Ross is a writer for Verywell with years of experience practicing pharmacy in various settings. She is also a board-certified clinical pharmacist and the founder of Off Script Consults.
Erika Prouty, PharmD, is a professional community pharmacist who aids patients in medication management and pharmacy services in North Adams, Massachusetts.
The Food and Drug Administration (FDA) has assigned a black box warning to Symbyax (olanzapine and fluoxetine). This medication isn't approved for use in children less than 10 years of age. It's also not approved for the treatment of dementia-related psychosis. In children, adolescents (teenagers), and young adults, Symbyax increases the risk of suicidal thoughts and behaviors. In older adults over 65 years of age, using antipsychotic medications—like Symbyax—for dementia-related psychosis increases the risk of death.
Symbyax (olanzapine and fluoxetine ) is a medication option for the treatment of depressive episodes in bipolar I disorder. It can also be used for treatment-resistant depression.
Symbyax is a combination medication that contains Zyprexa (olanzapine) and Prozac (fluoxetine). Olanzapine is a second general or atypical antipsychotic, and fluoxetine is a selective serotonin reuptake inhibitor (SSRI).
Olanzapine is thought to work by interfering with the activity of two naturally occurring brain chemicals called dopamine and serotonin. Fluoxetine works by increasing serotonin levels in the brain.
Symbyax is available as a prescription capsule.
Generic Name: Olanzapine and fluoxetine
Brand Name(s): Symbyax
Therapeutic Classification: Atypical (second-generation) antipsychotic and selective serotonin reuptake inhibitor (SSRI)
Administration Route: Oral (by mouth)
Active Ingredient: Olanzapine and fluoxetine
Dosage Form(s): Capsule
Symbyax is used to treat depressive episodes in bipolar I disorder. It can also be used for treatment-resistant depression.
In general, mental health conditions are common. Roughly 1 in 5 adults in the United States lives with one, and mental health conditions affect around 1 in 6 children between 6 and 17 years old.
For bipolar, it's estimated that nearly 3% of people are affected by this condition—with over 80% of cases being severe. Depression, on the other hand, affects around 8% of people in the United States.
There are several types of bipolar disorder. Symbyax is used in people with bipolar I disorder. People with this type of bipolar experience shifts between periods of mania and periods of depression.
Symbyax is also used to treat depression that hasn't improved with other medications. People with depression might feel hopeless and guilty. They may also have trouble with focus (concentration), and they no longer have interest in previously pleasurable activities.
Take Symbyax by mouth in the evening with or without food.
When you receive Symbyax from the pharmacy, keep it at room temperature, which is around 77 degrees Fahrenheit. Symbyax also has a short-term storage range between 59 degrees to 86 degrees F. When storing Symbyax, protect it from light and moisture.
In general, keep your medications tightly closed and out of the reach of children and pets, ideally locked in a cabinet or closet.
Avoid pouring unused and expired drugs down the drain or in the toilet. Visit the FDA's website to know where and how to discard all unused and expired drugs. You can also find disposal boxes in your area. Ask your pharmacist or healthcare provider if you have any questions about the best ways to dispose of your medications.
If you plan to travel with Symbyax, get familiar with your final destination's regulations. Checking with the U.S. embassy or consulate might be a helpful resource. In general, however, make a copy of your Symbyax prescription. It's also a good idea to keep your medication in its original container from your pharmacy with your name on the label. If you have any questions about traveling with your medicine, ask your pharmacist or healthcare provider.
You might notice an improvement in your symptoms at eight weeks of treatment with Symbyax.
Symbyax doesn't currently have any off-label uses.
This is not a complete list of side effects, and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your pharmacist or a healthcare provider. You may report side effects to the Food and Drug Administration (FDA) at fda.gov/medwatch or 800-FDA-1088.
Common side effects of Symbyax in adults may include:
Children and teenagers tend to experience the following common side effects with Symbyax:
Get medical help right away if you develop the following serious side effects:
Other severe side effects with Symbyax may also include:
Call 911 if your symptoms feel life-threatening.
Possible long-term side effects with Symbyax may include:
Symbyax may cause other side effects. Call your healthcare provider if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your provider may send a report to the FDA's MedWatch Adverse Event Reporting Program online or by phone (800-332-1088).
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
The following modifications should be kept in mind when using Symbyax:
Severe allergic reaction: Avoid using Symbyax if you have a known allergy to it or its ingredients. Ask your pharmacist or healthcare provider for a complete list of the ingredients if you're unsure.
Pregnancy: Side effects are possible in newborns exposed to olanzapine or fluoxetine later during the pregnancy (e.g., third trimester). Some newborns will quickly recover from these side effects after birth, but others may require more time. There are still some conflicting data about the effects of olanzapine or fluoxetine on the unborn fetus.
While your newborn might experience side effects with Symbyax, there are also risks to having untreated mental health conditions during pregnancy. Discuss with your healthcare provider if you plan to become pregnant or are pregnant. They will help weigh the benefits and risks of Symbyax during your pregnancy. They can also enroll you in the pregnancy exposure registry by visiting the National Pregnancy Registry for Psychiatric Medications website or calling 1-866-961-2388.
People assigned female at birth with childbearing or reproductive potential: Symbyax may result in high prolactin hormone levels, negatively affecting your fertility. These effects, however, are reversible.
Breastfeeding: Low levels of olanzapine are present in breast milk, but little is found in the bloodstream of nursing infants. Some experts support olanzapine as a go-to antipsychotic during breastfeeding, but there are reports of drowsiness or sleepiness with olanzapine in nursing babies.
Fluoxetine, on the other hand, is present in higher amounts in human breast milk. Fluoxetine is also found in the bloodstream of nursing infants. These fluoxetine levels are linked to the following side effects in nursing babies: colic (hours of crying), drowsiness, fussiness, and weight loss. According to some experts, however, there is no need to change fluoxetine if it successfully improved your mood symptoms before and during your pregnancy—especially when other similar medications didn't work for you.
If you're going to stay on Symbyax while breastfeeding, monitor your child. Report any side effects to your healthcare provider. If you're having breastfeeding difficulties, talk with your healthcare provider about this too. Breastfeeding troubles could also be due to fluoxetine, and your healthcare provider can provide additional support. In general, reach out to your healthcare provider if you plan to breastfeed. They can help you weigh the benefits and risks of Symbyax while nursing. They can also discuss the different ways available to feed your baby.
Adults over 65 years: Clinical studies haven't included a large enough number of people in this age group to see whether they respond to Symbyax differently compared to younger adults.
In olanzapine-specific studies, there were no differences in responses between older and younger adults. Olanzapine in older adults with dementia-related psychosis was linked to stroke, transient ischemic attacks (TIAs), and other side effects.
In fluoxetine-specific studies, there were also no response differences between older and younger adults. Older adults, however, might be more sensitive to fluoxetine side effects, such as low sodium blood levels.
Children: The FDA approved Symbyax to treat depressive episodes in bipolar I disorder for children 10 years and older. Children and teenagers tend to experience more changes in their cholesterol, liver-related labs, and prolactin hormone levels than adults.
Liver problems: If you have liver impairment—like cirrhosis—your liver might have trouble breaking down the fluoxetine component of Symbyax and clearing it from your body. As a result, you'll likely have a buildup of fluoxetine and a higher chance of side effects.
Bipolar: Symbyax can switch you from a depressive episode to a manic one. Therefore, your healthcare provider will screen you for bipolar before starting Symbyax. If you do have bipolar, they will monitor and manage possible mania symptoms.
Glaucoma: Symbyax might increase your risk of serious vision problems. You're more likely to experience this side effect if you have closed-angle glaucoma (high eye pressure). Before starting Symbyax, your healthcare provider may recommend an eye exam from an eye care professional (optometrist or ophthalmologist). Your eye care professional may provide any necessary preventive services or advice at your eye exam appointment.
History of low white blood cell (WBC) counts: Symbyax might result in low WBC levels. If you have a history of low WBC counts from a medical condition (e.g., HIV) or medication (e.g., clozapine antipsychotic), Symbyax might worsen this side effect. Therefore, your healthcare provider will closely monitor your WBC levels—especially during the first few months of treatment with Symbyax.
Medical conditions with an arrhythmia risk: Symbyax raises your risk of an abnormal heart rhythm, such as an arrhythmia. This risk is higher with certain medical conditions, such as a recent heart attack. If you have these medical conditions, your healthcare provider will closely monitor you for an abnormal heart rhythm.
Seizures: Seizures are possible with Symbyax. If you have a history of seizures, your healthcare provider will closely monitor your seizure condition.
If you accidentally forgot your Symbyax dose, take it as soon as you remember. If it's already close to your next scheduled dose, however, then skip the missed dose and take the following dose at your next scheduled dosing time. Don't double up to make up for the missed dose.
Find ways to help yourself remember to keep your appointments and take your medication. If you miss too many doses, Symbyax might be less effective. Missing too many doses may also result in some of the following discontinuation (withdrawal) side effects:
The symptoms of a suspected overdose of Symbyax include:
If you think that you're experiencing an overdose or life-threatening symptoms, seek immediate medical attention.
If you think you or someone else may have overdosed on Symbyax, call a healthcare provider or the Poison Control Center (800-222-1222).
If someone collapses or isn't breathing after taking Symbyax, call 911 immediately.
It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects.
Do not take this medicine with a monoamine oxidase (MAO) inhibitor (eg, isocarboxazid [Marplan®], linezolid [Zyvox®], methylene blue injection, phenelzine [Nardil®], selegiline [Eldepryl®], tranylcypromine [Parnate®]). Do not start taking this medicine during the 2 weeks after you stop a MAO inhibitor and wait 5 weeks after stopping this medicine before you start taking a MAO inhibitor. If you take them together or do not wait the proper amount of time, you may develop confusion, agitation, restlessness, stomach or intestinal symptoms, a sudden high body temperature, an extremely high blood pressure, or severe seizures.
Do not take thioridazine (Mellaril®) with this medicine, and wait 5 weeks after stopping this medicine before you start taking thioridazine. Do not use pimozide (Orap®) with this medicine. Using these medicines together can cause very serious heart problems.
This medicine may cause a serious condition called serotonin syndrome if taken together with some medicines. Do not use this medicine with buspirone (Buspar®), fentanyl (Abstral®, Duragesic®), lithium (Eskalith®, Lithobid®), tryptophan, St. John's wort, amphetamines, or some pain or migraine medicines (eg, rizatriptan, sumatriptan, tramadol, Frova®, Imitrex®, Maxalt®, Relpax®, Ultram®, Zomig®). Check with your doctor first before taking any other medicines.
For some children, teenagers, and young adults, this medicine can increase thoughts of suicide. Tell your doctor right away if you start to feel more depressed and have thoughts about hurting yourself. Report any unusual thoughts or behaviors that trouble you, especially if they are new or are getting worse quickly. Make sure the doctor knows if you have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. Tell the doctor if you have sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. Let the doctor know if you or anyone in your family has bipolar disorder (manic-depressive) or has tried to commit suicide.
Olanzapine may cause a condition called drug reaction with eosinophilia and systemic symptoms (DRESS). Tell your doctor if you have black, tarry stools, chest pain, chills, cough, fever, painful or difficult urination, sore throat, sores, ulcers, or white spots on the lips or in the mouth, swollen glands, trouble breathing, unusual bleeding or bruising, or unusual tiredness or weakness.
Check with your doctor right away if you have difficulty with breathing, fast heartbeat, high fever, high or low blood pressure, increased sweating, loss of bladder control, seizures, severe muscle stiffness, unusually pale skin, or tiredness. These could be symptoms of a serious condition called neuroleptic malignant syndrome (NMS).
This medicine may increase the amount of sugar in your blood. Check with your doctor right away if you have increased thirst or urination. If you have diabetes, you may notice a change in the results of your urine or blood sugar tests. If you have any questions, check with your doctor.
This medicine may increase your cholesterol and fats in the blood. If this condition occurs, your doctor may give you some medicines that can lower the amount of cholesterol and fats in the blood.
This medicine may increase your weight. Your doctor may need to check your weight regularly during treatment with this medicine.
This medicine may cause tardive dyskinesia (a movement disorder). Check with your doctor right away if you have lip smacking or puckering, puffing of the cheeks, rapid or worm-like movements of tongue, uncontrolled chewing movements, or uncontrolled movements of the arms and legs.
Tell your doctor right away if you develop a rash or hives, swelling of the face, eyes, or mouth, or trouble breathing after taking this medicine.
Dizziness, lightheadedness, or fainting may occur, especially when you get up from a lying or sitting position. Getting up slowly may help. If this problem continues or gets worse, check with your doctor.
This medicine can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
This medicine may increase your risk for bleeding problems. Make sure your doctor knows if you are also taking other medicines that thin the blood, including aspirin, NSAIDs (eg, diclofenac, ibuprofen, naproxen, Advil®, Aleve®, Celebrex®, Voltaren®), or warfarin (Coumadin®, Jantoven®).
Hyponatremia (low sodium in the blood) may occur with this medicine. Check with your doctor right away if you have confusion, difficulty concentrating, headaches, memory problems, weakness, and unsteadiness.
This medicine may make it more difficult for your body to cool itself down. Use care not to become overheated during exercise or hot weather since overheating may result in heat stroke.
Contact your doctor right away if you have dizziness, fainting, or a fast, pounding, or uneven heartbeat. Make sure your doctor knows if you have ever had a heart rhythm problem, including QT prolongation, or if you or a family member has had a heart attack, heart failure, low blood pressure, or a stroke.
This medicine may cause drowsiness, trouble in thinking, trouble in controlling movements, or trouble in seeing clearly, which may lead to falls, fractures or other injuries. Make sure you know how you react to this medicine before you drive, use machines, or do other jobs that require you to be alert, well-coordinated, or able to think or see well.
Do not suddenly stop taking this medicine without first checking with your doctor. If you have been instructed to stop taking this medicine, ask your doctor how to slowly decrease the dose. This is to decrease the chance of having symptoms including agitation, breathing problems, chest pain, confusion, diarrhea, dizziness or lightheadedness, fast heartbeat, headache, increased sweating, muscle pain, nausea, restlessness, runny nose, trouble with sleeping, trembling or shaking, unusual tiredness or weakness, vision changes, or vomiting.
Check with your doctor right away if you have decreased interest in sexual intercourse, delayed or inability to have an orgasm in women, inability to have or keep an erection in men, or loss in sexual ability, desire, drive, or performance. These could be symptoms of sexual dysfunction.
The use of alcohol is not recommended in patients who are using this medicine.
Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.
Before taking Symbyax, talk with your healthcare provider if any of the following applies to you:
In addition to MAOIs, pimozide, and thioridazine, use caution when taking Symbyax with the following:
Talk with your pharmacist or healthcare provider for more detailed information about medication interactions with Symbyax.
And be sure to talk with your healthcare provider about any other medicines you take or plan to take, including over-the-counter, nonprescription products, vitamins, herbs, or plant-based medicines.
Symbyax is the only medication available that contains a combination of an atypical (second generation) antipsychotic and a selective serotonin reuptake inhibitor (SSRI). It's also the only combination medication approved for depressive episodes in bipolar I disorder and treatment-resistant depression.
Symbyax is available with a prescription from your healthcare provider. Your local retail pharmacy may carry this medication. If it doesn't have Symbyax in stock, the pharmacy staff will likely be able to order it for you.
Symbyax is available as generic products, which might help you save on cost.
If cost is a concern, the manufacturer of brand-name Symbyax does have a Foundation Patient Assistance program. For eligibility questions, visit Lilly's website or call 1-800-545-6962.
Other potentially helpful resources include RxAssist, NeedyMeds, FundFinder, Simplefill, BenefitsCheckUp, Medicare Rights Center, State Pharmaceutical Assistance Programs (SPAPs), and Rx Outreach.
The number of medications varies per person. Bipolar, however, typically requires multiple medications to control symptoms. Some people may also require several medications for depression.
Bipolar is a lifelong medical condition. In some people with depression, lifelong treatment is necessary to prevent depression symptoms from coming back.
If you have any questions about your treatment plan, speak with your healthcare provider before making any changes.
If you're experience tardive dyskinesia (TD), don't suddenly stop Symbyax. Abruptly discontinuing Symbyax may worsen symptoms or cause withdrawal side effects.
Instead, reach out right away to your healthcare provider. They will advise you on next steps. If stopping Symbyax is necessary, they will help you slowly and safely stop this medication.
If you're taking Symbyax, chances are your depressive episodes of bipolar or your treatment-resistant depression have been negatively affecting your quality of life. You may have tried different approaches or treatments.
While living with a mental health condition does have its challenges, there are ways to help improve your quality of life. Refer below for some general suggestions to help you manage bipolar and depression.
Verywell Health's drug information is meant for educational purposes only and is not intended as a replacement for medical advice, diagnosis, or treatment from a healthcare provider. Consult your healthcare provider before taking any new medication(s). IBM Watson Micromedex provides some of the drug content, as indicated on the page.
Food and Drug Administration. Symbyax label.
Food and Drug Administration. Zyrexa label.
National Alliance on Mental Illness. Mental health by the numbers.
National Alliance on Mental Illness. Bipolar disorder.
National Alliance on Mental Illness. Depression.
National Kidney Foundation. 10 signs you may have kidney disease.
Roberts JA, Pea F, Lipman J. The clinical relevance of plasma protein binding changes. Clinical Pharmacokinetics. 2013;52:1-8. doi: https://doi.org/10.1007/s40262-012-0018-5
Hirschfeld RMA, Bowden CL, Gitlin MJ, et al. Practice guideline for the treatment of patients with bipolar disorder. American Psychiatric Association. 2010:1-82.
Gelenberg AJ, Freeman MP, Markowitz JC, et al. Practice guidelines for the treatment of patients with major depressive disorder. American Psychiatric Association. 2010:1-52.
National Institute of Mental Health. Bipolar disorder.
By Ross Phan, PharmD, BCACP, BCGP, BCPS Ross is a writer for Verywell with years of experience practicing pharmacy in various settings. She is also a board-certified clinical pharmacist and the founder of Off Script Consults.
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