BSN Tracker

imipramine

Brand: Tofranil

⚠ BBW Beers Criteria TDM Required Prototype: amitriptyline
Drug Class: tricyclic antidepressant (TCA)
Drug Family: antidepressant
Subclass: tertiary amine TCA
Organ Systems: cns

Mechanism of Action

Inhibits serotonin and norepinephrine reuptake; also blocks muscarinic, histamine H1, and alpha-1 adrenergic receptors. The noradrenergic effects on bladder sphincter are responsible for its use in nocturnal enuresis.

NET (norepinephrine transporter)SERT (serotonin transporter)muscarinic receptorsH1 histamine receptoralpha-1 adrenergic receptor

Indications

  • major depressive disorder
  • nocturnal enuresis in children
  • panic disorder
  • off-label: ADHD
  • off-label: chronic pain

Contraindications

  • concurrent MAOI use
  • acute post-MI recovery
  • QT prolongation

Adverse Effects

Common

  • dry mouth
  • constipation
  • urinary retention
  • blurred vision
  • sedation
  • orthostatic hypotension

Serious

  • cardiac arrhythmias
  • QT prolongation
  • seizures in overdose
  • suicidal ideation

Pharmacokinetics (ADME)

Absorption well absorbed orally; first-pass metabolism results in bioavailability ~19-35%
Distribution protein binding ~85-95%; large Vd; highly lipophilic
Metabolism demethylated to active metabolite desipramine via CYP2D6; further oxidized by CYP1A2 and CYP2C19
Excretion primarily renal as metabolites
Half-life 9-28 hours
Onset 2-4 weeks for antidepressant effect
Peak 1-2 hours
Duration 24 hours
Protein Binding 85-95%
Vd 9-23 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
MAOIs serotonin syndrome and hypertensive crisis contraindicated
CYP2D6 inhibitors increase imipramine and desipramine levels major
antihypertensives orthostatic hypotension potentiation moderate

Nursing Considerations

  1. Imipramine has the first FDA approval for pediatric nocturnal enuresis; doses for this indication (25-50 mg at bedtime) are much lower than antidepressant doses.
  2. Cardiac monitoring is essential — baseline ECG, periodic ECGs, and immediate evaluation if palpitations, syncope, or irregular rhythm develops.
  3. Store medication securely and dispense in limited quantities (1-2 week supply) in patients with suicidal ideation, as TCA overdose is highly lethal at low multiples of therapeutic dose.
  4. Orthostatic hypotension assessment at each visit: measure supine and standing BP after 1 minute of standing; hold drug and notify prescriber if orthostatic drop >20 mmHg systolic.

Clinical Pearls

  • Imipramine was the first clinically used antidepressant, discovered serendipitously in the 1950s; its discovery established the monoamine hypothesis of depression.
  • For nocturnal enuresis, imipramine's noradrenergic effects increase bladder outlet resistance and reduce bladder contractility, allowing children to maintain continence through the night.

Safety Profile

Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Major Depressive Disorder Nocturnal Enuresis In Children Off-label: ADHD Off-label: Chronic Pain Panic Disorder Tricyclic Antidepressant (TCA)
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