II. Background

  1. Fused three ring compound, active at central nerve Synapses
  2. Tricyclic Antidepressants block reuptake of monoamine Neurotransmitters (Norepinephrine and Serotonin)
  3. Reuptake inhibition increases Neurotransmitter concentrations at the Synapse, as well as down regulation of post-synaptic receptors
  4. Historically used as Antidepressants, and largely replaced by SSRI and SNRI Antidepressants

IV. Pharmacokinetics

  1. Tricyclic Antidepressants are well absorbed and widely distributed
  2. High plasma Protein binding
  3. Most commonly used Tricyclic Antidepressants have long half lives (up to 45 hours for Amitriptyline and Nortriptyline)
    1. Half life is even more prolonged in the elderly (slower Drug Metabolism)

V. Preparations: Tricyclic Antidepressants - First generation (Tertiary amines)

  1. General
    1. Greater Analgesic properties than second generation
  2. Agents
    1. Amitriptyline (Elavil, Endep)
    2. Clomipramine (Anafranil)
    3. Imipramine (Tofranil)
    4. Trimipramine (Surmontil)
    5. Doxepin (Sinequan, Adapin)

VI. Preparations: Tricyclic Antidepressants - Second generation (Secondary amines)

  1. General
    1. Less adverse effects than first generation
  2. Agents
    1. Nortriptyline (Pamelor, Aventyl)
    2. Desipramine (Norpramin)
    3. Protriptyline (Vivactil)

VII. Preparations: Tetracyclic Antidepressants (rarely used)

  1. Maprotiline (Ludiomil)
    1. Increased seizure Incidence
  2. Amoxapine (Asendin)
    1. Severe Extrapyramidal Side Effects

VIII. Adverse Effects

  1. General (applies primarily to the full doses historically used in Major Depression)
    1. Unable to tolerate full Major Depression dose: 80%
      1. Lower doses in Chronic Pain are better tolerated
      2. Medication discontinued due to adverse effects: 30%
    2. Secondary amines (e.g. Nortriptyline) are much better tolerated
  2. Anticholinergic Symptoms
    1. Dry Mouth
    2. Constipation
    3. Blurred Vision
  3. Antihistaminergic effects
    1. Sedation (limits use)
    2. Weight gain
  4. Serotoninergic Effects
    1. Sexual Dysfunction
  5. Cardiovascular effects: Orthostatic Hypotension
  6. Pro-Arrhythmic Effects (Class I Antiarrhythmic type)
    1. Sinus Tachycardia
    2. Supraventricular Tachycardia
    3. Ventricular Tachycardia
    4. Ventricular Fibrillation
    5. Prolongation of PR, QRS or QT Interval
    6. ST Segment and T Wave changes
    7. Bundle Branch Block or complete Heart Block
  7. Antidepressant Withdrawal (shaking chills, myalgias, malaise)
    1. See Antidepressant Withdrawal
    2. Prevent by tapering gradually, even over months

IX. Drug Interactions: Cardiovascular

  1. Absolute Contraindications
    1. Clonidine (Hypotension)
    2. Monoamine Oxidase Inhibitors
    3. Class I Antiarrhythmics (e.g. Quinidine, Flecainide)
      1. Prolonged QT Interval
  2. Other interactions
    1. Coumadin (increases ProTime)
    2. Aspirin (increases Tricyclic Antidepressant level)
    3. Fluoxetine (increases Tricyclic Antidepressant level)

X. Precautions: Overdosage effects

  1. See Tricyclic Antidepressant Overdose
  2. Cardiotoxicity
  3. Death

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Related Studies

Ontology: Tricyclic Antidepressive Agents (C0003290)

Definition (NCI_NCI-GLOSS) A type of drug used to treat depression.
Definition (NCI) Mood-stimulating agents which contain a tricyclic structure and are used primarily in the treatment of affective disorders and related conditions. This group of agents appear to act through brain catecholamine systems.
Definition (MSH) Substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system.
Definition (CSP) class of antidepressants with 3 ring chemical structures; mechanism unknown, but believed to involve serotonin metabolism, transport, or receptor sensitivity.
Concepts Pharmacologic Substance (T121)
MSH D000929
SnomedCT 283013009, 33219003, 373253007
LNC LP14735-2, MTHU001920
English Agents, Tricyclic Antidepressive, Antidepressants, Tricyclic, Antidepressive Agents, Tricyclic, Tricyclic Antidepressants, Antidepressant Drugs, Tricyclic, Drugs, Tricyclic Antidepressant, Tricyclic antidepressant drug, TRICYCLIC ANTIDEPRESSANTS, tricyclic antidepressive agents, tricyclic antidepressants (medication), tricyclic antidepressants, [CN601] TRICYCLIC ANTIDEPRESSANTS, Tricyclic Antidepressive Agents, anti depressant tricyclic, tricyclic antidepressant drugs, tricyclic anti depressant, tricyclic anti-depressants, antidepressant drug tricyclic, antidepressants tricyclic, anti depressants tricyclic, antidepressants tricyclics, Tricyclic Antidepressant, Tricyclic antidepressant drug (substance), Tricyclic antidepressants, tricyclic antidepressant, Tricyclic antidepressant, Tricyclic antidepressant (product), Tricyclic antidepressant (substance), Tricyclic antidepressant, NOS, Tricyclic Antidepressant Drugs, Tricyclics
French Médicaments antidépresseurs tricycliques, Antidépresseurs tricycliques
Swedish Antidepressiva medel, tricykliska
Czech antidepresiva tricyklická
Finnish Trisykliset masennuslääkkeet
Italian Farmaci antidepressivi triciclici, Antidepressivi triciclici
Polish Leki przeciwdepresyjne trójcykliczne
Japanese 三環系抗うつ剤, 抗うつ剤-三環系, 三環式抗抑うつ薬, 三環系抗うつ薬, 三環系抗鬱剤, 抗鬱剤-三環系, 三環式抗抑鬱薬, 抗鬱薬-三環系
Portuguese Agentes Antidepressivos Tricíclicos, Antidepressivos Tricíclicos
Spanish Antidepresivos Tricíclicos, Agentes Antidepresivos Tricíclicos, antidepresivo tricíclico (producto), antidepresivo tricíclico (sustancia), antidepresivo tricíclico
German Antidepressiva, trizyklische, Antidepressivische Mittel, tricyclische, Trizyklische antidepressive Mittel

Ontology: Tetracyclic antidepressant (C0360108)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
SnomedCT 11430001, 372576002
English tetracyclic antidepressant, antidepressants tetracyclic, Tetracyclic antidepressant, Tetracyclic antidepressant drug, Tetracyclic antidepressant (product), Tetracyclic antidepressant (substance), Tetracyclic antidepressant, NOS
Spanish antidepresivo tetracíclico (producto), antidepresivo tetracíclico (sustancia), antidepresivo tetracíclico