What is lithium, and how does it work (mechanism of action)?

Lithium is used for the treatment of manic/depressive (bipolar) and depressive disorders. Lithium is a positively charged element or particle that is similar to sodium and potassium. It interferes at several places inside cells and on the cell surface with other positively charged atoms such as sodium, potassium, calcium, and magnesium which are important in many cellular functions.

Lithium interferes with the production and uptake of chemical messengers by which nerves communicate with each other (neurotransmitters). Lithium also affects the concentrations of tryptophan and serotonin in the brain. In addition, lithium increases the production of white blood cells in the bone marrow. Lithium’s effects usually begin within 1 week of starting treatment, and the full effect is seen by 2 to 3 weeks.

Lithium has been used since the 1950’s. The FDA approved lithium carbonate, the most common lithium preparation in 1970.

What brand names are available for lithium?


Is lithium available as a generic drug?


Do I need a prescription for lithium?


What are the uses for lithium?

What are the side effects of lithium?


Lithium toxicity is closely related to serum lithium concentrations, and can occur at doses close to therapeutic concentrations. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy

Common side effects

The most common side effects that can occur in persons taking lithium are:

Many of the gastrointestinal side effects (nausea, taste alterations, diarrhea) often disappear with continued therapy. Additionally, they may be less common if lithium is taken in divided doses with meals. If diarrhea or excessive urination lead to dehydration, lithium toxicity is possible. Lithium also can cause changes in the electrocardiogram (EKG, ECG), low blood pressure, and decreased heart rate.


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What is the dosage for lithium?

  • Doses vary widely and are adjusted based on measurements of the levels of lithium in the blood. Recommended blood levels are 0.6-1.2 mEq/L.
  • Early in therapy, dose adjustments are made as often as every 5 to 7 days to establish the correct dose.
  • Most patients require 900-2400 mg daily in 2-4 divided doses depending on the formulation being used.
  • Patients with kidney disease excrete less lithium from the body and, therefore, require lower doses.

Which drugs or supplements interact with lithium?

  • Nonsteroidal anti-inflammatory drugs (NSAIDs), (for example, ibuprofen [Motrin, Advil], naproxen [Naprosyn, Aleve], indomethacin [Indocin], nabumetone [Relafen], diclofenac [Voltaren, Cataflam, Arthrotec], ketorolac [Toradol]), reduce the kidney’s ability to eliminate lithium and lead to elevated levels of lithium in the blood andside effects from lithium. Blood concentrations of lithium may need to be measured for 4 to 7 days after an NSAID is either added or stopped during lithium therapy. Aspirin and sulindac (Clinoril) do not appear to affect lithium concentrations in the blood.
  • Diuretics (water pills) should be used cautiously in patients receiving lithium. Diuretics that act at the distal renal tubule, (for example, hydrochlorothiazide [Hydrodiuril], spironolactone [Aldactone], triamterene [Dyrenium; Dyazide, Maxzide]), can increase blood concentrations of lithium. Diuretics that act at the proximal tubule, (for example, acetazolamide [Diamox]), are more likely to reduce blood concentrations of lithium. Diuretics such as furosemide (Lasix) and bumetanide (Bumex) may have no affect on lithium concentrations in blood.
  • ACE inhibitors, (for example, enalapril [Vasotec], lisinopril [Zestril, Prinivil], benazepril [Lotensin], quinapril [Accupril], moexipril [Univasc], captopril [Capoten], ramipril [Altace]), may increase the risk of developing lithium toxicity by increasing the amount of lithium that is reabsorbed into the body in the tubules of the kidney and thereby reducing the excretion of lithium.
  • When carbamazepine (Tegretol) and lithium are used together, some patients may experience side effects, including dizziness, lethargy, and tremor. Central nervous system side effects also may occur when lithium is used with antidepressants, (for example, fluoxetine [Prozac] sertraline [Zoloft], and paroxetine [Paxil], fluvoxamine [Luvox], amitriptyline [Elavil], imipramine [Tofranil], desipramine [Norpramin]). Combining lithium with monoamine oxidase inhibitor (MAOI) class of antidepressants (for example, isocarboxazid [Marplan], phenelzine [Nardil], tranylcypromine [Parnate], selegiline [Eldepryl], and procarbazine [Matulane]) or other drugs that inhibit monoamine oxidase (for example, linezolid [Zyvox]) may lead to serious reactions.
  • Medications which cause the urine to become alkaline (the opposite of acidic) can increase the amount of lithium that is lost into the urine. This results in lower blood concentrations of lithium and reduces the effects of lithium. Such drugs include potassium acetate, potassium citrate (Urocit-K), sodium bicarbonate, and sodium citrate (Bicitra, Cytra-2, Liqui-Citra, Oracit, Shohl’s).
  • Caffeine appears to reduce serum lithium concentrations, and side effects of lithium have increased in frequency when caffeine is consumed.
  • Both diltiazem (Cardizem-CD, Tiazac, Dilacor-XR) and verapamil (Calan-SR, Isoptin-SR, Verelan, Covera-HS) have been reported to have variable effects on lithium levels in blood. In some patients there may be decreased lithium blood levels and in others lithium toxicity.
  • Methyldopa (Aldomet) may increase the likelihood of lithium toxicity.
  • Various reactions have resulted when lithium is administered with phenothiazines, (for example, chlorpromazine [Thorazine], thioridazine [Mellaril], trifluoperazine [Stelazine] or with haloperidol [Haldol]). Such reactions have included delirium, seizures, encephalopathy, high fever or certain neurologic reactions that affect movement of muscles, called extrapyramidal symptoms.
  • Lithium can cause goiter or hypothyroidism. The use of lithium with potassium iodide can increase the likelihood of this adverse reaction.
  • The use of the beta blocker, propranolol (Inderal), with lithium can lead to a slow heart rate and dizziness. Other beta blockers, (for example, metoprolol [Lopressor], atenolol [Tenormin]) also may interact with lithium and be associated with a slow heart rate.

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Is lithium safe to take if I’m pregnant or breastfeeding?


  • Lithium crosses the placenta and has been associated with toxicity in the fetus. Children born to women taking lithium during pregnancy have an increased risk of goiter and cardiac anomalies. If possible, lithium should be withheld during the first trimester. Women of childbearing age who may require lithium should be counseled about becoming pregnant.
  • Lithium is secreted into breast milk. Symptoms of lithium toxicity, including changes in the electrocardiogram, have been seen in some breastfed infants, whose mothers were taking lithium. If possible, women taking lithium should not breastfeed their infants.

What else should I know about lithium?

What preparations of lithium are available?
  • Tablets: 300 mg.
  • Tablets (extended release): 300 and 450 mg.
  • Capsules: 150, 300 and 600 mg.
  • Syrup: 300 mg/5 ml
How should I keep lithium stored?

All formulations should be kept at room temperature, 15 C to 30 C (59 F to 86 F).


Another term that has been previously used for bipolar disorder is ___________________. See Answer

Medically Reviewed on 7/2/2019



FDA Prescribing Information