Antipsychotics are named for their first use, treating psychosis, but several newer ones are also FDA-approved for mood disorders. Being prescribed one does not necessarily mean a clinician thinks you have psychosis. NIMH notes that atypical antipsychotics are sometimes used to treat bipolar depression or depression in people who have not responded to an antidepressant alone.
Part of our guide: A Patient’s Guide to Psychiatric Medication
In bipolar disorder, some are labeled to treat manic or depressive episodes. In major depression, some are labeled as add-ons to an antidepressant. The benefits can be real but are often modest in depression, and side effects need regular monitoring, so the decision is a trade-off worth discussing openly.
If you are thinking about suicide or are in crisis: call or text 988 (988 Suicide & Crisis Lifeline), call 911 or go to the nearest ER.
What antipsychotics are
Older, first-generation antipsychotics came first. Newer second-generation medications, sometimes called atypical antipsychotics, are commonly used because they treat a broader range of symptoms. These newer medications are the ones this article focuses on.
How they help mood is not fully understood. The quetiapine label says its mechanism is unclear and could involve blocking dopamine and serotonin receptors. Aripiprazole's label describes a different combination of partial activity at some dopamine and serotonin receptors and blocking at another. Because these medications affect several brain chemical systems, their effects reach beyond psychosis, though no one label explains exactly why they lift mood.
Which ones are approved for mood disorders
Approved uses differ from drug to drug, including for ages and for bipolar I versus II. This table gives examples from current FDA labels, for the mood uses only, and is not a complete list. For example, the fluoxetine label also describes using olanzapine with fluoxetine for bipolar I depression and treatment-resistant depression. Clinicians may also prescribe outside these uses, so ask how your medication's use relates to the evidence.
| Medication | Bipolar uses on the label | Major depression use on the label |
|---|---|---|
| Quetiapine and quetiapine XR | Manic episodes; depressive episodes; maintenance in bipolar I as an add-on to lithium or divalproex | XR form: add-on to an antidepressant |
| Aripiprazole | Manic and mixed episodes in bipolar I | Add-on to an antidepressant |
| Cariprazine | Manic or mixed episodes; depressive episodes in bipolar I | Add-on to an antidepressant |
| Lurasidone | Depressive episodes in bipolar I | Not listed |
| Lumateperone | Depressive episodes in bipolar I or II | Add-on to an antidepressant |
| Brexpiprazole | Not listed | Add-on to an antidepressant |
Why they are used in bipolar disorder
Bipolar disorder involves episodes in both directions, and antidepressants on their own can be a concern because they may precipitate a mixed or manic episode in people with bipolar disorder. Antipsychotics give clinicians another way to treat a current episode. Some, like lurasidone and lumateperone, can be used alone or with lithium or valproate for bipolar depression.
Your plan may also include a mood stabilizer. NIMH describes mood stabilizers as typically used to treat bipolar disorder. The right mix depends on your episodes, history and side effects. For more on the broader picture, see how psychiatric treatment helps depression and bipolar disorder.
Why they are added for depression
When an antidepressant has helped only partly, or not at all, a clinician may suggest adding a medication, which is called augmentation. A 2022 network meta-analysis of 65 studies found significant response rates versus placebo for several options, including aripiprazole, brexpiprazole, quetiapine, cariprazine and lithium. Cariprazine also had higher discontinuation rates than placebo, and the authors noted limits, including differing definitions of treatment-resistant depression.
The size of the benefit deserves honest framing. A 2013 meta-analysis of 14 short-term trials of four add-on options (aripiprazole, olanzapine/fluoxetine, quetiapine and risperidone) found they improved remission and depression scores, yet the average change was modest, at 2.69 points on a standard depression scale. On functioning and quality of life, they produced no benefit or a very small one, except risperidone, which had a small-to-moderate effect on quality of life. The authors also warned that study design problems may have inflated the benefits and understated the side effects. For some people the trade-off is worth it, and for others it may not be. There are also other options to discuss if depression has not responded, which is why it helps to read about what happens when one medication does not work.
Side effects and monitoring
These are the main issues to discuss before starting and to keep watching afterward. How likely each one is varies by medication.
- Weight, blood sugar and cholesterol. The quetiapine label says atypical antipsychotics have been associated with metabolic changes, including high blood sugar, unhealthy cholesterol changes and weight gain. NIMH says clinicians may ask for regular monitoring of weight, glucose and lipids. See which blood tests psychiatric medications need.
- Restlessness. The 2013 review linked aripiprazole to akathisia, an uncomfortable inner restlessness and urge to move. It can be mistaken for worsening anxiety, so report it.
- Sleepiness. Sedation was linked to several drugs in that review, and quetiapine's label warns that sleepiness and dizziness on standing can lead to falls.
- Involuntary movements. The labels warn of tardive dyskinesia, a potentially irreversible condition involving involuntary movements. Mention any new movements in the face, tongue or limbs, even if they seem minor.
- Compulsive behaviors. Aripiprazole's label warns of pathological gambling and other compulsive behaviors. Tell your clinician about any new urges.
- Neuroleptic malignant syndrome. This rare, potentially fatal reaction involves very high fever, muscle rigidity and altered mental status. It needs emergency care.
Boxed warnings
Current labels for these medications carry two boxed warnings. One says that elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death, and these medications are not approved to treat dementia-related psychosis. Brexpiprazole is the one to ask about specifically: it is approved for agitation associated with dementia due to Alzheimer's disease, and its boxed warning still applies. If a relative with dementia takes an antipsychotic, raise this with the prescriber rather than stopping it on your own. The other relates to suicidal thoughts and behaviors. It applies because these medications are labeled for depression, and it reflects the antidepressant finding of higher risk in children and young adults in short-term studies. Close monitoring is advised for everyone taking one, especially in the first few months and after dose changes.
What to share before starting
Your personal risk shapes this decision, so tell your clinician about any of the following:
- Diabetes, high cholesterol or weight concerns, including in your family.
- Heart problems, fainting or dizziness on standing.
- Past movement problems or restlessness on any medication.
- A history of gambling or other hard-to-control urges.
- Pregnancy, plans for pregnancy or breastfeeding.
- For a child or teen, any blood pressure concerns. The quetiapine label calls for monitoring blood pressure at the start of and periodically during treatment in this age group.
Questions to ask your prescriber
- Why this medication, and what result is it meant to achieve?
- Is this use on the FDA label for the condition being treated?
- Which side effects are most likely, given your health history?
- What will be checked at the start, how often afterward, and who will follow up on the results?
- How long is treatment expected to last, and when will the plan be reassessed?
- What alternatives exist, including therapy or other medications?
If you want to stop or switch
Please do not stop on your own, even if side effects are frustrating. Quetiapine's label describes acute withdrawal symptoms such as insomnia, nausea and vomiting after abrupt stopping, and stopping treatment can also risk a return of mood symptoms. Make any change only with your prescriber, who can help you plan it. If side effects are hard to live with, call the office and say so. Our guide to medication adherence in bipolar disorder may also be useful.
Where to go from here
If you have questions about an antipsychotic in your treatment plan, bipolar disorder treatment and medication management at Mind Body Seven can cover those. You can request a consultation, and the intake team confirms fit, scheduling and costs.
FAQs
Does being prescribed an antipsychotic mean having psychosis?
Not necessarily. These medications have uses beyond psychosis, including bipolar disorder and depression. If you are unsure why one was prescribed for you, ask your clinician to explain the reason and what it is meant to treat.
Does an antipsychotic have to be taken forever?
Not necessarily. How long depends on your diagnosis, your history and how you respond. In depression, it is reasonable to ask when the medication will be reassessed. In bipolar disorder, NIMH says treatment is usually lifelong, though that does not mean any one medication is. Make any change only with your prescriber.
Can an antidepressant be continued with an antipsychotic?
In major depression, labels for medications such as aripiprazole describe use alongside an antidepressant. Combinations should be chosen and monitored by your prescriber, who should know every medication and supplement you take.
