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How Does Lithium Treat Bipolar Disorder?
The Science Behind Mood Stabilizers

For over 70 years, lithium has been the gold standard in treating bipolar disorder. It’s one of the oldest psychiatric medications still in use—and also one of the most effective. But many people with bipolar disorder don’t know how lithium works, why it’s prescribed, or what makes it different from other mood stabilizers.

This post explores the science behind lithium and other commonly used mood stabilizers—how they affect the brain, what benefits they offer, and what side effects to watch for.

Why Lithium Is Still the Gold Standard

Despite the development of many newer medications, lithium remains the most well-studied treatment for bipolar disorder. It’s effective for:

  • Preventing both manic and depressive episodes

  • Reducing suicide risk by up to 60%

  • Treating acute mania

  • Stabilizing long-term mood fluctuations

In fact, among all psychiatric drugs, lithium has one of the strongest evidence bases. It’s particularly beneficial for people with classic Bipolar I, especially those with a family history of bipolar disorder or euphoric mania rather than mixed or agitated states.

How Does Lithium Work in the Brain?

While the exact mechanism isn’t fully understood, lithium appears to work by:

  • Regulating neurotransmitter activity (especially dopamine, serotonin, and glutamate)

  • Reducing excitatory signals in the brain that can lead to mania

  • Increasing the stability of neuronal firing, making mood shifts less extreme

  • Protecting brain cells from damage caused by inflammation and oxidative stress

Some researchers also believe lithium has neuroprotective effects—it may help prevent the structural brain changes seen in people with recurrent, untreated bipolar episodes.

What About Other Mood Stabilizers?

While lithium is highly effective, it’s not the only option. Other mood stabilizers used in bipolar treatment include:

1. Valproate (Divalproex, Depakote)

  • Best for acute mania and mixed states

  • Works by enhancing GABA (a calming neurotransmitter)

  • Often used when lithium is not tolerated

2. Lamotrigine (Lamictal)

  • More effective for bipolar depression than mania

  • Regulates glutamate and stabilizes neuronal activity

  • Requires slow titration to avoid rare skin rash (Stevens-Johnson syndrome)

3. Carbamazepine (Tegretol)

  • Helpful for rapid cycling or treatment-resistant mania

  • Also used for seizure disorders

  • Has complex interactions with other medications

These medications were originally developed as anticonvulsants, but were found to have mood-stabilizing effects. They’re often used in combination with lithium or antipsychotics depending on the presentation.

Antipsychotics as Mood Stabilizers

In addition to lithium and anticonvulsants, some second-generation antipsychotics (SGAs) are used as mood stabilizers. These include:

  • Quetiapine (Seroquel): Approved for mania, depression, and maintenance

  • Olanzapine (Zyprexa): Effective for acute mania and relapse prevention

  • Lurasidone (Latuda): Commonly used for bipolar depression

These medications primarily work by blocking dopamine and serotonin receptors, and they can be useful in people with psychotic features, agitation, or poor response to traditional mood stabilizers.

Monitoring and Side Effects: What to Watch For

Lithium, while effective, requires regular monitoring:

  • Blood levels must be checked to ensure the dose is in the therapeutic range

  • Kidney and thyroid function should be monitored long-term

  • Hydration and salt balance are essential, as lithium is excreted through the kidneys

Common side effects of lithium include:

  • Increased thirst and urination

  • Hand tremors

  • Weight gain

  • Cognitive slowing (“brain fog”)

  • Acne or skin issues

With anticonvulsants and antipsychotics, side effects vary but can include:

  • Drowsiness

  • Weight gain

  • Gastrointestinal issues

  • Risk of metabolic syndrome (especially with SGAs)

Working closely with a provider can help balance benefits and side effects over time.

Why People Stop Lithium—and Why That’s Risky

Some people stop taking lithium due to side effects, stigma, or a desire to go off medications entirely. However, abrupt discontinuation is associated with:

  • High risk of relapse, especially into mania

  • Increased risk of suicide, particularly within the first few months

  • Mood instability that can be harder to regain control over

If you’re considering stopping or switching medications, it’s essential to do so gradually and under medical supervision.

A Tool—Not a Cure

Lithium and other mood stabilizers are not cures for bipolar disorder. They’re tools—powerful ones—that help manage the biological aspects of mood dysregulation. For many people, medication works best when combined with:

  • Therapy

  • Routine and sleep regulation

  • Psychoeducation

  • Supportive relationships

There is no one-size-fits-all solution. But understanding how and why mood stabilizers work can empower you to make informed choices about your treatment.

If you’re struggling with bipolar disorder, click here to check out my services. If your loved one is struggling with the disorder, click here to learn about how I can help your family.

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