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Tricyclic Antidepressant (TCA) Pregnancy: Avoid if possible — neonatal withdrawal and anticholinergic effects. Sertraline preferred.

Imipramine

Brand names: Tofranil

Adult dose

Dose: Depression: 75mg OD at night initially (or 25mg TDS); increase over 1–2 weeks to 150–200mg daily; maximum 300mg daily (hospitalised). Nocturnal enuresis: 25mg at bedtime (assess after 3 months).
Route: Oral
Frequency: Once daily at night (depression) or once nightly (enuresis)
Max: 300mg daily (inpatient depression); 50mg ON (enuresis in children — weight-based)
Imipramine was the first TCA developed — prototype tricyclic. Less sedating than amitriptyline. Licensed for nocturnal enuresis in children (alongside alarm therapy). Imipramine is metabolised to desipramine (active). Cardiotoxicity in overdose — same risk profile as amitriptyline; ECG monitoring recommended at doses >100mg.

Paediatric dose

Route: Oral
Frequency: Once daily at night
Max: 50mg ON (children ≥11 years); 25mg ON (7–10 years)
BNFc: Nocturnal enuresis: 7–10 years: 25mg ON; 11–16 years: 25–50mg ON. Reassess after 3 months — do not continue without reassessment. Not licensed for depression under 18 years. Seek specialist paediatric opinion.

Dose adjustments

Renal

Use with caution — potential accumulation of active metabolite (desipramine) in severe renal impairment.

Hepatic

Avoid in severe hepatic impairment.

Clinical pearls

  • Nocturnal enuresis: imipramine is effective but NICE recommends alarm therapy first — drug therapy reserved for when alarm therapy fails or is not practical. Risk of cardiotoxicity in accidental overdose in children — store securely
  • Overdose antidote: IV sodium bicarbonate for QRS widening (TCA cardiac toxicity) — same as all TCAs
  • Metabolised to desipramine (active noradrenergic metabolite) — drug level monitoring available (combined target 200–350 ng/mL)
  • Largely superseded by SSRIs for depression — now primarily used for enuresis and occasionally treatment-resistant depression

Contraindications

  • Recent MI
  • Arrhythmias, heart block
  • Mania
  • MAOIs within 14 days
  • Closed-angle glaucoma
  • Urinary retention
  • Hypersensitivity to imipramine or TCAs

Side effects

  • Orthostatic hypotension
  • Dry mouth, constipation (anticholinergic)
  • Sedation (less than amitriptyline)
  • QTc prolongation
  • Seizures (dose-related)
  • Weight gain
  • Sexual dysfunction

Interactions

  • MAOIs — contraindicated (hypertensive crisis, serotonin syndrome)
  • CYP2D6 inhibitors (paroxetine, fluoxetine) — increase imipramine and desipramine levels
  • Antihypertensives — imipramine may antagonise or potentiate (complex)
  • Adrenaline — enhanced pressor response

Monitoring

  • ECG (QTc) at doses >100mg
  • Blood pressure (orthostatic)
  • Anticholinergic symptoms
  • Enuresis frequency (paediatric use — reassess at 3 months)

Reference: BNFc; BNF 90; NICE CG111 (Nocturnal Enuresis). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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