's own label does not list anemia at all, and trimipramine was not the drug studied in either case report, so this is class extrapolation of a rare, idiosyncratic reaction, not drug-specific evidence or a nutrient-deficiency finding.

Full detail, limits and 2 references

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: Both source findings are single-case or rare-postmarketing-frequency signals with no incidence data; neither label's hematologic section separately names anemia by frequency class above "infrequent" or "postmarketing," and trimipramine's own label does not name it at all, a genuine difference recorded here rather than merged across drugs.
  • At-risk subgroups: Not established for trimipramine. For the class-level sources: patients with pre-existing autoimmune disease (Sato 2000) and depression-range (not low insomnia-range) dosing (Wolf 1989) are the only subgroup signals available, neither confirmed for trimipramine.
  • Counter-evidence on record: Trimipramine's own label silence on anemia, confirmed by a full re-read this session, is itself recorded as counter-evidence against assuming this class signal necessarily extends to trimipramine. Crossref queries this session for trimipramine plus hemolytic anemia/pancytopenia terms were rate-limited before completion and could not independently confirm or rule out a trimipramine-specific case report; this is disclosed as a tooling limitation, not a confirmed negative, and is flagged for a future revision.

Regulatory status

Trimipramine's own label was re-checked in full this session for "anemia," "hemoglobin," "hematocrit," and related terms and contains none; its only hematologic caution is the bone-marrow-depression list (agranulocytosis, eosinophilia, purpura, thrombocytopenia) already excluded under Hard Rule 2 elsewhere in this dossier. By contrast, the Silenor (doxepin) label lists "Blood and Lymphatic System Disorders: Infrequent: anemia" in its pre-marketing adverse-reaction table, and clomipramine's (Anafranil) label states "There have been postmarketing reports of leukopenia, agranulocytosis, thrombocytopenia, anemia, and pancytopenia in association with Anafranil use."

Population evidence

Tier C, class extrapolation. Wolf B, Conradty M, Grohmann R, Ruther E, Witzgall H, Londong V, "A case of immune complex hemolytic anemia, thrombocytopenia, and acute renal failure associated with doxepin use," J Clin Psychiatry 1989, PMID 2925599 (human case report, doxepin 100 mg/day, depression-range dosing): Coombs-positive immune-complex hemolytic anemia, reversible on withdrawal. Sato T, Kogawa K, Hirayama Y, et al, "Pure red cell aplasia induced by clomipramine hydrochloride in a patient with SLE," Rinsho Ketsueki 2000, PMID 11020992 (human case report): a 48-year-old woman with systemic lupus erythematosus developed normochromic normocytic anemia with erythroid hypoplasia following clomipramine, resolving after withdrawal; the authors note the concurrent SLE diagnosis raised the possibility of an immune-mediated rather than direct marrow-toxic mechanism. Trimipramine was the drug in neither case and is absent from both labels' anemia listings - cohort test explicitly fails for this drug (Hard Rule 6); doxepin and clomipramine are cited as companion tricyclics already reviewed in this project (B008), clomipramine sharing trimipramine's own dibenzazepine tertiary-amine ring system.

Mechanism

Named in both source cases: an idiosyncratic immune-mediated process (Coombs-positive hemolysis in Wolf 1989; possible autoimmune erythroid-precursor suppression in Sato 2000, in a patient with pre-existing SLE), not a nutrient-cofactor or iron-handling mechanism, and not the drug's own intended pharmacology.

Counter-evidence held on record

Never present this as trimipramine causing iron-deficiency anemia, or as a reason to supplement iron; both class-level mechanisms identified are immune-mediated, not nutrient-mediated, and trimipramine's own label does not even list anemia. The appropriate response to unexplained anemia on any tricyclic is clinical evaluation, not nutrient repletion. See Iron above for the explicit disclosure of why this entry is not counted as iron-status evidence (Overlap map).

ATP production - mechanistic extrapolation sharing its evidentiary core with Mitochondrial burden above; no direct ATP measurement in trimipramine or any companion tricyclic resolves a single direction

Yellow — Low

See study details

The same class-level sources supporting Mitochondrial burden imply opposite effects on ATP-synthesis capacity depending on the compound: imipramine's enhanced respiration state implies more ATP-synthesizing capacity, while clomipramine's and desipramine's electron-transport-chain inhibition and (for desipramine) directly measured ATP depletion imply less; trimipramine itself has no direct ATP data from any source.

Full detail, limits and 5 references

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 source located, for trimipramine or any companion tricyclic, directly measures ATP content in therapeutic-dose, non-supraclinical conditions; the Bizerra and Lee concentrations are both supraphysiological to supraclinical relative to typical TCA therapeutic exposure, stated explicitly rather than left implicit.
  • At-risk subgroups: None established in humans for any TCA including trimipramine on this specific category.
  • Counter-evidence on record: The direction conflict between the enhancing (imipramine) and impairing (clomipramine, desipramine) class sources is itself the central counter-evidence, recorded rather than resolved; see Overlap map for the shared sourcing with Mitochondrial burden, which must not be double-counted as independent confirmation. Two further leads (Plenge-Tellechea 1999, PMID 10496985; Soler 2000, PMID 11768746, both on TCA-class Ca2+-ATPase inhibition) were checked this session; PubMed's search index associates both with trimipramine, but a detailed OpenAlex concepts query did not list trimipramine among either paper's tested compounds (only desipramine, clomipramine, and imipramine), and the actual abstracts could not be opened despite repeated attempts across PubMed, Semantic Scholar, and the publisher pages (all rate-limited or returned no content this session). Given that conflict, trimipramine's inclusion is explicitly unconfirmed and neither source is cited as evidence here; both are flagged by PMID for a future revision once those channels are reachable. A PubMed title-only lead from the original review, Hamilton et al., "Chronic stress and antidepressant treatment alter purine metabolism and beta oxidation within mouse brain and serum" (PMID 33093530, names imipramine), remains unconfirmed this session for the same reason (repeated rate-limiting) and is not cited as evidence.

Regulatory status

Not addressed in trimipramine's own label; the Overdosage section was re-checked in full this session specifically for "ATP," "cellular energy," "metabolic acidosis," and "hypoglycemia" (language that appears in some other tricyclics' overdose sections) and contains none of them - only cardiac dysrhythmia, hypotension, convulsions, and CNS depression are named.

Population evidence

Tier C, class extrapolation, directionally mixed, sharing sourcing with Mitochondrial burden above (see Overlap map). Enhancing-direction inference: Katyare & Rajan 1988 (PMID 3207998) found increased state 3 (ADP-stimulated, ATP-synthesis-coupled) respiration with imipramine in rat liver, and Liu et al. 2022 (PMID 35995281) found imipramine activating a mitochondrial fatty-acid-oxidation pathway (CPT2) in mouse liver; neither study directly assayed ATP content or yield. Impairing-direction, more direct: Bizerra et al. 2023 (clomipramine, rat liver mitochondria, 50-300 µM) directly measured a lowered ADP/O ratio (ATP molecules synthesized per oxygen atom consumed) alongside State III respiration inhibition up to 95%, and the clomipramine (Anafranil) label's own Overdosage section separately states tricyclic toxicity can produce "decreased ATP production" in overdose, language trimipramine's own label does not contain. Lee et al. 2015 (desipramine, SH-SY5Y cells, 50-60 µM) directly measured ATP depletion alongside mitochondrial membrane depolarization. Trimipramine was not tested by any of these sources - cohort test explicitly fails (Hard Rule 6).

Mechanism

Indirect inference only on the enhancing side (state 3 respiration and CPT2 pathway activation implying, not measuring, ATP synthesis capacity); more direct on the impairing side (Bizerra 2023's ADP/O ratio and Lee 2015's direct ATP assay). Neither mechanism is confirmed for trimipramine itself.

Counter-evidence held on record

Class extrapolation only, in a direction that is genuinely contested across TCA class members, with trimipramine itself confirmed absent from every cited cohort and no direct ATP assay located for it anywhere. Do not present this as trimipramine either depleting or boosting cellular ATP, and do not use it to justify CoQ10, carnitine, or B-vitamin "energy support" supplementation.

How the body handles this medication

Metabolism / CYP enzymes
Extensively hepatic. The label discusses trimipramine through cytochrome P450 2D6 (debrisoquin hydroxylase), the polymorphic enzyme shared across tricyclics; Drugs.com's professional monograph adds CYP3A4, CYP2C19, and CYP2C9 as contributing pathways, with the active metabolite desmethyltrimipramine formed in the liver. The label itself does not name the metabolite.DailyMed label [Source 1]; Drugs.com monograph [Source 2]
Enzyme induction/inhibition
No enzyme induction is documented anywhere reached this session - the classical "accelerated catabolism" depletion mechanism (Step 2, mechanism B) is absent. Trimipramine is a CYP2D6 substrate; the label states drugs that inhibit CYP2D6 "may require lower doses" of co-administered tricyclics. A single case-report-level source (Kowalewski et al. 2020, confirmed by title/journal/DOI metadata only, full text not opened this session) indicates trimipramine itself may also inhibit CYP2D6-mediated clearance of a co-administered drug (venlafaxine) - noted here as an unconfirmed lead, not relied on for any graded entry.DailyMed label [Source 1]; Kowalewski et al. 2020 [Source 9, title/metadata only]
Elimination route
"Trimipramine capsules are known to be substantially excreted by the kidney" (label). Drugs.com adds that the drug is "excreted principally in urine." Neither source gives a percentage excreted unchanged versus as metabolites, and that figure could not be confirmed via the channels reachable this session.DailyMed label [Source 1]; Drugs.com monograph [Source 2]
Renal/hepatic impairment
Label: "should be used with caution in patients with impaired liver function." No quantified renal- or hepatic-impairment accumulation data (e.g., AUC fold-change) was located in the label or the literature reachable this session.DailyMed label [Source 1]
Pharmacokinetic variability
Drugs.com reports a wide elimination half-life range (14-46 hours) and bioavailability of approximately 41-43%, with peak plasma concentration at 2-6 hours. Kirchheiner et al. 2003 administered a single 75 mg oral dose to healthy volunteers stratified by CYP2D6, CYP2C9, and CYP2C19 genotype and found genotype-dependent differences in trimipramine exposure, consistent with the wide half-life range; the exact poor-metabolizer-to-extensive-metabolizer fold-difference could not be confirmed this session because the full article was blocked by rate-limiting (see access note).Drugs.com monograph [Source 2]; Kirchheiner et al. 2003 [Source 4]
Electrolyte/water handling
Label lists "syndrome of inappropriate ADH (antidiuretic hormone) secretion" under Neurological adverse reactions, naming trimipramine capsules directly - a dilutional/retention mechanism (Step 2, mechanism F), not a renal-wasting or absorption-interference depletion mechanism. Graded below under Sodium / water balance.DailyMed label [Source 1]
All references used above
  1. TRIMIPRAMINE capsule - FDA/DailyMed label — Regulatory label, Tier A. DailyMed setid 4f31df66-7dc2-1f04-e054-00144ff88e88, packager Breckenridge Pharmaceutical, Inc.
  2. Trimipramine Monograph for Professionals — Drugs.com, tertiary reference corroborating and extending the regulatory label (CYP3A4/CYP2C19/CYP2C9 contribution, desmethyltrimipramine metabolite, half-life, bioavailability, Tmax).
  3. ATC/DDD Index, code N06AA06 (trimipramine) — WHO Collaborating Centre for Drug Statistics Methodology. DDD 0.15 g, oral and parenteral, non-selective monoamine reuptake inhibitors.
  4. Kirchheiner J, Muller G, Meineke I, Wernecke KD, Roots I, Brockmoller J. Effects of polymorphisms in CYP2D6, CYP2C9, and CYP2C19 on trimipramine pharmacokinetics. — 2003. PMID 14520122. Single oral 75 mg dose, healthy volunteers stratified by CYP genotype. Tier A/B, drug-specific. Journal name and exact fold-difference in exposure could not be confirmed this session - the full article page returned HTTP 429 on two separate attempts; title, authors, year, and PMID were confirmed via a PubMed search-listing page, not the article page itself.Full text not opened this session (HTTP 429). No numeric finding from this source is asserted beyond what the search-listing page itself stated (single 75 mg dose, genotype-stratified design).
  5. Degner D, Grohmann R, Kropp S, Ruther E, Bender S, Engel RR, Schmidt LG. Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP. — 2004. PMID 15052513. N=53,042 of 122,562 antidepressant-treated patients, 1993-2000. Trimipramine broken out individually (0.6% overall severe ADR, 0.3% probable/definite). Tier A, drug-specific. Journal name could not be independently confirmed this session (full-text/journal metadata not reachable beyond the abstract); abstract content confirmed directly.
  6. Duda W, Curzytek K, Kubera M, Connor TJ, Fagan EM, Basta-Kaim A, Budziszewska B, Leśkiewicz M, Regulska M, Lasoń W, Maes M. The Effect of Chronic Mild Stress and Imipramine on the Markers of Oxidative Stress and Antioxidant System in Rat Liver. — Neurotoxicity Research 2016;30(2):173-184. PMID 26961706. Male Wistar rats, chronic mild stress protocol × 5 weeks with concurrent imipramine. Tier C for trimipramine (imipramine tested, not trimipramine) - class extrapolation per Hard Rule 6.Cohort excluded trimipramine: imipramine only was tested. Cited strictly as Tier C class extrapolation supporting the Oxidative stress entry at yellow, not higher.
  7. Ait Chait Y, Mottawea W, Tompkins TA, Hammami R. Unravelling the antimicrobial action of antidepressants on gut commensal microbes. — Sci Rep 2020;10:17878. DOI 10.1038/s41598-020-74934-9. In vitro MIC assay, 12 ATCC gut commensal/pathogen strains, against phenelzine, venlafaxine, desipramine, bupropion, aripiprazole, and (S)-citalopram. Tier C for trimipramine (desipramine tested, not trimipramine) - class extrapolation per Hard Rule 6.Cohort excluded trimipramine: desipramine was the sole tricyclic tested. Cited strictly as Tier C class extrapolation supporting the Gut microbiome risk entry at yellow, not higher.
  8. Pinto J, Huang YP, Rivlin RS. Inhibition of riboflavin metabolism in rat tissues by chlorpromazine, imipramine, and amitriptyline. — J Clin Invest 1981;68. PMID 6262379. DOI 10.1172/jci110180. Rat liver/brain/heart.Cohort excluded trimipramine: chlorpromazine, imipramine, and amitriptyline only were tested. Cited here strictly as Tier C class extrapolation (Hard Rule 6), supporting the Vitamin B2 entry at yellow, not higher.
  9. Katyare SS, Rajan RR. Enhanced oxidative phosphorylation in rat liver mitochondria following prolonged in vivo treatment with imipramine. — Br J Pharmacol 1988;95(3):914-922. PMID 3207998. Rat, 1-2 weeks dosing. Drug-specific to imipramine (increased state 3 respiration, increased cytochrome aa3 and c+c1 content). Tier C for trimipramine (imipramine tested, not trimipramine) - class extrapolation per Hard Rule 6, supporting Mitochondrial burden and ATP production at yellow.Cohort excluded trimipramine: imipramine only was tested. Citation reused from this project's companion imipramine dossier (B008), which opened the source directly.
  10. Liu X, Hou S, Xiang R, Hu C, Chen Z, Li N, Yan H, Yu X, Li X, Chi Y, Yang J. Imipramine activates FAM3A-FOXA2-CPT2 pathway to ameliorate hepatic steatosis. — Metabolism 2022. DOI 10.1016/j.metabol.2022.155292. PMID 35995281. Mouse NAFLD model, imipramine activates a mitochondrial fatty-acid-oxidation pathway. Tier C for trimipramine (imipramine tested, not trimipramine) - class extrapolation, supporting Mitochondrial burden and ATP production at yellow.Cohort excluded trimipramine: imipramine only was tested. Full abstract text not independently re-confirmed this session; direction reused from this project's companion imipramine dossier (B008), disclosed as such.
  11. Bizerra PFV, Itou da Silva FS, Gilglioni EH, et al. The harmful acute effects of clomipramine in the rat liver: Impairments in mitochondrial bioenergetics. — Toxicology Letters 2023. DOI 10.1016/j.toxlet.2023.05.008. Isolated rat liver mitochondria, hepatocytes, and perfused liver; clomipramine 50-300 µM (supraphysiological). Dose-dependent decrease in oxygen consumption, State III respiration inhibition up to 95%, decreased membrane potential, inhibited Complex IV and NADH/succinate oxidase. Tier C for trimipramine (clomipramine tested, not trimipramine) - class extrapolation, supporting Mitochondrial burden and ATP production at yellow, in the direction opposite to Katyare 1988 and Liu 2022.Cohort excluded trimipramine: clomipramine only was tested. Citation reused from this project's companion clomipramine dossier (B008), which opened the source directly.
  12. Villa RF, Gorini A, Hoyer S. Brain non-synaptic and synaptic mitochondria from adult rats: effects of chronic desipramine. — Neuropharmacology 2017;121:30-38. Rat hippocampus, desipramine 15 mg/kg × 21 days. Compartment-dependent mixed findings (increased cytochrome oxidase in non-synaptic mitochondria, decreased ETC complex activity in heavy synaptic mitochondria). Tier C for trimipramine (desipramine tested, not trimipramine) - class extrapolation, supporting Mitochondrial burden and ATP production at yellow.Cohort excluded trimipramine: desipramine only was tested. Citation reused from this project's companion desipramine dossier (B009), which opened the source directly.
  13. Lee SH, et al. Desipramine decreases mitochondrial membrane potential and induces apoptosis in SH-SY5Y neuroblastoma cells. — Mol Cells 2015;38:732-738. Human neuroblastoma cell line, desipramine 50-60 µM (supraclinical). Decreased mitochondrial membrane potential, increased reactive oxygen species, decreased cellular ATP. Tier C for trimipramine (desipramine tested, not trimipramine) - class extrapolation, supporting Mitochondrial burden and ATP production at yellow.Cohort excluded trimipramine: desipramine only was tested. Citation reused from this project's companion desipramine dossier (B009), which opened the source directly.
  14. Schlegel-Zawadzka M, Nowak G. Alterations in serum and brain trace element levels after antidepressant treatment. Part II. Copper. — Biol Trace Elem Res 2000. DOI 10.1385/BTER:73:1:37. PMID 10949967. Rat, chronic imipramine, citalopram, and electroconvulsive shock. Imipramine significantly decreased serum copper by approximately 14 percent; brain copper (hippocampus, cerebellum) unchanged. Tier C for trimipramine (imipramine tested, not trimipramine) - class extrapolation per Hard Rule 6, supporting the Copper entry at yellow.Cohort excluded trimipramine: imipramine, citalopram, and ECT only were tested. Citation reused from this project's companion imipramine dossier (B008), which opened the source directly and confirmed imipramine drug-specific in the paper's own primary text.
  15. Yeragani VK, Pohl R, Baton R, Ramesh C, Weinberg P. Imipramine-induced jitteriness and decreased serum iron levels. — Neuropsychobiology 1992. DOI 10.1159/000118801. PMID 1603294. Human, panic disorder patients treated with imipramine; those who developed jitteriness had significantly lower serum iron (p=0.01) than those without. Tier C for trimipramine (imipramine tested, not trimipramine) - class extrapolation per Hard Rule 6, supporting the Iron entry at yellow.Cohort excluded trimipramine: imipramine only was tested. Citation reused from this project's companion imipramine dossier (B008); whether iron was measured pre-treatment or only during the jitteriness episode is unresolved, a limitation disclosed in the Iron entry above.
  16. Wolf B, Conradty M, Grohmann R, Ruther E, Witzgall H, Londong V. A case of immune complex hemolytic anemia, thrombocytopenia, and acute renal failure associated with doxepin use. — J Clin Psychiatry 1989. PMID 2925599. Human case report, doxepin 100 mg/day. Coombs-positive immune-complex hemolytic anemia, reversible on withdrawal. Tier C for trimipramine (doxepin tested, not trimipramine) - class extrapolation per Hard Rule 6, supporting Oxygen delivery/utilization at yellow.Cohort excluded trimipramine: doxepin only was tested. Citation reused from this project's companion doxepin dossier (B008).
  17. Sato T, Kogawa K, Hirayama Y, et al. Pure red cell aplasia induced by clomipramine hydrochloride in a patient with SLE. — Rinsho Ketsueki (Japanese Journal of Clinical Hematology) 2000. PMID 11020992. Human case report, 48-year-old woman with SLE; normochromic normocytic anemia with erythroid hypoplasia following clomipramine, resolved on withdrawal. Tier C for trimipramine (clomipramine tested, not trimipramine) - class extrapolation per Hard Rule 6, supporting Oxygen delivery/utilization at yellow.Cohort excluded trimipramine: clomipramine only was tested. Citation reused from this project's companion clomipramine dossier (B008).
  18. Blaess M, Kaiser L, Sommerfeld O, Csuk R, Deigner HP. Drug triggered pruritus, rash, papules, and blisters - is AGEP a clash of an altered sphingolipid-metabolism and lysosomotropism of drugs accumulating in the skin? — Lipids Health Dis 2021. DOI 10.1186/s12944-021-01552-3. PMID 34743684. Open access, full text opened this session. Names trimipramine specifically as having "lysosomotropic and photosensitizing" properties, alongside amiodarone, chlorpromazine, and amitriptyline. Discusses UV/photosensitizer-induced local ATP and NAD(P)H depletion in skin cells as part of a dermatologic hypothesis mechanism, not a systemic mitochondrial or ATP finding for trimipramine itself. Checked and explicitly not cited as supporting evidence for Mitochondrial burden or ATP production for this reason.
  19. Plenge-Tellechea F, Soler F, Fernandez-Belda F. Tricyclic antidepressants inhibit the Ca2+-dependent ATPase activity from plasma membrane. — Arch Biochem Biophys 1999. DOI 10.1006/abbi.1999.1375. PMID 10496985. PubMed's search index returns this record for "trimipramine" AND "ATP"; one OpenAlex summarization pass reported trimipramine as a keyword, but a second, more detailed OpenAlex concepts query for the same record listed only desipramine, clomipramine, and imipramine as tested compounds, not trimipramine. The abstract itself could not be opened this session (PubMed, Semantic Scholar, and the Elsevier publisher page all returned HTTP 429 or no content; Unpaywall confirms no open-access copy exists). Trimipramine's inclusion in this study's actual tested cohort is therefore explicitly unconfirmed and this source is not cited as evidence for any graded entry, consistent with the prohibition on citing a source not actually opened.Full text not opened this session (HTTP 429/no content, repeated, across three channels). Flagged as an unexplored, unconfirmed lead in the Mitochondrial burden and ATP production entries above for a future revision.
  20. Soler F, Plenge-Tellechea F, Fortea I, Fernandez-Belda F. Clomipramine and related structures as inhibitors of the skeletal sarcoplasmic reticulum Ca2+ pump. — J Bioenerg Biomembr 2000. DOI 10.1023/a:1005519312463. PMID 11768746. Same conflicting-signal pattern as the Plenge-Tellechea 1999 source directly above: PubMed's search index returns this record for "trimipramine" AND "ATP," but a detailed OpenAlex concepts query did not list trimipramine among the tested compounds, and the abstract could not be opened this session. Not cited as evidence for any graded entry for the same reason.Full text not opened this session. Flagged as an unexplored, unconfirmed lead in the Mitochondrial burden and ATP production entries above for a future revision.
  21. Kowalewski J, [additional authors not confirmed]. Cytochrome P450-mediated inhibition of venlafaxine metabolism by trimipramine: Erratum. — International Clinical Psychopharmacology 2020. DOI 10.1097/yic.0000000000000289. Confirmed by Crossref title/journal/DOI metadata only; full text not opened this session, and this being an erratum notice means the underlying original case report was not independently located either. Cited only as an unconfirmed PK lead in the pharmacokinetic basis section above, not relied on for any graded entry.Title/metadata only; full text not opened this session.
  22. 7 Important Nutrients Depleted by Psychiatric Drugs — Optimal Living Dynamics (consumer health content). Tier D. Names amitriptyline, doxepin, imipramine, desipramine, nortriptyline, and protriptyline specifically for CoQ10, magnesium, melatonin, vitamin B2, B6, B12, and folate. Checked specifically for "trimipramine" and "Surmontil" - neither term appears anywhere on the page. Also checked for "copper," "iron," "mitochondria," "ATP," "oxygen," and "hemoglobin" - none appear, drug-specific or general. Negative check, recorded for completeness; this is why the Fails verification section above is empty.
  23. Medications that Deplete B Vitamins: Why It Happens + How to Prevent Deficiency — LivOnLabs (consumer health content). Checked specifically for a tricyclic-antidepressant/trimipramine/Surmontil mention; the article covers PPIs, antibiotics, anticonvulsants, anti-inflammatories, diuretics, metformin, oral contraceptives/HRT, and GLP-1 medications only - no tricyclic antidepressants of any kind are referenced. Negative check, recorded for completeness.
  24. Extensive impact of non-antibiotic drugs on human gut bacteria (Maier et al.) — Nature 2018;555:623-628. DOI 10.1038/nature25979. Large-scale in vitro screen of ~1,000 marketed drugs against ~40 gut bacterial strains. The accessible portion of the full text (abstract, discussion, and reference list) does not name trimipramine, desipramine, or any individual tricyclic antidepressant by name; drug-level results appear to sit in supplementary data tables not reachable this session.Whether trimipramine specifically was among the tested compounds, and its individual result, could not be confirmed this session (supplementary data not reachable). Not cited as evidentiary support in the Gut microbiome risk entry for this reason (Hard Rule 6 cohort test).
  25. Hamilton PJ, et al. Chronic stress and antidepressant treatment alter purine metabolism and beta oxidation within mouse brain and serum. — PMID 33093530. Title and bibliographic existence confirmed via a PubMed search-listing page only (names imipramine). Full abstract page returned HTTP 429 on two separate attempts this session, roughly 70 seconds apart, and could not be opened.Full text not opened this session (HTTP 429, repeated). No finding or magnitude from this source is cited anywhere in this dossier; flagged in the ATP production ungraded entry as an unexplored lead for a future revision.
  26. Rochoy M, Zakhem-Stachera C, Bene J, Berkhout C, Gautier S; French Pharmacovigilance Centers Network. Antidepressive agents and hyponatremia: A literature review and a case/non-case study in the French Pharmacovigilance database. — 2018. PMID 29773358. Title and bibliographic existence confirmed via a PubMed search-listing page only. Full abstract page returned HTTP 429 on repeated attempts this session and could not be opened.Full text not opened this session (HTTP 429, repeated). No finding is cited anywhere in this dossier from this source; flagged in the Sodium entry as an unexplored lead for a future revision.