Does Norpramin (desipramine) cause side effects?

Norpramin (desipramine) is a tricyclic antidepressant (TCA) used to treat depression. Off label uses (uses not approved by the FDA) include the treatment of anxiety, ADHD, cataplexy, chronic itching, bulimia, neuropathic pain, panic attacks, and depression caused by a traumatic brain injury

It is believed that in some patients with depression, abnormal levels of neurotransmitters (chemicals that nerves use to communicate with each other) may be the cause of depression. Norpramin elevates mood by raising the level of neurotransmitters in nerves of the brain. Norpramin also is responsible for the antidepressant effects of imipramine because imipramine is converted by the body to desipramine. 

Common side effects of Norpramin include

Serious side effects of Norpramin include

  • elevated pressure in the eyes of some patients with glaucoma,
  • life-threatening abnormal heart rhythms or seizures if overdosed,
  • withdrawal symptoms following abrupt discontinuation after prolonged therapy (nausea, vomiting, or diarrhea), and
  • increased risk of suicidal thinking and behavior in children and adolescents with depression and other psychiatric disorders. 

Drug interactions of Norpramin include other medications and drugs that slow the brain's function, such as alcohol, barbiturates, benzodiazepines, zolpidem, and narcotics.

  • Reserpine has a stimulatory effect on patients taking TCAs. Norpramin and other TCAs should not be used with monoamine oxidase inhibitors (MAOIs) since high fever, convulsions and even death can occur when these drugs are used together.
  • Cimetidine can increase Norpramin blood levels, possibly causing side effects. Other drugs which can increase Norpramin blood levels include propafenone, flecainide, quinidine, and fluoxetine. TCAs may inhibit the antihypertensive effect of clonidine.
  • Therefore, combining TCAs with clonidine may lead to dangerous elevations in blood pressure

Safe use of Norpramin during pregnancy and lactation has not been established. If it is to be given to pregnant patients or women of childbearing potential, the possible benefits must be weighed against the possible hazards to mother and child. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including Norpramin, during pregnancy.

Norpramin is secreted in breast milk and the effect on nursing infants is known. Breastfeeding should be avoided while taking Norpramin.

What are the important side effects of Norpramin (desipramine)?

The most commonly encountered side effects associated with desipramine include:

Desipramine also causes elevated pressure in the eyes of some patients with glaucoma. Overdoses of desipramine can cause life-threatening abnormal heart rhythms or seizures. Sexual dysfunction also has been associated with desipramine.

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

Therefore, many doctors recommend a gradual reduction in dose when TCAs are 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 desipramine 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.

Norpramin (desipramine) side effects list for healthcare professionals

Included in the following listing are a few adverse reactions that have not been reported with this specific drug. However, the pharmacologic similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when Norpramin is given.

To report Suspected Adverse Reactions, contact Validus Pharmaceuticals LLC at 1-866-982-5438 (1-866-9VALIDUS) or FDA at 1-800-FDA-1088 or

What drugs interact with Norpramin (desipramine)?

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 ΙC antiarrhythmics propafenone and flecainide).
  • While all the SSRIs, e.g., fluoxetine, sertraline, paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition.
  • The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration 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 cotherapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.
  • Close supervision and careful adjustment of dosage are required when this drug is given concomitantly with anticholinergic or sympathomimetic drugs.
  • Patients should be warned that while taking this drug their response to alcoholic beverages may be exaggerated.
  • If Norpramin is to be combined with other psychotropic agents such as tranquilizers or sedative/hypnotics, careful consideration should be given to the pharmacology of the agents employed since the sedative effects of Norpramin and benzodiazepines (e.g., chlordiazepoxide or diazepam) are additive. Both the sedative and anticholinergic effects of the major tranquilizers are also additive to those of Norpramin.
  • Concomitant use of Monoamine Oxidase Inhibitors (MAOIs) and serotonergic drugs may potentially cause life threatening adverse events.

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Medically Reviewed on 1/12/2021
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.