Olanzapine and Fluoxetine: One Capsule, Two Medicines

What this combination is

This capsule contains two medicines in one: olanzapine, an atypical antipsychotic, and fluoxetine, a selective serotonin reuptake inhibitor (SSRI). Current FDA labels on DailyMed are for generic capsules, so this page uses the generic name.

It is often grouped with add-on medicines, but it differs in one practical way: the antidepressant is already inside. The patient information says that if you take this capsule, you should not take other medicines that contain olanzapine or fluoxetine. If you already take one of them, your prescriber needs to know.

Exactly what the label approves

The label lists two approved uses, shown below. Its definition of treatment resistant depression is narrower than how people sometimes use the phrase, and the capsule is not approved simply as a first treatment for depression. Fluoxetine alone and olanzapine alone have their own labels and uses, and MedlinePlus covers them on separate pages. The fluoxetine page notes that fluoxetine is used along with olanzapine for depression and for episodes of depression in bipolar I disorder.

The boxed warning says the capsules are not approved for children under 10. The label says safety and effectiveness have not been established for bipolar I depression under age 10, or for treatment resistant depression under age 18. To see where it fits with other options, read our guide on what can happen when a first antidepressant does not help.

• Acute depressive episodes in bipolar I disorder.
• Treatment resistant depression, which the label defines as major depressive disorder in people who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode.

How it is thought to work

The label says the mechanism is unclear. It says the combined effect of the two medicines on serotonin, norepinephrine and dopamine systems in the brain could be responsible. MedlinePlus describes olanzapine as changing the activity of certain natural substances in the brain.

What taking it can be like

The most common side effects in adults on the label are sedation, weight gain, increased appetite, dry mouth, fatigue, swelling, tremor, trouble with attention and blurred vision.

Weight and blood sugar need planning. The label calls for fasting blood sugar and blood fat tests before starting and during treatment, along with regular weight checks. If side effects are hard to live with, tell your prescriber. The label warns about discontinuation effects, including dizziness, irritability, anxiety, sensory disturbances and insomnia, particularly with abrupt stopping, so do not stop suddenly.

Boxed warnings

The label has two boxed warnings, the FDA's strongest kind.

• Suicidal thoughts and behaviors: antidepressants increased these risks in children, teens and young adults in short-term studies. The studies did not show an increase in people over 24, and there was a reduction in people 65 and older. People of all ages starting antidepressant treatment need close monitoring, and families and caregivers should watch for changes. If you are in crisis, call or text 988, or call 911. Locascio Wellness does not provide emergency services.
• Older people with dementia: older adults with dementia-related psychosis treated with antipsychotics are at an increased risk of death. The capsules are not approved for this use.

Contraindications and other serious warnings

MAOIs, pimozide and thioridazine are contraindicated on the label. The rest of this list covers its other serious warnings.

• MAOIs: risk of serotonin syndrome. An MAOI intended for psychiatric disorders must not be used with this capsule or within 5 weeks of stopping it, and the capsule must not be used within 14 days of stopping an MAOI. It should not be started in someone being treated with linezolid or intravenous methylene blue.
• Pimozide and thioridazine: risk of QT prolongation, a heart rhythm problem. Thioridazine also must not be used within 5 weeks of discontinuing the capsule.
• Metabolic changes: high blood sugar, sometimes extreme and with ketoacidosis, coma or death; changes in blood fats; and weight gain.
• Serotonin syndrome: reported especially with other serotonin medicines.
• Mania: the capsule can activate mania or hypomania, so screening for bipolar disorder matters.
• Bleeding: fluoxetine can raise bleeding risk, including with aspirin, NSAIDs or warfarin.
• Also on the label: neuroleptic malignant syndrome, a severe reaction called DRESS, rash and allergic reactions, angle-closure glaucoma, tardive dyskinesia, low blood pressure and fainting, low white blood cell counts, seizures, low sodium and QT prolongation.
• Pregnancy: if you are pregnant, planning a pregnancy or breastfeeding, tell your prescriber.

Can it be managed online in Pennsylvania and New York

The video visit is only part of the picture here. The label calls for blood sugar and blood fat tests and regular weight monitoring, which happen in person, so ask how that would be arranged. Whether it is an option for you is a decision for you and your prescriber. Ask us whether our psychiatrist can help, using our medication inquiry form.

A licensed psychiatrist on our team treats depression by secure video for people physically located in Pennsylvania or New York during each visit. See online depression treatment, online psychiatry in New York and our medicines list. Our therapists do not prescribe, and they see clients in Pennsylvania, West Virginia, Arizona, Colorado and Florida, not New York. Ask us about fees and insurance.