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Imipramine (Tofranil)

A first-generation tricyclic antidepressant, historically foundational and still used for depression and childhood enuresis, with a heavy anticholinergic and cardiac profile.

Medically reviewed by Shariq Refai, MD, MBA Last reviewed: June 8, 2026

What it treats

Imipramine is approved by the U.S. Food and Drug Administration to treat depression and to treat nocturnal enuresis (bedwetting) in children age 6 and older.

Off-label uses include panic disorder, chronic pain, and some anxiety conditions. Off-label means a purpose the label doesn't formally list even though evidence and practice support it.

How it works

Imipramine acts on serotonin and norepinephrine, two of the brain's chemical messengers. It also blocks histamine and acetylcholine, which is why sedation, dry mouth, and constipation are common.

As with other antidepressants, the antidepressant effect isn't from the first dose. It comes from slower changes in the brain over the following weeks. For bedwetting in children, the mechanism seems to involve effects on bladder and sleep architecture rather than antidepressant activity per se.

Receptor mechanism (detail)

Imipramine is a tertiary-amine tricyclic antidepressant. It inhibits both the serotonin transporter (SERT) and the norepinephrine transporter (NET), and it also blocks muscarinic (M1), histamine (H1), and alpha-1 adrenergic receptors. That off-target load is what drives dry mouth, blurred vision, constipation, urinary retention, sedation, weight gain, and orthostatic hypotension. Imipramine is metabolized in part to desipramine, which is itself a NET-selective active drug.

Potency and typical dosing pattern

Ranges are typical framework only, not a prescription for any individual.

For depression: start at 25 mg three times a day or 75 mg at bedtime, titrating to 150 to 300 mg per day. For pediatric enuresis (age 6 and up): 25 to 75 mg at bedtime, dosed by age. Serum levels of imipramine plus desipramine can help guide dose in refractory cases, aiming roughly 150 to 300 ng/mL combined.

Safety monitoring

  • ECG at baseline, and periodically at higher doses. Tricyclics prolong QRS, PR, and QTc.
  • Overdose is dangerous. Narrow therapeutic index; even modest overdoses can cause fatal arrhythmias.
  • Anticholinergic burden. Meaningful in adults and especially in older adults; Beers Criteria caution.
  • Orthostatic vitals.
  • Suicidality in the first 4 weeks, especially under age 25 (FDA boxed warning).
  • Serotonin syndrome, avoid MAOIs.
  • Seizure threshold lowered, especially at higher doses.
  • Reassess at 2, 4, and 6 to 8 weeks.

What to expect

The first weeks tend to follow a familiar shape. Side effects often show up before benefits.

The first days to two weeks

Sedation, dry mouth, constipation, and dizziness on standing are the common early complaints. Splitting the dose or moving more of it to bedtime can help.

Common side effects

Common side effects include:

  • Dry mouth.
  • Drowsiness.
  • Constipation.
  • Blurred vision.
  • Weight gain.
  • Dizziness on standing.
  • Sweating.

Several of these come from the anticholinergic effect. If a side effect is severe, or it isn't improving, that's a conversation to have with the prescriber rather than a reason to stop on your own.

Serious side effects and warnings

Serious problems are uncommon, but a few are worth knowing.

Boxed warning. Like all antidepressants, imipramine carries an FDA boxed warning that it can increase suicidal thoughts and behaviors in children, teenagers, and young adults under 25, especially in the first weeks of treatment or after a dose change. This doesn't mean the medication harms most people. It means the early period deserves close attention.

  • Effects on heart rhythm. Tricyclics affect cardiac conduction, and caution is needed in people with heart disease.
  • Danger in overdose. Tricyclics are more dangerous than newer antidepressants in overdose, which a prescriber weighs when choosing them.
  • Anticholinergic burden. Confusion and falls become real considerations in older adults. Imipramine is on the Beers list.
  • Seizure risk at higher doses.
  • Serotonin syndrome. Do not combine with MAOIs.

Sexual side effects

Imipramine can reduce sex drive and make orgasm or erection more difficult. These effects tend to be more common at antidepressant doses than at lower doses used for other purposes.

Weight, appetite, and sleep

Imipramine commonly increases appetite and causes weight gain, which is a real drawback for many people. It's sedating, so it's often taken at bedtime.

Starting and dosing basics

This section is general background, not a dosing instruction for any individual. The right dose is a decision for a prescriber.

Imipramine comes as tablets. For depression in adults, the total daily dose is often split, or given largely at bedtime. For pediatric enuresis, doses are lower and given at bedtime, weight-adjusted. A prescriber sets and adjusts the dose based on response, tolerability, and, sometimes, a serum level.

Missed doses and interactions

If you miss a dose, take it when you remember, unless it's almost time for the next dose. Skip the missed dose and carry on. Don't take two doses to make up for one.

A few interactions matter. Imipramine must not be combined with MAOI antidepressants, and a gap is needed when switching. Alcohol and other sedating medications add to drowsiness. CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion) can raise imipramine and desipramine levels significantly. Other anticholinergic medications pile on top of imipramine's own. Give every prescriber and pharmacist a full list of your medications and supplements, including over-the-counter ones.

Stopping and tapering

Imipramine isn't a controlled substance and isn't habit-forming in the usual sense.

The body does adjust to it, though, and stopping abruptly can cause discontinuation symptoms: nausea, headache, cholinergic rebound (sweating, GI upset), sleep disturbance, and low mood. A gradual taper planned with a prescriber is the way to avoid most of this.

Pregnancy and breastfeeding

This is an area where individual circumstances matter and the decision belongs with a clinician. Untreated depression carries its own risks during pregnancy, and imipramine passes into breast milk. Anyone who is pregnant, planning a pregnancy, or breastfeeding should talk it through with their prescriber so the specific risks and benefits can be weighed for their situation.

Cost and generic availability

Imipramine has been available as a generic for many years and is inexpensive. Generic imipramine contains the same active medication as the brand name Tofranil and works the same way. Most insurance plans cover it.

Common questions

Is imipramine still used? Yes, though not as often as newer antidepressants. It has a real place in refractory depression, chronic pain, and pediatric enuresis. In most straightforward depression, gentler options come first.

Why is it used for bedwetting? Imipramine has decades of evidence for reducing nocturnal enuresis in children age 6 and up. The mechanism seems to involve bladder and sleep effects rather than mood.

Why is an ECG needed? Tricyclics affect the heart's electrical rhythm, and an ECG at baseline (and periodically at higher doses) catches problems that would change how the drug is dosed.

Is it dangerous in overdose? Yes, meaningfully so. That's part of why prescribers weigh alternatives, especially when suicide risk is present.

Will it make me gain weight? It often does. If weight gain becomes a concern, raise it with your prescriber; there are other options.

Questions to ask your prescriber

  • What are we treating with this, and how will we know it's working?
  • Given the anticholinergic and cardiac profile, is imipramine the best fit for me?
  • Which side effects should I expect, and which should I call about?
  • How long should I plan to take it?
  • If we decide to stop it later, how would we do that safely?

Sources

This guide draws on current prescribing information and public health references and current as of June 8, 2026. It is reviewed for clinical accuracy and updated as guidance changes.

Define this drug class in the network glossary Tricyclic antidepressant on Shrinktionary

THE KNOWLEDGE PATH

Walk this topic outward.

  1. MEDICATION Imipramine (Tofranil) (current)
  2. CLASS Tricyclic antidepressants
  3. CONDITION Major Depressive Disorder (on Shrinkopedia)
  4. MAP The Depression Map (on DR)
  5. CARE Depression care at shrinkMD

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Want to understand more first?

When to call your prescriber or seek urgent help

Antidepressants are usually safe and helpful, but the first weeks of a new medication, or a recent dose change, are the time to watch for warning signs and tell your prescriber promptly. People under 25 carry a recognized higher risk of new suicidal thoughts early in treatment.

  • New or worsening thoughts of suicide or self-harm.
  • A sudden change in mood, including new agitation, restlessness, or unusual energy or sleeplessness.
  • High fever, fast heartbeat, severe muscle stiffness, shivering, or confusion, which can be signs of serotonin syndrome.

If you or someone else is in immediate danger, or thinking about suicide: in the U.S., call or text 988 for the Suicide and Crisis Lifeline, call 911, or go to the nearest emergency room. Outside the U.S., see findahelpline.com for a local crisis line.

Managing a medication needs a prescriber

Any psychiatric medication has to be started and adjusted by a clinician who can follow you over time. If you don't have a prescriber, our guides section explains the options, including in-person care and telepsychiatry, and how to choose between them.