II. 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)

III. 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)

IV. Preparations: Tetracyclic Antidepressants (rarely used)

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

V. Adverse Effects

  1. General
    1. Unable to tolerate full dose: 80%
    2. Medication discontinued due to adverse effects: 30%
    3. Secondary amines 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
    1. Prevent by tapering gradually, even over months

VI. Drug Interactions: Cardiovascular

  1. Absolute Contraindications
    1. Clonidine (Hypotension)
    2. 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)

VII. Precautions: Overdosage effects

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

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