Mood Stabilizers for Bipolar Disorder: What You Should Know

Mood stabilizers are the foundation of bipolar disorder treatment. They are the medications that keep the ceiling from rising too high and the floor from dropping too low. Yet for something so central to managing the condition, there is a surprising amount of confusion about what these drugs actually do, how they work, and what to expect from them.

This is not a substitute for talking to your psychiatrist. It is a starting point for understanding the landscape of medications you may be prescribed or asked to consider.

What "Mood Stabilizer" Actually Means

The term "mood stabilizer" is used loosely in psychiatry. There is no official FDA category with that name. In practice, it refers to any medication that treats or prevents manic and depressive episodes without making the other pole worse. Lithium is the prototypical mood stabilizer. Several anticonvulsants and atypical antipsychotics also function as mood stabilizers, though they were originally developed for other conditions.

The ideal mood stabilizer would treat acute mania, treat acute depression, prevent future manic episodes, and prevent future depressive episodes. No single drug does all four equally well. Treatment plans often involve combinations tailored to the individual's pattern of episodes.

Lithium

Lithium has been used to treat bipolar disorder since the late 1940s. It remains one of the most effective medications available, particularly for preventing manic episodes and reducing suicide risk. A 2014 meta-analysis by Cipriani and colleagues in the American Journal of Psychiatry confirmed that lithium is the only psychiatric medication with consistent evidence of reducing suicide and self-harm in bipolar disorder.

Lithium works for acute mania, maintenance therapy, and has moderate evidence for bipolar depression. It is particularly effective in people with "classic" bipolar presentations: distinct episodes of euphoric mania followed by depression, with clear intervals of normal mood between episodes.

The downsides are well documented. Lithium has a narrow therapeutic window, meaning the effective dose is close to the toxic dose. Regular blood level monitoring is required, typically every few months once a stable dose is established. Long-term use requires monitoring of kidney and thyroid function, as lithium can impair both over time. Common side effects include tremor, increased thirst and urination, weight gain, and cognitive dulling.

Despite these drawbacks, many clinicians consider lithium the gold standard. When it works, it works remarkably well, and some patients remain stable on it for decades.

Valproate (Depakote)

Valproate, marketed as Depakote, is an anticonvulsant that became widely used for bipolar disorder in the 1990s. It is effective for acute mania, particularly for mixed episodes and rapid cycling, where lithium may be less reliable. Its evidence for preventing depressive episodes is weaker.

Side effects include weight gain, tremor, hair thinning, gastrointestinal issues, and sedation. Valproate requires blood level monitoring, though less frequently than lithium. Liver function should also be checked periodically.

Lamotrigine (Lamictal)

Lamotrigine stands apart from the other mood stabilizers because its primary strength is preventing depressive episodes rather than manic ones. For people with Bipolar II, where depression is often the dominant problem, lamotrigine has become a first-line treatment.

It was approved by the FDA for maintenance treatment of Bipolar I in 2003, based on two pivotal trials showing it significantly delayed the time to a new depressive episode. Its effect on preventing mania is less robust, which is why it is sometimes combined with lithium or an atypical antipsychotic.

Lamotrigine is generally well-tolerated. It does not cause the weight gain seen with lithium, valproate, or most antipsychotics. It does not require blood level monitoring for therapeutic purposes. The main concern is a rare but serious skin reaction called Stevens-Johnson syndrome, which is minimized by starting at a very low dose and increasing slowly over several weeks. This slow titration is inconvenient but essential.

Atypical Antipsychotics

Several atypical antipsychotics have become standard parts of bipolar treatment, either as monotherapy or in combination with traditional mood stabilizers.

Metabolic side effects are a significant concern across this class, though the degree varies by drug. Weight gain, elevated blood sugar, and changes in cholesterol are common enough that regular metabolic monitoring is recommended. Quetiapine and olanzapine carry the highest metabolic risk; aripiprazole and lurasidone are generally more favorable on this front.

Carbamazepine and Oxcarbazepine

Carbamazepine (Tegretol) is another anticonvulsant with evidence for acute mania. It is used less frequently than lithium or valproate due to drug interactions and the need for blood monitoring, but it remains an option when first-line treatments fail or are not tolerated. Oxcarbazepine, a related compound, is sometimes used off-label with a potentially better side effect profile, though its evidence base for bipolar disorder is thinner.

What About Antidepressants?

Antidepressants are not mood stabilizers. This distinction matters. While they are sometimes used adjunctively for bipolar depression, their role is limited and contested. The 2018 CANMAT/ISBD guidelines recommend against antidepressant monotherapy in bipolar disorder and advise caution even when combining them with mood stabilizers, due to the risk of triggering mania or accelerating cycling between episodes.

When antidepressants are used, SSRIs and bupropion are generally preferred over tricyclics and SNRIs, which carry a higher switch risk. Even so, the evidence that antidepressants add meaningful benefit beyond mood stabilizers alone is surprisingly mixed.

Finding the Right Combination

Most people with bipolar disorder will try more than one medication before finding what works. This is normal and expected. Factors that influence the choice include the predominant polarity (more mania or more depression), episode pattern, tolerance of side effects, other medical conditions, reproductive plans, and prior treatment responses.

Medication is not the entire answer. Psychotherapy, sleep hygiene, exercise, and stress management all contribute to stability. But for the vast majority of people with bipolar disorder, medication is the non-negotiable foundation on which everything else is built.