Lithium salts:

The use of Lithium as a treatment of Bipolar Disorder was first discovered by Dr. John Cade.

Lithium salts have long been used as a first-line treatment for bipolar disorder. The therapeutic effect of lithium salts appears to be entirely due to the lithium ion, Li+. The two lithium salts used for bipolar therapy are lithium carbonate (mostly) and lithium citrate (sometimes). Approved for the treatment of acute mania in 1970 by the U.S. Food and Drug Administration (FDA), lithium has been an effective mood-stabilizing medication for many people with bipolar disorder. Lithium is also noted for reducing the risk of suicide in major affective disorders, such as bipolar disorder: suicide risk on the whole drops to below the average level for society (Baldessarini, 2003). Although lithium is among the most effective mood stabilizer, most persons taking it experience side effects ranging from manageable to intolerable. Regular blood testing is required when taking lithium to determine the correct lithium levels since the therapeutic dose is close to the toxic dose. Adjusting lithium levels can sometimes be difficult since they are changed depending on a person's water and/or salt intake; therefore one must be watchful for signs of lithium toxicity.

The mechanism of lithium salt treatment is believed to work as follows: some symptoms of bipolar disorder appear to be caused by the enzyme inositol monophosphatase (IMPase), an enzyme that splits inositol monophosphate into free inositol and phosphate. It is involved in signal transduction and is believed to create an imbalance in neurotransmitters in bipolar patients. The lithium ion is believed to produce a mood stabilizing effect by inhibiting IMPase by substituting for one of two magnesium ions in IMPase's active site, slowing down this enzyme.

The song Lithium by Nirvana is about bipolar disorder, and was named due to Lithium salts being a treatment for bipolar disorder. Nirvana frontman Kurt Cobain probably suffered from bipolar disorder, and the song is about the mood swings he would experience because of it.

Anticonvulsant mood stabilizers:

Anticonvulsant medications, particularly valproate and carbamazepine, have been used as alternatives or adjuncts to lithium in many cases. Valproate was FDA approved for the treatment of acute mania in 1995, and is now considered by many to be the first line of therapy for bipolar disorder. It is preferable to lithium because its side effect profile seems to be less severe, compliance with the medication is better, and fewer breakthrough manic episodes occur. However, valproate is not as effective as lithium in preventing or managing depressive episodes, so patients taking valproate may also need an SSRI or other antidepressant as an adjunct medicinal therapy. Newer anticonvulsant medications, including lamotrigine, gabapentin, and topiramate, have been studied to determine their efficacy as mood stabilizers in bipolar disorder. Some research suggests that different combinations of lithium and anticonvulsants may be helpful. Topiramate has not done well in clinical trials, which may be because it seems to help a few patients very much but most not at all. Lamotrigine is particularly promising as there is evidence it helps bipolar persons with severe depression. Unfortunately, there are some studies that show that gabapentin is very effective for certain types of epilepsy but ineffective for bipolar disorder.

According to studies conducted in Finland in patients with epilepsy, valproate may increase testosterone levels in teenage girls and produce polycystic ovary syndrome in women who began taking the medication before age 20. Increased testosterone can lead to polycystic ovary syndrome with irregular or absent menses, obesity, and abnormal growth of hair. Therefore, young female patients taking valproate should be monitored carefully by a physician.

During a depressive episode, people with bipolar disorder commonly require additional treatment with antidepressant medication. Typically, lithium or anticonvulsant mood stabilizers are prescribed along with an antidepressant to protect against a switch into mania or rapid cycling. The comparative efficacy of various antidepressants in bipolar disorder is currently being studied. It is very important that a definitive diagnosis be made between bipolar and major depression, since bipolar persons taking antidepressants alone have a great risk of induced mania.