Moclobemide and Amitriptyline: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amitriptyline
Moclobemide
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
These two medicines should not be taken together. Amitriptyline (Elavil) is an antidepressant, and moclobemide is a type of antidepressant called an MAOI. When you combine them, both drugs push up the levels of certain brain chemicals like serotonin. Too much can cause a dangerous reaction called serotonin syndrome, with high blood pressure, high fever, muscle jerking, confusion, and even seizures.
This is serious, but very manageable when your care team knows about it. If you have been prescribed both, or you are switching from one to the other, please talk with your doctor or pharmacist before taking them. They will guide the safe timing and choose the right treatment for you.
Contraindicated. Combining the TCA amitriptyline with the MAOI moclobemide risks serotonin syndrome (hypertension, hyperthermia, myoclonus, altered mental status), neurotoxicity, seizures, and death.
- Mechanism: additive serotonergic and catecholaminergic effect via altered catecholamine reuptake and inhibited monoamine metabolism. Neither is a prodrug; the effect is additive/pharmacodynamic.
- Direction: increased serotonergic activity.
- Onset: delayed. Evidence: probable.
- Management: avoid concurrent use. Allow at least 14 days after discontinuing the MAOI before starting amitriptyline; initiate at low dose and titrate gradually to response.
What happens
Neurotoxicity, seizures, or serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Deep Dive
Taking a TCA together with a MAOI has led to hyperpyrexia, seizures, and fatalities. The simultaneous use of MAOIs and TCAs has additionally been described as producing serotonin syndrome121120. This uncommon yet potentially lethal state of serotonergic overstimulation presents with hypertension, hyperthermia, myoclonus, and altered mental status10. Giving amitriptyline alongside a MAOI is contraindicated21.
Why it happens (mechanism)
Altered catecholamine uptake and metabolism
How to manage this interaction
These drugs are not used together. Your care team will avoid this combination and choose a safer plan for you.
- If you are switching from moclobemide to amitriptyline, expect a washout period of at least 14 days after the MAOI is stopped before amitriptyline is started.
- When amitriptyline is later begun, it is typically started at a low dose and increased slowly to the best response.
- Do not start, stop, or change either medicine on your own. Contact your prescriber or pharmacist first.
- Seek urgent care for fever, agitation, confusion, muscle twitching, or a racing heart.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
7 reports — tap to read
a) Using monoamine oxidase inhibitors (MAOIs) together with tricyclic antidepressants (TCAs) was formerly regarded as an absolute contraindication and continues to be listed that way by the manufacturers. The combination has been linked to reports of excitation, hyperpyrexia, convulsions, and possible death 345678. The mechanism may be related to the joint inhibition of catecholamine reuptake into the central nervous system along with inhibition of catecholamine metabolism 9.
b) Serotonin syndrome was reported after a TCA was given following MAOI therapy. In a double-blind, crossover trial evaluating clorgyline and clomipramine for the treatment of obsessive-compulsive disorder, two participants experienced severe reactions typical of serotonin syndrome. In the study, patients received clorgyline therapy, then a washout interval of about four weeks, followed by clomipramine therapy. After the initial 100 mg dose of clomipramine, one patient developed coarse myoclonic jerking in both legs, hyperreflexia, diaphoresis, and arrhythmia. A second patient developed a comparable reaction after the first dose, presenting with upper motor neuron symptoms, myoclonic movements, and cardiac irritability. The symptoms in both patients cleared several hours afterward, and both were subsequently treated successfully with clomipramine without adverse effects 1.
c) A drug interaction was reported when a 76-year-old woman who had taken clomipramine 50 mg daily for several months was changed to moclobemide 300 mg daily. The patient developed somnolence, confusion, and fever, which then advanced to further mental impairment, muscle stiffness, myoclonus, and convulsive attacks. Her symptoms were described as meeting the diagnostic criteria for serotonin syndrome and resolved a few days later after all antidepressant medications were stopped 2.
d) A 39-year-old woman with bipolar disorder developed serotonin syndrome after imipramine was added to moclobemide. She was receiving moclobemide 300 mg twice daily when imipramine was begun at 50 mg daily, followed by two increases of imipramine to 200 mg and a reduction of moclobemide to 150 mg twice daily. Five days after imipramine was raised to 200 mg per day, she developed symptoms of serotonin syndrome, including sweating, shivering, confusion, fever, and spasms in the extremities. She was treated with chlorpromazine and the symptoms resolved over the next few days without further complications 11.
e) Three patients with bipolar disorder developed manic symptoms while receiving concurrent therapy with isocarboxazid and amitriptyline. In all three cases the patients had received MAOIs and TCAs individually without complications. Symptoms of mania only appeared when the drugs were used together, suggesting a synergistic effect 12.
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 several doses, the patient developed nausea and profuse sweating, followed by pyrexia, dyspnea, and agitation. The hyperpyrexical state led to disseminated intravascular coagulation and eventual death 13.
g) Evidence indicates that MAOIs and TCAs can be given together in patients who had not previously responded to the MAOI or TCA alone. Several precautions must be observed, including: a) avoiding large doses (no more than 150 mg amitriptyline or its equivalent, 45 mg phenelzine, or 60 mg isocarboxazid), b) oral administration, c) avoiding clomipramine, imipramine, desipramine, and tranylcypromine in any combination, and d) close monitoring of patients 14561516. The combination can be employed in one of two ways. Most often, the recommendation is to discontinue all prior antidepressants (five to ten days for TCAs and 14 days for MAOIs); the combination is then started simultaneously 17. Alternatively, in a patient already taking a TCA, small doses of the MAOI may be added gradually (Schoonover, 1983). Some sources indicate that the combination of amitriptyline and isocarboxazid is preferred 17. Numerous studies in patients with refractory depression or phobic anxiety states have successfully used the combination of MAOIs and TCAs 18619.
Common questions
Can I take Moclobemide and Amitriptyline together?
Amitriptyline and moclobemide should not be taken together because of the risk of serotonin syndrome, seizures, and other serious harm; allow at least 14 days between stopping the MAOI and starting amitriptyline, and let your care team plan the switch. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Moclobemide and Amitriptyline interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Moclobemide and Amitriptyline interaction managed?
These drugs are not used together. Your care team will avoid this combination and choose a safer plan for you. If you are switching from moclobemide to amitriptyline, expect a washout period of at least 14 days after the MAOI is stopped before amitriptyline is started. When amitriptyline is later begun, it is typically started at a low dose and increased slowly to the best response. Do not start,… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Moclobemide or Amitriptyline need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (21)
- Insel TR, Roy BF, Cohen RM, et al: Possible development of the serotonin syndrome in man. Am J Psychiatry 1982; 139:954-955. PubMed
- Spigset O, Mjorndal T, & Lovheim O: Serotonin syndrome caused by a moclobemide-clomipramine interaction. Br Med J 1993; 306:248. PubMed
- Lockett MF & Milner G: Combining the antidepressant drugs (letter). Br Med J 1965; 1:921. DOI
- Brachfeld J, Wirtshafter A, & Wolfe S: Imipramine-tranylcypromine incompatibility. Near fatal toxic reaction. JAMA 1963; 186:1172. DOI
- Winston F: Combined antidepressant therapy. Br J Psychiatry 1971; 118:301-304. PubMed
- Schuckit M, Robins E, & Feighner JP: Tricyclic antidepressants and monoamine oxidase inhibitors. Combination therapy in the treatment of depression. Arch Gen Psychiatry 1971; 24:509-514. PubMed
- Sargent W: Combining the antidepressant drugs (letter). Br Med J 1965; 1:251. PubMed
- Spiker DG & Pugh DD: Combining tricyclic and monoamine oxidase inhibitor antidepressants. Arch Gen Psychiatry 1976; 33:828-830. PubMed
- Sjoqvist F: Psychotropic drugs (2). Interaction between monoamine oxidase (MAO) inhibitors and other substances. Proc R Soc Med 1965; 58:967-978. PubMed
- Sternbach H: The serotonin syndrome. Am J Psychiatr 1991; 148:705-713. PubMed
- Brodribb TR, Downey M, & Gilbar PJ: Efficacy and adverse effects of moclobemide (letter). Lancet 1994; 343:475. DOI
- de la Fuente JR, Berlanga C, & Leon-Andrade C: Mania induced by tricyclic-MAOI combination therapy in bipolar treatment-resistant disorder: case reports. J Clin Psychiatry 1986; 47:40-41.
- Tackley RM & Tregaskis B: Fatal disseminated intravascular coagulation following a monoamine oxidase inhibitor/tricyclic interaction. Anaesthesia 1987; 42(7):760-763. PubMed
- Kline NS: Experimental use of monoamine oxidase inhibitors with tricyclic antidepressants. JAMA 1974; 227:807.
- White K & Simpson G: The combined use of MAOIs and tricyclics. J Clin Psychiatry 1984; 45:67-69.
- Rom WN & Benner EJ: Toxicity by interaction of tricyclic antidepressant and monoamine oxidase inhibitor. Calif Med 1972; 117:65-66.
- Perry PJ, Alexander B, & Liskow BIPerry PJ, Alexander B, & Liskow BI: Psychotropic Drug Handbook, 6th. Harvey Whitney Books Company, Cincinnati, OH, 1991.
- Ponto LB, Perry PJ, Liskow BI, et al: Drug therapy reviews: tricyclic antidepressant and monoamine oxidase inhibitor combination therapy. Am J Hosp Pharm 1977; 34:954-961. DOI
- Ashcroft GW: Psychological medicine: management of depression. Br Med J 1975; 2:372-376. PubMed
- Neuvonen PJ, Pohjola-Sintonen S, Tacke U, et al: Five fatal cases of serotonin syndrome after moclobemide-citalopram or moclobemide-clomipramine overdoses (letter). Lancet 1993; 342:1419. PubMed
- Product Information: Elavil(R), amitriptyline hydrochloride. Zeneca Pharmaceuticals, Wilmington, DE, 1998. DailyMed
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