Tofranil

Tofranil (imipramine hydrochloride) is a tricyclic antidepressant (TCA) with a well-established efficacy profile for managing major depressive disorders, particularly in cases where first-line treatments have proven insufficient. As one of the earliest developed antidepressants, it remains a cornerstone in psychopharmacology due to its robust mechanism of action and predictable therapeutic outcomes. Its use extends beyond depression to several off-label applications, supported by decades of clinical evidence and a deep understanding of its pharmacokinetic properties.

Features

• Active ingredient: Imipramine hydrochloride
• Drug class: Tricyclic antidepressant (TCA)
• Available forms: 10 mg, 25 mg, 50 mg oral tablets
• Mechanism: Potent inhibitor of norepinephrine and serotonin reuptake
• Half-life: Approximately 11–25 hours
• Bioavailability: High oral absorption with significant first-pass metabolism

Benefits

• Provides effective relief from symptoms of major depressive disorder, including low mood, anhedonia, and psychomotor retardation.
• Demonstrates efficacy in treatment-resistant depression where SSRIs or SNRIs have failed.
• Offers additional therapeutic benefits for certain anxiety disorders, neuropathic pain, and enuresis.
• Supports long-term maintenance therapy to prevent relapse in chronic depressive conditions.
• Improves sleep architecture and reduces somatic symptoms associated with depression.
• Serves as a cost-effective alternative to newer antidepressants with comparable efficacy in indicated populations.

Common use

Tofranil is primarily indicated for the treatment of major depressive disorder (MDD) in adults. Its use is often reserved for cases where selective serotonin reuptake inhibitors (SSRIs) or other first-line antidepressants have been ineffective or poorly tolerated. Beyond depression, it is FDA-approved for the management of nocturnal enuresis in children aged 6 years and older, though this application requires careful pediatric supervision. Off-label uses include panic disorder, generalized anxiety disorder, neuropathic pain syndromes (such as diabetic neuropathy or postherpetic neuralgia), and adjunctive therapy in certain chronic pain conditions. Its utility in these areas stems from its dual action on norepinephrine and serotonin pathways, which modulates both mood and pain perception.

Dosage and direction

Dosage must be individualized based on severity of symptoms, patient response, and tolerability. For depression in adults, initial dosing typically begins at 25–50 mg orally once daily at bedtime, gradually increasing by 25 mg every 3–7 days as tolerated. The therapeutic range for depression is generally 75–150 mg daily, though some patients may require up to 300 mg/day in divided doses. For elderly patients or those with hepatic impairment, initiation at 10–25 mg daily is recommended with slower titration. For pediatric enuresis (ages 6+), the starting dose is 25 mg one hour before bedtime, which may be increased to 50 mg nightly if needed. Maximum dose for enuresis should not exceed 50 mg for children under 12 years or 75 mg for those 12 and older. Tablets should be swallowed whole with water; administration with food may minimize gastrointestinal upset. Regular monitoring of therapeutic response and side effects is essential during dose adjustments.

Precautions

Tofranil carries several important precautions. It may prolong the QT interval, increasing risk of serious arrhythmias, particularly in patients with pre-existing cardiac conditions or electrolyte imbalances. Baseline and periodic ECG monitoring is advised. Use with caution in patients with a history of seizures, as it lowers the seizure threshold. It can cause orthostatic hypotension; advise patients to rise slowly from sitting or lying positions. Anticholinergic effects (e.g., dry mouth, constipation, urinary retention) are common and may be problematic for elderly patients or those with prostatic hypertrophy. May cause drowsiness or blurred vision; patients should avoid driving or operating machinery until response is known. Abrupt discontinuation may lead to withdrawal symptoms including nausea, headache, and malaise; taper gradually over several weeks.

Contraindications

Tofranil is contraindicated in patients with known 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. Avoid use in patients with untreated narrow-angle glaucoma or severe urinary retention. Not recommended during pregnancy unless potential benefit justifies potential risk to the fetus. Contraindicated in breastfeeding due to excretion in breast milk.

Possible side effect

Common side effects (≥1%) include dry mouth, blurred vision, constipation, dizziness, drowsiness, weight gain, orthostatic hypotension, and increased sweating. Less frequently (0.1–1%), patients may experience tachycardia, palpitations, confusion, nightmares, tinnitus, rash, or sexual dysfunction. Rare but serious adverse effects (<0.1%) include agranulocytosis, seizures, hepatitis, paralytic ileus, and neuroleptic malignant syndrome. Psychiatric side effects such as anxiety, insomnia, or hypomania may occur, particularly in bipolar patients. Elderly patients are more susceptible to anticholinergic and cardiovascular effects.

Drug interaction

Tofranil interacts significantly with multiple drug classes. Concomitant use with MAOIs may cause hypertensive crisis or serotonin syndrome. CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) can increase imipramine levels. Anticholinergic drugs may potentiate side effects. May enhance effects of CNS depressants including alcohol, benzodiazepines, and opioids. Concurrent use with other QT-prolonging agents (e.g., antipsychotics, antiarrhythmics) increases arrhythmia risk. Sympathomimetics may lead to hypertension or tachycardia. Barbiturates may reduce imipramine levels through enzyme induction. Antihypertensives may have reduced efficacy.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next scheduled dose. In that case, skip the missed dose and resume the regular dosing schedule. Do not double the dose to make up for a missed one. Consistent daily administration at the same time(s) is important to maintain steady plasma concentrations. Patients should contact their healthcare provider if multiple doses are missed or if uncertainty exists about how to resume dosing.

Overdose

Tofranil overdose is potentially fatal and constitutes a medical emergency. Symptoms may include severe drowsiness, agitation, confusion, hallucinations, tachycardia, hypotension, respiratory depression, seizures, coma, and cardiac arrhythmias. QT prolongation and torsades de pointes may occur. Management involves immediate gastric lavage if presented early, activated charcoal, and comprehensive supportive care with continuous cardiac monitoring. There is no specific antidote; treatment is symptomatic and supportive. Sodium bicarbonate may be administered for QRS widening. Forced diuresis is not effective due to extensive protein binding.

Storage

Store at controlled room temperature (20–25°C or 68–77°F) in a tight, light-resistant container. Keep away from moisture and excessive heat. Do not freeze. Keep out of reach of children and pets. Do not use beyond the expiration date printed on the packaging. Properly dispose of any unused or expired medication through take-back programs or following FDA-recommended disposal methods.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Tofranil is a prescription medication that should be used only under the supervision of a qualified healthcare professional. Individual response to therapy may vary. Patients should not initiate, discontinue, or change dosage without consulting their prescribing physician. The full prescribing information should be reviewed before use.

Reviews

Clinical studies and decades of use demonstrate Tofranil’s efficacy in treatment-resistant depression, with many patients achieving significant symptom improvement where other antidepressants failed. Many psychiatrists report reliable response in appropriate patient populations, though side effect management requires careful attention. Patient experiences vary; some report life-changing benefits after struggling with depression for years, while others find side effects challenging. The drug’s established history provides clinicians with predictable pharmacokinetics and well-documented management strategies for both efficacy and adverse effects.