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Lithium

Also indexed as: Eskalith®, Lithobid®, Lithonate®, Lithotabs®

The prescription drug lithium is a mineral with antidepressant and antimanic actions. It is used to treat bipolar disorder (manic-depression) and severe depression.

Interactions with Dietary Supplements

Essential fatty acids
In one report, supplementation with essential fatty acids in the form of safflower oil (3–5 grams per day) reversed symptoms of lithium toxicity such as tremor and ataxia (an abnormality of gait).1 Controlled studies are needed to confirm the benefit of a lithium-essential fatty acid combination.

Folic acid
Some studies have found that people taking lithium long term who have high blood levels of folic acid respond better to lithium.2 3 Not all studies have confirmed these findings, however.4

A double-blind study was conducted combining 200 mcg folic acid per day with lithium therapy.5 Even though the volunteers in this study were doing well on lithium alone before the study, addition of folic acid further improved their condition, whereas placebo did not. There is no evidence that folic acid reduces side effects of lithium. Based on the available evidence, it is suggested people taking lithium also take at least 200 mcg of folic acid per day.

Inositol
Lithium therapy has been shown to deplete brain stores of inositol.6 While it has been suggested that inositol supplementation (e.g., 500 mg three times daily) could reduce adverse effects of lithium therapy without reducing the drug’s therapeutic effectiveness,7 8 the safety and efficacy of this combination has not been proven. Until more is known, concomitant use of lithium and inositol cannot be recommended.

L-tryptophan
A small double-blind study found that combining 2–4 grams three times per day of L-tryptophan with lithium significantly improved symptoms in people with bipolar disorder or a mild form of schizophrenia.9 L-tryptophan is only available from doctors. It should be taken several hours before or after meals.

Sodium
Lithium may cause sodium depletion, especially during initial therapy until consistent blood levels are achieved.10 A low-sodium (salt-restricted) diet can decrease lithium elimination, leading to increased lithium levels and risk of toxicity in lithium users who reduce their salt intake.11 Changing to a higher salt intake may cause increased losses of lithium, resulting in the return of mood symptoms.12 13 People using lithium therapy should maintain adequate water intake as well as a normal diet and salt intake. Sodium loss due to diarrhea, illness, extreme sweating, or other causes may alter lithium levels.

Interactions with Herbs

Psyllium (Plantago ovata)
Addition of psyllium husk two times per day to the regimen of a woman treated with lithium was associated with decreased lithium blood levels and lithium levels increased after psyllium was stopped.14

Interactions with Foods and Other Compounds

Food
Lithium should be taken with food to avoid stomach upset.15

Foods that alkalinize the urine may increase elimination of lithium from the body, potentially decreasing the actions of the drug.16 Urine-alkalinizing foods include dairy products, nuts, fruits, vegetables (except corn and lentils), and others.

Coffee
Mild hand tremor is a common side effect of lithium therapy. Two cases of women treated with lithium who experienced increased tremor when they stopped drinking coffee have been reported.17 Lithium levels increased almost 50% in one of the women, who had been drinking 17 cups of coffee per day, requiring a 20% reduction in her lithium dose. In 11 people treated with lithium who drank four to six cups of coffee per day, two weeks without coffee resulted in increased lithium blood levels, anxiety, and depression.18 Lithium levels, anxiety, and depression ratings returned to base line two weeks after resuming coffee consumption. Until more is known, people taking lithium should avoid abrupt changes in their coffee consumption.

Summary of Interactions for Lithium

Depletion or interference Inositol
Adverse interaction None known
Side effect reduction/prevention Essential fatty acids*
Inositol*
Supportive interaction Folic acid
L-tryptophan*
Reduced drug absorption/bioavailability None known
Other (see text) Coffee
Psyllium
Sodium

For the convenience of the reader, the information in the summary is categorized as follows: “Depletion or interference” indicates the drug may deplete or interfere with the absorption or function of the supplement or herb. “Adverse interaction” indicates that the supplement or herb used together with the drug may result in undesirable effects. “Side effect reduction/prevention” indicates the supplement or herb may reduce the likelihood and/or severity of a potential side effect caused by the drug. “Supportive interaction” indicates the supplement or herb may support or aid the function of the drug. “Reduced drug absorption/bioavailability” indicates that the supplement or herb may decrease the absorption and/or activity of the drug in the body. An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

References:

1. Lieb J. Linoleic acid in the treatment of lithium toxicity and familial tremor. Prostaglandins Med 1980;4:275–9.

2. Coppen A, Abou-Saleh MT. Plasma folate and affective morbidity during long-term lithium therapy. Br J Psychiatry 1982;141:87–9.

3. Lee S, Chow CC, Shek CC, et al. Folate concentration in Chinese psychiatric outpatients on long-term lithium treatment. J Affect Disorders 1992;24:265–70.

4. Stern SL, Brandt JT, Hurley RS, et al. Serum and red cell folate concentrations in outpatients receiving lithium carbonate. Int Clin Psychopharmacol 1988;3:49–52.

5. Coppen A, Chaudhry S, Swade C. Folic acid enhances lithium prophylaxis. J Affect Disorders 1986;10:9–13.

6. Silverstone PH, Rotzinger S, Pukhovsky A, Hanstock CC. Effects of lithium and amphetamine on inositol metabolism in the human brain as measured by 1H and 31P MRS. Biol Psychiatry 1999;46:1634–1.

7. Colodny L, Hoffman RL. Inositol -- Clinical applications for exogenous use. Altern Med Rev 1998;3:432–47.

8. Johnson EC, Gray-Keller MP, O’Day PM. Rescue of excitation by inositol following Li(+)-induced block in Limulus ventral photoreceptors. Vis Neurosci 1998;15:105–12.

9. Brewerton TD, Reus VI. Lithium carbonate and L-tryptophan in the treatment of bipolar and schizoaffective disorders. Am J Psychiatry 1983;140:757–60.

10. Threlkeld DS, ed. Central Nervous System Drugs, Antipsychotic Agents, Antimanic Agents, Lithium. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, May 1998, 268a–8f.

11. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 158.

12. Demers RG, Harris RL. The effect of dietary sodium on renal lithium excretion in the manic-depressive. Dis Nerv Syst 1972;33:372–5.

13. Demers RG, Heninger GR Sodium intake and lithium treatment in mania. Am J Psychiatry 1971;128:100–4.

14. Perlman BB. Interaction between lithium salt and ispaghula husk. Lancet 1990;335:416.

15. Threlkeld DS, ed. Central Nervous System Drugs, Antipsychotic Agents, Antimanic Agents, Lithium. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, May 1998, 268a–8f.

16. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 157.

17. Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988;49:72–3.

18. Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995;37:348–50.