Side Effects of Tofranil (imipramine)

Does Tofranil (imipramine) cause side effects?

Tofranil (imipramine) is a tricyclic antidepressant (TCA) used to treat depression, bedwetting, and chronic pain.

Depression is defined as an all-pervasive sense of sadness and gloom. In patients with depression, abnormal levels of chemicals in the brain (called neurotransmitters) may be the cause of their depression. These neurotransmitters are chemicals that the nerves in the brain use to communicate with each other. Tofranil is believed to elevate mood by raising the levels of neurotransmitters in the brain. 

Common side effects of Tofranil include

Serious side effects of Tofranil include

Abrupt discontinuation of TCAs, including Tofranil, could lead to withdrawal symptoms such as

Drug interactions of Tofranil include other medications and drugs that slow the brain's processes, such as alcohol, barbiturates, benzodiazepines, zolpidem, and narcotics, which may add to the effect of Tofranil on the brain.

Reserpine, given to patients taking TCAs, can cause agitation and anxiety.

Tofranil and other TCAs should not be used with monoamine oxidase inhibitors (MAOIs) since high fever, convulsions and death can occur.

Concurrent use of cimetidine can increase Tofranil blood levels by reducing elimination of Tofranil from the body and possibly lead to Tofranil-related side effects. Other drugs which share this effect include propafenone, flecainide, quinidine, methylphenidate, and fluoxetine.

Use of Tofranil during pregnancy has not been adequately evaluated.

Available evidence suggests Tofranil may be excreted in breast milk and may be harmful to the infant. Consult your doctor before breastfeeding

What are the side effects of Tofranil (imipramine)?

The most common side effects of imipramine are:

Other important side effects include:

Imipramine also can cause elevated pressure in the eyes of some patients with glaucoma.

Following prolonged therapy with high doses, abrupt discontinuation of TCAs, including imipramine, could lead to withdrawal symptoms such as

  • nausea,
  • vomiting,
  • diarrhea, or
  • restlessness.

Therefore, many experts recommend gradually reducing the dose of drug if the drug is to be discontinued.

Antidepressants increased the risk of suicidal thinking and behavior in short-term studies in children and adolescents with depression and other psychiatric disorders. Anyone considering the use of imipramine  or any other antidepressant in a child or adolescent must balance this risk with the clinical need.

Patients who are started on therapy should be closely observed for

  • clinical worsening,
  • suicidal thinking or behavior, and
  • unusual changes in behavior.

Tofranil (imipramine) side effects list for healthcare professionals

Note – Although the listing which follows includes a few adverse reactions which have not been reported with this specific drug, the pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when Tofranil is administered.

Note – In enuretic children treated with Tofranil the most common adverse reactions have been

These usually disappear during continued drug administration or when dosage is decreased. Other reactions which have been reported include

  • constipation,
  • convulsions,
  • anxiety,
  • emotional instability,
  • syncope, and
  • collapse.

All of the adverse effects reported with adult use should be considered.

What drugs interact with Tofranil (imipramine)?

Drugs Metabolized By P450 2D6

  • The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so-called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available.
  • Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses.
  • Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8-fold increase in plasma AUC of the TCA).
  • In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers.
  • An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide).
  • While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition.
  • The extent to which SSRI-TCA interaction may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved.
  • Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other.
  • Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).
  • Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug.
  • Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required.
  • It is desirable to monitor TCA plasma levels whenever a TCA is going to be coadministered with another drug known to be an inhibitor of P450 2D6.
  • The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary.
  • In occasional susceptible patients or in those receiving anticholinergic drugs (including antiparkinsonism agents) in addition, the atropine-like effects may become more pronounced (e.g., paralytic ileus).
  • Close supervision and careful adjustment of dosage is required when imipramine hydrochloride is administered concomitantly with anticholinergic drugs.
  • Avoid the use of preparations, such as decongestants and local anesthetics, that contain any sympathomimetic amine (e.g., epinephrine, norepinephrine), since it has been reported that tricyclic antidepressants can potentiate the effects of catecholamines.
  • Caution should be exercised when imipramine hydrochloride is used with agents that lower blood pressure. Imipramine hydrochloride may potentiate the effects of CNS depressant drugs.
  • Patients should be warned that imipramine hydrochloride may enhance the CNS depressant effects of alcohol.


Tofranil (imipramine) is a tricyclic antidepressant (TCA) used to treat depression, bedwetting, and chronic pain. Common side effects of Tofranil include nausea, vomiting, weakness, confusion, anxiety, insomnia, increased heart rate, heart palpitations, blurred vision, difficulty urinating, dry mouth, constipation, weight gain or loss, rash, hives, and impotence. Use of Tofranil during pregnancy has not been adequately evaluated. Available evidence suggests Tofranil may be excreted in breast milk and may be harmful to the infant.

Treatment & Diagnosis

Medications & Supplements

FDA Logo

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.