There isn’t a single universal “top 10” list for bipolar disorder because the best medication depends on which phase you’re treating: mania, depression, or long-term maintenance. But a handful of medications consistently form the backbone of bipolar treatment, and most people with bipolar disorder will be prescribed one or more from this group. Here are the medications prescribed most often, what each one does best, and what to expect from taking them.
1. Lithium
Lithium remains the gold standard for bipolar disorder after more than 60 years of use. It treats acute mania, reduces the risk of future manic and depressive episodes, and is one of the few psychiatric medications shown to lower suicide risk. Because it has a narrow window between an effective dose and a toxic one, you’ll need regular blood draws. The therapeutic range is generally 0.6 to 1.2 mEq/L, and levels are typically checked twice a week when you first start, then less frequently once you’re stable. Blood should be drawn 8 to 12 hours after your last dose for an accurate reading.
Lithium can affect your kidneys and thyroid over time, so those are monitored too. Common side effects include thirst, frequent urination, mild hand tremor, and weight gain. Staying well hydrated matters more than usual because dehydration can push lithium levels dangerously high.
2. Valproate (Depakote)
Valproate is one of the most widely prescribed mood stabilizers for acute mania and mixed episodes. It tends to work faster than lithium for bringing a manic episode under control. Side effects can include drowsiness, weight gain, and stomach upset.
The biggest concern with valproate is pregnancy risk. First-trimester exposure is associated with up to an 11% rate of birth defects, more than three times the background rate. At higher doses, that number climbs dramatically. Children exposed to valproate during pregnancy also show a roughly threefold increase in the likelihood of autism spectrum disorder, and between 19% and 62% of exposed children need additional educational support. If you’re of childbearing age, your prescriber should discuss these risks clearly and consider alternatives.
3. Lamotrigine (Lamictal)
Lamotrigine fills a gap that most other bipolar medications leave open: it’s one of the best options for preventing depressive episodes. It’s approved for long-term maintenance in bipolar I disorder and is often used off-label for bipolar II, where depression is the dominant problem. It doesn’t do much for active mania.
The tradeoff is a very slow dose increase. You’ll typically start at 25 mg daily and won’t reach a full dose of 200 mg until around week six. This gradual ramp-up exists to minimize the risk of a serious skin reaction called Stevens-Johnson syndrome, which occurs in roughly 0.08% to 0.3% of adults taking the drug. That rate is low, but the condition is severe enough that any new rash while starting lamotrigine needs immediate medical attention. Once you’re at a stable dose, lamotrigine is generally well tolerated, with fewer weight and sedation issues than most alternatives.
4. Quetiapine (Seroquel)
Quetiapine is one of only three medications specifically approved for bipolar depression, and it’s also approved for acute mania and maintenance. That versatility makes it one of the most commonly prescribed bipolar medications overall. It works across both poles of the illness.
Sedation is the most noticeable effect, which can be helpful if insomnia is part of the picture but limiting during the day. Quetiapine also carries a moderate risk of metabolic side effects: weight gain, increased blood sugar, and changes in cholesterol. Regular metabolic screening is standard for anyone taking it long term.
5. Lurasidone (Latuda)
Lurasidone was approved in 2013 specifically for depressive episodes in bipolar I disorder. It has become a popular choice because it causes less weight gain and fewer metabolic problems than quetiapine or olanzapine. The typical dose range is 20 to 120 mg daily, and it needs to be taken with food (at least 350 calories) to be absorbed properly.
Its main limitation is that it only covers bipolar depression. It’s not approved for mania or maintenance, so it’s usually prescribed alongside a mood stabilizer like lithium or valproate.
6. Aripiprazole (Abilify)
Aripiprazole is approved for acute manic and mixed episodes and for maintenance treatment in bipolar I. It works differently from older antipsychotics by partially activating certain brain receptors rather than simply blocking them, which tends to produce less sedation and a lower risk of weight gain compared to quetiapine or olanzapine. The most common side effects are restlessness (akathisia), insomnia, and nausea. Some people find the restlessness intolerable enough to switch medications.
7. Cariprazine (Vraylar)
Cariprazine stands out because it’s approved for both manic episodes and bipolar depression, making it one of the few medications that covers both phases. For mania, the dose range is 3 to 6 mg daily. For bipolar depression, doses are lower, starting at 1.5 mg with a potential increase to 3 mg after two weeks. It has a very long half-life, meaning its effects (and side effects) can linger for days after stopping it. Common side effects include restlessness, drowsiness, and digestive issues.
8. Olanzapine/Fluoxetine (Symbyax)
This combination pill pairs an antipsychotic with an antidepressant and is specifically approved for acute bipolar depression. It’s effective, but it comes with a significant downside: olanzapine causes more weight gain than nearly any other medication in this class. The risk of metabolic syndrome, including elevated blood sugar and cholesterol, is rated high. For that reason, it’s often reserved for people who haven’t responded to options with a lighter side-effect profile.
9. Olanzapine (Zyprexa)
Olanzapine on its own is approved for acute mania and maintenance therapy. It’s a potent medication that can bring severe mania under control relatively quickly. The same metabolic concerns apply here as with the combination pill. Average weight gain is among the highest of any bipolar medication, and long-term use requires careful monitoring of blood sugar, cholesterol, and waist circumference.
10. Risperidone (Risperdal)
Risperidone is approved for acute manic and mixed episodes. It’s often effective at relatively low doses, and it’s available as a long-acting injection for people who have difficulty taking daily pills. Side effects include weight gain (though typically less than olanzapine), elevated prolactin levels (which can affect menstrual cycles and cause breast tenderness), and sedation.
Long-Term Side Effects to Know About
All of the antipsychotic medications on this list carry some risk of tardive dyskinesia, a condition involving involuntary movements of the face, tongue, or limbs that can become permanent. With second-generation antipsychotics (the newer class that includes most medications listed here), the annualized risk is roughly 2.6% per year. The risk rises with age and cumulative exposure, which is why prescribers aim for the lowest effective dose.
Metabolic monitoring matters for any antipsychotic. Weight, blood sugar, and cholesterol should be checked regularly. Lithium and valproate each have their own monitoring needs: kidney and thyroid function for lithium, liver function and blood counts for valproate.
Why Sticking With Treatment Is Difficult
Bipolar disorder has one of the highest rates of medication non-adherence in psychiatry. In a large nationwide study, 59% of people with bipolar disorder had at least one unfilled prescription for a mood stabilizer or antipsychotic, and 31% were non-adherent to 20% or more of their prescriptions. The reasons are predictable: side effects like weight gain and cognitive dulling, feeling fine during stable periods and questioning whether medication is still needed, and the loss of hypomanic energy that some people experience as a creative or productive state.
If side effects are pushing you to skip doses or stop, that’s worth raising with your prescriber rather than quietly tapering off. Abruptly stopping certain medications, especially lithium, can trigger rebound episodes that are worse than what you started with. In many cases, switching to a different medication within the same category or adjusting the dose can preserve the benefit while making the experience more livable.