Imipramine

Brand Names: Tofranil

Drug Class: Tricyclic Antidepressant (TCA), Dibenzazepine derivative

Overview

Imipramine is a tricyclic antidepressant (TCA) primarily used to treat major depressive disorder. It works by increasing the levels of serotonin and norepinephrine in the brain. It is also used off-label for conditions like panic disorder, neuropathic pain, and nocturnal enuresis (bedwetting) in children.

Mechanism of Action

Imipramine inhibits the reuptake of serotonin and norepinephrine at presynaptic neuronal membranes, increasing their concentration in the synaptic cleft. It also has significant anticholinergic, antihistaminic, and alpha-1 adrenergic blocking properties.

Indications

  • Major Depressive Disorder
  • Nocturnal Enuresis (bedwetting) in children aged 6 years and older
  • Off-label: Panic disorder, Neuropathic pain, Attention-deficit/hyperactivity disorder (ADHD)

Dosage

For depression in adults: Initial dose 75 mg/day orally, may increase gradually to 150-200 mg/day (max 300 mg/day). For elderly: Start at 30-40 mg/day. For nocturnal enuresis in children (≥6 years): 25 mg orally 1 hour before bedtime, may increase to 50 mg if needed (max 50 mg for children <12 years, 75 mg for ≥12 years).

Contraindications

  • Hypersensitivity to imipramine or other TCAs
  • Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOIs
  • During acute recovery phase after myocardial infarction
  • Narrow-angle glaucoma
  • Severe urinary retention

Side Effects

  • Common: Dry mouth, blurred vision, constipation, urinary retention, dizziness, drowsiness, weight gain, orthostatic hypotension
  • Serious: Cardiac arrhythmias, seizures, serotonin syndrome, neuroleptic malignant syndrome, suicidal ideation, bone marrow depression, hepatotoxicity

Interactions

  • MAOIs: Risk of serotonin syndrome and hypertensive crisis
  • Other serotonergic drugs (SSRIs, SNRIs, triptans): Increased risk of serotonin syndrome
  • Anticholinergic drugs: Enhanced anticholinergic effects
  • Antihypertensives: May reduce antihypertensive effect
  • CNS depressants (alcohol, benzodiazepines): Enhanced sedation
  • Sympathomimetics: Increased cardiovascular effects
  • CYP2D6 inhibitors (fluoxetine, paroxetine): Increased imipramine levels