Tofranil (Imipramine) - Oral

Warning:

The Food and Drug Administration (FDA) assigned a black box warning to Tofranil (imipramine). In general, antidepressant medications—like imipramine—are linked to a higher risk of suicidal thoughts and behaviors in children and young adults during the first few months of treatment. If you or your loved ones notice any abnormal mood or behavior changes, inform your healthcare provider immediately.

What Is Tofranil?

Tofranil (imipramine) is available as prescription imipramine hydrochloride tablets. Imipramine is a medication treatment option for depression. It may also be used for nighttime bedwetting in children 6 years and older.

As a tricyclic antidepressant (TCA), imipramine is thought to work by raising the amounts of naturally-occurring brain chemicals, such as norepinephrine.

Drug Facts

Generic Name: Imipramine

Brand Name(s): Tofranil

Drug Availability: Prescription

Therapeutic Classification: Tricyclic antidepressant (TCA)

Available Generically: Yes

Controlled Substance: No

Administration Route: Oral (by mouth)

Active Ingredient: Imipramine

Dosage Form(s): Tablets

What Is Tofranil Used For?

Tofranil (imipramine) is a medication treatment option for depression.

In 2020, millions of children and adults in the United States (U.S.) had at least one episode of major depression—the majority of whom are people assigned female at birth. People who have depression may experience the following symptoms:

  • Appetite changes
  • Feeling hopeless, worthless, or guilty
  • Feeling sad or empty
  • Lack of interest in previously enjoyable activities
  • Suicidal thoughts
  • Tiredness or low energy
  • Under- or over-sleeping
  • Weight changes

Imipramine hydrochloride tablets may also be used for nighttime bedwetting in children 6 years or older. Bedwetting is a common condition that affects millions of children in the U.S. While bedwetting usually goes away over time, some children will still experience bedwetting at7 years and older.

How to Take Tofranil

Generally, people can take Tofranil (imipramine) with or without food. If imipramine is used for depression, it's usually taken by mouth once daily or in divided doses.

For nighttime bedwetting, on the other hand, children will typically take imipramine one hour before bedtime. Children can also take imipramine in divided doses—with one dose in the mid-afternoon and another around bedtime.

Storage

When you receive imipramine from the pharmacy, store it at room temperature—between 68 degrees to 77 degrees Fahrenheit (F)—away from environments with excess heat and moisture.

To be safe, you can use a locked cabinet or closet to keep your medication out of the reach of children and pets.

If you plan to travel with imipramine, get familiar with your final destination's regulations. Checking with the U.S. embassy or consulate might be a helpful resource. In general, however, make sure to copy your imipramine prescription. If possible, keep your medication in its original container from your pharmacy with your name on the label. Ask your pharmacist or healthcare provider if you have any questions about traveling with your medicine.

You can also ask your pharmacist or healthcare provider about the best ways to dispose of your medications. The FDA's website is a potentially helpful resource for knowing where and how to discard all unused and expired drugs. You can also find disposal boxes in your area.

Off-Label Uses

Healthcare providers have used imipramine for the following off-label uses:

  • Bulimia nervosa: Bulimia is an eating disorder. Bulimia is characterized by behaviors of binge-eating followed by purging (e.g., vomiting). Experts recommend tricyclic antidepressants (TCAs)—like imipramine—as a second-choice treatment option for bulimia in people with low suicide risk.
  • Irritable bowel syndrome (IBS): IBS is a medical condition of the digestive system. Common symptoms of IBS may include stomach cramps and bloating. In IBS, some people primarily experience constipation (IBS-C), and others have more diarrhea (IBS-D). Experts recommend TCAs—like imipramine—as treatment options for IBS.
  • Nerve pain: You might see imipramine used for nerve pain. Some experts, however, don't recommend imipramine for diabetic nerve pain due to limited supporting evidence.
  • Panic disorder: In panic disorder, people tend to experience multiple panic attacks. Experts recommend TCAs—like imipramine—as possible treatment options for panic disorder.

How Long Does Tofranil Take to Work?

You may notice an improvement in your symptoms within one to three weeks of treatment with Tofranil (imipramine).

What Are the Side Effects of Tofranil?

This is not a complete list of side effects and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your pharmacist or a healthcare provider. You may report side effects to the Food and Drug Administration (FDA) at fda.gov/medwatch or 800-FDA-1088.

Common Side Effects

Common side effects with Tofranil (imipramine) may include:

  • Appetite changes
  • Constipation
  • Drowsiness
  • Dry mouth
  • Excessive sweating
  • Frequent urination
  • Jitteriness
  • Nausea
  • Nightmares
  • Sexual-related effects (e.g., low libido or sex drive)
  • Skin sensitivity to the sun
  • Tiredness
  • Urination difficulties
  • Weakness
  • Weight changes

Severe Side Effects

Get medical help right away if you develop the following serious side effects:

  • Severe allergic reaction symptoms (e.g., rash, breathing difficulties)
  • Abnormal changes in mood or behavior
  • Abnormal gait (e.g., shuffling walk)
  • Abnormal heartbeat
  • Blood sugar changes
  • Excessive shaking or tremors
  • Infection-like symptoms (e.g., fever, sore throat)
  • Jaundice (yellowing of the eyes or skin)
  • Muscle spasms of the jaw, neck, or back
  • Seizures
  • Speech difficulties
  • Suicidal thoughts
  • Swallowing difficulties
  • Vision changes

Call 911 if your symptoms feel life-threatening.

Long-Term Side Effects

Possible long-term side effects of Tofranil (imipramine) might include:

  • Abrupt (sudden) withdrawal (discontinuation) symptoms (e.g., headache, nausea)
  • Dry mouth
  • Excessive sweating
  • Rapid heart rate
  • Weight changes

Report Side Effects

Tofranil (imipramine) may cause other side effects. Call your healthcare provider if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your provider may send a report to the FDA's MedWatch Adverse Event Reporting Program or by phone (800-332-1088).

Dosage: How Much Tofranil Should I Take?

Drug Content Provided and Reviewed by IBM Micromedex®

The dose of this medicine 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 this medicine. 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 (capsules):
    • For depression:
      • Adults—At first, 75 milligrams (mg) once a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 200 mg per day, unless you are in the hospital. Some hospitalized patients may need higher doses.
      • Teenagers and older adults—At first, 25 to 50 mg per day using the tablets. Your doctor may adjust your dose as needed and switch you to the capsule form. However, the dose is usually not more than 100 mg per day.
      • Children—Use and dose must be determined by your doctor.
  • For oral dosage form (tablets):
    • For depression:
      • Adults—At first, 75 milligrams (mg) per day. Your doctor may adjust your dose as needed. However the dose is usually not more than 200 mg per day. Some hospitalized patients may need higher doses.
      • Teenagers and older adults—30 to 40 mg per day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 100 mg per day.
      • Children—Use and dose must be determined by your doctor.
    • For enuresis (bedwetting):
      • Children 6 years of age and older—At first, 25 milligrams (mg) once a day, taken 1 hour before bedtime. Your doctor may adjust the dose as needed.
      • Children younger than 6 years of age—Use and dose must be determined by your doctor.

Modifications

The following modifications (changes) should be kept in mind when using Tofranil (imipramine):

Severe allergic reaction: Avoid using imipramine if you have a known allergy to it or its ingredients. Ask your pharmacist or healthcare provider for a complete list of the ingredients if you're unsure.

Pregnancy: Imipramine studies in pregnant people are limited. Based on available information. Imipramine might be connected to negative effects on the unborn fetus. While this link is unclear, it can't be ruled out.

Discuss with your healthcare provider if you plan to become pregnant or are pregnant. They will help weigh the benefits and risks of taking imipramine during pregnancy.

Breastfeeding: Imipramine is present in low amounts in human breastmilk, but it's not detected in the bloodstream of nursing infants. Based on available data, imipramine hasn't been linked to negative effects in nursing babies—especially when they're older than 2 months. Some experts recommend imipramine as one of the go-to choices during breastfeeding. Other options, however, should be considered if you're using high imipramine doses or breastfeeding a newborn or preterm baby.

Talk with your healthcare provider if you plan to breastfeed. Your healthcare provider will help you weigh the benefits and harms of taking imipramine while nursing. They can also discuss different ways to feed your baby.

Adults over 65: Imipramine may increase fall risk in patients over 65. Imipramine manufacturers recommend a lower starting dose for older adults. Additionally, older adults shouldn't take more than 100 milligrams (mg) daily.

Children: Imipramine hydrochloride tablets are used in adolescents (teenagers) for depression. The FDA also approved imipramine hydrochloride tablets for nighttime bedwetting in children 6 years and older.

The imipramine starting dose and maximum daily dose are generally lower for children and adolescents compared to young adults. It's important to note that Tofranil PM (imipramine pamoate) is not approved for individuals younger than 17.

Kidney or liver problems: The kidneys and liver are usually responsible for clearing out medications from your body. However, if your kidneys and liver aren't working as well, drugs—like imipramine—might build up in the body and cause side effects. Therefore, use imipramine with caution in people with kidney or liver impairment.

Mental health conditions: People with schizophrenia might experience psychosis with imipramine. This might require lowering the imipramine dose. If you have inadequately treated bipolar disorder, imipramine might lead to mania symptoms. Therefore, your healthcare provider might hold off on starting imipramine until your bipolar condition is well-treated.

Recent heart attack: If you're recovering from a recent heart attack, your healthcare provider won't start you on imipramine. If you're taking imipramine, your healthcare provider will help safely hold (pause) your treatment with this medication.

Elective procedures: An elective procedure is a phrase that's usually used for procedures (e.g., surgeries, operations) that can be scheduled in advance. If you have an elective procedure, your healthcare provider may safely pause your imipramine treatment for as long as necessary.

Missed Dose

If you accidentally forgot your Tofranil (imipramine) dose, take it as soon as you remember. If it's already close to your next scheduled dose, then skip the missed dose and take the following dose at your next scheduled dosing time.

Try to find ways that work for you to help yourself remember to routinely keep your appointments and take your medication. If you miss too many doses, imipramine might be less effective. Additionally, you might experience withdrawal symptoms (e.g., headache, nausea).

Overdose: What Happens If I Take Too Much Tofranil?

The symptoms of a suspected overdose of Tofranil (imipramine) may include:

  • Abnormal heart rhythm
  • Abnormal muscle movements
  • Agitation
  • Balance problems
  • Blueish skin color
  • Coma
  • Dangerously low blood pressure
  • Decreased awareness or consciousness
  • Dilated (wide or big) pupils
  • Drowsiness
  • Extremely fast muscle reflexes
  • Fever
  • Rapid heartbeat
  • Restlessness
  • Rigid (stiff) muscles
  • Seizures
  • Slow breathing rate
  • Sweating
  • Vomiting

If you think you're experiencing an overdose or life-threatening symptoms, seek immediate medical attention.

What Happens If I Overdose on Tofranil?

If you think you or someone else may have overdosed on Tofranil (imipramine), call a healthcare provider or the Poison Control Center (800-222-1222).

If someone collapses or isn't breathing after taking imipramine, call 911 immediately.

Precautions

Drug Content Provided and Reviewed by IBM Micromedex®

It is very important that your doctor check your progress at regular visits to allow for changes in your dose and to check for any unwanted effects. Blood tests may be needed to check for any unwanted effects. Check with your doctor right away if you start having a fever or sore throat while taking this medicine.

Do not take imipramine with a monoamine oxidase (MAO) inhibitor (eg, isocarboxazid [Marplan®], linezolid [Zyvox®], methylene blue injection, phenelzine [Nardil®], selegiline [Eldepryl®, or tranylcypromine [Parnate®]). Do not start taking imipramine during the 2 weeks after you stop a MAO inhibitor and wait 2 weeks after stopping imipramine before you start taking a MAO inhibitor. If you do take them together or do not wait 2 weeks, you may develop confusion, agitation, restlessness, stomach or intestinal symptoms, a sudden high body temperature, an extremely high blood pressure, or severe convulsions.

Imipramine may cause some teenagers and young adults to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Some people may have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. If you, your child, or your caregiver notice any of these side effects, tell your doctor or your child's doctor right away. Let the doctor know if you or anyone in your family has bipolar disorder (manic-depressive) or has tried to commit suicide.

Imipramine may cause a serious condition called serotonin syndrome if taken together with some medicines. Do not use imipramine with buspirone (Buspar®), fentanyl (Abstral®, Duragesic®), lithium (Eskalith®, Lithobid®), methylene blue injection, tryptophan, St. John's wort, or some pain or migraine medicines (eg, rizatriptan, sumatriptan, tramadol, Frova®, Imitrex®, Maxalt®, Relpax®, Ultram®, Zomig®). Check with your doctor first before taking any other medicines with imipramine.

Do not suddenly stop taking this medicine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This will decrease the chance of having withdrawal symptoms such as agitation, breathing problems, chest pain, confusion, diarrhea, dizziness or lightheadedness, fast heartbeat, headache, increased sweating, muscle pain, nausea, restlessness, runny nose, trouble in sleeping, trembling or shaking, unusual tiredness or weakness, vision changes, or vomiting.

This medicine will add to the effects of alcohol and other central nervous system (CNS) depressants (medicines that cause drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies or colds, sedatives, tranquilizers, or sleeping medicines, prescription pain medicine or narcotics, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine.

Before having any kind of surgery, tell the medical doctor in charge that you are using this medicine. Taking imipramine together with medicines used during surgery may increase the risk of side effects.

This medicine may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests, or if you have any questions, check with your doctor.

This medicine may make your skin more sensitive to sunlight. Use a sunscreen when you are outdoors. Avoid sunlamps and tanning beds.

This medicine may cause some people to become drowsy or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are drowsy or not alert.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

What Are Reasons I Shouldn’t Take Tofranil?

Before taking Tofranil (imipramine), talk with your healthcare provider if any of the following applies to you:

  • Severe allergic reaction: If you have a severe allergic reaction to imipramine or any of its components (ingredients), imipramine isn't a viable option for you.
  • Pregnancy: Imipramine might be linked to negative effects on the unborn fetus. Reach out to your healthcare provider to discuss the benefits and risks of taking imipramine during your pregnancy.
  • Breastfeeding: Small amounts of imipramine are present in human breastmilk, but imipramine wasn't detected in the bloodstream of nursing infants. Imipramine is unlikely to adversely affect nursing babies—especially those over 2 months. Therefore, some experts recommend imipramine as one of the go-to choices during breastfeeding. Other options, however, should be considered if you're taking high imipramine doses or breastfeeding a newborn or preterm baby. Discuss with your healthcare provider about the benefits and harms of taking imipramine while breastfeeding.
  • Children: Imipramine hydrochloride tablets are used for depression in adolescents (teenagers). Imipramine hydrochloride tablets are also used to prevent nighttime bedwetting in children 6 years and older. In general, the starting and maximum daily imipramine doses in children are lower than in young adults.
  • Older adults over 65: Based on available data, older and younger adults don't respond differently to imipramine. However, caution is recommended as older adults may take several medications for multiple medical conditions. The starting and maximum daily imipramine doses in older adults are generally less than in younger adults.
  • Monoamine oxidase inhibitor (MAO-I) use: If you've taken an MAO-I—like selegiline for depression or Parkinson's disease (PD)—in the last 14 days, avoid imipramine. Combining these two medications raises your risk of serotonin syndrome. Serotonin syndrome is a rare but life-threatening condition. High levels of serotonin (a naturally-occurring brain chemical) can lead to symptoms of confusion, tremors, and sweating.
  • Recent heart attack: If you're recovering from a recent heart attack, your healthcare provider wouldn't start you on imipramine. If you're already taking imipramine, your healthcare provider will safely hold (pause) your treatment with this medication.
  • Elective procedures: If you're having an elective procedure, your healthcare provider may safely pause your imipramine medication.

What Other Medications Interact With Tofranil?

In addition to avoiding monoamine oxidase inhibitors (MAO-Is), use caution when taking Tofranil (imipramine) with the following medications:

  • Serotonergic medications: Serotonergic medications are medications that raise serotonin levels. Too much serotonin increases your risk of serotonin syndrome, a rare but life-threatening condition. If possible, avoid combining imipramine with other serotonergic medications, such as selective serotonin reuptake inhibitors (SSRIs)—like Lexapro (escitalopram) for depression.
  • Cytochrome P450 (CYP450)-inducing medications: CYP450 is a family of proteins in the liver. These proteins are responsible for breaking down medications—like imipramine. CYP450-inducing medications—like phenobarbital for seizures—encourage these proteins to break down medications like imipramine quickly. The low amount of imipramine in the body will be less effective at doing its job. Therefore, your healthcare provider may need to adjust your imipramine dosage.
  • CYP2D6-inhibiting medications: The CYP2D6 protein is part of the CYP450 family. CYP2D6-inhibiting medications—like terbinafine antifungal—prevent CYP2D6 from working as well to break down imipramine. This can lead to a build-up of imipramine in the body, resulting in more side effects. If you have to take a CYP2D6-inhibiting medication, your healthcare provider may need to lower your imipramine dose and closely monitor you.
  • Anticholinergic medications: Anticholinergic medications interfere with the activity of a naturally-occurring chemical called acetylcholine. Benadryl (diphenhydramine) is a typical example of an anticholinergic medication. In general, anticholinergics might cause several side effects, such as constipation. Since imipramine has similar side effects, combining anticholinergics with imipramine may result in worsening side effects.
  • Alcohol and other medications that suppress the central nervous system (CNS): The CNS includes the brain and spinal cord. Alcohol is a CNS suppressant or CNS depressant. Alcohol and similar medications—like the sleeping medication Ambien (zolpidem)—slow down the CNS and cause side effects (e.g., drowsiness). Imipramine might worsen these side effects.
  • Blood pressure medications: Combining blood pressure medications—like Benicar (olmesartan)—with imipramine might lower your blood pressure even further. Take your time to safely get up from sitting or laying down to prevent fainting and falling from drastic drops or dips in your blood pressure.
  • Sympathomimetic medications: Sympathomimetic medications may raise some naturally-occurring chemicals, such as epinephrine or norepinephrine. These medications might also activate (stimulate) adrenergic receptors (binding sites) that epinephrine or norepinephrine use. Imipramine may increase the effects (e.g., faster heart rate, higher blood pressure) of sympathomimetics—like Sudafed (pseudoephedrine).

Talk with your pharmacist or healthcare provider for more detailed information about medication interactions with imipramine.

And be sure to talk with your healthcare provider about any other medicines you take or plan to take, including over-the-counter (OTC), nonprescription products, vitamins, herbs, or plant-based medicines.

What Medications Are Similar?

Tofranil (imipramine) is a tricyclic antidepressant (TCA). Other TCAs may include:

  • Amitriptyline
  • Clomipramine
  • Desipramine
  • Doxepin
  • Nortriptyline
  • Protriptyline
  • Trimipramine

More head-to-head comparison studies between different TCAs are needed. Based on available data, however, the following is some interesting information about a few different TCAs.

  • Many TCAs are equally effective for most uses, but amitriptyline might have better effectiveness and safety profile for depression.
  • Most TCAs are not used in children under age 12, but imipramine hydrochloride tablets can be used by children 6 years and older for nighttime bedwetting.
  • Clomipramine is the only TCA effective for obsessive-compulsive disorder (OCD).
  • Compared to other TCAs, amitriptyline, clomipramine, and trimipramine might be linked to more anticholinergic effects, such as blurry vision, dry mouth, constipation, and urination (peeing) difficulties.
  • Doxepin is more likely to cause drowsiness than other TCAs.

Since all of these medications are TCAs, they're not typically taken together. If you have any questions or concerns, talk with your healthcare provider.

Frequently Asked Questions

  • Where is Tofranil available?

    Tofranil (imipramine) is available as a prescription from your healthcare provider. Local retail pharmacies may carry imipramine. However, if your pharmacy doesn't have the medication in stock, staff may need to order it for you.

  • How much does Tofranil cost?

    Tofranil is available as generic imipramine hydrochloride tablets. So, this may help save you some money.

    If cost is a concern, consider looking into the following potentially helpful resources: RxAssist, NeedyMeds, Simplefill, BenefitsCheckUp, Medicare Rights Center, State Pharmaceutical Assistance Programs (SPAPs), Rx Outreach, or FundFinder.

  • What uses do tricyclic antidepressants (TCAs) have?

    TCAs can generally be used for many medical conditions, including depression, nerve pain, migraines, or tension-type headaches.

    Specific TCAs may also have other uses. Tofranil (imipramine), for example, can be used to prevent nighttime bedwetting in children 6 years and older. A different TCA called clomipramine may also be used for obsessive-compulsive disorder (OCD).

    Some TCAs might also have some off-label uses. Imipramine, for example, has been used for bulimia nervosa, irritable bowel syndrome (IBS), and panic disorder.

  • How long do I have to take Tofranil?

    The duration of Tofranil (imipramine) treatment will vary per person.

    After successful treatment of bedwetting with imipramine, your healthcare provider may suggest safely stopping this medication and monitoring your symptoms.

    If you're taking imipramine for other medical conditions (e.g., depression), your healthcare provider may recommend continuing this medication—even if you feel better. Continuing your treatment might be necessary to prevent your condition from getting worse or frequently coming back.

How Can I Stay Healthy While Taking Tofranil?

If you're taking Tofranil (imipramine), depression or bedwetting may have negatively affected your quality of life. Depression or bedwetting have their challenges. You may have tried different approaches or treatments.

For depression, refer below for some general tips to support your health:

  • Take antidepressants as recommended by your healthcare provider.
  • Regular exercise might help improve your mood.
  • Find ways to manage your stress.
  • Eat a healthy diet.
  • Avoid alcohol.
  • Get adequate amounts of sleep.
  • Build a solid social support network.
  • Consider support groups or work with a mental health professional to help you find coping strategies that change how you think, feel, react, or respond to living with depression.

For bedwetting, refer below for some general tips:

  • Take bedwetting-related medications as recommended by your healthcare provider.
  • Consider keeping a diary to keep track of patterns and habits.
  • Use a bedwetting alarm that helps wake up your child at night if they start to urinate (pee).
  • Encourage your child to urinate at normally scheduled times during the day, night, and before bedtime.
  • Decrease how much fluid your child drinks a few hours before bedtime.
  • Please encourage your child not to hold their urine for too long.
  • Reward your child if they initiate using the bathroom on their own or if there was no bedwetting the night before.

Medical Disclaimer

Verywell Health's drug information is meant for educational purposes only and is not intended to replace medical advice, diagnosis, or treatment from a healthcare provider. Consult your healthcare provider before taking any new medication(s). IBM Watson Micromedex provides some of the drug content, as indicated on the page.

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Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Ross Phan, PharmD, BCACP, BCGP, BCPS
Ross is a writer for Verywell with years of experience practicing pharmacy in various settings. She is also a board-certified clinical pharmacist and the founder of Off Script Consults.