Desipramine

Desipramine comes as a tablet to take by mouth. It is usually taken one or more times a day and may be taken with or without food. Take desipramine at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take desipramine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Your doctor may start you on a low dose of desipramine and gradually increase your dose.

It may take 2 to 3 weeks for you to feel the full benefit of desipramine. Continue to take desipramine even if you feel well. Do not stop taking desipramine without talking to your doctor. If you suddenly stop taking desipramine, you may experience withdrawal symptoms such as nausea, headache, and weakness. Your doctor will probably want to decrease your dose gradually.

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Desipramine may cause side effects. Call your doctor if any of these symptoms become severe or do not go away:

• nausea
• drowsiness
• weakness or tiredness
• nightmares
• dry mouth
• skin more sensitive to sunlight than usual
• changes in appetite or weight
• constipation
• difficulty urinating
• frequent urination
• changes in sex drive or ability
• excessive sweating

Some side effects can be serious. If you experience any of the following symptoms, or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS section, call your doctor immediately or get emergency medical treatment:

• jaw, neck, and back muscle spasms
• slow or difficult speech
• shuffling walk
• uncontrollable shaking or movement of a part of the body
• fever
• difficulty breathing or swallowing
• severe rash
• yellowing of the skin or eyes
• irregular heartbeat
• seizures
• sore throat, fever, and other signs of infection

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of the reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Keep all appointments with your doctor.

Do not allow anyone else to take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Serious side effects have been reported with desipramine including the following:

• serotonin syndrome. This is a condition that can happen when you take multiple medications that increase the levels of serotonin in your brain. Very high levels of serotonin can lead to the following symptoms. Tell your healthcare provider right away if you experience any of the following symptoms of serotonin syndrome:
  • hyperactivity
  • sweating
  • redness of the skin
  • fever
  • nausea
  • diarrhea
  • confusion
• increased risk for suicidality, or suicidal behavior. You should be monitored closely by family and caregivers for any changes in behavior, and report any changes in behavior to your doctor right away.
• confusion including disorientation (more common in the elderly)
• hallucinations
• seizures. Desipramine should be used cautiously if you have a history of seizures because it may increase your chance of having a seizure. Seizures have preceded cardiac (heart) rhythm problems and death in some patients. Do not abruptly stop taking desipramine. If your doctor lowers your dose, this should be down so slowly over time.
• Decreased blood counts leading to an increased risk of infection. This medication may cause the number of white blood cells in your blood to decrease. This makes you more susceptible to getting an infection. Tell your doctor right away if you notice any signs of infection such as a fever or sore throat.
• shuffling walk
• severe rash
• tremors, or uncontrollable shaking of any part of the body
• jaw, neck, and back muscle spasms
• nightmares
• cardiovascular collapse, which rarely has been fatal with use of this medication. Tell your doctor if you notice any of the following symptoms of cardiac (heart problems):
  • rapid heart beat
  • felling like your heart is "beating out of your chest"
  • shortness of breath
  • chest pain
• heart attack. Tell your doctor if you have ever had a heart attack. Also tell your doctor if you or anyone in your family has ever been told they have an irregular heartbeat or has died suddenly. Tell your doctor if you have a history of cardiovascular disease such as heart attack, stroke, atherosclerosis (hardening of the arteries), or chest pain.
• increased thoughts of suicide or suicidal actions. It should be noted there is also an increased risk of suicide in patients with depression.
• QT prolongation. This is a condition when changes in the electrical activity of your heart occur, causing irregular heartbeats that can be life threatening. Talk to your healthcare provider about other medicines you are taking before you start taking desipramine. Tell your healthcare provider right away if you have any signs or symptoms of QT prolongation:
  • feeling faint
  • lightheadedness
  • dizziness
  • feeling like your heart is beating irregularly or quickly
• angle-closure glaucoma. This is a condition in which fluid from the eye does not drain properly and can build up pressure in the eye, leading to loss of vision. Talk to your doctor about a complete eye exam before starting this medication. Call your doctor or seek emergency medical treatment right away if you experience any of the following symptoms:
  • nausea
  • eye pain
  • changes in vision, including seeing colored rings or halos around lights
  • swelling or redness in or around the eye
• smoking may decrease how well desipramine works. Tell your doctor if you smoke, and talk to your doctor or pharmacist about quitting. If you do quit smoking while using desipramine, tell your doctor right away.
• liver disease. Tell your doctor right away if you experience yellowing of the skin or white parts of your eyes.
• slow speech or difficulty speaking. Tell your doctor right away if you experience this.
• changes in sexual functioning, including increased or decreased libido and impotence
• gynecomastia. Gynecomastia is a condition in which males grow enlarged breasts.
• galactorrhea. Galactorrhea refers to the discharge of breast milk from the nipple that is unrelated to breastfeeding.

Desipramine can cause drowsiness. Do not drive or operate heavy machinery until you know how desipramine affects you.

Do not take desipramine if you:

• are allergic to desipramine, or any of its ingredients
• have been treated with MAOIs such as isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) for within the last 14 days. These two medications should not be used within 14 days of each other
• have recently suffered a heart attack

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Desipramine falls into category C. Safe use of desipramine during pregnancy and lactation has not been established; therefore, if it is to be given to pregnant patients, nursing mothers, or women of childbearing potential, the possible benefits must be weighed against the possible hazards to mother and child. Animal reproductive studies have been inconclusive.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if desipramine crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using desipramine.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your age

The recommended dose range of Norpramin (desipramine) for the treatment of depression in adults is 100-300 mg per day. This may be given as a single dose or as divided doses spaced throughout the day.

If you take too much desipramine, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

Suicidality and Antidepressant Drugs

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of desipramine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Desipramine is not approved for use in pediatric patients.

Take desipramine only as directed by your doctor to benefit your condition as much as possible. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

desipramine should come with a Medication Guide. Read and follow the instructions carefully. Ask your doctor or pharmacist if you have any questions.

Tell your doctor if you are also using other medicine to treat depression, such as amitriptyline, citalopram, fluoxetine, nortriptyline, paroxetine, or sertraline. You must wait at least 5 weeks after you stop using fluoxetine before you can start using desipramine.

Dosing

The dose of desipramine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of desipramine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For depression:
    • Adults—100 to 200 milligrams (mg) once a day or in divided doses during the day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 300 mg per day.
    • Older adults and teenagers—25 to 100 mg once a day or in divided doses during the day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 150 mg per day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of desipramine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• It is used to treat low mood (depression).
• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hard stools (constipation).
• Dry mouth.
• Dizziness.
• Feeling sleepy.
• Upset stomach or throwing up.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time desipramine is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take desipramine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to desipramine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Depression: Individual responses vary; however, 4 to 8 weeks of treatment is needed before determining if a patient is partially or nonresponsive (APA, 2010).

Time to Peak

Plasma: ~6 hours (Weiner, 1981)

Half-Life Elimination

Adults: 15 to 24 hours (Weiner, 1981)

The ratio of 2-hydroxydesipramine to desipramine may be elevated due to decreased renal elimination with aging.

There are no dosage adjustments provided in the manufacturer’s labeling.

Frequency not defined. Some reactions listed are based on reports for other agents in this same pharmacologic class, and may not be specifically reported for desipramine.

Cardiovascular: Cardiac arrhythmia, cerebrovascular accident, edema, flushing, heart block, hypertension, hypotension, myocardial infarction, palpitations, premature ventricular contractions, tachycardia, ventricular fibrillation, ventricular tachycardia

Central nervous system: Agitation, anxiety, ataxia, confusion, delusions, disorientation, dizziness, drowsiness, drug fever, EEG pattern changes, extrapyramidal reaction, falling, fatigue, hallucination, headache, hypomania, insomnia, neuroleptic malignant syndrome, nightmares, numbness, peripheral neuropathy, psychosis (exacerbation), restlessness, seizure, tingling of extremities, tingling sensation, withdrawal syndrome

Dermatologic: Alopecia, diaphoresis (excessive), pruritus, skin photosensitivity, skin rash, urticaria

Endocrine & metabolic: Decreased libido, decreased serum glucose, galactorrhea, gynecomastia, increased libido, increased serum glucose, SIADH, weight gain, weight loss

Gastrointestinal: Abdominal cramps, anorexia, constipation, diarrhea, epigastric distress, increased pancreatic enzymes, melanoglossia, nausea, paralytic ileus, parotid gland enlargement, stomatitis, sublingual adenitis, unpleasant taste, vomiting, xerostomia

Genitourinary: Breast hypertrophy, impotence, nocturia, painful ejaculation, testicular swelling, urinary hesitancy, urinary retention, urinary tract dilation

Hematologic & oncologic: Agranulocytosis, eosinophilia, petechia, purpura, thrombocytopenia

Hepatic: Abnormal hepatic function tests, cholestatic jaundice, hepatitis, increased liver enzymes, increased serum alkaline phosphatase

Neuromuscular & skeletal: Tremor, weakness

Ophthalmic: Accommodation disturbance, blurred vision, increased intraocular pressure, mydriasis

Otic: Tinnitus

Renal: Polyuria

Miscellaneous: Fever

Limited to important or life-threatening: Angle-closure glaucoma, serotonin syndrome, suicidal ideation

Data not available

US BOXED WARNINGS:
Suicidality and Antidepressant Drugs
-Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of this drug or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
-Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24. There was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older.
-Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior.
-Families and caregivers should be advised of the need for close observation and communication with the prescriber.
-This drug is not approved for use in pediatric patients.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Data not available

Benefit should outweigh risk. Excreted into human milk: Data not available Excreted into animal milk: Data not available Comments: The effects in the nursing infant are unknown.

Summary of Use during Lactation

Milk levels of desipramine and its metabolite are low and have not been detected in the serum of breastfed infants. Immediate side effects have not been reported and a limited amount of follow-up has found no adverse effects on infant growth and development. Desipramine use during breastfeeding would usually not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months.

Drug Levels

Desipramine is metabolized to 2-hydroxydesipramine which has antidepressant activity equal to that of desipramine.[1]

Maternal Levels. A mother who was taking desipramine 300 mg daily had average milk desipramine plus 2-hydroxydesipramine milk levels of 338 mcg/L at 9 hours after the dose 10 to 11 weeks postpartum.[2]

Infant Levels. Two infants whose mothers were taking desipramine during pregnancy and lactation had no detectable serum desipramine (<25 mcg/L) with a maternal dosage of 200 mg daily. One infant was tested at 2.3 and 14.9 weeks of age while breastfeeding 7 to 9 times daily and the other was tested at 5.4 weeks of age while breastfeeding 10 to 12 weeks of age. Two other infants whose mothers began desipramine postpartum had undetectable (<10 mcg/L) serum desipramine levels. One infant whose mother took desipramine 150 mg daily was tested at 12.3 weeks of age while breastfeeding 4 to 6 times daily; the other whose mother took desipramine 37 mg daily was tested at 33 weeks of age while breastfeeding 0 to 3 times daily.[3]

Effects in Breastfed Infants

One infant whose mother took desipramine 100 mg daily for 8 weeks starting at 16 weeks postpartum was followed up at 36 months of age. No adverse effects on growth and development were found.[4]

Effects on Lactation and Breastmilk

Desipramine has caused increased serum prolactin levels in some patients.[5] The clinical relevance of these findings in nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 30% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge.[6] The antidepressants used by the mothers were not specified.

Alternate Drugs to Consider

Nortriptyline, Paroxetine, Sertraline

References

1. Weissman AM, Levy BT, Hartz AJ et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004;161:1066-78. PMID: 15169695

2. Stancer HC, Reed KL. Desipramine and 2-hydroxydesipramine in human breast milk and the nursing infant's serum. Am J Psychiatry. 1986;143:1597-600. PMID: 3789215

3. Birnbaum CS, Cohen LS, Bailey JW et al. Serum concentrations of antidepressants and benzodiazepines in nursing infants: a case series. Pediatrics. 1999;104:e11. PMID: 10390297

4. Misri S, Sivertz K. Tricyclic drugs in pregnancy and lactation: a preliminary report. Int J Psychiatry Med. 1991;21:157-71. PMID: 1894455

5. Madhusoodanan S, Parida S, Jimenez C. Hyperprolactinemia associated with psychotropics--a review. Hum Psychopharmacol. 2010;25:281-97. PMID: 20521318

6. Venkatesh KK, Castro VM, Perlis RH et al. Impact of antidepressant treatment during pregnancy on obstetric outcomes among women previously treated for depression. Am J Obstet Gynecol. 2017;216:S466-S467.