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

Ontology: Imipramine (C0020934)

Definition (NCI) A synthetic tricyclic derivative, antidepressant Imipramine enhances monoamine neurotransmission in certain areas of the brain. It also induces sedation through histamine 1 receptor blockage; hypotension through beta-adrenergic blockage; and diverse parasympatholytic effects. Imipramine has less sedative effect than other members of its therapeutic family. It is used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. (NCI04)
Definition (MSH) The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group.
Definition (CSP) dibenzazepine tricyclic antidepressant.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D007099
SnomedCT 36113004, 372718005
LNC LP16166-8, MTHU005180
English Imipramine, Imidobenzyle, Imizin, Norchlorimipramine, 5H-Dibenz(b,f)azepine-5-propanamine, 10,11-dihydro-N,N-dimethyl-, Imipramine [Chemical/Ingredient], imipramine, IMIPRAMINE, Imipramine (product), Imipramine (substance)
Swedish Imipramin
Czech imipramin
Finnish Imipramiini
Russian IMIZIN, IMIDOBENZIL, IMIPRAMIN, ИМИДОБЕНЗИЛ, ИМИЗИН, ИМИПРАМИН
Japanese イミプラミン塩酸塩, イミドベンジル, イミドール, 塩酸イミプラミン, トフラニール, イミジン, イミプラミン
Croatian IMIPRAMIN
Polish Imipramina, Tofranil
Spanish imipramina (producto), imipramina (sustancia), imipramina, Imipramina, Imizina, Imidobencil
French Imipramine
German Imidobenzyle, Imipramin, Imizin
Italian Imipramina
Portuguese Imidobenzila, Imipramina, Imizina

Ontology: Tofranil (C0025231)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D007099
English tofranil, Tofranil