Nialamide 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
Nialamide
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 nialamide is an older type of antidepressant called an MAOI. When combined, they can push the levels of certain brain chemicals too high. This can cause a dangerous reaction with high blood pressure, high fever, muscle twitching, confusion, and even seizures. This has been serious and sometimes fatal in the past.
The good news is this is very manageable when your care team plans ahead. If you are switching from one to the other, your doctor will leave a safe gap in between. Please talk with your pharmacist or doctor before starting either drug so they can keep you safe.
Contraindicated combination. Co-administration of a TCA (amitriptyline) with an MAOI (nialamide) risks serotonin syndrome, hyperpyrexia, seizures, and death via altered catecholamine uptake and metabolism, producing excessive serotonergic and adrenergic stimulation.
- Direction: additive/synergistic serotonergic and sympathomimetic toxicity (increased effect).
- Onset: delayed; Evidence: probable.
- Management: Do not use concurrently. Allow a minimum 14-day washout after discontinuing the MAOI before initiating amitriptyline. Start amitriptyline low and titrate to response.
- Monitor for: hypertension, hyperthermia, myoclonus, mental status changes.
What happens
Neurotoxicity, seizures, or serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Deep Dive
The combined administration of TCAs and MAOIs has led to hyperpyrexia, seizures, and fatalities. There are also reports that taking MAOIs together with TCAs can produce serotonin syndrome112201. This uncommon yet potentially lethal state arises from excessive serotonergic stimulation 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
These two are not used together. This combination is contraindicated, so the main step your care team takes is avoiding overlap.
- If you are switching from nialamide (the MAOI) to amitriptyline, your team will allow at least 14 days after stopping the MAOI before starting amitriptyline.
- When amitriptyline is started, it is typically begun at a low dose and increased slowly, individualized by your team.
- Keep taking your medications exactly as prescribed, and do not stop or start either on your own.
Tell your pharmacist or prescriber right away if you develop fever, high blood pressure, muscle jerking, sweating, or confusion.
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 previously regarded as an absolute contraindication and continues to be listed as such by the manufacturers. Accounts of excitation, hyperpyrexia, convulsions, and possible death have been ascribed to this combination 345678. The underlying mechanism may involve the simultaneous inhibition of catecholamine reuptake into the central nervous system and inhibition of catecholamine metabolism 9.
b) Serotonin syndrome developed in two patients given a TCA following MAOI therapy. In a double-blind, crossover study assessing clorgyline and clomipramine for treating obsessive-compulsive disorder, two participants experienced severe reactions typical of serotonin syndrome. Over the course of the study, patients had received clorgyline therapy, then a washout interval of roughly four weeks, followed by clomipramine therapy. After the first 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 resolved several hours afterward, and both were subsequently treated successfully with clomipramine without adverse effects 1.
c) A drug interaction arose in a 76-year old woman who had been on clomipramine 50 mg daily for several months and was then changed to moclobemide 300 mg daily. The patient experienced somnolence, confusion, and fever, which then advanced to further mental impairment, muscle stiffness, myoclonus, and convulsive attacks. Her symptoms were characterized 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. The patient was on 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 the moclobemide dose to 150 mg twice daily. Five days after imipramine was raised to 200 mg per day, the patient developed serotonin syndrome symptoms, including sweating, shivering, confusion, fever, and spasms in the extremities. The patient 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 therapy with isocarboxazid and amitriptyline. In all three cases the patients had received MAOIs and TCAs individually without complications. Symptoms of mania appeared only 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 tranylcypromine regimen 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 resulted in disseminated intravascular coagulation and eventual death 13.
g) There is evidence that MAOIs and TCAs can be administered together in patients who were previously unresponsive to the MAOI or the TCA on its own. A few 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 may be used 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); the combination is then started 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 combination of amitriptyline and isocarboxazid is preferred 17. Numerous studies in patients with refractory depression or phobic anxiety states have successfully employed the combination of MAOIs and TCAs 18619.
Common questions
Can I take Nialamide and Amitriptyline together?
Do not take amitriptyline and nialamide together, as the combination can cause life-threatening serotonin syndrome, seizures, or high fever. If switching, your doctor will allow at least 14 days between stopping the MAOI and starting amitriptyline. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Nialamide 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 Nialamide and Amitriptyline interaction managed?
These two are not used together. This combination is contraindicated, so the main step your care team takes is avoiding overlap. If you are switching from nialamide (the MAOI) to amitriptyline, your team will allow at least 14 days after stopping the MAOI before starting amitriptyline. When amitriptyline is started, it is typically begun at a low dose and increased slowly, individualized by your t… 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 Nialamide 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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