Amitriptyline with S-Adenosylmethionine Interaction Details
Brand Names Associated with Amitriptyline
- Amitid®
- Amitril®
- Amitriptyline
- Duo-Vil® (as a combination product containing Amitriptyline, Perphenazine)
- Elavil®
- Endep®
- Etrafon® (as a combination product containing Amitriptyline, Perphenazine)
- Limbitrol® (as a combination product containing Amitriptyline, Chlordiazepoxide)
- Triavil® (as a combination product containing Amitriptyline, Perphenazine)
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 13, 2023
Interaction Effect
An increased risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Summary
A single case has been reported of serotonin syndrome likely resulting from the combination of S-adenosylmethionine (SAMe) and clomipramine. SAMe was shown to hasten the onset of therapeutic response of imipramine in a clinical trial involving 40 patients, without serotonergic side effects . If therapy is initiated with SAMe and a tricyclic antidepressant, the patient should be monitored closely for early signs of serotonin syndrome. Serotonin syndrome is a condition of serotonergic hyperstimulation and manifests as restlessness, myoclonus, changes in mental status, hyperreflexia, diaphoresis, shivering, and tremor. If the syndrome is not recognized and correctly treated, death can result .
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
S-adenosylmethionine (SAMe) used concomitantly with imipramine was found to decrease depressive symptoms sooner than imipramine alone (Berlanga et al, 1992). One case has been reported of serotonin syndrome likely resulting from concomitant use of SAMe and clomipramine (Iruela et al, 1993). If SAMe and a tricyclic antidepressant are used together, use low doses of each and titrate upward slowly, while monitoring closely for early signs of serotonin syndrome such as increasing anxiety, confusion, and disorientation.
Mechanism Of Interaction
Additive pharmacologic effects resulting in excessive serotonergic stimulation
Literature Reports
A) A 71 year-old female was hospitalized with anxiety, agitation, confusion, and symptoms of serotonin syndrome. She had been taking S-adenosylmethionine 100 milligrams (mg) intramuscularly daily and clomipramine 25 mg daily for 10 days, which was then increased to 75 mg/day. Within 48-72 hours of the increased clomipramine dosage, she became progressively anxious, agitated, and confused. On admission she was verbally unresponsive and stuporous, with heart rate 130 beats/minute, respiratory rate 30 breaths/minute, temperature 40.5 degrees Celsius, diarrhea, myoclonus, generalized tremors, rigidity, hyperreflexia, shivering, diaphoresis, and dehydration. Temperature increased to 43 degrees Celsius during her hospital stay, with no documented infection. White blood cell count (WBC) was 13,040 mm3, lactic dehydrogenase was 662 units/liter (U/L), creatine phosphokinase was 8920 U/L, serum potassium 2.7 milliequivalents/liter (mEq/L), creatinine 1.1 mg/100 milliliter (mL) (laboratory reference values were not provided). A cranial computed tomography (CT) scan was normal. The patient was not taking neuroleptics. Serum benzodiazepine and tricyclic antidepressant levels were normal. Symptoms resolved gradually with 4 days of hydration and supportive care. The interaction was proposed to be a result of synergistic activity of S-adenosylmethionine and clomipramine .
Amitriptyline Overview
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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.
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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.
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