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MyDeficiencies

Desipramine

Tricyclic antidepressant, secondary amine

Also sold as Norpramin.

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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.

Desipramine's own regulatory label rules out the two mechanisms that drive most drug-nutrient depletion claims. It is extensively hepatically metabolized (CYP2D6 is the dominant pathway, with CYP1A2, CYP3A4, and CYP2C contributing) to an active metabolite, roughly 70% is excreted in urine, and desipramine inhibits CYP2D6 rather than inducing any CYP enzyme - so there is no enzyme-induction-driven accelerated nutrient catabolism of the kind seen with true inducers (barbiturates, rifampin, some anticonvulsants). No chelation, transporter-competition, or renal-wasting mechanism for any classical vitamin or mineral is documented in the label or in the literature this review could reach. What is real and drug-specific is the opposite of depletion: the label states plainly that desipramine-associated hyponatremia "appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)" - a water-retention disorder, not a dietary sodium deficiency, and it is graded and framed as such below.

Tricyclic antidepressant, secondary amine · ATC N06AA01 · also sold as Norpramin · 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 Desipramine 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 to susceptible patients

Orange — Moderate

See study details

Desipramine can cause clinically significant hyponatremia through SIADH. This is a water-retention disorder, not a dietary sodium deficiency, and the label does not establish it as a universal or high-frequency effect.

Full detail and limits

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: None quantified in the label; this is a disclosed adverse-event signal, not a controlled incidence study, and that limits it to orange rather than red.
  • At-risk subgroups: Elderly patients, the early weeks of treatment or after a dose increase, concurrent diuretic use, and renal impairment (which the label separately flags as a desipramine accumulation risk, compounding SIADH risk).
  • Counter-evidence on record: No population-level controlled study quantifying hyponatremia incidence specifically in desipramine users was located via the channels reachable this session (Crossref, DailyMed; PubMed and Europe PMC were rate-limited for this specific query - see access note). The bounded, orange grade rests on the label's own pharmacovigilance language plus the class mechanism, not a stratified incidence study.

Regulatory status

FDA label (DailyMed): "Hyponatremia has occurred as a result of treatment with desipramine hydrochloride. In many cases, hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)." Symptoms listed: headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness.

Population evidence

Tier A, drug-specific (the label itself, naming desipramine hydrochloride directly). No incidence figure is given. The underlying class mechanism is corroborated by published case reports in the chemical class - Parker 1984 ( Drug Intell Clin Pharm 18:890) and Mitsch & Lee 1986 - but both of those name imipramine, not desipramine, in the patient population, so they support plausibility (Tier C for this drug) rather than counting toward a second Tier A source.

Mechanism

Named: potentiation of antidiuretic hormone (AVP) release/action, consistent with the serotonergic/noradrenergic SIADH mechanism documented across antidepressant classes.

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 closely related tricyclics chlorpromazine, imipramine, and amitriptyline inhibit riboflavin's conversion to its active coenzyme form in rat tissue; desipramine - imipramine's own primary active metabolite - 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: Desipramine'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 desipramine users rests on its direct structural and metabolic relationship to imipramine (positive in this study), not on independent data.
  • Counter-evidence on record: No desipramine-specific riboflavin study of any kind was located via DailyMed, Drugs.com, Crossref, or the partially-reachable Europe PMC/PubMed channels this session.

Regulatory status

Not addressed in desipramine'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. Desipramine was not among the drugs tested - cohort test explicitly fails for this drug (Hard Rule 6).

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.

Coenzyme Q10 - indirect mechanistic plausibility only; CoQ10 itself never measured

Yellow — Low

See study details

Desipramine-specific studies show altered electron-transport-chain complex activity and mitochondrial membrane potential, which is mechanistically adjacent to CoQ10's role as an ETC electron carrier - but no study located measured CoQ10 levels or synthesis directly in desipramine-exposed tissue.

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: Neither source includes a CoQ10-specific assay.
  • At-risk subgroups: None established.
  • Counter-evidence on record: This is the most indirect entry in the dossier by design. Targeted searches for a desipramine-specific or TCA-class CoQ10 study (Crossref, DailyMed) found none.

Population evidence

Tier B, indirect. Same underlying sources as the Mitochondrial burden entry: Villa et al. 2017 (rat hippocampal ETC complex decrease in heavy synaptic mitochondria) and Lee et al. 2015 (SH-SY5Y mitochondrial membrane potential loss). See Overlap map.

Mechanism

Theoretical only: CoQ10 shuttles electrons between Complex I/II and Complex III. A drug that alters ETC complex activity could plausibly also alter CoQ10 utilization or status, but this has not been demonstrated for desipramine.

Counter-evidence held on record

Do not recommend CoQ10 supplementation on this basis. This entry documents mechanistic plausibility only, not a measured deficiency, and is graded yellow specifically because CoQ10 itself remains unmeasured and theoretical.

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 - compartment-dependent enzyme and membrane-potential changes, animal/cell data only

Yellow — Low

See study details

Two independent drug-specific preclinical studies show desipramine alters mitochondrial enzyme activity and membrane potential, with the direction depending on the mitochondrial compartment and model studied, not a single uniform "mitochondrial damage" signal.

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: Villa et al. explicitly found no significant change in intra-synaptic light mitochondria bioenergetics - recorded here rather than omitted.
  • At-risk subgroups: None established in humans; both studies are preclinical (rat intraperitoneal/oral dosing at 15 mg/kg; supraclinical 50-60 µM in vitro concentrations).
  • Counter-evidence on record: The mixed direction (some parameters up, ETC complexes down) is itself the main counter-evidence against framing this as simple mitochondrial "damage"; see Overlap map for shared sourcing with ATP production, Oxidative stress, and Coenzyme Q10 below.

Population evidence

Tier B. Villa et al. 2017, Neuropharmacology 121:30-38 (male Sprague-Dawley rats, desipramine 15 mg/kg × 21 days): in non-synaptic hippocampal mitochondria, desipramine increased cytochrome oxidase and glutamate dehydrogenase activity; in intra-synaptic light mitochondria, no significant bioenergetic change; in intra-synaptic heavy mitochondria, desipramine increased malate dehydrogenase while decreasing electron-transport-chain (ETC) complex activities. Lee et al. 2015, Mol Cells 38:732-738 (SH-SY5Y human neuroblastoma cells, desipramine 50-60 µM in vitro): decreased mitochondrial membrane potential (JC-1/MitoTracker staining).

Mechanism

Named: direct, compartment-specific modulation of mitochondrial enzyme activity and ETC complex function; Villa et al. interpret the pattern as an adaptive shift in energy allocation between pre- and post-synaptic compartments, not uniform toxicity.

Counter-evidence held on record

Preclinical only; rat intraperitoneal/oral dosing and supraclinical in vitro concentrations are not directly comparable to human oral therapeutic dosing. No validated human mitochondrial-function biomarker exists for monitoring. Not a basis for any supplement recommendation.

Oxidative Stress

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

Oxidative stress - tissue/model-dependent direction, including one protective finding

Yellow — Low

See study details

Two independent drug-specific studies show desipramine raising oxidative markers in rat liver and human neuroblastoma models, while a separate dopaminergic cell-death model found desipramine protective and antioxidant-inductive - direction is model/tissue dependent, not a documented depletion of a specific antioxidant nutrient in humans.

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: The direction reversal itself (protective in the dopaminergic-neuron title vs. pro-oxidant in liver and neuroblastoma data) is recorded explicitly as the central counter-finding; oxidative stress is not presented here as a one-directional story.
  • At-risk subgroups: None established clinically; all data preclinical, with (a) using intraperitoneal rat dosing and (b) using supraclinical in vitro concentrations.
  • Counter-evidence on record: See mechanism/null findings above. Vircheva et al. 2012 ( Cell Biochem Funct, "Effects of desipramine on the antioxidant status in rat tissues at carrageenan-induced paw inflammation," DOI 10.1002/cbf.1812) is a fourth drug-specific, title-confirmed oxidative-stress study that could not be opened at any point this session (Wiley 403, PubMed/Semantic Scholar page content unavailable, Unpaywall reports no open-access copy) and is therefore deliberately not cited as evidentiary support anywhere in this entry.

Population evidence

Tier B, two independent pro-oxidant findings: (a) [Authors not independently confirmed], Acta Biomed 2023;94(2), "Crocin lessens desipramine-induced phospholipidosis biomarker levels" (adult male rats, n=40/4 groups, desipramine 10 mg/kg/day intraperitoneal × 3 weeks): desipramine alone raised total oxidant status (TOS) and lowered total antioxidant capacity (TAC)/superoxide dismutase (SOD) versus control, alongside hepatic phospholipidosis. (b) Lee et al. 2015, Mol Cells 38:732-738 (SH-SY5Y cells, desipramine 50-60 µM): increased reactive oxygen species (DCF-DA fluorescence), measured in the same experiment as the mitochondrial-membrane-potential finding above. Set against these, a third study's title and indexed metadata only (full text blocked by repeated proxy rate-limiting this session - see access note) indicate the opposite direction in a different model: PLoS ONE 2012;7(11):e50138, "Desipramine Protects Neuronal Cell Death and Induces Heme Oxygenase-1 Expression in Mes23.5 Dopaminergic Neurons." Heme oxygenase-1 is an antioxidant-response enzyme; the title itself states a protective, antioxidant-inductive finding, but dose, magnitude, and full methodology could not be independently verified this session and are not asserted as confirmed detail here.

Mechanism

Named for (a)/(b): direct reactive-oxygen-species generation and/or antioxidant-enzyme suppression. For the metadata-only third source: Nrf2/heme-oxygenase-1 antioxidant-response induction (title-level only).

Counter-evidence held on record

All preclinical; no validated human oxidative-stress biomarker tied to desipramine 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

Not graded — disclosed evidence gap

See study details

No evidence at any tier, and no circulating consumer claim to rebut, was located for desipramine and copper status.

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. Channels tried: DailyMed label (no mention); Drugs.com monograph (no mention); Crossref API, query "desipramine copper iron trace mineral" (5 results returned, all mineralogy/ore-processing or unrelated chemistry papers, zero biological matches); Europe PMC REST API, query "desipramine AND copper" (returned results on an unrelated NBIA movement-disorder review and chemistry papers, no copper-nutrient-status study); PubMed search-listing pages, Semantic Scholar API, and OpenAlex API all returned repeated HTTP 429 rate-limiting for copper-specific queries during this session (see access note) and could not be completed. No circulating consumer depletion claim naming copper for desipramine was located either - the consumer source identified for this drug (Sources 10) names CoQ10, magnesium, B2, B6, B12, and folate specifically, plus an undifferentiated longer list that does not include copper. This is recorded as a genuine literature gap as currently accessible, with the caveat that the rate-limited channels were not exhausted; a later revision should re-run the Europe PMC/Semantic Scholar/OpenAlex queries for "desipramine copper" once those hosts are reachable.

Iron

Not graded — disclosed evidence gap

See study details

No evidence at any tier, and no circulating consumer claim to rebut, was located for desipramine and iron status.

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. Channels tried: DailyMed label (no mention of iron, ferritin, or anemia as a nutrient-status issue - the label's hematologic caution concerns leukocyte/neutrophil blood dyscrasia, a drug-toxicity monitoring point under Hard Rule 2, not an iron-nutrient finding, and is therefore excluded here); Drugs.com monograph (no mention); Crossref API, combined query covering copper/iron trace-mineral terms (no biological matches, see Copper entry); Europe PMC and PubMed channels returned repeated HTTP 429 during this session for iron-specific queries and could not be completed (see access note). No circulating consumer claim naming iron for desipramine was located in the one consumer depletion source identified for this drug. Genuine literature gap as currently accessible; flagged for re-check once the rate-limited channels are reachable.

Gut Microbiome Risk

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

Gut microbiome risk - in vitro inhibition of commensal gut bacteria, including beneficial species

Yellow — Low

See study details

Desipramine directly inhibits growth of 10 of 12 tested gut commensal bacterial strains in vitro, including beneficial species, at concentrations not yet confirmed to be reached in the human gut lumen at therapeutic oral doses.

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: Faecalibacterium prausnitzii and Eubacterium rectale were comparatively resistant (MIC >800 µg/mL) - recorded explicitly rather than omitted.
  • At-risk subgroups: None established in vivo; this is the central evidentiary gap (see counter-evidence).
  • Counter-evidence on record: In vitro MIC assay only; no human or animal in vivo gut-concentration or 16S/metagenomic composition data for desipramine specifically were located despite searches against Europe PMC and Crossref this session (both partially rate-limited - see access note). A broader non-antibiotic-drug gut-bacteria screen (Maier et al. 2018, Nature 555:623-628) covers antidepressants generally, but desipramine's specific inclusion and result in that screen could not be confirmed this session, so it is not cited as supporting evidence here (cohort test, Hard Rule 6).

Population evidence

Tier B. Ait Chait, Mottawea, Tompkins & Hammami 2020, Sci Rep 10:17878 (in vitro minimum inhibitory concentration [MIC] assay against 12 ATCC gut commensal/pathogen strains). Desipramine was active against 10/12 strains, MIC 75-800 µg/mL. Most sensitive: Akkermansia muciniphila (MIC 75 µg/mL) and Escherichia coli (MIC 150 µg/mL). Bifidobacterium animalis showed a 3-log colony reduction and Bacteroides fragilis a >5-log reduction at 600-800 µg/mL.

Mechanism

Named: direct antimicrobial/membrane action attributed to the cationic amphiphilic tricyclic structure, a mechanism shared across several TCAs in the same study.

Counter-evidence held on record

In vitro MIC findings do not by themselves establish an in vivo dysbiosis effect. 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.

ATP production - reduced in a supraclinical neuronal model, mixed/adaptive in rat hippocampal mitochondria

Yellow — Low

See study details

Desipramine reduced cellular ATP directly in a supraclinical in vitro dopaminergic/neuroblastoma model, and shifted (not uniformly suppressed) specific ATP-pathway enzyme activities in rat hippocampal mitochondria 21 days after dosing.

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: Villa et al. found no significant bioenergetic change in light synaptic mitochondria; the cytochrome oxidase increase in non-synaptic mitochondria runs counter to a simple "ATP suppression" narrative.
  • At-risk subgroups: None established clinically; in vitro concentrations (50-60 µM) exceed typical therapeutic plasma levels.
  • Counter-evidence on record: Directionally mixed across mitochondrial compartments in the rat model (see above); not a simple, one-directional "energy depletion" finding.

Population evidence

Tier B. Lee et al. 2015, Mol Cells 38:732-738 (SH-SY5Y cells, desipramine 50-60 µM): direct ATP depletion measured alongside mitochondrial membrane depolarization. Villa et al. 2017, Neuropharmacology 121:30-38 (rat hippocampus, 15 mg/kg × 21 days): cytochrome oxidase (a terminal ATP-synthesis-pathway enzyme) activity increased in non-synaptic mitochondria while ETC complex activity decreased in heavy synaptic mitochondria - net direction is compartment-dependent, not a uniform ATP-production deficit.

Mechanism

Named: direct mitochondrial/ETC modulation; shares its underlying sources with the Mitochondrial burden entry (see Overlap map).

Counter-evidence held on record

Preclinical and, for the ATP-depletion finding, supraclinical. No validated human ATP or cellular-energy biomarker exists for monitoring. Not a basis for CoQ10, carnitine, or B-vitamin "energy support" supplementation claims (see the Coenzyme Q10 entry below and Fails verification).

Oxygen delivery/utilization

Not graded — disclosed evidence gap

See study details

No evidence at any tier, and no circulating consumer claim to rebut, was located for desipramine and hemoglobin, hematocrit, or tissue oxygen delivery.

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. Channels tried: DailyMed label (documents only a neutrophil/leukocyte blood-dyscrasia monitoring warning - a white-cell adverse-effect caution, not an erythrocyte/oxygen-delivery finding, and excluded here under Hard Rule 2 as the drug's own toxicity profile rather than a nutrient-mediated effect); Drugs.com monograph (no mention); Crossref API, query "desipramine hemoglobin hematocrit oxygen tissue" (5 results returned, all general oxygen-transport physiology papers unrelated to desipramine, zero matches); Europe PMC, PubMed, Semantic Scholar, and OpenAlex returned repeated HTTP 429 rate-limiting for this category's queries during this session and could not be completed (see access note). No circulating consumer claim regarding desipramine and oxygen-carrying capacity, hemoglobin, or hematocrit was located. Genuine literature gap as currently accessible; flagged for re-check once the rate-limited channels are reachable.

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

  • Magnesium

    Where it comes from: Consumer medication-nutrient depletion list naming desipramine/Norpramin specifically (Sources 10)

    Why it fails: No mechanism from the Step 2 screen applies: no documented renal magnesium wasting, GI chelation, or cofactor-antagonism literature for desipramine or the TCA class. Crossref search for TCA-magnesium serum-level literature returned no on-topic results. Label is silent on magnesium.

  • Vitamin B6

    Where it comes from: Same consumer source, justified there only as psychiatric drugs "alter these neurotransmitters"

    Why it fails: Vague neurotransmitter-pathway reasoning does not meet even Tier C. No study of desipramine or TCA-class effects on B6/pyridoxine status was located despite a Crossref search targeting this specifically. Label is silent on B6.

  • Vitamin B12

    Where it comes from: Same consumer source

    Why it fails: The only literature connecting TCAs/antidepressants to B12 located this session is correlational and runs the opposite direction: low baseline B12 predicts poorer antidepressant treatment response (confounding by indication, Hard Rule 6), not desipramine lowering B12. No interventional/longitudinal study showing TCA treatment reduces B12 was found.

  • Folate

    Where it comes from: Same consumer source

    Why it fails: Same confounding-by-indication problem as B12: the depression-folate-homocysteine literature describes a baseline association with depression severity and treatment response, not a desipramine-induced depletion mechanism. No drug-specific interventional evidence was found.

  • Broad undifferentiated list (Vitamin D, B1, Biotin, essential fatty acids/omega-3s, "sodium" as a deficiency claim, glutathione, calcium, vitamin K, vitamin C, vitamin B3, vitamin A, carnitine, zinc, selenium, manganese)

    Where it comes from: Same consumer source, listed under "Antidepressants" as a class with no mechanism specified for any item

    Why it fails: This is Tier D consumer content by the protocol's own definition: a depletion list without drug-specific primary citations. No drug-specific or defensible class-level primary evidence was located for any item in this list. The "sodium" item specifically inverts the real, graded finding above: desipramine's documented sodium effect is retention/dilution (SIADH), not depletion.

How the body handles this medication

Metabolism / CYP enzymes
Extensively hepatic, oxidized to the active metabolite 2-hydroxydesipramine principally by CYP2D6, with CYP1A2, CYP3A4, and CYP2C contributing. Up to a 36-fold inter-individual variation in plasma level has been reported at the same oral dose.DailyMed label; Drugs.com monograph [Sources 1-2]
Enzyme induction/inhibition
Desipramine itself inhibits CYP2D6, raising levels of co-administered CYP2D6-substrate drugs. It does not induce any CYP enzyme - the classic "accelerated catabolism" depletion mechanism (Step 2, mechanism B) is absent for this drug.DailyMed label [Source 1]
Elimination route
Approximately 70% is excreted in urine, almost entirely as metabolites after hepatic clearance; the label also notes tricyclics and their metabolites are "to some extent excreted through the gastric mucosa and reabsorbed" (enterohepatic-type recirculation).DailyMed label [Source 1]
Renal/hepatic impairment
"Known to be substantially excreted by the kidney," with higher toxicity risk flagged in renal impairment; the 2-hydroxydesipramine:desipramine ratio rises in elderly patients, attributed to decreased renal clearance with age.DailyMed label [Source 1]
Direction-of-interaction check (Hard Rule 4)
Barbiturates, alcohol, and tobacco smoke induce hepatic enzymes and reduce desipramine plasma levels. This is a substance affecting the drug, not the drug depleting a nutrient, and is filed here as a PK fact, not a graded entry.DailyMed label [Source 1]
Electrolyte/water handling
Label states hyponatremia "has occurred as a result of treatment with desipramine hydrochloride," in many cases attributed to SIADH - 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. DESIPRAMINE HYDROCHLORIDE tablet, film coated - FDA/DailyMed label — Regulatory label, Tier A. DailyMed setid a3b4b25d-0ddb-4531-badb-f1ba3168ac07.
  2. Desipramine Monograph for Professionals — Drugs.com, tertiary reference corroborating the regulatory label (CYP2D6 metabolism/inhibition, renal elimination, hematologic monitoring language).
  3. ATC/DDD Index, code N06AA01 (desipramine) — WHO Collaborating Centre for Drug Statistics Methodology. DDD 0.1 g, oral, non-selective monoamine reuptake inhibitors.
  4. Villa RF, Ferrari F, Bagini L, Gorini A, Brunello N, Tascedda F. Mitochondrial energy metabolism of rat hippocampus after treatment with the antidepressants desipramine and fluoxetine. — Neuropharmacology 2017;121:30-38. DOI 10.1016/j.neuropharm.2017.04.025. Male Sprague-Dawley rats, desipramine 15 mg/kg × 21 days. Tier B, drug-specific animal study.
  5. Lee MY, Hong S, Kim N, Shin KS, Kang SJ. Tricyclic Antidepressants Amitriptyline and Desipramine Induced Neurotoxicity Associated with Parkinson's Disease. — Mol Cells 2015;38(8):732-738. DOI 10.14348/molcells.2015.0131. SH-SY5Y cells in vitro (desipramine and amitriptyline, 50-60 µM) and C57BL/6 mice in vivo (amitriptyline arm reported; desipramine data used here from the in vitro portion only). Tier B, drug-specific.
  6. 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. Tier B, drug-specific.
  7. Crocin lessens desipramine-induced phospholipidosis biomarker levels — Acta Biomed 2023;94(2). DOI 10.23750/abm.v94i2.14442. Adult male rats, n=40/4 groups, desipramine 10 mg/kg/day intraperitoneal × 3 weeks. Tier B, drug-specific. Full author list not independently confirmed this session (bibliographic API rate-limited); title, journal, year, and findings confirmed from the publisher page directly.
  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 desipramine: 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. Desipramine Protects Neuronal Cell Death and Induces Heme Oxygenase-1 Expression in Mes23.5 Dopaminergic Neurons — PLoS ONE 2012;7(11):e50138. DOI 10.1371/journal.pone.0050138.Full text could not be opened: two separate attempts this session returned HTTP 429 at the WebFetch proxy, the second with an explicit instruction not to retry. Cited in the Oxidative stress entry from title/indexed metadata only; no detailed findings from this source are asserted as independently confirmed.
  10. 7 Important Nutrients Depleted by Psychiatric Drugs — Optimal Living Dynamics (consumer health content). Tier D. Names desipramine (Norpramin) specifically for CoQ10, magnesium, vitamin B2 ("inhibits absorption"), B6, B12, and folate, plus an undifferentiated longer list attributed only to "antidepressants." Source of the circulating claims audited in Fails verification and in the B2/CoQ10 yellow-tier entries above.
  11. Medications that Deplete B Vitamins: Why It Happens + How to Prevent Deficiency — LivOnLabs (consumer health content). Checked specifically for a tricyclic-antidepressant/desipramine mention; none found. Negative check, recorded for completeness rather than used as a claim source.
  12. Effects of desipramine on the antioxidant status in rat tissues at carrageenan-induced paw inflammation (Vircheva et al.) — Cell Biochem Funct 2012. DOI 10.1002/cbf.1812. PMID 21953526.Could not be opened at any point this session: Wiley publisher page returned HTTP 403; PubMed and Semantic Scholar pages returned no retrievable abstract text; Unpaywall confirms no open-access copy exists. Title and bibliographic existence confirmed via three independent indexes, but no findings from this source are cited anywhere in this dossier.
  13. 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, confirmed to cover antidepressants broadly via OpenAlex metadata.Whether desipramine specifically was among the tested compounds, and its individual result, could not be confirmed this session (full text/supplementary data not reachable). Not cited as evidentiary support in the Gut microbiome risk entry for this reason (Hard Rule 6 cohort test).