Citalopram with Imipramine Interaction Details
Brand Names Associated with Citalopram
- Celexa®
- Citalopram
Brand Names Associated with Imipramine
- Imipramine
- Tofranil®
- Tofranil® PM
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 11, 2023
Interaction Effect
An increase in the bioavailability and half-life of desipramine, the major metabolite of imipramine, an increased risk of QT interval prolongation and an increased risk of serotonin syndrome
Interaction Summary
Concomitant use of citalopram and imipramine is not recommended due to a potential for additive effects on QT interval prolongation and an increased risk of serious cardiovascular effects and serotonin syndrome. If concomitant use is required, monitor for ECG changes and emergence of serotonin syndrome. Do not exceed citalopram doses of 40 mg/day, and discontinue citalopram in patients who have persistent QTc measurements greater than 500 milliseconds or who have serotonin syndrome. Institute supportive therapy if symptoms of serotonin syndrome occur. Imipramine pharmacokinetics were not influenced by citalopram when the two were coadministered . However, citalopram may increase exposure to desipramine, the major metabolite of imipramine by approximately 50% . Clinical events have not been reported and, in an isolated report, citalopram was successfully substituted for PARoxetine in a patient who had experienced elevated tricyclic antidepressant levels during PARoxetine treatment. Citalopram is an inhibitor of cytochrome P450 2D6 enzymes, and imipramine, a tertiary amine, is converted to a secondary amine (desipramine) by N-demethylation. The secondary amine then undergoes hydroxylation, a process which is controlled by the oxidative enzymes of the CYP2D6 system .
Severity
Major
Onset
Rapid
Evidence
Probable
How To Manage Interaction
Concomitant use of citalopram and imipramine is not recommended due to a potential for additive effects on QT interval prolongation and an increased risk of serious cardiovascular effects and serotonin syndrome. If concomitant use is required, monitor for ECG changes and emergence of serotonin syndrome. Do not exceed citalopram doses of 40 mg/day, and discontinue citalopram in patients who have persistent QTc measurements greater than 500 milliseconds or who have serotonin syndrome. Institute supportive therapy if symptoms of serotonin syndrome occur.
Mechanism Of Interaction
Inhibition of desipramine metabolism, the major metabolite of imipramine; additive QT interval prolongation; additive serotonergic effects
Literature Reports
A) Eight healthy male volunteers completed three phases of an interaction study to determine the effects of coadministered imipramine and citalopram. All subjects were extensive metabolizers of sparteine, indicating normal cytochrome P450 2D6 enzyme activity. Each subject received citalopram 40 mg alone as a single daily dose for 10 days, imipramine 100 mg as a single oral dose, and a single oral dose of imipramine 100 mg coadministered on day 7 of citalopram therapy. At least two weeks separated each treatment phase. Results showed that the concurrent administration of citalopram and imipramine resulted in a 50% increase in the desipramine area under the concentration-time curve (AUC) and a similar decrease in the 2-hydroxy-desipramine AUC. Also, the desipramine half-life was approximately seven hours longer when administered with citalopram (27 hours vs. 20 hours). The AUC and half-life of imipramine were not affected by citalopram administration. These results showed that citalopram is an inhibitor of cytochrome P450 2D6 hepatic enzymes, since most tricyclic antidepressants rely on this system for metabolism .
B) A case report describes a 45-year-old white female with major depressive disorder and dysthymia. This patient failed several trials of antidepressants from all available drug classes, as well as electroconvulsive therapy. The patient's medications included pindolol, desipramine, clonazePAM, and OLANZapine. PARoxetine was initiated and titration to 40 mg/day occurred over 3 months. The patient developed light-headedness, ataxia, and increased confusion after the titration. Desipramine serum levels were 1810 nanograms/mL (ng/mL; 6794 nanomoles/L (nmol/L)) (therapeutic range 75-300 ng/mL (280 to 1130 nmol/L)). After decreasing the daily desipramine 200 mg, the serum desipramine level was still 1665 ng/mL (6250 nmol/L). The reduction in side effects were evident when the PARoxetine dose was decreased to 30 mg/day and desipramine dose was decreased to 150 mg/day. Despite the dosage reduction of both drugs the patient's serum desipramine level was 1153 ng/mL (4328 nmol/L). PARoxetine was discontinued and desipramine dose was decreased to 100 mg/day in divided doses. Citalopram was initiated and titrated to 40 mg/day. Over the next two months the patient's desipramine level decreased to 195 ng/mL (732 nmol/L). Depressive symptoms also improved. Desipramine toxicity is presumed to be caused by hepatic cytochrome P450 2D6 (CYP2D6) isoenzyme blockade from PARoxetine. The author concludes that the switch to citalopram likely is responsible for diminished desipramine serum levels, although alternative explanations should not be discounted .
Citalopram Overview
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Citalopram is used to treat depression. Citalopram is in a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.
Imipramine Overview
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Imipramine tablets and capsules are used to treat depression. Imipramine tablets are also used to prevent bedwetting in children. Imipramine is in a class of medications called tricyclic antidepressants. It treats depression by increasing the amounts of certain natural substances in the brain that are needed to maintain mental balance. There is not enough information to explain how imipramine prevents bedwetting.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.