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If the “popular” antidepressants haven’t helped you, know that you’re not alone. It’s common for people to try different treatments (with the help of their healthcare providers) until they find the right medications and dosages. If medications such as SSRIs and SNRIs haven’t helped your depression, other treatment options are available; one such treatment is imipramine (Tofranil).
Read on to learn about imipramine’s uses, side effects, dosage, and more.
What is imipramine?
Imipramine (Tofranil) is an antidepressant medication. It belongs to an older class of prescription drugs called tricyclic antidepressants (TCAs). Imipramine was approved by the Food and Drug Administration (FDA) back in the 1950s (Fayez, 2021).
How exactly imipramine works isn’t fully understood. The thought is that tricyclic antidepressants (named for their three-ring chemical structure) enhance the availability of brain chemicals that regulate mood, such as norepinephrine (Mallinckrodt, 2017; Mallinckrodt, 2014).
Note that there are two versions of imipramine. Imipramine hydrochloride (brand name: Tofranil) is a tablet; imipramine pamoate (brand name: Tofranil-PM) is a capsule. Both versions contain the same active ingredient—imipramine— and are available as generic drugs (FDA, n.d.).
Antidepressants: types, side effects, uses, and risks
The FDA approves imipramine for the treatment of depression (also called unipolar depression, major depressive disorder, or MDD) in adults and for the treatment of nocturnal enuresis (bedwetting) in kids ages six years and up (Mallinckrodt, 2017; Mallinckrodt, 2014).
It was one of the most popular treatments for depression until 1987 when a new antidepressant—fluoxetine (brand name Prozac; see Important Safety Information), the first SSRI—came onto the scene. Even though imipramine is FDA-approved for depression, it’s no longer a first-choice among prescribers because drugs in this class (TCAs) can cause more side effects than newer treatments. Now, healthcare providers prescribe imipramine for people with treatment-resistant depression. Treatment-resistant depression is depression that does not improve after trying two or more different medications (Chockalingam, 2019; Thase, 2021).
Sometimes, healthcare providers use imipramine “off-label” to treat other conditions, meaning the FDA didn’t explicitly approve it for those uses. A healthcare provider can prescribe medications for off-label use if they decide that it’s the proper treatment for their patient.
Off-label drugs: what are they?
Off-label uses for imipramine include:
- Panic disorder (Fayez, 2021).
- Chronic neuropathy (nerve pain) or fibromyalgia: a complex medical condition involving long-term, widespread musculoskeletal pain (Hearn, 2013).
- Parasomnia: a type of sleep disorder involving unusual behaviors or experiences during sleep, such as sleepwalking or night terrors (Kierlin, 2011).
Imipramine side effects
Common side effects of imipramine in adults include (Mallinckrodt, 2017; Mallinckrodt, 2014):
- Dry mouth
- Blurred vision
- Fast heart rate
- Heart palpitations
- Increased appetite
- Impaired balance or coordination
- Increased sweating
Less commonly, people experience other side effects of imipramine like (Mallinckrodt, 2017; Mallinckrodt, 2014):
- Orthostatic hypotension (drop in blood pressure and dizziness upon standing)
- High blood pressure
- Glaucoma (increased pressure inside the eye)
- Urinary retention (when your bladder doesn’t completely empty when you urinate)
- Weight gain
- Reduced sex drive
- Gynecomastia (breast tissue growth in males)
Note that imipramine’s more common side effects are different in children taking it for bedwetting than those seen in adults. Kids (ages 6 to 17) may more commonly develop side effects that include nervousness, trouble sleeping, daytime tiredness, and upset stomach (Mallinckrodt, 2017).
Because of imipramine’s possible side effects, it’s best to avoid driving while taking this medication until you become familiar with how it affects you. If you have concerns about the side effects of drugs, your healthcare provider or pharmacist can discuss them with you.
Zoloft vs. Prozac: differences and similarities
Imipramine is a medication that you take by mouth. It comes in these forms and strengths (Mallinckrodt, 2017; Mallinckrodt, 2014):
- Tablet: 10 milligrams (mg), 25 mg, and 50 mg
- Capsule: 75 mg, 100 mg, 125 mg, and 150 mg
The typical starting dose of imipramine for depression in adults is 75 mg, taken in the evening. The usual starting dose for bedwetting is 25 mg, given one hour before bedtime.
Imipramine doesn’t start working right away. You may not notice any improvement until one to three weeks after beginning treatment or longer. Your healthcare provider may adjust your dose based on your symptoms or any side effects. Always consult your healthcare provider before changing your dose or stopping this medication.
Important warning for imipramine
The Food and Drug Administration (FDA) requires antidepressants, including imipramine, to carry a boxed warning for their rare but serious risk of suicidal thoughts and behaviors.
This increased risk mainly occurs in children, adolescents, and young adults up to age 25, especially during the early stages of treatment or after dose increases. If you notice changes in how you think and behave since starting imipramine or have thoughts of harming yourself, help is available. Tell your healthcare provider right away or seek emergency medical care (Mallinckrodt, 2017; Mallinckrodt, 2014).
Before prescribing imipramine, your healthcare provider will go over your medical history as well as the treatment’s risks. They will want to know if any of these conditions or factors apply to you, as they could increase your risk for severe side effects (Mallinckrodt, 2017; Mallinckrodt, 2014):
- Recent heart attack, stroke, or heart disease
- Bladder or urination problems
- Overactive thyroid
- Liver or kidney disease
- Bipolar disorder
- Other mental health disorders or medical condition
- Alcohol use
- Pregnant or breastfeeding
- Past allergic reaction to imipramine or other tricyclic antidepressants (TCAs). A few examples of other TCAs are amitriptyline, clomipramine, doxepin, and nortriptyline.
Diazepam (Valium): dosage, uses, side effects, and risks
Imipramine can interact with several types of medications. Your healthcare provider or pharmacist can provide more information regarding your medications.
Risk of serotonin syndrome
Several medications can increase serotonin levels, a molecule that regulates your mood, if you take them with imipramine. If serotonin levels get too high, something called serotonin syndrome can occur. Serotonin syndrome is rare and ranges from mild to life-threatening. Taking the following medications can raise the risk of serotonin syndrome if used with imipramine (Mallinckrodt, 2017; Mallinckrodt, 2014):
- Other antidepressants including monoamine oxidase inhibitor (MAOI) drugs (such as phenelzine, tranylcypromine, linezolid, rasagiline); other tricyclic antidepressants (such as amitriptyline, clomipramine, doxepin, and nortriptyline); SSRIs (such as citalopram, escitalopram [brand name Lexapro; see Important Safety Information], fluoxetine, and sertraline [brand name Zoloft; see Important Safety Information]); and SNRIs (such as duloxetine [brand name Cymbalta; see Important Safety Information] and venlafaxine [brand name Effexor XR; see Important Safety Information])
- Triptans, a type of migraine medication
- Tramadol, a pain medication
- St. John’s Wort, an herbal remedy
This list does not include all of imipramine’s possible interactions. Before taking imipramine, your healthcare provider or pharmacist will check for interactions with your other medications, so be sure to tell them everything you take.
- Chockalingam, R., Gott, B. M., & Conway, C. R. (2019). Tricyclic antidepressants and monoamine oxidase inhibitors: are they too old for a new look? Handbook of experimental pharmacology, 250, 37–48. doi: 10.1007/164_2018_133. Retrieved from https://pubmed.ncbi.nlm.nih.gov/30105472/
- Fayez, R., Gupta, V. (2021). Imipramine. [Updated May 27, 2021]. In: StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK557656/
- FDA. (n.d.) Drugs@FDA: FDA-Approved Drugs. Retrieved October 15, 2021 from https://www.accessdata.fda.gov/scripts/cder/daf/
- Hearn, L., Derry, S., Phillips, T., Moore, R. A., & Wiffen, P. J. (2014). Imipramine for neuropathic pain in adults. The Cochrane database of systematic reviews, 2014(5), CD010769. doi: 10.1002/14651858.CD010769.pub2. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485593/
- Kierlin, L., & Littner, M. R. (2011). Parasomnias and antidepressant therapy: a review of the literature. Frontiers in psychiatry, 2, 71. doi: 10.3389/fpsyt.2011.00071. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235766/
- Mallinckrodt. (2014). Tofranil: imipramine pamoate capsules. Retrieved October 15, 2021 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017090s078lbl.pdf
- Mallinckrodt. (2017). Tofranil: imipramine hydrochloride tablets. Retrieved October 15, 2021 from https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1827a5aa-733a-49d9-89d9-48ea0367b230&type=display
- Thase, M., & Connolly, K.R. (2021). Unipolar depression in adults: Choosing treatment for resistant depression. In P. P. Roy-Byrne & D. Solomon (Eds.). Retrieved October 15, 2021 from https://www.uptodate.com/contents/unipolar-depression-in-adults-choosing-treatment-for-resistant-depression
Felix Gussone is a physician, health journalist and a Manager, Medical Content & Education at Ro.