The Discovery and History of Lithium as a Mood Stabilizer

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When was lithium first discovered as a drug for mental health, and what is the history of this medication? How does it actually work? And what is the current thought and controversy considering the role of lithium in the treatment of bipolar disease?


Lithium is a naturally occurring element (number three on the periodic table) that was first discovered in 1817 and was found in mines in Australia and Chili. Its mood-stabilizing effects, however, were not recognized until late in that century. In fact, some concluded that gout was the cause of mood disorders.

Lithium-rich mineral springs have historically been touted for their healing properties. It was first used for mania in the late 1800s, with Denmark leading the way, but little was published about the medication for more than half a century.

It was Australian psychiatrist John Cade who, in 1949, published one of the first papers on the use of lithium in the treatment of acute mania. From that time on, lithium was increasingly prescribed.

The U.S. Food and Drug Administration (FDA) did not approve lithium for use until 1970. The use of lithium in the U.S. began later, and shifted to other drugs earlier, compared to many other countries around the world.

How It Works

Knowing that lithium is a naturally occurring element, one might think that prescribing the drug may support a deficiency. However, research has never indicated that that bipolar disorder is caused by a lithium deficiency. Rather, it happens that this naturally occurring substance has the fortunate effect of acting as a mood stabilizer.

For over 50 years, manic-depressive people were treated with lithium even though medical science did not have a clear understanding of why or how it worked. (The name manic-depressive disorder was officially changed to bipolar disorder in 1980.)

Although the exact mechanisms by which lithium exerts its mood-stabilizing effects are not fully known, there has been much contemporary research into this question. Lithium interacts with a number of neurotransmitters, neuron receptors, and other chemical systems in brain cells.

Neurotransmitters and Mental Health

How do messages in one part of the brain travel, and in doing so, result in actions? It's only been in the last few decades—when scientists have isolated neurotransmitters, the chemical messengers of the brain that act to convey information from one region to another—that we are beginning to understand this process.

Neurotransmitters are contained at the end of one neuron (or nerve.) An electrical impulse travels along the nerve and results in neurotransmitters being released into the space (the synapse) between one nerve and the next. Some neurotransmitters bind to receptors on the next nerve cell, which respond by transforming that message into another electrical impulse.

Neurotransmitters that are left in the synapse (those which do not bind to receptors on the next neuron) are taken back up into the original neuron to be used again.

There are several types of neurotransmitters in the brain. Some of these include:

  • Serotonin
  • Norepinephrine
  • Dopamine
  • Acetylcholine
  • GABA (gamma-aminobutyric acid)
  • Glutamate

Lithium is thought to interact with many of these systems in complex ways.

Other Potential Uses

In addition to bipolar disorder, lithium is sometimes used in the treatment of unipolar depression (major depression) and schizoaffective disorder.

Because of lithium's stabilizing effect on glutamate receptors, scientists are also studying whether this medication can protect from the cell death that occurs in conditions such as Parkinson's, Huntington's, and Alzheimer's disease.

Toxicity and Side Effects

As with many medications on the market, lithium comes with a list of side effects and precautions. Lithium toxicity can be very serious, with both acute and chronic effects. The side effects of lithium are common as well, and as with many mental health medications, these side effects often interfere with its use.

In addition, lithium is known to interact with a wide variety of medications, such as other mental health drugs, blood pressure medications, and some painkillers.

There are few medications available for the treatment of bipolar disorder that do not have significant side effects.

Role in Treatment of BPD

The answer to the question, "What role should lithium play in the treatment of bipolar disease today?" will vary depending on who you ask and where you live.

In addition to a roller-coaster history, there are widely varying opinions regarding the use of lithium today. Some clinicians have called lithium "dangerous nonsense" whereas others view lithium as the best established long-term treatment available for bipolar disorder. Some professionals claim that lithium is the single most important treatment for mental health which has been discovered.

As with many other issues related to mental health, the real answer probably lies somewhere between these extremes and is reflected in different practices around the world.

The United States has the reputation of being the "last in and first out" with regard to the use of the drug, being late among countries to adopt its use, and early to recommend alternatives (other mood stabilizers such as Depakote (valproic acid) and antipsychotic medications).

In the U.S., lithium is seldom used as a first-line treatment for people with bipolar disorder, though it is still frequently used for severe bipolar disorder in combination with other medications.

However, a 2017 study suggested that there is a strong role for lithium first line in the treatment of mania in the elderly. There is also evidence to support lithium's role in decreasing suicide risk.

The Bottom Line

The history of lithium is an interesting study in scientific discovery and the methods scientists have used to investigate the chemical nature of mood disorders in the brain.

This newer understanding of the chemical messengers in the brain responsible for mental health disorders is important in further reducing the stigma of mental health disorders. While there is still a long way to go, and mental health still suffers more of a stigma than say heart disease, the research going on today—such as the mechanism by which lithium works—is an excellent step in the right direction.

5 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Chiu CT, Wang Z, Hunsberger JG, Chuang DM. Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder. Pharmacol Rev. 2013;65(1):105-42.  doi:10.1124/pr.111.005512

  2. Alda M. Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics. Mol Psychiatry. 2015;20(6):661-70.  doi:10.1038/mp.2015.4

  3. Rybakowski JK. Challenging the Negative Perception of Lithium and Optimizing Its Long-Term Administration. Front Mol Neurosci. 2018;11:349.  doi:10.3389/fnmol.2018.00349

  4. US National Library of Medicine. Lithium toxicity.

  5. De fazio P, Gaetano R, Caroleo M, et al. Lithium in late-life mania: a systematic review. Neuropsychiatr Dis Treat. 2017;13:755-766.  doi:10.2147/NDT.S126708

Additional Reading

By Marcia Purse
Marcia Purse is a mental health writer and bipolar disorder advocate who brings strong research skills and personal experiences to her writing.