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Tips for tapering off imipramine (Tofranil)


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Aka Antideprin, Deprimin, Deprinol, Depsol, Depsonil, Dynaprin, Eupramin, Imipramil, Irmin, Janimine, Melipramin, Surplix, melipramine

From http://www.drugs.com/pro/imipramine.html

  • Metabolized by liver enzyme P450 cyp 2D6
  • Imipramine hydrochloride supplied as 10 mg, 25 mg, and 50 mg tablets
  • Imipramine Pamoate supplied as 75, 100, 125, and 150mg capsules

Drug Interactions

Drugs Metabolized by P450 2D6
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.... 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 Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).

....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,

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 (see WARNINGS).

To see if Imipramine is interacting with any drug you are taking, use the Drug Interactions Checker here http://www.drugs.com/drug_interactions.html
Reduce by 10% per month to start
The 10% rule holds for imipramine, just like other psychiatric drugs: Reduce by 10% per month, calculated on the last dosage. (The amount of the reduction gets progressively smaller.)

See Why taper by 10% of my dosage?

Get your prescription filled with the lower dosage tablets
As imipramine comes in a range of dosages, you may be able to cut the lower-dosage tablets (10mg, 25mg) into quarters and decrease by 2.5mg or 6.25mg at a time for much of your taper. (Hint: Prescriptions may be written to take xxmg twice a day.)
Use a liquid solution to taper
Titrating using a liquid is very good for very small measured decreases in dosage, allowing more precise measurements.

Use a combination of tablets or capsules and liquid

Rather than switch directly to an all-liquid dose, you may wish to take part of your dose in liquid and part in lower-dose tablets or capsules, gradually converting to all liquid as you get to lower dosages. This can be very convenient and reduce any problems switching from one form of the drug to another.


If your doctor prescribes liquid and tablets or capsules at the same time, most likely he or she will have to indicate "divided doses" in the prescriptions to get the drugs covered by insurance.

Edited by Altostrata

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

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