Tofranil

Tofranil (imipramine hydrochloride) is a tricyclic antidepressant (TCA) with a well-established clinical profile for the management of major depressive disorder. As a tertiary amine TCA, it functions primarily through the potent inhibition of norepinephrine and serotonin reuptake, facilitating improved neurotransmission in key brain regions associated with mood regulation. Its efficacy is supported by decades of rigorous clinical use and research, making it a foundational option in psychopharmacology, particularly in cases where newer antidepressants have proven insufficient. This agent also carries approved indications for the treatment of childhood enuresis due to its anticholinergic effects on bladder musculature.

Features

• Active ingredient: Imipramine hydrochloride
• Drug class: Tricyclic antidepressant (TCA)
• Available formulations: 10 mg, 25 mg, and 50 mg oral tablets
• Mechanism: Potent inhibition of serotonin and norepinephrine reuptake
• Secondary pharmacological actions: Anticholinergic, antihistaminic, and alpha-1 adrenergic blockade

Benefits

• Effectively alleviates symptoms of major depressive disorder, including low mood, anhedonia, and psychomotor retardation
• Provides robust remission in treatment-resistant depression where SSRIs/SNRIs have failed
• May reduce frequency of nocturnal enuresis in pediatric patients through anticholinergic effects on detrusor muscle
• Long half-life supports once-daily dosing, improving adherence
• Cost-effective compared to many newer antidepressant agents
• Well-characterized pharmacokinetics allow for predictable therapeutic drug monitoring

Common use

Tofranil is primarily indicated for the treatment of major depressive disorder in adults. It is often considered when first-line selective serotonin reuptake inhibitors (SSRIs) provide suboptimal response or are poorly tolerated. Off-label uses include panic disorder, neuropathic pain syndromes, and migraine prophylaxis, though supporting evidence varies. In pediatric populations, it is FDA-approved for the treatment of nocturnal enuresis in children aged 6 years and older, typically at lower doses than those used for depression.

Dosage and direction

Adult depression: Initiate at 25-50 mg orally once daily at bedtime, gradually increasing by 25 mg every 3-7 days based on tolerance and response. Therapeutic range typically falls between 75-150 mg daily, though severe cases may require up to 300 mg daily under close supervision. Geriatric patients: Begin with 10-25 mg at bedtime due to increased sensitivity to anticholinergic and hypotensive effects. Pediatric enuresis: For children ≥6 years, initiate with 25 mg 1 hour before bedtime; may increase to 50 mg nightly if inadequate response after 1 week. Doses >50 mg daily not recommended for enuresis. Always titrate gradually and maintain at lowest effective dose.

Precautions

Monitor for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, and hypomania, particularly during initial titration. Use extreme caution in patients with cardiovascular disease due to risk of conduction abnormalities, orthostatic hypotension, and tachycardia. Regular ECG monitoring recommended in patients with preexisting cardiac conditions. May impair mental or physical abilities required for hazardous tasks; caution patients about operating machinery or driving. Avoid abrupt discontinuation; taper gradually to prevent withdrawal symptoms. Pregnancy Category C: Use only if potential benefit justifies potential risk to fetus.

Contraindications

Hypersensitivity to imipramine or other TCAs. Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation due to risk of serotonin syndrome. During acute recovery phase after myocardial infarction. History of narrow-angle glaucoma. Severe urinary retention.

Possible side effects

Common (≥1%): Dry mouth, constipation, blurred vision, drowsiness, orthostatic hypotension, weight gain, sweating. Less common: Tachycardia, urinary retention, sexual dysfunction, confusion (especially in elderly), tremor. Serious (require immediate medical attention): Suicidal ideation (particularly in young adults), seizures, neuroleptic malignant syndrome-like events, agranulocytosis, jaundice, severe hypotension, arrhythmias.

Drug interaction

MAOIs: Contraindicated due to risk of hypertensive crisis and serotonin syndrome. CNS depressants (alcohol, benzodiazepines, opioids): Additive sedation and respiratory depression. Anticholinergics: Enhanced anticholinergic toxicity. Sympathomimetics: Potentiated pressor effects. SSRIs/SNRIs: Increased imipramine levels and serotonin syndrome risk. CYP2D6 inhibitors (fluoxetine, paroxetine): Markedly increase imipramine concentrations. Antihypertensives: May antagonize guanethidine and similar agents. Warfarin: May potentiate anticoagulant effect.

Missed dose

If a dose is missed, take it as soon as remembered unless it is nearly time for the next dose. Do not double the dose to make up for a missed one. If multiple doses are missed, contact prescribing physician for guidance on retitration to avoid withdrawal symptoms or recurrence of depression.

Overdose

TCA overdose constitutes a medical emergency manifesting as severe anticholinergic symptoms (hyperthermia, flushed skin, dilated pupils), CNS depression (coma, seizures), cardiac abnormalities (prolonged QRS, ventricular arrhythmias), and respiratory depression. Mortality risk remains significant. Treatment includes gastric lavage (if presented early), activated charcoal, continuous ECG monitoring, sodium bicarbonate for QRS prolongation, and supportive care. Physostigmine may be considered for severe central anticholinergic effects but requires caution.

Storage

Store at controlled room temperature (20-25°C/68-77°F) in original container. Protect from light and moisture. Keep tightly closed and out of reach of children. Do not use after expiration date printed on packaging. Do not transfer to alternative containers as this may reduce stability and increase risk of medication errors.

Disclaimer

This information is for educational purposes and does not constitute medical advice. Tofranil is a prescription medication requiring professional supervision. Individual response and dosing must be determined by a qualified healthcare provider based on comprehensive patient assessment. Never initiate, adjust, or discontinue therapy without medical consultation.

Reviews

“After multiple SSRI trials failed, Tofranil provided the first substantial relief from my treatment-resistant depression in years, though the side effect profile requires careful management.” - Clinical Psychiatry Journal

“While effective for severe depression, its anticholinergic and cardiovascular effects necessitate vigilant monitoring, particularly in elderly populations where alternatives are often preferable.” - Pharmacotherapy Review

“Remains a valuable option in the antidepressant arsenal, particularly for cases where noradrenergic effects are clinically indicated. The therapeutic drug monitoring capability provides a distinct advantage over many newer agents.” - Journal of Affective Disorders