Clorgyline 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
Clorgyline
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 clorgyline is a type of drug called an MAO inhibitor. When they are combined, they can push levels of certain brain chemicals too high. This can lead to a dangerous reaction called serotonin syndrome, with high blood pressure, high fever, muscle twitching, confusion, and even seizures. In serious cases it has been fatal.
The good news is this is well understood and completely avoidable. Please do not start, stop, or change either medicine on your own. Talk with your pharmacist or doctor, who can choose a safe plan and, if switching, allow enough time between the two drugs.
Contraindicated: concurrent TCA (amitriptyline) and MAOI (clorgyline) therapy.
- Effect: risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, altered mental status), neurotoxicity, seizures, and hyperpyrexia; potentially fatal.
- Mechanism: MAOI inhibition of monoamine oxidase plus TCA blockade of catecholamine/serotonin reuptake produces excessive serotonergic and adrenergic stimulation.
- Onset: delayed. Evidence: established.
- Management: avoid combination. Allow a minimum 14-day washout after discontinuing the MAOI before initiating amitriptyline. Start amitriptyline at low dose and titrate gradually to response.
What happens
Neurotoxicity, seizures, or serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Deep Dive
The combined use of TCAs and MAOIs has led to hyperpyrexia, seizures, and fatalities. Additionally, taking MAOIs together with TCAs has been described as producing a state known as serotonin syndrome121121. This uncommon yet potentially lethal disorder involves excessive serotonergic stimulation and presents with hyperthermia, hypertension, myoclonus, and altered mental status10. Giving amitriptyline alongside a MAOI is contraindicated22.
Why it happens (mechanism)
Altered catecholamine uptake and metabolism
How to manage this interaction
The core rule here: these two are not used together. Your care team will avoid combining amitriptyline with clorgyline.
- If you are switching from the MAOI (clorgyline) 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 titrated up slowly, individualized to your response.
- Keep taking your medicines exactly as prescribed, and never start or stop either one on your own.
- Bring your full medication list to your pharmacist or prescriber and ask them to confirm your plan is safe.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
7 reports — tap to read
a) In the past, giving monoamine oxidase inhibitors (MAOIs) together with tricyclic antidepressants (TCAs) was regarded as an absolute contraindication, and manufacturers continue to classify it as such. The combination has been linked to reports of excitation, hyperpyrexia, convulsions, and possible death 345678. The underlying mechanism may involve the simultaneous blocking of catecholamine reuptake into the central nervous system along with the blocking of catecholamine metabolism 9.
b) Serotonin syndrome was reported to occur when a TCA was given following MAOI treatment. In a double-blind, crossover study evaluating clorgyline and clomipramine for treating obsessive-compulsive disorder, two participants experienced severe reactions typical of serotonin syndrome. Over the course of the study, patients received clorgyline therapy, then a washout interval of about four weeks, and afterward clomipramine therapy. Following the first 100 mg dose of clomipramine, one patient experienced coarse myoclonic jerking in both legs, hyperreflexia, diaphoresis, and arrhythmia. A second patient had a comparable reaction after the first dose, showing 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 was reported in a 76-year-old woman who had been taking clomipramine 50 mg daily for several months and was then 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 characterized 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 experienced serotonin syndrome after imipramine was added to moclobemide. She was taking moclobemide 300 mg twice daily when imipramine was initiated at 50 mg daily, which was then increased twice to reach 200 mg, along with 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 her 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. Manic symptoms only appeared when the drugs were used together, 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, which were 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 previously did not respond 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) using the oral route c) avoiding clomipramine, imipramine, desipramine, and tranylcypromine in any combination, and d) monitoring patients closely 14561516. The combination may be applied in one of two ways. Most commonly, the recommendation is to discontinue all previous antidepressants (five to ten days for TCAs and 14 days for MAOIs), after which the combination is started simultaneously 17. Alternatively, in a patient already receiving a TCA, small doses of the MAOI may be added slowly 20. 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 Clorgyline and Amitriptyline together?
Amitriptyline and clorgyline (an MAOI) should not be taken together because of the risk of serotonin syndrome, seizures, and other severe reactions; if switching, at least 14 days must pass after stopping the MAOI. Talk to your pharmacist or doctor before making any changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clorgyline 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 Clorgyline and Amitriptyline interaction managed?
The core rule here: these two are not used together. Your care team will avoid combining amitriptyline with clorgyline. If you are switching from the MAOI (clorgyline) 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 titrated up slowly, individualized to your respons… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Clorgyline 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 (22)
- 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
- Schoonover SC: Depression In: Bassuk EL, Schoonover SC, & Gelenberg AJ (Eds): The Practitioner's Guide to Psychoactive Drugs, 2nd. Plenum Medical Book Company, New York, NY, 1983. DOI
- 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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