Rexulti (brexpiprazole) is not a mood stabilizer. It is classified as an atypical antipsychotic, sometimes called a second-generation antipsychotic. The FDA has approved it for three specific uses: as an add-on treatment for major depressive disorder in adults, for schizophrenia in patients 13 and older, and for agitation related to Alzheimer’s disease. None of these approvals involve bipolar disorder or mood stabilization.
Why People Confuse It With a Mood Stabilizer
The confusion is understandable. Rexulti affects brain chemicals involved in mood, specifically dopamine and serotonin, and some other atypical antipsychotics (like quetiapine and olanzapine) are commonly used as mood stabilizers for bipolar disorder. Because these medications share a drug class, it’s natural to assume Rexulti works the same way. It doesn’t, at least not with any evidence to back that up.
True mood stabilizers are medications that prevent or reduce the extreme highs (mania) and lows (depression) of bipolar disorder. Lithium is the classic example. Several atypical antipsychotics have earned FDA approval for bipolar disorder based on clinical trial data. Rexulti is not one of them.
Rexulti Was Tested for Bipolar Disorder and Failed
Lundbeck, the company behind Rexulti, did attempt to get it approved for bipolar disorder. Two Phase III clinical trials enrolled 650 patients with manic episodes associated with bipolar I disorder. Both were three-week, placebo-controlled studies measuring improvement on a standard mania rating scale. Neither study met its primary endpoint. Rexulti did not separate from placebo, meaning it performed no better than a sugar pill at reducing manic symptoms. After those results, development for that use stopped.
What Rexulti Actually Does
Rexulti works by fine-tuning the activity of dopamine and serotonin in the brain. It partially activates dopamine receptors, meaning it can dial dopamine activity up or down depending on existing levels rather than simply blocking it. Compared to aripiprazole (Abilify), a closely related medication, Rexulti has a lighter touch on dopamine, producing less of a direct suppressive effect on dopamine-producing neurons.
It also acts as a full activator of certain serotonin receptors that help regulate mood and anxiety, while blocking a different type of serotonin receptor involved in norepinephrine signaling. This combination of effects is why it can help with depression when added to an antidepressant, even though it doesn’t work as a standalone mood stabilizer for bipolar disorder.
Its Proven Role in Depression
Where Rexulti does have strong evidence is as an add-on to antidepressants for major depressive disorder. If an antidepressant alone isn’t fully resolving your depression, Rexulti is one of the options a prescriber might consider adding. Canadian clinical guidelines from 2023 list it as a first-line adjunctive treatment for difficult-to-treat depression.
For this use, the typical starting dose is 0.5 to 1 mg once daily, gradually increased to a target of 2 mg daily, with a maximum of 3 mg. The doses are notably lower than those used for schizophrenia, where the target range is 2 to 4 mg daily.
Side Effects Worth Knowing About
Akathisia, a restless feeling that makes it hard to sit still, is one of the more common side effects. In depression trials, it affected about 9% of patients taking Rexulti compared to 2% on placebo. The risk climbs with dose: 4% at 1 mg per day, 7% at 2 mg, and 14% at 3 mg. This is one reason prescribers usually start low and increase gradually.
Weight gain is another concern with atypical antipsychotics generally. In depression studies, about 5% of patients on 1 or 2 mg daily gained 7% or more of their body weight, compared to 2% on placebo. For schizophrenia patients, the numbers were higher, around 10 to 11%. These rates are moderate compared to some other drugs in the same class, but still worth monitoring.
Triglyceride levels can also shift. In depression trials, 13% of patients on 2 mg daily saw their triglycerides move from a normal range into a high range, compared to 6% on placebo. Periodic blood work is typical for anyone taking an atypical antipsychotic long-term.
If You Need a Mood Stabilizer
If you or your prescriber are looking for a medication to manage bipolar disorder, Rexulti is not the right tool. Established mood stabilizers include lithium and certain anticonvulsants. Several other atypical antipsychotics have FDA approval for bipolar mania, bipolar depression, or both. Rexulti’s role is narrower: boosting the effectiveness of antidepressants in unipolar depression and treating schizophrenia. Those are meaningful uses, but mood stabilization isn’t among them.