The most widely used mood stabilizers fall into three categories: lithium, anticonvulsants, and atypical antipsychotics. Lithium remains the gold standard, but several alternatives work well depending on whether the goal is controlling mania, preventing depressive episodes, or both. Here are the 10 most commonly prescribed mood stabilizers, what each one does best, and the tradeoffs that come with it.
1. Lithium
Lithium is the oldest and most studied mood stabilizer, effective for both manic and depressive episodes in bipolar disorder. It also has a unique benefit no other mood stabilizer can claim: it reduces the risk of suicide. For maintenance treatment, blood levels need to stay within a therapeutic window of 0.5 to 1.2 mmol/L, measured 8 to 12 hours after the last dose.
That narrow range is why lithium requires regular blood draws. Too little and it doesn’t work; too much and it becomes toxic. Long-term use can affect the thyroid and kidneys, yet monitoring rates are surprisingly poor. One study of Medicaid patients found that over 54% of people on lithium never received thyroid function tests, and only 4.2% received kidney function tests. If you’re on lithium, regular lab work for thyroid hormones and kidney function is essential, not optional.
2. Valproate (Valproic Acid / Divalproex)
Valproate is the most commonly prescribed alternative to lithium, particularly effective for acute mania and mixed episodes. It works through several mechanisms at once: it blocks certain calcium and sodium channels in the brain, boosts the calming neurotransmitter GABA so strongly that it essentially prevents GABA from converting into the excitatory chemical glutamate, and it even reduces inflammatory gene activity.
The main concerns with valproate are liver toxicity, weight gain (averaging around 1 to 2 kg in short-term trials), and serious birth defect risks. It should not be used during pregnancy. Like lithium, it requires blood level monitoring to stay in a safe and effective range.
3. Lamotrigine
Lamotrigine stands out because it’s one of the few mood stabilizers that works primarily against the depressive side of bipolar disorder rather than mania. It helps prevent depressive episodes from recurring and is often a first choice for bipolar II, where depression is the dominant problem.
The biggest concern is a rare but serious skin reaction called Stevens-Johnson syndrome. To minimize this risk, lamotrigine must be started at a very low dose and increased slowly over several weeks. For most patients, the starting dose is just 25 mg daily for the first two weeks, then 50 mg daily for weeks three and four, building to a target of around 200 mg by week five. Skipping this slow ramp-up or increasing the dose too quickly raises the risk of a dangerous rash. On the positive side, lamotrigine causes minimal weight gain and fewer cognitive side effects than many other options on this list.
4. Carbamazepine
Carbamazepine is FDA-approved for acute mania and mixed episodes. It works by blocking sodium channels and a type of calcium channel in nerve cells, which damps down the excessive electrical firing associated with mood episodes.
One important safety requirement: people of Asian ancestry need genetic testing for a specific gene variant (HLA-B*15:02) before starting carbamazepine. Carrying this variant dramatically increases the risk of Stevens-Johnson syndrome. A multi-center study found the odds ratio was 181, meaning carriers were roughly 181 times more likely to develop this severe skin reaction. If the test comes back positive, carbamazepine should not be used. This genetic screening is now considered standard of care for patients of Han Chinese, Malay, Indian, and Thai descent, among other Asian populations.
5. Oxcarbazepine
Oxcarbazepine is a close chemical relative of carbamazepine, sometimes chosen because it tends to have fewer drug interactions and a somewhat milder side effect profile. It’s used off-label for bipolar disorder, typically at doses of 900 to 1,200 mg per day. The clinical evidence behind it is less robust than for carbamazepine, resting mostly on positive open trials and case series rather than large controlled studies. Still, it can be a reasonable option when other mood stabilizers haven’t been tolerated well.
6. Quetiapine
Quetiapine is an atypical antipsychotic that has become one of the most versatile tools in bipolar treatment. It’s FDA-approved for bipolar mania, bipolar depression, and maintenance therapy, making it one of the few medications that covers all three phases. Clinical trials have shown it to be superior to placebo for bipolar depression, which is notoriously difficult to treat.
The tradeoff is sedation and metabolic effects. Weight gain with atypical antipsychotics is significantly greater than with traditional mood stabilizers. In short-term pediatric trials, antipsychotic monotherapy led to an average gain of 3.4 kg, compared to just 1.2 kg with mood stabilizer monotherapy. Combining an antipsychotic with a mood stabilizer produced the most weight gain, averaging 5.5 kg. These numbers apply to children and adolescents, but the general pattern holds for adults as well.
7. Olanzapine
Olanzapine is approved for both acute mania and maintenance treatment of bipolar disorder. It’s also available in a combination pill with the antidepressant fluoxetine, specifically for bipolar depression. Clinical data show it outperforms placebo for bipolar depression, though it carries the highest weight gain risk of any atypical antipsychotic. It also raises blood sugar and cholesterol levels in some patients, which means metabolic monitoring is a must.
8. Aripiprazole
Aripiprazole works differently from other atypical antipsychotics. Instead of simply blocking dopamine receptors, it acts as a partial regulator, dialing dopamine activity up or down depending on what the brain needs. It’s approved for acute mania and maintenance therapy in bipolar disorder.
The metabolic profile is more favorable than olanzapine or quetiapine. In one pediatric study, aripiprazole was actually associated with slight weight loss rather than gain. Common side effects tend more toward restlessness, insomnia, and nausea rather than the sedation and weight gain typical of other antipsychotics in this class.
9. Risperidone
Risperidone is FDA-approved for acute manic and mixed episodes in bipolar disorder. It’s effective at bringing mania under control quickly, which makes it useful in acute situations. However, it’s less commonly used for long-term maintenance compared to quetiapine or aripiprazole. Side effects include weight gain, elevated prolactin levels (which can cause breast tenderness or menstrual changes), and at higher doses, muscle stiffness or involuntary movements.
10. Topiramate
Topiramate is the most clearly off-label option on this list. It’s an anticonvulsant that has shown positive results in open trials and case series for bipolar symptoms, typically at doses ranging from 100 to 300 mg per day. Large controlled trials haven’t confirmed these benefits convincingly, so it’s generally reserved for situations where first-line options have failed.
What makes topiramate unusual is that it causes weight loss rather than weight gain. In pooled pediatric data, topiramate was the only mood-related medication associated with significant weight reduction. This makes it an appealing add-on for patients struggling with weight gain from other mood stabilizers. Common side effects include cognitive dulling, word-finding difficulty, and tingling in the hands and feet.
How These Medications Compare on Weight
Weight gain is one of the most common reasons people stop taking mood stabilizers, so it’s worth seeing the full picture. In short-term trials, traditional mood stabilizers like lithium and valproate cause modest weight gain, averaging about 1.2 kg as standalone treatments. Atypical antipsychotics cause roughly three times that amount on their own. The worst scenario is combining an antipsychotic with a mood stabilizer, which averaged 5.5 kg of gain in under 12 weeks.
On the other end of the spectrum, topiramate and aripiprazole stand out as the most weight-friendly options, with topiramate actually promoting weight loss and aripiprazole holding relatively neutral. Lamotrigine also tends to be weight-neutral for most people.
Choosing Between Them
The right mood stabilizer depends largely on which part of bipolar disorder is causing the most trouble. For acute mania, lithium, valproate, carbamazepine, and several atypical antipsychotics all have strong evidence. For preventing depressive episodes, lamotrigine and quetiapine have the clearest track records. For long-term maintenance that covers both poles, lithium remains the benchmark, with quetiapine and aripiprazole as alternatives.
Side effect tolerance matters just as much as effectiveness. Someone prone to weight gain might do better with lamotrigine or aripiprazole. Someone who needs quick control of severe mania might start with an antipsychotic and transition to lithium or valproate for maintenance. Most people with bipolar disorder end up trying more than one medication before finding the best fit, and combination therapy with two agents is common when a single drug doesn’t fully stabilize mood.