Symbyax Medication for Bipolar Disorder

Uses, Side Effects, and Research

Doctor Writing a Prescription

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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.


Symbyax may be prescribed for the treatment of the depressive phase of bipolar disorder. However, Symbyax has not gained much traction and has and has largely fallen out of favor with psychiatrists since there is no way to titrate separately the individual ingredients. It is now much more common to use a combination of lamotrigine (Lamictal) 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 or Latuda or Rexulti, is often used instead.

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 than they do manic days over the course of their illness.

Symbyax can also now be prescribed for treatment-resistant depression.

Common Side Effects

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


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

Discuss Your Medical History With Your Doctor

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 currently taking any medications
  • 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
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. FDA. 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.