Symbyax (Olanzapine/Fluoxetine) for Depression

Symbyax (olanzapine/fluoxetine) is a prescription medication approved by the U.S. Food and Drug Administration (FDA) in adults to treat treatment-resistant depression, which is major depressive disorder (MDD) that has not improved after two different antidepressant treatments.

How Symbyax Works and How It’s Taken

Symbyax is a type of medication called an antidepressant and antipsychotic combination that contains olanzapine and fluoxetine. It works by changing brain chemical systems that use serotonin, norepinephrine, and dopamine. The exact way it works is not fully known.

In depression, Symbyax may help improve mood symptoms by helping rebalance these brain signals.

Doctors prescribe Symbyax for adults with treatment-resistant depression. This means MDD that has not improved after two different antidepressant treatments taken at the right dose and for a long enough time during the current episode.

Symbyax is given as a capsule taken by mouth, typically once daily in the evening. It can be taken with or without food.

Typical Dosing for Depression

The recommended dose of Symbyax for treatment-resistant depression is 6 milligrams/25 milligrams taken once daily in the evening.

Studies showed antidepressant benefits with doses ranging from 6 milligrams to 18 milligrams of olanzapine and 25 milligrams to 50 milligrams of fluoxetine.

A doctor may start some individuals at 3 milligrams/25 milligrams or 6 milligrams/25 milligrams if they may be more sensitive to the medicine or may process it more slowly.

Do not change your dose or stop taking Symbyax without talking to your doctor first.

This information is based on the prescribing information, but your healthcare provider may tailor your treatment plan. Always follow their guidance.

Symbyax Side Effects

In short-term controlled clinical studies of Symbyax in adults, the most common side effects occurred in about 5 percent to 27 percent of people. These side effects were:

Somnolence (sleepiness or drowsiness)
Weight gain
Increased appetite
Dry mouth
Edema (swelling in the arms, hands, legs, or feet)
Fatigue (low energy)
Tremor (shaking)
Blurred vision
Trouble paying attention

Serious Side Effects and Warnings

Symbyax can cause serious side effects that may require immediate medical attention. These include:

Suicidal thoughts and behaviors — These can occur, especially in children, adolescents, and young adults.
Increased risk of death in older adults with dementia-related psychosis — Symbyax is not approved for this use.
Hyperglycemia and diabetes-related complications — High blood sugar can occur, including diabetic ketoacidosis or diabetic coma.
Dyslipidemia — Changes in cholesterol or triglyceride levels in the blood can occur.
Neuroleptic malignant syndrome (NMS) — This rare, life-threatening reaction can cause high fever, stiff muscles, confusion, and unstable blood pressure or heart rate.
Drug reaction with eosinophilia and systemic symptoms (DRESS) — This serious drug reaction can include rash, fever, swollen lymph nodes, and organ problems.
Weight gain — Weight gain can occur with Symbyax.
Serotonin syndrome — This potentially life-threatening reaction can cause agitation, confusion, sweating, fast heartbeat, muscle stiffness, or shaking.
Angle-closure glaucoma — A sudden rise in eye pressure can cause eye pain, vision changes, or nausea.
Severe allergic reactions and rash — Serious skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, can occur.
Activation of mania or hypomania — Mania or hypomania may occur.
Tardive dyskinesia — Uncontrolled movements may occur and may not go away.
Orthostatic hypotension and syncope — A sudden drop in blood pressure when standing and fainting can occur.
Falls — Falls can lead to fractures or other injuries.
Leukopenia, neutropenia, and agranulocytosis — Low white blood cell problems may increase infection risk.
Dysphagia — Trouble swallowing and aspiration, which can cause food or liquid to go into the lungs, can occur.
Seizures — Seizures can occur with Symbyax.
Cognitive and motor impairment — Problems with judgment, thinking, or movement can occur.
Increased bleeding risk — This risk may be higher if Symbyax is taken with medicines such as NSAIDs, aspirin, or blood thinners.
Hyponatremia — Low sodium levels can cause headache, confusion, weakness, or seizures.
Body temperature dysregulation — Problems controlling body temperature can occur.
QT prolongation and serious heart rhythm problems — Serious heart rhythm problems can occur, including Torsade de Pointes.
Rhabdomyolysis — Muscle breakdown can damage the kidneys.
Venous thromboembolism — Blood clots in veins can occur, including deep vein thrombosis or pulmonary embolism.
Hyperprolactinemia — This may cause breast changes, menstrual changes, or sexual side effects.

Get medical help right away if you think you are having a serious reaction.

What To Know Before Taking Symbyax

Before taking Symbyax, your doctor may check your blood sugar before treatment and during treatment.

Tell your doctor if you have any allergies to olanzapine/fluoxetine or any ingredients in Symbyax.

Tell your doctor about all medicines you take, including prescription drugs, over-the-counter medicines, vitamins, and herbal supplements.

Do not take Symbyax if you take a monoamine oxidase inhibitor (MAOI), pimozide, or thioridazine. Some medicines may interact with Symbyax and increase the risk of serious side effects.

Symbyax is also FDA-approved to treat depressive episodes associated with bipolar 1 disorder in adults and in children ages 10 to 17.

There is a pregnancy registry for those who are exposed to Symbyax during pregnancy. To learn more, visit the National Pregnancy Registry for Psychiatric Medications or call 866-961-2388.

If you are pregnant, planning to become pregnant, or breastfeeding while taking Symbyax, talk with your doctor about the risks and benefits.

Community FAQs

These answers are fact-checked by our editorial staff.

How effective is Symbyax?

In adults with treatment-resistant depression, three short-term studies found that Symbyax improved depression scores more than olanzapine or fluoxetine alone. In one study, depression scores dropped by 14.1 points with Symbyax, compared with 7.1 points with olanzapine and 8.3 points with fluoxetine.

In a 47-week study, 15.8 percent of people taking Symbyax had depression come back, compared with 31.8 percent of people taking fluoxetine. People taking Symbyax also went longer before relapse.

How long does Symbyax take to work for depression?

Clinical studies of Symbyax for treatment-resistant depression looked at improvement during short-term treatment, but the results do not mention exactly how long it may take for people to start feeling better. A longer study followed people for up to 47 weeks and found that continued treatment with Symbyax lowered the chance of depression returning compared with fluoxetine alone.

Because each person responds differently, some people may notice improvement sooner than others. Always take Symbyax exactly as prescribed by your doctor.

What tests or monitoring are needed with Symbyax for depression?

Before starting Symbyax, your doctor may check your blood sugar and cholesterol levels. These tests may also be repeated from time to time during treatment.

Your weight should be checked regularly while taking Symbyax. Some people may need closer blood count monitoring, especially those with a history of low white blood cell counts or past drug-related blood cell problems.