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imipramine

Adjunctive therapy

Brand: Tofranil

Published 2025-12-22 · Last reviewed 2025-12-29 · 4 references

Content sourced from FDA labeling (DailyMed) and peer-reviewed literature.

Print sheet Review evidence

At a glance

Class: Adjunctive therapy·Typical dose: Depression (adult): typical starting doses are 25–50 mg at bedtime, with increases of 25–50 mg every 3–7 days to 150–200 mg/day (single bedtime dose or divided). Maximum 300 mg/day is typically reserved for inpatient settings with monitoring.·Half-life: Single-dose mean 19 h; Steady-state mean 24 h·TDM range: 150–300 ng/mL·LAI available: No

Class: Adjunctive therapy
Typical dose: Depression (adult): typical starting doses are 25–50 mg at bedtime, with increases of 25–50 mg every 3–7 days to 150–200 mg/day (single bedtime dose or divided). Maximum 300 mg/day is typically reserved for inpatient settings with monitoring.
Half-life: Single-dose mean 19 h; Steady-state mean 24 h
TDM range: 150–300 ng/mL
LAI available: No

Quick answers

What is imipramine?: Imipramine is a tertiary amine tricyclic antidepressant used in treatment-resistant depression and pediatric nocturnal enuresis; its active metabolite desipramine adds potent noradrenergic activity.
What is Tofranil?: Tofranil is a brand name for imipramine.
What is Tofranil (imipramine) used for?: Label indications include: Depression; nocturnal enuresis in children (lower doses).
What drug class is Tofranil (imipramine)?: Tricyclic Antidepressant.
What is the mechanism of action of Tofranil (imipramine)?: Tricyclic antidepressant; blocks serotonin and norepinephrine reuptake with anticholinergic effects.
What strengths does Tofranil (imipramine) come in?: Tablets: 10 mg, 25 mg, 50 mg; capsules (pamoate) 75 mg, 100 mg, 125 mg, 150 mg.

General information

Imipramine is a tertiary amine tricyclic antidepressant used in treatment-resistant depression and pediatric nocturnal enuresis; its active metabolite desipramine adds potent noradrenergic activity.

Therapeutic benefit correlates with combined imipramine + desipramine concentrations (goal 150–300 ng/mL) guided by TDM; higher levels markedly increase anticholinergic and cardiac toxicity.

Substantial anticholinergic, antihistamine, and α-adrenergic blockade drive sedation, orthostasis, weight gain, constipation, and urinary retention; baseline ECG is advisable before initiating therapy in adults >40 years or those with cardiovascular disease.

The compare tool, the evidence library, and the Bipolar hub support side-by-side TCA counseling and augmentation planning.

U.S. approvals

Major depressive disorder (1959)
Nocturnal enuresis (children ≥6 years) (1965)

Formulations & strengths

Tablets: 10 mg, 25 mg, 50 mg; capsules (pamoate) 75 mg, 100 mg, 125 mg, 150 mg.

Generic availability

Generic tablets and capsules widely available.

Because of overdose lethality and cardiovascular risks, prescribers often restrict quantities and reserve imipramine for patients who fail SSRIs/SNRIs.

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Mechanism of action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Inhibits serotonin and norepinephrine reuptake transporters; desipramine metabolite enhances noradrenergic tone at steady state.

Antagonizes muscarinic, histamine H1, and α1-adrenergic receptors, explaining anticholinergic effects, sedation, weight gain, and orthostasis.

SERT and NET inhibition.
Strong M1, H1, and α1 antagonism.
Sodium channel blockade contributes to arrhythmogenicity in overdose.

Metabolism & pharmacokinetics

Oral bioavailability ~40–60%; peak concentrations occur 2–6 hours post-dose.
Hepatic metabolism via CYP2D6 (major) and CYP1A2/CYP3A4 to desipramine; half-life 12–24 hours (imipramine) and 12–30 hours (desipramine).
Protein binding ~80%; elimination primarily renal as metabolites with <5% unchanged drug.
Half-life extends in CYP2D6 poor metabolizers, elderly patients, and hepatic impairment, warranting lower dosing and TDM.

Dosing & administration

Depression (adult): typical starting doses are 25–50 mg at bedtime, with increases of 25–50 mg every 3–7 days to 150–200 mg/day (single bedtime dose or divided). Maximum 300 mg/day is typically reserved for inpatient settings with monitoring.
Nocturnal enuresis (children ≥6 years): typical starting doses are 10–25 mg at bedtime, titrated by 10 mg weekly to 50 mg (ages 6–12) or 75 mg (≥12 years); tapers after 2–3 months are often used to reassess need.
Starting and target doses are often reduced in older adults, hepatic impairment, or when co-administered with strong CYP2D6 inhibitors; slower titrations are common when tolerability issues arise.
Tapers are typically gradual (≥4 weeks) to reduce cholinergic rebound, anxiety, and insomnia.

Monitoring & labs

Baseline ECG and electrolytes when cardiac risk is present or when higher doses are used; recheck ECG when symptoms (palpitations, syncope) occur or when QT-active drugs are added.
Anticholinergic adverse effects (constipation, urinary retention, delirium), especially in older adults; dose reduction is often safer than adding more anticholinergics.
TDM for suspected toxicity, nonadherence, or poor response, particularly when CYP2D6 inhibitors are co-prescribed.

TCAs have high overdose lethality; monitoring is as much about safety planning and dispensing quantities as it is about symptom response.

Adverse effects

FDA boxed warnings

Antidepressants increase the risk of suicidal thoughts and behaviors in children, adolescents, and young adults; close monitoring is typically advised.

Common side effects (≥10%)

Anticholinergic effects: Dry mouth, blurred vision, constipation, urinary retention—prophylactic bowel regimens are sometimes used proactively.
Sedation and fatigue: Dosing is often weighted toward bedtime; daytime drowsiness can be a limiting effect.
Orthostatic hypotension: Education often includes slow position changes and adequate hydration.
Weight gain: Weight/BMI are commonly tracked; lifestyle interventions may help.
Sexual dysfunction: Discussions often cover expectations and management strategies.

Other notable effects

Cardiac conduction abnormalities (QTc prolongation, QRS widening); baseline and follow-up ECGs are often considered.
Seizure threshold reduction, especially when serum levels exceed 300 ng/mL.
Hyponatremia/SIADH (rare), particularly in older adults or diuretic use.
High lethality in overdose—safe storage and limited dispensing are emphasized when suicide risk is elevated.

Interactions

Contraindicated with MAOIs or within 14 days of MAOI therapy (hypertensive crisis/serotonin syndrome).
Strong CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine, bupropion) elevate imipramine/desipramine levels—dose reductions may be needed, and TDM can help guide dosing.
CYP3A4 inducers (carbamazepine, rifampin) and smoking can lower exposure; dose may need adjustment based on response.
Serotonergic agents increase serotonin syndrome risk; closer follow-up is often used when combinations occur.
Additive QTc prolongation with antiarrhythmics, certain antipsychotics, or macrolide antibiotics—ECG monitoring is often considered when combining.
Alcohol and CNS depressants exaggerate sedation; anticholinergics amplify cognitive impairment and urinary retention.

Other useful information

Baseline ECG/electrolytes and periodic monitoring are often considered, particularly when doses exceed 150 mg/day.
Therapeutic drug monitoring is valuable for poor response, suspected nonadherence, or signs of toxicity.
Counseling often covers overdose risks and safe storage; limited dispensing with close follow-up is sometimes used.

References

Related hubs:SMI toolkit·Support resources