Symbyax Medication for Bipolar Disorder

Uses, Side Effects, and Research

Doctor Writing a Prescription

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What is the most important information I should know about Symbyax?


You should not take Symbyax if:

  • you have taken an MAOI within the previous 14 days; or
  • you are taking pimozide or thioridazine.

Symbyax is a combination of olanzapine, the active ingredient in Zyprexa, and fluoxetine, the active ingredient in Prozac. It was the first FDA-approved medication for the depressive episodes that occur in bipolar disorder or bipolar depression.

Uses for Symbyax

Symbyax may be prescribed to treat the depressive phase of bipolar disorder. However, Symbyax has not gained much traction and has largely fallen out of favor with psychiatrists since there is no way to titrate the individual ingredients separately.

Instead, t is now much more common to use a combination of Lamictal (lamotrigine) with lithium if lamotrigine alone is not effective. If there is a need for further treatment, the addition of a second-generation medication, such as Vraylar, Latuda, or Rexulti, is often used.

Virtually all patients with this disorder experience the depressive phase, commonly referred to as bipolar depression. People with bipolar disorder typically have three times as many depressed days as they do manic days throughout their illness.

Symbyax has also been FDA-approved for treatment-resistant depression.

Common Side Effects of Symbyax

Common side effects that may go away with time include:

  • Appetite increase
  • Weight gain
  • Dry mouth
  • Diarrhea
  • Losing or not having strength
  • Sexual difficulties, including decreased interest or inability to orgasm
  • Erectile dysfunction
  • Twitching
  • Joint swelling, redness or pain

If any of these side effects don't go away or cause problems, be sure to tell your doctor.

Potentially Serious Side Effects

If you have any of the following side effects, it's important to contact your doctor right away as you may need medical treatment. These potentially serious side effects include:

  • Congestion
  • Runny nose
  • Cough
  • Tingling in your hands or feet
  • Dementia
  • Delusions
  • Body aches or pain
  • Gaining weight suddenly
  • Difficulty swallowing
  • Swelling in your arms, legs, hands, feet, or face
  • Difficulty breathing or speaking
  • Memory problems
  • Chest tightness
  • Vision changes
  • Irregular heartbeat
  • Dizziness

Research on Symbyax

According to a study done around the time the FDA approved Symbyax, Symbyax helped to treat the symptoms of bipolar depression more effectively and at a significantly faster rate than a placebo. In the eight-week studies, patients in the Symbyax group experienced significantly greater improvement in depressive symptoms than patients taking a placebo.

That robust symptom improvement was sustained throughout the entire eight weeks of the study. In addition, Symbyax patients had no statistically greater risk of treatment-emergent mania than patients taking a placebo.

A more recent study that looked at a series of other studies regarding Symbyax also showed its continued effectiveness in treating and keeping the depressive episodes of bipolar disorder at bay.

The only concern was that the side effects may be worse when using Symbyax than they are with other medications, particularly weight gain.

Warning and Precautions About Symbyax

Symbyax carries a black-box warning for an increased risk of suicidal thinking and behavior in children, teens, and young adults. Young people should be monitored to watch for increased symptoms of depression and suicidality, particularly during the onset of treatment.

If you are having suicidal thoughts, contact the National Suicide Prevention Lifeline at 988 for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.

For more mental health resources, see our National Helpline Database.

This medication also has a black-box warning of an increased risk of mortality in elderly patients with dementia-related psychosis. Symbyax is not approved for use in this population.

Other conditions that may occur after taking this condition include:

  • Neuroleptic malignant syndrome
  • Hyperglycemia
  • Hyperlipidemia
  • Serotonin syndrome
  • Tardive dyskinesia
  • Orthostatic hypertension
  • Seizures
  • Abnormal bleeding
  • Hypotaneremia

To minimize some of these risks, monitoring of fasting blood glucose and lipid profiles is recommended at the initiation and periodically throughout treatment.

If you are considering starting Symbyax, discuss your medical history with your healthcare provider. Be sure to tell your doctor if any of the following apply:

  • You are taking Prozac (fluoxetine) or Zyprexa (olanzapine)
  • You are taking or plan to take nonsteroidal anti-inflammatory drugs or aspirin
  • You are pregnant or plan to become pregnant
  • You are breastfeeding or plan to breastfeed
  • You are older than 65 and have dementia
  • You have high blood sugar, diabetes or a family history of diabetes
  • You have liver problems
  • You have seizures
  • You have high or low blood pressure
  • You have heart problems
  • You have had a stroke
  • You have an enlarged prostate
  • You have an eye problem called narrow-angle glaucoma
  • You have a stomach problem called paralytic ileus
  • You currently smoke
  • You drink alcohol
  • You exercise often

Always tell your doctor about any medications, supplements, or substances you are currently taking to avoid potentially dangerous drug interactions. This includes other medications that may increase serotonin levels, which can lead to a dangerous condition called serotonin syndrome.

4 Sources
Verywell Mind 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.
  1. U.S. Food and Drug Administration. Highlights of prescribing information: Symbyax.

  2. Kupka RW, Altshuler LL, Nolen WA, et al. Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorderBipolar Disord. 2007;9(5):531–535. doi:10.1111/j.1399-5618.2007.00467.x

  3. Brunner E, Tohen M, Osuntokun O, Landry J, Thase ME. Efficacy and safety of olanzapine/fluoxetine combination vs fluoxetine monotherapy following successful combination therapy of treatment-resistant major depressive disorderNeuropsychopharmacology. 2014;39(11):2549–2559. doi:10.1038/npp.2014.101

  4. Silva MT, Zimmermann IR, Galvao TF, Pereira MG. Olanzapine plus fluoxetine for bipolar disorder: a systematic review and meta-analysis. J Affect Disord. 2013;146(3):310–318. doi:10.1016/j.jad.2012.11.001

Additional Reading
  • Silva, M.T., Zimmermann, I.R., et. al. "Olanzapine plus fluoxetine for bipolar disorder: A systematic review and meta-analysis." Journal of Affective Disorders 146 (3), 2013.

By Marcia Purse
Marcia Purse is a mental health writer and bipolar disorder advocate who brings strong research skills and personal experiences to her writing.