Lithium Carbonate and Phenelzine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenelzine
Lithium Carbonate
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.
What happens
An increased risk of serotonin syndrome and an increased risk of malignant hyperpyrexia
Interaction Deep Dive
Concomitant use of phenelzine (MAO inhibitor) and lithium (serotonergic drug) is contraindicated due to increased risk of serotonin syndrome. Allow at least 14 days between discontinuation of phenelzine and initiation of lithium. Before initiating phenelzine after using lithium, a sufficient amount of time must be allowed for clearance of serotonergic drugs and its active metabolite1. Two patients experienced a fatal malignant hyperpyrexia syndrome following concomitant therapy with lithium and phenelzine. Although a direct causal relationship has not been established, it is advisable to avoid this combination if possible 23.
Why it happens (mechanism)
Additive serotonergic effects; increased 5-hydroxytryptamine in the brain
Literature reports
2 reports — tap to read
a) A 42-year-old woman experienced a sudden onset of restlessness, sweating, and confusion. Medication therapy included lithium 800 mg daily, L-tryptophan 1 g daily, diazePAM 6 mg daily, and triazolam 0.25 mg daily. Six weeks prior to the onset of symptoms, phenelzine 15 mg three times daily had been started. On admission, her lithium level was 0.38 mmol/L (therapeutic range 0.5 to 1.0 mmol/L). Within three hours of the onset of symptoms, the woman was comatose and a diagnosis of neuroleptic malignant syndrome was made. She was treated with intravenous dantrolene 60 mg three times daily with no success. Acute renal failure and severe disseminated intravascular coagulation followed, and the patient died on the sixth day of hospitalization 2.
b) A fatal malignant hyperpyrexia syndrome occurred in a 48-year-old female being treated with chlorproMAZINE 600 mg daily, lithium 800 mg daily, L-tryptophan 6 g daily, and phenelzine 45 mg daily. Symptoms of incoherent speech, reduced consciousness, muscular rigidity, nystagmus, and hyperreflexia occurred within a few weeks of the initiation of phenelzine therapy. She was diagnosed with neuroleptic malignant syndrome and treated with procyclidine. Respiratory and cardiac arrest soon followed, and the patient died. The timing of her death points to the effect of combined phenelzine, lithium, and L-tryptophan, since lithium and L-tryptophan had been coadministered for the previous four months before phenelzine was started 3.
Common questions
Can I take Lithium Carbonate and Phenelzine together?
An increased risk of serotonin syndrome and an increased risk of malignant hyperpyrexia Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lithium Carbonate and Phenelzine 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 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 Lithium Carbonate or Phenelzine 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 (3)
- Product Information: NARDIL(R) oral film coated tablets, phenelzine sulfate oral film coated tablets. Parke-Davis Div of Pfizer Inc (per DailyMed), New York, NY, 2020. DailyMed
- Brennan D, MacManus M, Howe J, et al: Neuroleptic malignant syndrome without neuroleptics (letter). Br J Psychiatry 1988; 152:578-579. PubMed
- Staufenberg EF & Tantam D: Malignant hyperpyrexia syndrome in combined treatment (letter). Br J Psychiatry 1989; 154:577-578. DOI
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