Iproniazid 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
Iproniazid
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 older antidepressant, and iproniazid belongs to a group called MAOIs. When combined, they can push the level of certain brain chemicals too high. This can lead to a dangerous reaction with high blood pressure, high fever, muscle twitching, confusion, and even seizures. This combination has caused serious harm and, in some cases, death.
The good news: this is well known, and your care team knows how to keep you safe. If you are switching from one to the other, they will build in a waiting period. Never start, stop, or combine these on your own. Talk with your pharmacist or doctor first.
Contraindicated combination. Concomitant use of amitriptyline (a TCA) with iproniazid (a nonselective MAOI) risks serotonin syndrome (hypertension, hyperthermia, myoclonus, altered mental status), hyperpyrexia, convulsions, and death.
- Mechanism: altered catecholamine and serotonin uptake plus impaired monoamine metabolism, causing serotonergic/adrenergic hyperstimulation. Neither agent is a prodrug requiring activation here.
- Direction: additive/synergistic pharmacodynamic toxicity.
- Onset: delayed; Evidence: probable.
- Management: avoid coadministration. Allow at least 14 days after stopping the MAOI before initiating amitriptyline; then use low starting doses titrated to response.
What happens
Neurotoxicity, seizures, or serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Deep Dive
When a TCA and a MAOI are taken together, cases of hyperpyrexia, convulsions, and fatalities have occurred. The combined use of MAOIs and TCAs has additionally been linked to what is known as serotonin syndrome112201. This serotonergic hyperstimulation syndrome, though uncommon, can prove fatal and 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
The key step here is not taking these together. This pairing is contraindicated, so your care team will avoid using them at the same time.
- If you are switching from iproniazid (the MAOI) to amitriptyline, expect a washout period of at least 14 days after stopping the MAOI before amitriptyline is started.
- When amitriptyline is begun, your team will typically use a low dose and increase it slowly, individualized to you.
- Do not start, stop, or change either medicine on your own.
- Tell your pharmacist and prescriber about every medicine you take so they can time any switch safely.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
7 reports — tap to read
a) Giving monoamine oxidase inhibitors (MAOIs) together with tricyclic antidepressants (TCAs) was regarded in the past as an absolute contraindication and is still described that way by the manufacturers. Cases of excitation, hyperpyrexia, convulsions, and possible death have been linked to this combination 345678. The underlying mechanism may involve the simultaneous blockade of catecholamine reuptake into the central nervous system together with inhibition of catecholamine metabolism 9.
b) There have been reports of serotonin syndrome arising when a TCA is given after MAOI therapy. In a double-blind, crossover trial evaluating clorgyline and clomipramine for treating obsessive-compulsive disorder, two participants experienced severe reactions consistent with serotonin syndrome. In the course of the study, patients received clorgyline, then a washout interval of about four weeks, and afterward clomipramine. Following the first 100 mg dose of clomipramine, one patient developed coarse myoclonic jerking in both legs, hyperreflexia, diaphoresis, and arrhythmia. A second patient had a similar reaction after the initial dose, exhibiting upper motor neuron symptoms, myoclonic movements, and cardiac irritability. The symptoms in both patients resolved several hours afterward, and both were subsequently treated successfully with clomipramine without adverse effects 1.
c) A 76-year old woman who had taken clomipramine 50 mg daily for several months was changed to moclobemide 300 mg daily. She experienced somnolence, confusion, and fever, which then advanced to further mental impairment, muscle stiffness, myoclonus, and convulsive attacks. Her symptoms were reported as meeting the diagnostic criteria for serotonin syndrome and resolved a few days later once 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 taking moclobemide 300 mg twice daily when imipramine was begun at 50 mg daily, after which imipramine was increased twice to reach 200 mg and moclobemide was reduced to 150 mg twice daily. Five days after imipramine was raised to 200 mg per day, she developed serotonin syndrome symptoms including sweating, shivering, confusion, fever, and spasms in the extremities. She was treated with chlorpromazine, and the symptoms resolved over the following few days without further complications 11.
e) Three patients with bipolar disorder developed manic symptoms during concurrent treatment with isocarboxazid and amitriptyline. In each of the three cases, the patients had received MAOIs and TCAs individually without complications. Symptoms of mania appeared only when the drugs were combined, indicating a synergistic effect 12.
f) In one case, clomipramine 10 mg twice daily was added to a stable tranylcypromine regimen in a physically healthy 34-year old man. After taking several doses, he developed nausea and profuse sweating, followed by pyrexia, dyspnea, and agitation. The hyperpyrexical state progressed to disseminated intravascular coagulation and eventual death 13.
g) There is evidence that MAOIs and TCAs can be administered together in patients who previously did not respond to either the MAOI or the 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) using oral administration, c) avoiding clomipramine, imipramine, desipramine, and tranylcypromine in any combination, and d) closely monitoring patients 14561516. The combination can be employed in one of two ways. Most commonly, the recommendation is to discontinue all prior antidepressants (five to ten days for TCAs and 14 days for MAOIs) and then start the combination simultaneously 17. Alternatively, in a patient already receiving a TCA, small doses of the MAOI may be added slowly (Schoonover, 1983). Some sources indicate that the amitriptyline and isocarboxazid combination 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 Iproniazid and Amitriptyline together?
Do not take amitriptyline and iproniazid together, as the combination can cause a dangerous, potentially fatal reaction. If switching, wait at least 14 days after stopping the MAOI, and let your doctor or pharmacist guide the change. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Iproniazid 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 Iproniazid and Amitriptyline interaction managed?
The key step here is not taking these together. This pairing is contraindicated, so your care team will avoid using them at the same time. If you are switching from iproniazid (the MAOI) to amitriptyline, expect a washout period of at least 14 days after stopping the MAOI before amitriptyline is started. When amitriptyline is begun, your team will typically use a low dose and increase it slowly, i… 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 Iproniazid 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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