Tofranil (imipramine hydrochloride) is a well-established tricyclic antidepressant (TCA) with a robust clinical history spanning decades. It is primarily indicated for the treatment of major depressive disorder and has proven efficacy in managing symptoms of depression by modulating key neurotransmitters in the brain. Its use extends to enuresis in children and off-label applications for certain anxiety and chronic pain conditions, under strict medical supervision. As a cornerstone in psychopharmacology, Tofranil offers a reliable option when newer antidepressants are ineffective or poorly tolerated.

Features

• Active ingredient: Imipramine hydrochloride
• Available in 10 mg, 25 mg, and 50 mg oral tablets
• Belongs to the tricyclic antidepressant (TCA) class
• Functions as a serotonin and norepinephrine reuptake inhibitor
• Bioavailability of approximately 40–70% after oral administration
• Peak plasma concentrations reached within 1–2 hours
• Half-life ranges from 11 to 25 hours
• Metabolized hepatically via cytochrome P450 enzymes (CYP2D6, CYP2C19)
• Excreted primarily renally

Benefits

• Effectively alleviates symptoms of major depressive disorder, including low mood, anhedonia, and fatigue.
• Provides an alternative for patients who have not responded to SSRIs or SNRIs.
• May help reduce the frequency of bedwetting in children aged 6 years and older when used for enuresis.
• Can be beneficial in managing certain neuropathic pain conditions and panic disorder off-label.
• Long half-life supports once-daily dosing in many cases, improving adherence.
• Well-studied profile with extensive real-world evidence supporting its efficacy and safety under medical guidance.

Common use

Tofranil is most commonly prescribed for the treatment of major depressive disorder in adults. It is also FDA-approved for the treatment of nocturnal enuresis (bedwetting) in children aged 6 years and older, after organic causes have been ruled out. Off-label, it may be used under specialist supervision for conditions such as panic disorder, neuropathic pain, and migraine prophylaxis. Its use is generally reserved for cases where first-line treatments like SSRIs have been ineffective or caused unacceptable side effects.

Dosage and direction

Dosage must be individualized based on patient response, tolerance, and indication. For depression in adults, the initial dose is usually 25–50 mg orally once daily at bedtime, which may be gradually increased by 25–50 mg every few days as tolerated. The typical maintenance dose ranges from 50–150 mg daily, though some patients may require up to 300 mg/day in divided doses. For enuresis in children, the recommended starting dose is 25 mg once daily 1 hour before bedtime; may be increased to 50 mg nightly in children aged 6–12 years, and up to 75 mg nightly for those aged 12 and older. Dosage should be tapered gradually when discontinuing to avoid withdrawal symptoms. Always take exactly as prescribed; do not crush or split tablets unless advised.

Precautions

Use with caution in patients with a history of cardiovascular disease, as TCAs can cause orthostatic hypotension, tachycardia, and prolonged QT interval. Regular ECG monitoring may be necessary. Avoid abrupt discontinuation. May impair mental or physical abilities required for driving or operating machinery. Use cautiously in patients with glaucoma, urinary retention, seizure disorders, or hyperthyroidism. Elderly patients are more susceptible to anticholinergic, sedative, and cardiovascular effects. Pregnancy Category C: use only if potential benefit justifies potential risk to the fetus. Not recommended during breastfeeding.

Contraindications

Hypersensitivity to imipramine or other TCAs. Should not be used concomitantly with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOI therapy due to risk of serotonin syndrome. Contraindicated in the acute recovery phase after myocardial infarction. Do not use in patients with severe liver impairment. Contraindicated in patients with narrow-angle glaucoma. Not recommended in those with a history of severe constipation or paralytic ileus.

Possible side effect

Common side effects may include dry mouth, drowsiness, dizziness, constipation, blurred vision, weight gain, and orthostatic hypotension. Less frequently, patients may experience sweating, nausea, sexual dysfunction, insomnia, or tremor. Serious side effects requiring immediate medical attention include chest pain, irregular heartbeat, severe dizziness, fainting, difficulty urinating, seizures, signs of infection (e.g., fever, sore throat), and symptoms of serotonin syndrome (agitation, hallucinations, fever, sweating). May also cause changes in blood sugar levels.

Drug interaction

MAOIs: risk of severe serotonin syndrome. Anticholinergic drugs: enhanced anticholinergic effects. CNS depressants (e.g., alcohol, benzodiazepines): additive sedation. Sympathomimetics: increased risk of hypertension. Antihypertensives: may reduce efficacy. CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) can increase imipramine levels. Warfarin: may increase anticoagulant effect. Thyroid hormones: may increase risk of cardiac arrhythmias. Use cautiously with other QT-prolonging agents.

Missed dose

If a dose is missed, take it as soon as remembered unless it is almost time for the next dose. Do not double the dose to catch up. If regular dosing is interrupted, contact a healthcare provider for guidance, especially if multiple doses are missed, as this may increase the risk of withdrawal symptoms or relapse.

Overdose

Tofranil overdose can be severe and potentially fatal. Symptoms may include severe drowsiness, agitation, confusion, hallucinations, tachycardia, hypotension, seizures, respiratory depression, coma, and cardiac arrhythmias. ECG changes (prolonged QT, QRS widening) are common. Immediate medical attention is critical. Treatment is supportive and may include gastric lavage, activated charcoal, ECG monitoring, and management of arrhythmias with sodium bicarbonate or other antiarrhythmics.

Storage

Store at room temperature (15–30°C or 59–86°F) in a tightly closed container, away from light, moisture, and heat. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging. Dispose of unused medication via a drug take-back program or according to local guidelines to prevent misuse.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Do not disregard professional medical advice or delay in seeking it because of something you have read here. The efficacy and safety of Tofranil should be evaluated by a healthcare professional based on individual patient factors.

Reviews

“After trying several SSRIs with limited success, my psychiatrist prescribed Tofranil. It took a few weeks to adjust to the side effects, but my depression symptoms have significantly improved. The dry mouth was bothersome at first, but it lessened over time.” – Maria, 42

“Used for neuropathic pain off-label. Not a first-line choice, but it helped where gabapentin failed. Sedation was an issue initially, so I take it at night. Regular blood pressure checks are a must.” – James, 58

“My 8-year-old son was prescribed Tofranil for enuresis. It reduced bedwetting frequency within two weeks. We monitor for mood changes carefully, but so far, so good.” – Parent

“Effective for my treatment-resistant depression, but the weight gain has been significant. Working with my doctor to manage diet and exercise alongside medication.” – Thomas, 36