Fluoxetine and Lithium Carbonate: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Fluoxetine
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
Interaction Deep Dive
The concomitant use of lithium with serotonergic drugs, such as SSRIs, may result in serotonin syndrome, which can be life-threatening. Signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms. Monitor all patients on lithium therapy for serotonin syndrome, especially during initiation. If concomitant use is required, notify patients of the increased risk and monitor for symptoms. Immediately discontinue treatment with lithium and any concomitant serotonergic agent if symptoms occur and initiate supportive treatment1. Plasma lithium levels should be monitored with appropriate adjustment to the lithium dose 2. Concomitant use of lithium and various SSRIs has been associated with enhanced side effects of either or both drugs, and with or without elevated lithium levels 567.
Why it happens (mechanism)
Additive serotonergic effects
Literature reports
7 reports — tap to read
a) Concomitant administration of oral lithium carbonate and oral FLUoxetine resulted in increased lithium serum levels with lithium toxicity in a 44-year old woman with a bipolar affective disorder. FLUoxetine 20 mg daily was added to a regimen of lithium 1200 mg daily following patient complaints of weakness, tiredness, decreased concentration, and early morning awakening. Lithium serum levels increased to 1.7 mEq/L from a range of 0.75 to 1.15 mEq/L prior to FLUoxetine. FLUoxetine was discontinued and the dose of lithium decreased; this resulted in a decrease in the lithium serum level within 48 hours to 1.2 mEq/L. The neurologic symptoms subsided within seven days as the lithium serum level decreased to 0.9 mEq/L. The contribution of FLUoxetine to lithium toxicity in this patient was obscured by the fact that the lithium was reduced at the time of FLUoxetine withdrawal 3.
b) A 53-year old woman who had been taking FLUoxetine 20 mg daily and LORazepam 0.5 mg four times daily for a major depressive disorder had lithium 900 mg per day added to her regimen in order to augment her response to FLUoxetine. Within 48 hours, the patient became confused, ataxic, and developed a coarse tremor in her right arm. Vital signs showed a rectal temperature of 101 degrees F, and laboratory values were normal except for an elevated leukocyte count and slightly elevated bilirubin level. After discontinuation of lithium and FLUoxetine, the patient's symptoms resolved over the next four days. At no point did the lithium levels reach a toxic level, suggesting that the patient's symptoms were due to a toxic reaction between FLUoxetine and lithium 4.
c) Serotonin syndrome was precipitated when lithium 300 mg twice daily was added to a three-month regimen of FLUoxetine 40 mg per day. Five days later, the patient's lithium level was measured at 0.65 mEq/L and the dose was increased to 300 mg three times daily. Two days after this dosage change, the patient experienced akathisia, myoclonus, hyperreflexia, shivering, tremor, diarrhea, and incoordination. After discontinuation of lithium and initiation of cyproheptadine therapy, the patient's symptoms began to improve. The patient was discharged on a regimen of FLUoxetine 40 mg per day without further symptoms of serotonin syndrome 5.
d) Serotonin syndrome was described in a 53-year-old patient who was stabilized on lithium 1400 mg daily (serum level 0.71 mmol/L) and was given fluvoxaMINE 50 mg daily. Over a 10-day period the fluvoxaMINE dose was increased to 200 mg daily; tremor and difficulty with fine hand movements developed. After two weeks, tremor, impaired motor function coordination, marked bilateral hyperreflexia of biceps and knee jerks, and clonus in both ankles were seen. After 12 weeks of continued therapy, during which time no further deterioration occurred, nortriptyline 100 mg daily replaced fluvoxaMINE, and the neuromuscular symptoms abated over a 2-week period. After four weeks the patient's neurological exam was normal 6.
e) Three cases of mania were reported in patients who were treated with lithium and fluvoxaMINE. The mania appeared 10 days, four weeks, and five weeks, respectively, after cotherapy was begun. FluvoxaMINE was discontinued and, in two of the three patients, the mania resolved, and successful treatment of depression occurred with lithium alone. The third patient improved, but depression reappeared within a month of fluvoxaMINE discontinuation 7.
f) In an open-labeled, placebo-controlled study, lithium 600 mg was administered to 16 subjects orally twice daily on days one through eight and once in the morning on day nine. In addition, oral sertraline 100 mg or placebo was given twice, ten hours and two hours prior to lithium dosing on day nine. The steady-state lithium level was only decreased by 1.4% (0.01 mEq/L) and the lithium renal clearance increased by 6.9% (0.11 L/hour) when sertraline was coadministered. Seven subjects experienced side effects, mainly tremors, after receiving lithium and sertraline, whereas no subjects who ingested placebo and lithium experienced side effects 8.
g) Coadministration of racemic citalopram (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium 2.
Common questions
Can I take Fluoxetine and Lithium Carbonate together?
An increased risk of serotonin syndrome Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fluoxetine and Lithium Carbonate interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
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 Fluoxetine or Lithium Carbonate 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 (8)
- Product Information: LITHOBID(R) oral extended-release tablets, lithium carbonate oral extended-release tablets. ANI Pharmaceuticals Inc (per DailyMed), Baudette, MN, 2018. DailyMed
- Product Information: LEXAPRO(R) oral tablets, oral solution, escitalopram oral tablets, oral solution. Abbvie, Inc (per FDA), North Chicago, IL, 2023. DailyMed
- Salama AA & Shafey M: A case of severe lithium toxicity induced by combined fluoxetine and lithium carbonate (letter). Am J Psychiatry 1989; 146:278. PubMed
- Noveske FG, Hahn KR, & Flynn RJ: Possible toxicity of combined fluoxetine and lithium (letter). Am J Psychiatry 1989; 146:1515. DOI
- Muly EC, McDonald W, Steffens D, et al: Serotonin syndrome produced by a combination of fluoxetine and lithium (letter). Am J Psychiatry 1993; 150:1565. PubMed
- Ohman R & Spigset O: Serotonin syndrome induced by fluvoxamine-lithium interaction. Pharmacopsychiatry 1993; 26:263-264. DOI
- Burrai C, Bocchetta A, & Del Zompo M: Mania and fluvoxamine (letter). Am J Psychiatry 1991; 148:1263. PubMed
- Wilner KD, Lazar JD, Von Deutsch DA, et al: The effects of sertraline on steady-state lithium levels and renal clearance of lithium. Biol Psychiatry 1991; 29:354S.
Keep reading about Fluoxetine
Keep reading about Lithium Carbonate
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