Lithium Therapy

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Compounds of the chemical element lithium (i.e., lithium carbonate, lithium cirrate) are common pharmaceutical treatments for the psychiatric condition bipolar disorder (formerly known as manic depression).

People suffering from bipolar disorder alternate between episodes of depression, episodes of mania (typically characterized by elevated mood, high self-estem, and high energy), and periods of normal mood and energy levels. Lithium treatments stabilize mood and help prevent future episodes of mania or depression in many people with bipolar disorder.

Lithium compounds were used in the 19th century to treat anxiety, seizures, and gout (Preston, O’Neal, & Talaga, 2008). In the 1940s, lithium was discovered as an effective treatment for bipolar disorder by Australian psychiatrist John Cade.

Cade thought that mania was caused by an overabundance of a toxin circulating in the bloodstream and that the depression in bipolar disorder was caused by having too little of an unknown substance.

Cade engaged in a tireless search for this hypothetical substance. In what he admitted was a fairly crude investigative approach, he injected the urine from manic patients into guinea pigs. He found that urine from manic patients was much more toxic than urine from other sources, killing the guinea pig more quickly.

Cade next separated urine into its chemical components to identify the specific toxin. The discovery of lithium as a treatment was often fortuitous. Cade found that studying one of the components, uric acid, was difficult because crystals of uric acid are insoluble in water.

To be able to dissolve uric acid, Cade added lithium to it, forming lithium urate. When he injected lithium urate, along with urea (another component of urine, which he had already found was highly toxic) into guinea pigs, he expected that the lithium urate would make urea even more toxic. Instesd, urea was less toxic. Cade had identified lithium as a substance that reduced toxicity of another substance (Cade, 1949).

To investigate the helpful role of lithium, Cade injected it into guinea pigs without also injecting urea. He used lithium carbonate rather than lithium urate to reduce the possibility of side effects. When he injected lithium carbonate into the guinea pigs, they became sedate, a marked contrast to their typical frenetic behavior.

Cade hypothesized that lithium could also have a calming effect on manic patients. His next step was to try the substance on himself to make sure it was safe. He suffered no ill effects and then tried lithium on 10 manic patients. His experiment was a success: the patients improved on the medication. In 1949, Cade published his findings in an article in the Medical Journal of Australia titleld “Lithium Salts in the Treatment of Psychotic Excitement.”

Lithium was a true success story in terms of treatment of psychiatric disorders; most medications in the 1940s and early 1950s were not very effective, and lithium not only alleviated current symptoms but could also prevent future episodes of mania or depression. It was used in many countries following the publication of Cade’s paper but was not widely utilized in the United States until its approval by the U.S. Food and Drug Adminsistration in 1970.

Lithium is still used as a medication for bipolar disorder; 60 percent of patients who suffer manic episodes experience improvements (Carney & Goodwin, 2005). Depressive episodes also respond to lithium, although less markedly.

Lithium is not effective for all individuals with bipolar disorder, and side effects are potentially very serious. Lithium should not be taken during pregnancy as it can cause birth defects (Preston et al., 2008). Some newer medications have comparable effectiveness as lithium with fewer side effects.

Other mood stabilizers used in the treatment of bipolar disorder include valproic acid, carbamazepine, and lamotrigine. Medications used in addition to mood stabilizers to treat bipolar disorder include antidepressants, benzodiazepines (e.g., Vallium), and antipsychotics (e.g., olanzepine; Preston et al., 2008). In 1998, valproic acid (divalproex, Depakote) replaced lithium as the most frequently prescribed drug for bipolar disorder (University of Texas Medical Branch, 1999).

It is not entirely clear how lithium achieves its therapeutic effect. One theory is that lithium may bring about changes within neurons, operating on substances called second messengers that prepare neurons for firing (Julien, 2007).

Other evidence suggests that lithium increases the activity of particular proteins and other chemicals within neurons, thereby improving the health of these neurons (Gray, Zhou, Du, Moore, & Manji, 2003). Lithium’s mechanism of action may operate through multiple routes. Ongoing research may determine how lithium and other mood-stabilizing medications help to stabilize the moods of bipolar patients.

See also:
  1. Healy, D. (2008). Mania: A short history of bipolar disorder. Baltimore: Johns Hopkins University Press.
  2. Lewis, J. (Producer), & Smith, D.K. (Director). (2004). Troubled minds: The lithium revolution [Motion Picture]. (Available from Screen Australia, GPO Box 3984, NSW 2001, Australia).
  3. Cade, J.F. (1949). Lithium salts in the treatment of psychotic excitement. Medical Journal of Australia, 2, 349 – 352.
  4. Cade, J. F. (1999). John Frederick Joseph Cade: Family memories on the occasion of the 50th anniversary of his discovery of the use of lithium in mania. Australia and New Zealand Journal of Psychiatry, 33, 615 – 618.
  5. Carney, S.M., & Goodwin, G.M. (2005). Lithium — a continuing story in the treatment of bipolar disorder. Acta Psychiatrica Scandinavica, 111 (Suppl. 426), 7 – 12.
  6. Gray, N. A., Zhou, R., Du, J., Moore, G.J. & Manji, H.K. (2003). The use of mood stabilizers as plasticity enhancers in the treatment of neuropsychiatric disorders. Journal of Clinical Psychiatry,64 (Suppl. 5), 3 – 17.
  7. Julien, R.M. (2007). A primer of drug action (11th ed.) New York: Worth.
  8. Mitchell, P.B., & Hadzi-Pavlovic, D. (2000). Lithium treatment for bipolar disorders. Bulletin of the World Health Organization, 78, 515 – 518.
  9. Preston, J. D., O’Neal, J.H., & Talaga, M.C. (2008). Handbook of clinical psychopharmacology for therapists (5th ed.). Oakland, CA: New Harbinger.