Pharm

Tricyclic Antidepressant

search

Tricyclic Antidepressant, Tetracyclic Antidepressant

  • 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
  • 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)
  • 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)
  • 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)
  • Preparations
  • Tetracyclic Antidepressants (rarely used)
  1. Maprotiline (Ludiomil)
    1. Increased seizure Incidence
  2. Amoxapine (Asendin)
    1. Severe Extrapyramidal Side Effects
  • 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
  • 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)
  • Precautions
  • Overdosage effects
  1. See Tricyclic Antidepressant Overdose
  2. Cardiotoxicity
  3. Death