Tofranil (imipramine hydrochloride) is a tricyclic antidepressant (TCA) with a well-established clinical profile for the management of major depressive disorder. Its primary mechanism of action involves the potent inhibition of norepinephrine and serotonin reuptake in the central nervous system, leading to increased synaptic concentrations of these critical neurotransmitters. This pharmacological activity underpins its efficacy in alleviating the core symptoms of depression, including low mood, anhedonia, and psychomotor disturbances. With decades of use and a substantial body of evidence supporting its role in psychiatric therapeutics, Tofranil remains a relevant option for patients, particularly in cases where newer antidepressants have proven ineffective or unsuitable.

Features

• Active Ingredient: Imipramine hydrochloride
• Drug Class: Tricyclic antidepressant (TCA)
• Available Formulations: 10 mg, 25 mg, and 50 mg oral tablets
• Mechanism of Action: Potent inhibitor of norepinephrine and serotonin reuptake pumps
• Bioavailability: High oral bioavailability with significant protein binding
• Metabolism: Hepatic, primarily via CYP2D6, CYP2C19, and CYP3A4 isoenzymes
• Half-life: Approximately 8–16 hours, permitting once-daily dosing in many cases
• Excretion: Primarily renal, with some fecal elimination

Benefits

• Effectively alleviates symptoms of major depressive disorder, including persistent sadness, loss of interest, and fatigue
• Provides robust anxiolytic effects, making it suitable for depression with comorbid anxiety
• May be used in treatment-resistant cases where SSRIs or SNRIs have failed
• Long half-life supports stable plasma levels and consistent therapeutic effect with once-daily dosing
• Off-label efficacy in certain pain syndromes, such as neuropathic pain and migraine prophylaxis
• Cost-effective compared to many newer antidepressant agents

Common use

Tofranil is primarily indicated for the treatment of major depressive disorder in adults. It is also used off-label for a range of conditions including panic disorder, enuresis in children (over age 6), and neuropathic pain syndromes. Its use in depression is often reserved for moderate to severe cases or after inadequate response to first-line antidepressants. Clinical response typically emerges within 2–4 weeks, though full therapeutic benefit may take longer. Dosage should be individualized based on symptom severity, patient tolerance, and comorbid conditions.

Dosage and direction

Initial dosing for depression in adults typically begins at 25–50 mg orally once daily at bedtime, which may be gradually increased by 25–50 mg every 3–4 days as tolerated. The effective dosage range 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, lower starting doses (10–25 mg/day) and slower titration are recommended. Tablets should be swallowed whole with water and may be taken with food to minimize gastrointestinal upset. Abrupt discontinuation should be avoided; taper gradually over several weeks to prevent withdrawal symptoms.

Precautions

Patients should be monitored for worsening depression, suicidality, or unusual changes in behavior, especially during initiation and dose adjustments. Use with caution in patients with cardiovascular disease, due to risk of orthostatic hypotension, tachycardia, and conduction abnormalities. Regular ECG monitoring is advised in patients with known heart disease or those receiving high doses. Caution is warranted in patients with glaucoma, urinary retention, seizure disorders, or hyperthyroidism. Tofranil may impair mental or physical abilities required for hazardous tasks; patients should avoid driving or operating machinery until they know how the drug affects them.

Contraindications

Tofranil is contraindicated in patients with known hypersensitivity to imipramine or other TCAs. It should not be used during the acute recovery phase after myocardial infarction or in patients with untreated narrow-angle glaucoma. Concomitant use with monoamine oxidase inhibitors (MAOIs) is contraindicated due to risk of serotonin syndrome; a minimum 14-day washout period is required when switching between these agents. Use is also contraindicated in patients with severe hepatic impairment or those with a history of TCA-induced agranulocytosis.

Possible side effect

Common side effects include dry mouth, blurred vision, constipation, dizziness, drowsiness, and weight gain. Orthostatic hypotension may occur, particularly in elderly patients. Less frequently, patients may experience urinary retention, increased intraocular pressure, tachycardia, or sexual dysfunction. Serious adverse effects, though rare, include seizures, agranulocytosis, and hepatotoxicity. Any signs of allergic reaction (e.g., rash, itching, swelling) require immediate medical attention.

Drug interaction

Tofranil interacts significantly with MAOIs, SSRIs, SNRIs, and other serotonergic agents, increasing risk of serotonin syndrome. It may potentiate effects of CNS depressants including alcohol, benzodiazepines, and opioids. Concomitant use with anticholinergic drugs may exacerbate side effects like dry mouth and constipation. Drugs that inhibit CYP2D6 (e.g., fluoxetine, paroxetine) can increase imipramine levels. Conversely, inducers of CYP enzymes (e.g., carbamazepine, rifampin) may reduce its efficacy. Quinidine-like effects may be amplified when used with other QT-prolonging agents.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next dose. In that case, skip the missed dose and resume the regular schedule. Doubling up on doses is not recommended, as it may increase the risk of adverse effects. Patients should inform their healthcare provider if multiple doses are missed, as dose readjustment may be necessary.

Overdose

Tofranil overdose is potentially life-threatening and may present with symptoms including severe drowsiness, agitation, confusion, tachycardia, hypotension, seizures, coma, and cardiac arrhythmias. ECG may show prolonged QRS or QT intervals. Management is supportive and includes gastric lavage (if presented early), activated charcoal, and continuous cardiac monitoring. Sodium bicarbonate is often administered to correct acidosis and mitigate cardiotoxic effects. Mechanical ventilation and anticonvulsants may be required in severe cases.

Storage

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

Disclaimer

This information is intended for educational purposes and does not replace professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before starting, changing, or discontinuing any medication. Individual response to Tofranil may vary, and only a licensed practitioner can determine its appropriateness based on a patient’s specific health status and history.

Reviews

Clinical studies and long-term use support Tofranil’s efficacy in treating refractory depression, though its side effect profile may limit tolerability for some patients. Many clinicians value its predictable pharmacokinetics and cost-effectiveness. Patient experiences often note improved mood and energy over time, though initial side effects like dry mouth and drowsiness are commonly reported. It remains a respected option in psychiatric practice, particularly for complex or treatment-resistant cases.