Sertraline and Lithium: 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
Lithium
No brand names on recordSertraline
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.
Both lithium and sertraline (an antidepressant) raise serotonin, a chemical messenger in your brain. When you take them together, serotonin activity can climb too high and, in rare cases, cause a serious reaction called serotonin syndrome.
Warning signs to watch for include feeling agitated or confused, a fast heartbeat, sweating, fever, shaking, muscle twitching or stiffness, and stomach upset. This is most likely when you first start or increase either drug. The good news is your care team knows about this pairing and can manage it. Keep taking both as prescribed, watch for those symptoms, and if any show up, get medical help right away.
Effect: Additive serotonergic activity between lithium and sertraline (an SSRI) increases the risk of serotonin syndrome. This is a pharmacodynamic interaction, not a prodrug or CYP-based one.
Evidence: Established. Severity: Major. Onset: Unspecified, but risk is highest at initiation or dose escalation.
- Monitor for mental status changes, autonomic instability (tachycardia, labile BP, hyperthermia, diaphoresis), neuromuscular signs (tremor, rigidity, myoclonus, hyperreflexia), seizures, and GI symptoms.
- Combined use may also enhance side effects of either drug, with or without elevated lithium levels, so monitor plasma lithium and adjust dose as needed.
- If serotonin syndrome develops, discontinue both agents immediately and start supportive care.
What happens
An increased risk of serotonin syndrome
Interaction Deep Dive
Taking lithium together with serotonergic agents like SSRIs can lead to serotonin syndrome, a condition that may be fatal. The presentation can involve altered mental status (for example, agitation, hallucinations, delirium, and coma), autonomic instability (for example, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular manifestations (for example, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal disturbances. Every patient receiving lithium should be watched for serotonin syndrome, particularly when therapy is being started. When combined use cannot be avoided, inform patients that their risk is increased and observe them for symptoms. Should symptoms develop, stop both lithium and any accompanying serotonergic drug right away and begin supportive care1. Plasma lithium concentrations warrant monitoring, with the lithium dose adjusted as needed 2. Using lithium alongside various SSRIs has been linked to intensified adverse effects of one or both agents, occurring either with or without raised lithium levels 567.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
If your prescriber has you on both, that can be an intentional, monitored choice. Do not stop or change either medication on your own.
- Keep taking both as prescribed unless your care team tells you otherwise.
- Know the warning signs: agitation, confusion, fast heartbeat, sweating, fever, tremor, muscle stiffness or twitching, and stomach upset, especially soon after starting or increasing a dose.
- Your team may check plasma lithium levels and adjust your lithium dose, and watch you more closely during the first weeks.
- Seek emergency care right away if serotonin syndrome symptoms appear.
Ask your pharmacist or prescriber any time you notice new symptoms.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
7 reports — tap to read
a) Simultaneous use of oral lithium carbonate and oral FLUoxetine led to elevated lithium serum concentrations accompanied by lithium toxicity in a 44-year old woman with bipolar affective disorder. FLUoxetine 20 mg daily was introduced alongside lithium 1200 mg daily after the patient reported weakness, tiredness, reduced concentration, and early morning awakening. Lithium serum concentrations rose to 1.7 mEq/L from a prior range of 0.75 to 1.15 mEq/L before FLUoxetine. FLUoxetine was stopped and the lithium dose lowered; this produced a fall in the lithium serum concentration to 1.2 mEq/L within 48 hours. The neurologic symptoms resolved within seven days as the lithium serum concentration declined to 0.9 mEq/L. The role of FLUoxetine in this patient's lithium toxicity was confounded by the simultaneous lithium dose reduction at the time FLUoxetine was withdrawn 3.
b) A 53-year old woman who had been on 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 enhance her response to FLUoxetine. Within 48 hours, the patient became confused and ataxic and developed a coarse tremor in her right arm. Vital signs revealed a rectal temperature of 101 degrees F, and laboratory findings were normal apart from an elevated leukocyte count and a slightly raised bilirubin level. Following discontinuation of lithium and FLUoxetine, the patient's symptoms cleared over the following four days. At no time did lithium levels reach a toxic value, indicating that the patient's symptoms stemmed from a toxic reaction between FLUoxetine and lithium 4.
c) Serotonin syndrome was triggered when lithium 300 mg twice daily was added to a three-month regimen of FLUoxetine 40 mg per day. Five days afterward, the patient's lithium level measured 0.65 mEq/L and the dose was raised to 300 mg three times daily. Two days following this dosage change, the patient developed akathisia, myoclonus, hyperreflexia, shivering, tremor, diarrhea, and incoordination. After lithium was stopped and cyproheptadine therapy started, the patient's symptoms began to resolve. The patient was discharged on FLUoxetine 40 mg per day with no further symptoms of serotonin syndrome 5.
d) Serotonin syndrome was reported 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 span the fluvoxaMINE dose was raised to 200 mg daily; tremor and difficulty with fine hand movements arose. After two weeks, tremor, impaired coordination of motor function, marked bilateral hyperreflexia of the biceps and knee jerks, and clonus in both ankles were observed. After 12 weeks of continued therapy, during which no additional deterioration occurred, nortriptyline 100 mg daily was substituted for fluvoxaMINE, and the neuromuscular symptoms subsided over a 2-week period. After four weeks the patient's neurological examination was normal 6.
e) Three cases of mania were reported in patients treated with lithium and fluvoxaMINE. The mania emerged 10 days, four weeks, and five weeks, respectively, after cotherapy was started. FluvoxaMINE was discontinued and, in two of the three patients, the mania resolved and depression was successfully treated with lithium alone. The third patient improved, but depression returned within a month of stopping fluvoxaMINE 7.
f) In an open-labeled, placebo-controlled study, lithium 600 mg was given to 16 subjects orally twice daily on days one through eight and once in the morning on day nine. Additionally, oral sertraline 100 mg or placebo was administered twice, ten hours and two hours before the lithium dose on day nine. The steady-state lithium level fell by only 1.4% (0.01 mEq/L) and lithium renal clearance rose by 6.9% (0.11 L/hour) when sertraline was coadministered. Seven subjects had side effects, mainly tremors, after receiving lithium and sertraline, while no subjects who took placebo and lithium had side effects 8.
g) Concurrent administration 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 either citalopram or lithium 2.
Common questions
Can I take Sertraline and Lithium together?
Combining lithium and sertraline can raise the risk of serotonin syndrome, so watch for agitation, fever, fast heartbeat, sweating, and muscle twitching, and get help fast if they appear. Your care team can safely manage this with monitoring and lithium level checks. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Lithium 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 is the Sertraline and Lithium interaction managed?
If your prescriber has you on both, that can be an intentional, monitored choice. Do not stop or change either medication on your own. Keep taking both as prescribed unless your care team tells you otherwise. Know the warning signs: agitation, confusion, fast heartbeat, sweating, fever, tremor, muscle stiffness or twitching, and stomach upset, especially soon after starting or increasing a dose. Y… 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 Sertraline or Lithium 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. PubMed
- 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. PubMed
- 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 Lithium
Keep reading about Sertraline
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