Updated August 28, 2015.

In the pantheon of medical treatments, the drug lithium holds a special place.  Lithium is one of the few drugs that's an element (technically it's administered as the salt lithium carbonate which quickly dissociates into lithium ions in the body); whereas, most other medications are organic (carbon-based) molecules with complicated structures.  Other elements widely used to treat disease include oxygen, potassium (salts) and sodium (salts).


  However, these other elements have predictable uses: Oxygen is used to help with breathing, and potassium and sodium are used to reestablish homeostasis or balance after metabolic derangement.  Lithium, however, helps people with bipolar disorder, a serendipitous discovery made decades ago.

Bipolar disorder is characterized by shifts between manic, depressive, hypomanic and mixed states.  These shifts can begin abruptly and can be exacerbated by stressors.  Untreated bipolar disorder destroys lives, and depending on their mood state, people with bipolar disorder experience the following symptoms:

• flight of ideas;
• mood states ranging from irritable to euphoric;
• sleep disturbance;
• racing thoughts;
• manic behaviors including spending sprees, impulsivity and sexual acting out;
• depressive behaviors including loss of interest in life activities or suicidal ideas;
• headaches;
• change in appetite.

Of note, bipolar disorder is a lot more complicated than what I've presented above.  However, as you can probably infer, bipolar disorder is a roller coaster of emotions, thoughts and states that requires immediate treatment and lifelong maintenance therapy to avoid future bipolar mood swings.

In the mid-1800s, lithium was first used to treat gout.  By the 1940s, physicians were using lithium to treat hypertension, but it soon proved too toxic for this use.  In 1949, John Cade discovered that lithium helped treat bipolar disorder.  Cade's work inspired a series of clinical trials that proved lithium's efficacy as monotherapy when treating the manic phase of bipolar disorder.

Through the 1990s, lithium was considered the drug-of-choice when treating bipolar disorder.  Specifically, lithium proved remarkably effective when treating the manic phase of bipolar disorder with 80 percent of nonhospitalized patients taking the drug experiencing remission.  Moreover, 60 percent of people with bipolar disorder who took lithium as maintenance therapy remained well.  (The success rate of lithium as maintenance therapy in those with severe bipolar disorder is lower.)

Currently with the introduction of newer mood-stablizing and antipsychotic drugs like valproate, olanzapine and risperidone, lithium is no longer first-line treatment in most people with bipolar disorder.  (If you're wondering, the use of antidepressant drugs to treat bipolar disorder is tricky business because antidepressant drugs can precipitate a manic state.) These newer drugs act faster and have fewer adverse effects than lithium.  Nevertheless, many psychiatrists still tout the benefits of lithium, and this drug is still used in combination with other drugs to treat severe cases of bipolar disorder.  Interestingly, lithium has also proven useful when treating schizoaffective disorder and major depression.  

Lithium's mechanism of action isn't completely understood.  A prevailing hypothesis regarding how lithum works involves phosphoinositol turnover in the brain.  By messing with phosphoinositol turnover, lithium initiates a cascade of intracellular changes that alter gene expression and protein production which underlie mood stabilization.  Another hypothesis regarding the mechanism of action of lithium involves the substitution of lithium cations for sodium cations thus mitigating the generation action potentials in brain areas responsible for the mood maintenance.

On a final note, if you or someone you love is taking lithium as maintenance or prophylactic long-term treatment, please understand that your blood levels for the drug must be closely monitored by your physician.  Lithium has serious adverse effects including renal impairment, nephrogenic diabetes insipidus, arryththmia and decreased thyroid function.  If you're experiencing any symptoms suggestive of these adverse effects while on lithium, go the emergency room or immediately see your physician.  

<sub>Selected Sources

DeBattista C. Antipsychotic Agents & Lithium. In: Katzung BG, Trevor AJ. eds. Basic & Clinical Pharmacology, 13e. New York, NY: McGraw-Hill; 2015. Accessed August 27, 2015.

Papadakis MA, McPhee SJ. Bipolar Disorder. In: Papadakis MA, McPhee SJ. eds. Quick Medical Diagnosis & Treatment 2015. New York, NY: McGraw-Hill; 2015. Accessed August 27, 2015.

Radiolab. (2015, December 24). Elements [Sound recording]. http://www.radiolab.org/story/elements/</sub>