Could Lithium Work for Depression?

Mental health professionals have used lithium for years to treat people with bipolar disorder, especially to prevent the major depressive episode so characteristic of that disease. But is lithium also effective for depression without bipolar disorder? It may be for some patients.

Although depression is highly treatable with antidepressant medications, up to 30 percent of depressed patients don't respond to their first treatment. This is called treatment-resistant depression. Often these individuals do respond to a different antidepressant, or to the addition of another therapy (augmentation). This is where lithium seems to play an important role.

For more than 20 years, lithium carbonate in low doses has helped some patients with treatment-resistant depression. Lithium affects the flow of sodium through nerve and muscle cells, and for some reason, seems to make antidepressants more effective.

Charles Raison, MD, a psychiatrist who recently answered questions about lithium and depression on CNN, said the Food and Drug Administration has not approved lithium as an augmented therapy for depression. However, he says, it's often used when people don't respond to antidepressants, and it works at lower levels for depression alone than patients with bipolar disorder need. Patients usually respond within a few weeks if the lithium is effective. Lithium may work by increasing the activity of serotonin. Serotonin is a neurotransmitter, and the target for Selective Serotonin Reuptake Inhibitors (SSRIs) antidepressants.

In the early 2000s, the National Institute for Mental Health conducted STAR*D (Sequenced Treatment Alternatives to Relieve Depression), an extensive study of depression treatment options. Participants in STAR*D advanced through four treatment levels. If they didn't respond to a lower level of treatment, they moved to the next level where they received a new, or an additional form of, treatment. At level three, physicians added lithium or triiodothronine (T3) to existing drug therapies to boost medication effectiveness. Both drugs provided modest improvements, although T3 had fewer side effects.

Lithium is not the right treatment for everyone. In a recent study, researchers found that Prozac was superior to lithium in preventing recurrence of major depressive episodes in patients with bipolar disorder type II. Patients taking lithium risked suffering a depressive relapse sooner. Lithium may produce side effects, including increased urination, tremors or shaking, dulling of thinking, nausea, and sedation. It can also cause kidney or thyroid disorders and may interact with some medications.

If your antidepressant isn't providing you significant relief from symptoms, ask your physician if augmenting your depression treatment with lithium might be effective.


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