Imipramine (Tofranil, Janimine, Antideprin, Depremil, Deprimin, Deprinol, Depsonil, Dynaprin)

Imipramine was the first tricyclic antidepressant to be manufactured. It was synthesized in the 1940's and was originally developed as an antipsychotic. During clinical trials it became apparent that imipramine has antidepressive actions, but does not have antipsychotic actions.

Imipramine was approved by the FDA in 1959 for treating depression. In 1973, it was approved to treat bedwetting.

Imipramine is the "gold standard" of antidepressants. It works in the most treatment resistant depressions, and is the medication other antidepressants are compared to.

Imipramine is no longer used as a first-line treatment for depression because newer antidepressants have fewer side effects. It is still, however, the most effective medication for treating resistant depressive states.

The Bottom Line: What You Really Need to Know

Uses of imipramine

Imipramine is used to treat depression, especially depression that is resistant to treatment with other medications. It is also approved to treat bedwetting in children older than 5 years old. Imipramine is also sometimes used to treat migraine headaches, attention deficit disorder, post-concussive disorder, panic disorder, chronic pain, Kleine-Levin syndrome, night terrors, eating disorders and obsessive-compulsive disorder.

Dosage and instructions

You usually start taking a low dose of imipramine and increase the dose gradually to minimize side effects. Most people start with 25 mg three times a day and gradually increase the dose in 25 mg/day increments up to 150 mg/day. It takes up to two weeks to feel the full effect of taking imipramine, and some people may need to increase the dose to as much as 200 mg/day. Occasionally even higher doses are needed, but hospitalization is recommended in those cases.

After the full therapeutic effect is felt and you are stabilized at that dose, the dose is gradually decreased to the minimum dose that will maintain the effect. It can be taken in divided doses throughout the day or in one bedtime dose. There is a form of imipramine formulated to be taken in one daily dose at bedtime (Tofranil PM).

Elderly people need reduced doses of imipramine. They should begin with 30-40 mg/day and gradually increase to no more than 100 mg/day.

The dose for bedwetting is 10-25 mg one hour before bedtime. If bedwetting occurs early in the night, half of the dose can be taken in the late afternoon. Children over the age of 12 may need up to 75 mg/day, but the dose of imipramine in children should never exceed 2.5 mg/kg/day.

How imipramine works

Depression is probably at least partly caused by imbalances in the chemicals that are released from nerve endings. These chemicals are released into the space between nerve cells. The chemicals bond to the outer membrane of the next nerve cell; this is how messages and impulses are passed from one nerve cell to the next. Some of the chemical that doesn't bond on the next cell is reabsorbed by the first cell. There has to be a certain amount of the chemical left in the space between nerve cells, however, for the system to work. Mood and anxiety disorders seem to appear when the chemical levels are depleted.

Antidepressants help to increase the level of chemicals in that space. Imipramine keeps the first cell from reabsorbing chemicals, especially serontin and norepinephrine. That allows serontin and norepinephrine to slowly accumulate and relieves the depression and anxiety.

It is not known how imipramine helps bedwetting.

Side effects

Most tricyclic antidepressants cause mild and transient side effects when you first start to take them. The most frequently experienced side effects with imipramine are tremor, drowsiness, fatigue, insomnia, dizziness, headaches, tingling and numbness, dry mouth, blurred vision, constipation, sweating, flushing, low blood pressure and dizziness when you first stand up, rapid heart beat and weight gain.

Less frequent side effects include:


Imipramine commonly interacts with many other medications.

It increases the brain effects of alcohol, barbiturates, sedatives, narcotics and anesthetics

It increases the effect of anticholinergic medications such as those used to treat Parkinson's disease

It can cause fatal heart rhythm problems if taken with quinidine and similar antiarrhythmic heart medications.

Other medications that imipramine interacts with are:

Serious interactions can occur if imipramine is taken at the same time as other antidepressants (see the section on warnings and precautions).


You should not stop taking imipramine suddenly. Sudden discontinuation can cause severe symptoms such as gastrointestinal upsets, anxiety, twitching muscles and tremors.

Warnings, precautions and contraindications

Imipramine should not be taken with MAOI antidepressants. A serious and severe reaction can occur with high fever, muscle rigidity, seizures, coma and death. At least two weeks should elapse between taking an MAOI and imipramine.

Imipramine should not be taken with SSRI antidepressants, particularly fluoxetine. Serotonin syndrome, a serious toxic reaction can occur. Symptoms can be as mild as anxiety, tremor and sweating or as serious as high fever, seizures, cardiovascular collapse and death. Two to five weeks should elapse between taking an SSRI and imipramine.

All antidepressants increase the risk of suicide, particularly in the early weeks of therapy. Anyone who starts taking an antidepressant should have weekly visits with a physician or therapist and should be monitored by friends or family daily. Any thoughts of harm to self or others, changes in mood, unusual thoughts or behaviors should be reported to the physician immediately.

Imipramine can make psychosis worse in people with schizophrenia.

Imipramine can trigger mania or hypomania (less manic mania) in people with bipolar disorder.

Elderly people who take imipramine can have episodes of delirium and psychosis, especially at night (Sundown Syndrome), which can make them prone to falls.

Imipramine should be used with caution in people who have:

Infants who are born to women who are taking imipramine can experience withdrawal symptoms, including trouble breathing, lethargy, colic, irritability, blood pressure problems, tremors and spasms. Imipramine is found in breast milk so breast feeding is not recommended if you are taking it.

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