How does lithium treat bipolar disorder?

Dr. Michael Roizen, MD
Internal Medicine

Lithium is used as a mood stabilizer, maintaining a balance between the highs and lows of bipolar disorder, but substitutes for calcium and modulates sodium flux in nerve endings. It is better at decreasing the mania than increasing mood in depression. It was the first mood-stabilizing drug approved by the Food and Drug Administration (FDA) in the early 1970s, back when Bruce Springsteen and the Jackson 5 rocked their way to the top of the charts.

Lithium affects the flow of sodium through nerve and muscle cells. Sodium flow determines how excited or manic you feel, so by taking lithium you are less likely to be hyperactive, have rushed speech, and be as aggressive and angry as a lioness separated from her cub.

But if you take lithium, you have to be closely monitored and you will need frequent blood tests. Lithium can cause kidney and thyroid problems and other side effects like weight gain, tremors, and problems with digestion.
Although the exact mechanism of the antimanic and antidepressant action is not known, research suggests that lithium interferes with the formation and action of certain neurotransmitters. Lithium increases the synthesis and release of serotonin. Onset of the immediate antimanic effect is usually seen in five to seven days, and the full therapeutic effect in 10 to 20 days.

John Preston, PsyD

Lithium in the treatment of bipolar disorder

Lithium was the first drug discovered to treat bipolar disorder. Among “mood stabilizers” it is one of the few that does the following: treats acute manic episodes, treats bipolar depression (if lithium blood levels are at least 0.8) and works to prevent recurrence of both mania and depression. The most serious concern with bipolar disorder is possible suicide. Up to 19% of people who suffer from bipolar disorder take their own lives (this is most often due to repeated failures on medication treatment; often due to significant side effects of the drugs and patients discontinuing medication).

Lithium has been shown to dramatically decrease suicides in people with bipolar disorder. It does this much more effectively than any other bipolar medication. It is important to note that lithium taken in an accidental or intentional overdose is very toxic. For this reason, if a person is experiencing a severe episode of bipolar depression or mixed mania (a manic episode but with significant depression rather than euphoria) lithium can be risky at this point in treatment, since it is so toxic. When the person is in the throes of an episode, as noted above, over-dose suicide attempts with lithium can be fatal. Where lithium has such promise in treating bipolar and preventing suicide generally is when the medication is started at a time that the person is not feeling acutely suicidal. Then, once on lithium, it affords protection from suicide.

Lithium has a number of problematic side effects and about 30% of those tried on it cannot take it due to excessive side effects. Bipolar treatment experts are puzzled by the low rates of use of lithium used to treat bipolar in the USA. In Canada, England and Europe it is a common treatment used for bipolar disorder.

How does lithium work: there are a number of theories, but no definitely identified mechanism of action has been found. Lithium is non-habit forming and always a drug of choice if other bipolar medications have been ineffective and, as noted above, when significant suicidal behaviors have been experienced during bipolar episodes.

The first known mood stabilizer, lithium (brand names Eskalith, Lithobid, Lithonate) is actually an element rather than a compound (a substance synthesized by a laboratory). Lithium was first found to have behavioral effects in the 1950s and has been used as a mood stabilizer in the United States for 30 years.

Lithium appears to be most effective for individuals with more "pure" or euphoric mania (where there is little depression mixed in with the elevated mood). It is also helpful for depression, especially when added to other medications. Lithium appears to be less effective in mixed manic episodes and in rapid-cycling bipolar disorder. Monitoring blood levels of lithium can reduce side effects and ensure that the patient is receiving an adequate dose to help produce the best response.
Lithium was the first effective drug for the treatment of bipolar disorder. It remains a very useful drug, working in some individuals when nothing else works. There has been great debate in the decades since its discovery about how it works, but current thinking is that it works at the level of the "biologic clock" on a compound called "BDNF" or brain derived neurotrophic factor and glycogene synthase kinase beta and phosphotidyl inositol turnover (for the neurochemists amongst us). Regardless of how it works, it is particularly effective in non-rapid cyclers, but thought to be not as effective in rapid cyclers. Unfortunately, lithium has some problematic long-term risks and problematic immediate side effects that cause us to typically reserve it for use after other agents have failed.

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Important: This content reflects information from various individuals and organizations and may offer alternative or opposing points of view. It should not be used for medical advice, diagnosis or treatment. As always, you should consult with your healthcare provider about your specific health needs.