Symbyax (Olanzapine and Fluoxetine) - Oral

Warning:

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.

What Is Symbyax?

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.

Drug Facts

Generic Name: Olanzapine and fluoxetine

Brand Name(s): Symbyax

Drug Availability: Prescription

Therapeutic Classification: Atypical (second-generation) antipsychotic and selective serotonin reuptake inhibitor (SSRI)

Available Generically: Yes

Controlled Substance: No

Administration Route: Oral (by mouth)

Active Ingredient: Olanzapine and fluoxetine

Dosage Form(s): Capsule

What Is Symbyax Used For?

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.

How to Take Symbyax

Take Symbyax by mouth in the evening with or without food.

Storage

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.

How Long Does Symbyax Take to Work?

You might notice an improvement in your symptoms at eight weeks of treatment with Symbyax.

Off-Label Uses

Symbyax doesn't currently have any off-label uses.

What Are the Side Effects of Symbyax?

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

Common side effects of Symbyax in adults may include:

  • Attention (concentration) difficulties
  • Drowsiness or sleepiness
  • Dry mouth
  • Edema (swelling from fluid buildup)
  • Increased appetite
  • Tiredness or low energy
  • Tremors
  • Vision changes
  • Weight gain

Children and teenagers tend to experience the following common side effects with Symbyax:

Severe Side Effects

Get medical help right away if you develop the following serious side effects:

  • Abnormal bleeding
  • Abnormal heart rhythm
  • Abnormal white blood cell (WBC) amounts
  • Eye pain
  • Seizures
  • Redness in or around your eye
  • Suicidal thoughts and behavior
  • Swallowing difficulties
  • Swelling in or around your eye
  • Vision changes

Other severe side effects with Symbyax may also include:

  • Body temperature dysregulation: You might have trouble controlling your body temperatures. As a result, you're more likely to overheat and become dehydrated.
  • Cognitive and movement impairment: Symbyax is linked to some cognitive impairment. You might experience memory, concentration, and decision-making difficulties. Symbyax might also cause some muscle movement impairment. Be careful when driving or handling heavy machinery until you know how Symbyax will affect you.
  • Drug reaction with eosinophilia and systemic symptoms (DRESS): DRESS is a severe drug allergy linked to an increase in eosinophils (a type of white blood cell). Symptoms may include fever, rash, kidney injury, and liver injury. Be on the lookout for blood in foamy urine, dark-colored urine, and yellowing of the eyes or skin.
  • Dysphagia: Symbyax is linked to dysphagia, which is a problem with swallowing. Dysphagia might raise your risk of breathing contents (e.g., food) from your digestive system into your lungs. This is called aspiration pneumonia.
  • Hyperprolactinemia: Symbyax might raise your prolactin hormone levels. High prolactin levels may result in symptoms of enlarged breasts, absence of menstrual periods, or milky discharge from nipples. Some people may also experience erection or orgasm problems.
  • Hyponatremia: Symbyax is linked to hyponatremia, a condition of low sodium levels in your blood. Symptoms may include confusion, difficulty concentrating (focus), and memory problems. You might also feel weak or unsteady.
  • Low postural (positional) blood pressure: You might suddenly experience low blood pressure when you quickly get up from lying or sitting down. Take your time when you get up, to prevent dizziness and fainting spells.
  • Mania: If you have bipolar, starting Symbyax might switch you to mania. Mania symptoms begin with an elevated mood and improved productivity, but mania can quickly change into an irritable mood, impulsive decisions, and psychosis.
  • Metabolic changes: Symbyax might result in metabolic changes, which include high blood sugar, high cholesterol, and weight gain.
  • Neuroleptic malignant syndrome (NMS): Antipsychotics—like olanzapine in Symbyax—are linked to a serious but rare side effect called NMS. Symptoms of NMS may include confusion, excessive sweating, high fever, and stiff (rigid) muscles. You might also experience blood pressure changes.
  • Serotonin syndrome is a rare but life-threatening condition when your serotonin levels are too high. Symptoms may include seizures, sweating, and tremors.
  • Severe allergic reaction: If you have a severe allergic reaction to Symbyax, symptoms may include itchiness, rash, swelling, and breathing difficulties.
  • Sexual-related side effects: The fluoxetine component in Symbyax is linked to sexual-related side effects, which may include low libido (sex drive), erectile dysfunction (ED), and ejaculation or orgasm problems.
  • Tardive dyskinesia (TD): People with TD typically experience uncontrollable muscle movements of the face and tongue.

Call 911 if your symptoms feel life-threatening.

Long-Term Side Effects

Possible long-term side effects with Symbyax may include:

  • Abnormal bleeding: Long-term use of the fluoxetine component in Symbyax may increase your risk of bleeding. Combining it with blood thinners will likely enhance this side effect.
  • Cerebrovascular effects: Symbyax is linked to cerebrovascular effects in adults over 65 years of age with dementia-related psychosis. Cerebrovascular effects may include stroke or transient ischemic attack (TIA).
  • Hyperprolactinemia: High prolactin hormone levels may result in low bone density over time. With Symybyax's other side effects of drowsiness, sleepiness, low blood pressure, and muscle movement impairment, you're also more likely to fall. Your low bone density and risk of falls will increase your likelihood of bone fractures (breaks).
  • Metabolic changes: Symbyax raises your long-term risk of metabolic changes, which include high blood sugar, high cholesterol, and weight gain.
  • Tardive dyskinesia (TD): TD is a side effect of uncontrollable muscle movements from long-term antipsychotic use. TD typically affects the muscles in the face and tongue. In some people, TD might be irreversible.

Report Side Effects

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).

Dosage: How Much Symbyax Should I Take?

Drug Content Provided and Reviewed by IBM Micromedex®

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.

  • For oral dosage form (capsules):
    • For treatment of bipolar I depression:
      • Adults—At first, 1 capsule containing 6 milligrams (mg) of olanzapine and 25 mg of fluoxetine once a day in the evening. Your doctor may adjust your dose as needed. However the dose is usually not more than 18 mg of olanzapine and 75 mg of fluoxetine per day.
      • Children 10 to 17 years of age—At first, 1 capsule containing 3 milligrams (mg) of olanzapine and 25 mg of fluoxetine once a day in the evening. Your doctor may adjust your dose as needed. However the dose is usually not more than 12 mg of olanzapine and 50 mg of fluoxetine per day.
      • Children younger than 10 years of age—Use and dose must be determined by your doctor.
    • For treatment resistant depression:
      • Adults—At first, 1 capsule containing 6 milligrams (mg) of olanzapine and 25 mg of fluoxetine once a day in the evening. Your doctor may adjust your dose as needed. However the dose is usually not more than 18 mg of olanzapine and 75 mg of fluoxetine per day.
      • Children—Use and dose must be determined by your doctor.

Modifications

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.

Missed Dose

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:

Overdose: What Happens If I Take Too Much Symbyax?

The symptoms of a suspected overdose of Symbyax include:

  • Abnormal heart rhythm
  • Aggression
  • Agitation
  • Blood pressure changes
  • Coma
  • Confusion
  • Drowsiness or sleepiness
  • Low energy
  • Psychosis
  • Seizures
  • Speech problems
  • Tremors
  • Unsteady balance or movement

If you think that you're experiencing an overdose or life-threatening symptoms, seek immediate medical attention.

What Happens If I Overdose on Symbyax?

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.

Precautions

Drug Content Provided and Reviewed by IBM Micromedex®

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.

What Are Reasons I Shouldn’t Take Symbyax?

Before taking Symbyax, talk with your healthcare provider if any of the following applies to you:

  • Severe allergic reaction: If you have a severe allergic reaction to Symbyax, this medication isn't a viable option for you.
  • Pregnancy: Your newborn may experience side effects if exposed to Symbyax during late pregnancy (e.g., third trimester). Some newborns will quickly recover, but others might require more time. There are still conflicting data about the effects of olanzapine and fluoxetine on the unborn fetus. While there's a chance that your newborn might have side effects from Symbyax, there are certain risks with untreated mental health conditions too. Discuss with your healthcare provider the benefits and risks of Symbyax during pregnancy.
  • Breastfeeding: Symbyax will likely be present in human breast milk—with higher levels of fluoxetine than olanzapine. As a result, more fluoxetine will likely end up in the nursing infant's bloodstream compared to olanzapine. Nursing babies will likely experience the following side effects with Symbyax: colic (hours of crying), drowsiness, fussiness, sleepiness, or weight loss. You may also have trouble with breastfeeding. Reach out to your healthcare provider for breastfeeding support or a discussion about the benefits and harms of Symbyax while nursing.
  • Children: The Food and Drug Administration approved Symbyax to treat depressive episodes of bipolar I disorder in children 10 years and older. Children and teenagers tend to experience greater changes in cholesterol, liver-related labs, and prolactin hormone levels than adults.
  • Older adults over 65 years of age: There are likely no differences in responses to Symbyax between older and younger adults, but older adults might be more sensitive to fluoxetine's side effects, such as low sodium blood levels. Olanzapine, however, might also result in stroke, transient ischemic attacks (TIAs), and other side effects when used in older adults with dementia-related psychosis.
  • Monoamine oxidase inhibitors (MAOI) use: Avoid taking Symbyax with MAOIs, such as the linezolid antibiotic (Zyvox) or selegiline (brand names Zelapar and Eldepryl) for Parkinson's disease (PD). It's recommended that you don't start Symbyax until 14 days after you stop an MAOI. If you're switching from Symbyax to an MAOI, on the other hand, you'll need to wait a minimum of five weeks before taking an MAOI. Combining MAOIs and Smbyax dangerously raises serotonin levels, increasing your serotonin syndrome risk. Serotonin syndrome is a rare but life-threatening side effect of Symbyax. Side effects may include seizures, sweating, and tremors.
  • Pimozide use: Orap (pimozide) can be used to treat Tourette's. Avoid taking pimozide and Symbyax together. Both medications have the side effect of abnormal heart rhythm. Additionally, Symbyax can prevent the CYP2D6 liver protein from breaking down pimozide, leading to high pimozide levels and more side effects. Therefore, combining them can dangerously worsen abnormal heart rhythm problems.
  • Thioridazine: Mellaril (thioridazine) is a medication option for schizophrenia. Taking thioridazine and Symbyax together isn't recommended. Like pimozide, thioridazine also has the side effect of abnormal heart rhythm. Symbyax also blocks the CYP2D6 protein from breaking down thioridazine. Therefore, you're more likely to have a buildup of thioridazine and more side effects, such as serious, abnormal heart rhythm problems.

What Other Medications Interact With Symbyax?

In addition to MAOIs, pimozide, and thioridazine, use caution when taking Symbyax with the following:

  • Alcohol can worsen drowsiness, sleepiness, and low blood pressure.
  • Anticholinergics are medications that block a naturally occurring chemical in the body called acetylcholine. This can result in several side effects, such as constipation and urination difficulties. The olanzapine component of Symbyax might cause this. So taking it with other anticholinergics (e.g., Benadryl (diphenhydramine) for allergies) may worsen these side effects.
  • Antihypertensives are used to treat high blood pressure. These medications may have additive blood pressure-lowering effects with Symbyax. Examples of antihypertensives include lisinopril and hydrochlorothiazide, combined in the brand-name drug Zestoretic.
  • Benzodiazepines: Similar to alcohol, benzodiazepines (e.g., Valium (diazepam)) may also worsen drowsiness, sleepiness, and low blood pressure.
  • Carbamazepine is an anti-seizure medication (one brand name is Tegretol). When taken with Symbyax, high carbamazepine levels might result in toxicity.
  • Clozapine (one brand name is Clozaril): is an antipsychotic medication. When combined with Symbyax, you might have a buildup of clozapine in the body and more side effects.
  • Diuretics are water pills. You may have seen diuretics being used to treat high blood pressure. Combining diuretics with Symbyax, however, may increase your risk of low sodium blood levels.
  • Fluoxetine: Since Symbyax already contains fluoxetine, don't take other medications that have fluoxetine.
  • Luvox (fluvoxamine): Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that can be used for obsessive-compulsive disorder (OCD). Combined with Symbyax, it can raise olanzapine levels and increase the likelihood of side effects. Your healthcare provider will likely choose a lower dose of the olanzapine component in Symbyax.
  • Haldol (haloperidol) is an antipsychotic medication. Similar to clozapine, an increase in haloperidol levels and its effects may happen when combined with Symbyax.
  • Levodopa and dopamine agonists: Levodopa and dopamine agonists (like Mirapex (pramipexole)) are typically used in Parkinson's disease (PD). Symbyax might work against the effects of these medications.
  • Medications broken down by CYP2D6: The fluoxetine component in Symbyax is a strong inhibitor of the CYP2D6 protein in the liver. So, fluoxetine prevents CYP2D6 from working to break down certain medications, such as the perphenazine antipsychotic used for nausea. As a result, there will be a buildup of these medications and a higher likelihood of side effects.
  • Medications that bind to proteins in the blood: The fluoxetine component in Symbyax tightly binds to proteins in the blood. Certain drugs—like digoxin for heart failure symptoms (one brand name is Lanoxin)—also tightly bind to these proteins. So, fluoxetine and these other medications might compete for the same binding spots. When medications bind to these proteins, they're inactive (not working). The competition might result in certain medications being less protein-bound and more active, which increases the chance of side effects.
  • Medications that raise serotonin levels: Symbyax can boost your serotonin levels. Taking other medicines that can also do this will raise your serotonin levels and increase your risk of serotonin syndrome. An example of a serotonin-raising medication is St. John's wort, which is available over-the-counter (OTC) for depression.
  • Medications that thin the blood: Long-term, fluoxetine may slightly thin out your blood. As a result, be careful with other blood thinners, such as warfarin (brand names Coumadin and Jantoven) and aspirin.
  • Medications with a side effect of abnormal heart rhythm: Symbyax has the potential side effect of abnormal heart rhythm. Taking medications that cause abnormal heart rhythm may worsen this side effect. An example of a medication with this side effect includes the erythromycin antibiotic.
  • Olanzapine: Since Symbyax already contains olanzapine, don't take other medications containing olanzapine.
  • Dilantin (phenytoin): Phenytoin is an anti-seizure medication. When combined with Symbyax, you might experience increased phenytoin levels and toxicity.
  • Tricyclic antidepressants (TCAs): Symbyax may affect TCA levels. Therefore, your healthcare provider may need to monitor your TCA levels and adjust the TCA dose accordingly. Amitriptyline is a common TCA.

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.

What Medications Are Similar?

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.

Frequently Asked Questions

  • Where is Symbyax available?

    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.

  • How much does Symbyax cost?

    Symbyax is available as a generic product, which might help you save on cost.

    If cost is a concern, ask your healthcare provider about financial assistance programs that may be available to you.

  • Will I need to take other medications in addition to Symbyax?

    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.

  • How long do I have to take Symbyax?

    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 I'm having tardive dyskinesia, what do I do?

    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.

How Can I Stay Healthy While Taking Symbyax?

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.

  • Take mood-related medications as recommended by your healthcare provider.
  • Share your condition with loved ones when you're ready. Having strong social support is essential.
  • Consider keeping a diary to record your moods and become more aware of your triggers.
  • Have a healthy diet.
  • Regularly exercise.
  • Find ways to manage stress.
  • Make sure that you get enough sleep.
  • Consider support groups or mental health professionals to help you find coping strategies that change how you think, feel, react, or respond to living with bipolar or depression.

Medical Disclaimer

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.

17 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  8. National Kidney Foundation. 10 signs you may have kidney disease.

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  10. LactMed. Fluoxetine.

  11. MedlinePlus. Pimozide.

  12. ScienceDirect. CYP2D6.

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  14. 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

  15. Hirschfeld RMA, Bowden CL, Gitlin MJ, et al. Practice guideline for the treatment of patients with bipolar disorder. American Psychiatric Association. 2010:1-82.

  16. 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.

  17. 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.