The depressive episodes of bipolar disorder can be some of the hardest depression to treat. The options are narrower than for other depression, partly because some standard antidepressants can tip people toward mania. Spravato works on a different system in the brain, and for many people whose bipolar depression hasn’t lifted, it’s the next step.
Can Spravato be used for bipolar depression?
Yes. Spravato (esketamine) is FDA-approved for treatment-resistant depression in adults, which means depression that hasn’t responded to at least two antidepressants.1 What qualifies you is the depression and how it has responded to treatment, whether it comes from major depression or from bipolar disorder. In bipolar disorder, it’s given alongside your mood stabilizer, as an addition to a stable treatment plan, never a replacement for it.
The large trials behind Spravato’s approval were done in people with major depression. The studies in bipolar depression are smaller, and they’re encouraging.
What the studies show
- Results similar to other treatment-resistant depression. In a multicenter Italian study, people with treatment-resistant bipolar depression did about as well on esketamine as people with treatment-resistant unipolar depression.3
- Meaningful improvement in many patients. A 2023 review that pooled ketamine and esketamine studies in bipolar depression found meaningful improvement in many patients, and called for larger trials to build on it.2
- Promising across the research. An overview of the systematic reviews concluded that ketamine and esketamine show promise in both unipolar and bipolar depression, while noting that most of the bipolar studies are small.4
What about mania?
That’s the question everyone with bipolar disorder asks about any depression treatment, and the evidence here is reassuring. In the studies so far, switching into mania after esketamine was uncommon, and in the Italian study improvement wasn’t linked to switching.3 A large 2025 records study of more than two thousand adults with bipolar depression found no increase in manic switching with esketamine used alongside mood stabilizers.5 That’s how we use it.
How we decide together
We don’t practice cookie-cutter medicine. At your evaluation we look at how stable your mood has been, what you take now, which treatments you’ve already tried, and any history of mania or psychosis. Where it helps, we coordinate with the psychiatrist who manages your bipolar disorder. For most people whose bipolar depression hasn’t responded, that means Spravato alongside a mood stabilizer, with your care coordinated from the start.
Will insurance cover it?
Most plans cover Spravato for treatment-resistant depression, with a prior authorization, which we handle. The one exception to know about is Horizon NJ Health: its Spravato policy excludes anyone with a history of bipolar disorder. We check your plan before you commit to anything.