Amitriptyline with Pargyline Interaction Details

Brand Names Associated with Amitriptyline

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 13, 2023

Interaction Effect

Neurotoxicity, seizures, or serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)

Interaction Summary

Concomitant TCA and MAOI use has resulted in hyperpyrexia, convulsions, and death. Concurrent use of MAOIs and TCAs has also been reported to result in a condition termed serotonin syndrome. Serotonin syndrome is a rare but potentially fatal condition of serotonergic hyperstimulation characterized by hypertension, hyperthermia, myoclonus, and changes in mental status . The concurrent administration of amitriptyline and a MAOI is contraindicated .

Severity

Contraindicated

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Amitriptyline is contraindicated with monoamine oxidase inhibitor (MAOI) therapy. If amitriptyline is replacing treatment with a MAOI, a minimum of 14 days should elapse after the MAOI is discontinued before amitriptyline is initiated. Low doses of amitriptyline should be employed and gradually titrated to optimum response.

Mechanism Of Interaction

Altered catecholamine uptake and metabolism

Literature Reports

A) Concomitant administration of monoamine oxidase inhibitors (MAOIs) with tricyclic antidepressants (TCAs) has been considered an absolute contraindication in the past and still is listed as such by the manufacturers. Reports of excitation, hyperpyrexia, convulsions, and possible death have been attributed to the combination . The mechanism may relate to the combined inhibition of catecholamine reuptake into the central nervous system and inhibition of catecholamine metabolism .

B) Serotonin syndrome occurred in two patients administered a TCA after MAOI therapy. In a double-blind, crossover study examining the effects of clorgyline and clomipramine for the treatment of obsessive-compulsive disorder, two subjects developed severe reactions characteristic of serotonin syndrome. During the study, patients had received clorgyline therapy, followed by a washout period of approximately four weeks and subsequent clomipramine therapy. After taking the first 100 mg dose of clomipramine, one patient developed coarse myoclonic jerking in both legs, hyperreflexia, diaphoresis, and arrhythmia. Another patient developed a similar reaction after the first dose, with upper motor neuron symptoms, myoclonic movements, and cardiac irritability. Both patient's symptoms resolved several hours later, and both patients were later treated successfully with clomipramine without adverse effects .

C) A drug interaction occurred in a 76-year old woman who had been taking clomipramine 50 mg daily for several months and subsequently switched to moclobemide 300 mg daily. The patient experienced somnolence, confusion, and fever which then progressed to further mental impairment, muscle stiffness, myoclonus, and convulsive attacks. The patient's symptoms were described as fulfilling the diagnostic criteria for serotonin syndrome and were resolved a few days later after discontinuing all antidepressant medications .

D) A 39-year old woman with bipolar disorder developed serotonin syndrome after imipramine was added to moclobemide. The patient was taking moclobemide 300 mg twice daily when imipramine was started at 50 mg daily, followed by two dosage increases of imipramine to 200 mg and a reduction of moclobemide dosage to 150 mg twice daily. Five days after the increase in imipramine to 200 mg per day, the patient developed symptoms of serotonin syndrome, including sweating, shivering, confusion, fever, and spasms in the extremities. The patient was treated with chlorpromazine and symptoms resolved over the next few days without further complications .

E) Three patients with bipolar disorder developed manic symptoms while undergoing concurrent therapy with isocarboxazid and amitriptyline. In all three cases the patients had been given MAOIs and TCAs alone without complications. It was only when the drugs were used in combination that symptoms of mania emerged, suggesting a synergistic effect .

F) In one case, clomipramine 10 mg twice daily was added to a stable regimen of tranylcypromine in a physically healthy 34-year old man. After taking several doses, the patient developed symptoms of nausea and profuse sweating, followed by pyrexia, dyspnea, and agitation. The hyperpyrexical state led to disseminated intravascular coagulation and eventual death .

G) There is evidence that MAOIs and TCAs can be given concomitantly in patients previously unresponsive to the MAOI or TCA alone. A few precautions must be followed including: a) avoidance of large doses (no more than 150 mg amitriptyline or its equivalent, 45 mg phenelzine, or 60 mg isocarboxazid) b) oral administration c) avoidance of clomipramine, imipramine, desipramine, and tranylcypromine in any combination, and d) close monitoring of patients . The combination may be utilized in one of two ways. Most frequently, the recommendation is to stop all previous antidepressants (five to ten days for TCAs and 14 days for MAOIs); the combination is then simultaneously started . Alternatively, in a patient previously receiving a TCA, small doses of the MAOI may be slowly added (Schoonover, 1983). Some sources suggest that the combination of amitriptyline and isocarboxazid is preferred . Numerous studies in patients with refractory depression or phobic anxiety states have successfully used the combination of MAOIs and TCAs .

Amitriptyline Overview

• Amitriptyline is used to treat symptoms of depression. Amitriptyline is in a class of medications called tricyclic antidepressants. It works by increasing the amounts of certain natural substances in the brain that are needed to maintain mental balance.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.