III. Background

  1. See Tricyclic Antidepressant
  2. Imipramine was the prototypal, first marketed Tricyclic Antidepressant (first synthesized in 1951, released in 1957)

IV. Safety

  1. Unknown safety in pregnancy
  2. Safe in Lactation

V. Mechanism

  1. See Tricyclic Antidepressant
  2. Imipramine inhibits both Serotonin and Norepinephrine reuptake
  3. Imipramine is demethylated to Desipramine, which primarily inhibits Norepinephrine reuptake

VI. Pharmacokinetics

  1. Obtain serum levels in pediatric population
  2. Avoid as full dose Antidepressant
  3. Serum Half Life: 11 to 25 hours
  4. Therapeutic plasma level: 200 to 350

VII. Dosing: Major Depression

  1. Adults
    1. Start: 50 to 75 mg orally at bedtime (or divided twice daily)
    2. Titrate to 75 to 100 mg orally at bedtime (or divided twice daily)
    3. Maximum: 150 mg mg/day
    4. Therapeutic range 50 to 150 mg/day
  2. Teens and Elderly
    1. Start 30 to 40 mg orally at bedtime
    2. Advance to 50 to 100 mg orally daily or divided twice daily as tolerated and to effect
    3. Maximum: 100 mg/day

VIII. Dosing: Nocturnal Enuresis in Children

  1. Consider other measures for Nocturnal Enuresis first
  2. Consider baseline EKG before starting medication
  3. Initial dose
    1. Avoid in age <6 years
    2. Start at 10 mg orally nightly given one hour before bedtime
  4. Maximum dosing: up to 0.9 to 1.5 mg/kg
    1. Age 6-8 years
      1. May increase dose by 10 mg every 1-2 weeks as needed up to 25-50 mg per night one hour before bed
    2. Age 8-12 years
      1. May increase dose by 10 mg every 1-2 weeks as needed up to 50 mg per night one hour before bed
    3. Age over 12 years
      1. May increase dose by 10 mg every 1-2 weeks as needed up to 75 mg per night one hour before bed
  5. Discontinue after 3-6 months (some guidelines suggest maximum of 3 months)
    1. Taper to one half dose nightly for 2 weeks
    2. Taper to one half dose every other night for 2 weeks

IX. Efficacy: Nocturnal Enuresis

  1. Response in up to 60% of children
  2. Relapse is common soon after stopping medication

X. Adverse effects

  1. See Tricyclic Antidepressants
  2. Tricyclic Antidepressant Overdose
  3. Significant adverse effects
    1. Anticholinergic Symptoms
    2. Drowsiness (but less than with Amitriptyline)
    3. Sleep problems
    4. Gastrointestinal upset
    5. Orthostatic Hypotension
    6. Cardiac Arrhythmia (Quinidine-like effect)
    7. Weight gain

XI. Precautions

  1. See Tricyclic Antidepressants
  2. Serious cardiotoxicity in overdosage

XIII. References

  1. (2023) Med Lett Drugs Ther 62(1592): 25-32
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 38-9
  3. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  4. Thiedke (2003) Am Fam Physician 67:1499-510 [PubMed]

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Related Studies

Cost: Medications

imipramine (on 9/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
IMIPRAMINE HCL 10 MG TABLET Generic $0.09 each
IMIPRAMINE HCL 25 MG TABLET Generic $0.09 each
IMIPRAMINE HCL 50 MG TABLET Generic $0.14 each
IMIPRAMINE PAMOATE 75 MG CAP Generic $5.00 each