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Symbyax is a drug that combines the antidepressant Prozac and antipsychotic Zyprexa. The drug is used to treat bipolar depression, but it has been linked to severe side effects, including birth defects when taken during pregnancy.

Symbyax (fluoxetine/olanzapine) is a drug that combines an SSRI antidepressant (selective serotonin reuptake inhibitor) called fluoxetine (Prozac) with an atypical antipsychotic called olanzapine (Zyprexa). The U.S. Food and Drug Administration (FDA) originally approved the drug manufactured by Eli Lilly for the treatment of bipolar depression in 2003, and in 2009 it was approved for depression that is resistant to other drugs. Specifically, Symbyax can be used in adults with depression who have tried two other drugs to control depression unsuccessfully. Prior to approving Symbyax for treating resistant depression in 2009, the FDA denied Eli Lilly's application twice. Critics of antipsychotics say that doctors prescribe them for unapproved uses and that these drugs should only be used in critically ill patients with schizophrenia. Up until the drug became available in generic form in 2012, it made more than $80 million in annual sales for Eli Lilly in the U.S. alone. Lilly also manufactured the billion-dollar blockbuster drugs Zyprexa and Prozac (fluoxetine). Despite the drug's success, it is not without risks. In fact, Symbyax has a long list of side effects, including a low risk of fatal birth defects when taken by pregnant women. Because it is a combination drug, it carries the potential for side effects arising from antipsychotic drugs as well as SSRI antidepressants.

What is Symbyax?

While researchers are not exactly sure how Symbyax works, makers of the drug say that it works by altering the levels of three chemicals in the brain that lessen feelings of depression: serotonin, norepinephrine and dopamine. According to Eli Lilly, animals that were given the drug in studies had an increase in all three of these chemicals. The two medicines in Symbyax are delivered in a pill with different dosages of each medicine depending on the patient's needs. If you are a female, are older and are a nonsmoker, this medicine may take longer to work or take longer to leave the body. The drug is mostly metabolized in the liver. Adults take one dose once a day in the evening, and it can be taken with or without food. Eli Lilly did not test the safety of using the drug for longer than 8 weeks before putting it on the market. However, most people with bipolar depression or treatment-resistant depression have a chronic illness and may have to take Symbyax for the rest of their lives.

Use in Children and Black-Box Warning

Symbyax has a black box warning – the FDA's most severe warning – for suicidal thoughts and behaviors in children, adolescents and young adults 24 or younger. The drug is made for use in both adults and children 10-17 years of age, but the dose for children is lower than the dose recommended for adults and has only been tested for effectiveness and safety in controlling bipolar depression. The use of Symbyax in children younger than 18 for depression was not tested. Children tend to suffer more side effects than adults, especially when it comes to weight gain, fatigue and an increase in cholesterol and triglyceride levels. For this reason, the risks and benefits of using the drug in children should be carefully considered. In animal studies, Symbyax was toxic to muscle tissue, reproductive organs and bones in young animals. These risks exist for human children as well, and there have been some reports of these side effects.

Use in Elderly Adults and Black-Box Warning

There have not been enough clinical trials involving people 65 or older to determine whether Symbyax works the same in them as in younger patients. There is a black-box warning on the medication for older adults with dementia because Symbyax almost doubles the risk of death in these patients. Researchers also found an increase in stroke and mini strokes in dementia patients who took Symbyax. Older patients are also at risk for hyponatremia – a condition where there is too little salt in the blood. When this happens, patients can suffer from symptoms, including:
  • Confusion
  • Convulsions
  • Fatigue
  • Muscle weakness
  • Vomiting
  • Nausea

Symbyax Birth Defects

Since Symbyax combines two drugs, there is a longer list of potential side effects and drug interactions. Some of the side effects are severe and can be life threatening. Because Symbyax contains an SSRI antidepressant called fluoxetine, known by the brand-name Prozac, the drug carries a low risk of birth defects when taken by a pregnant woman. Other SSRIs like Zoloft and Paxil also have been linked to severe birth defects, including: Symbyax has not been specifically tested in pregnant women, although doctors are allowed to prescribe it to them. It carries a pregnancy safety warning of “C,” which means adverse events have been reported in animal studies, but it has not been tested on human babies. The antipsychotic in Symbyax, olanzapine, also carries risks for unborn babies. Children born to mothers who used Symbyax while pregnant may have symptoms of withdrawal, including:
  • Agitation
  • Respiratory distress
  • Feeding disorders
The severity of these symptoms varies, and some babies may need intensive care and prolonged hospitalization.

Other Side Effects of Symbyax

Symbyax may also cause a number of serious side effects, including high blood pressure, pneumonia, seizures and bleeding. Less serious complications can include weight gain.

Neuroleptic Malignant Syndrome (NMS)

This is a side effect of antipsychotics like olanzapine and can be fatal. The symptoms of this syndrome include:
  • Irregular pulse
  • Altered mental state
  • Muscle tightness and rigidity
  • Irregular blood pressure

High Blood Sugar (Hyperglycemia)

Symbyax may cause high blood sugar in adults and children, which may lead to type 2 diabetes. Some patients even had to continue treatment for high blood sugar after discontinuing Symbyax. The drug is also risky for people who have type 2 diabetes. There were some severe cases reported that led to coma or death.

High Cholesterol and Triglycerides (Hyperlipidemia)

Triglycerides are a type of fat found in your blood, and normal limits are less than 150 milligrams per deciliter. In studies, researchers found Symbyax increased triglyceride levels to as much as 500 milligrams per deciliter. It is also known to increase cholesterol. High triglycerides and cholesterol increase the risk for heart attack and stroke.

Serotonin Syndrome

Serotonin syndrome is a potentially fatal condition that occurs when the body makes too much serotonin. Because Symbyax works by increasing serotonin, there is a chance that the body may have too much. Taking Symbyax with other medicines that increase serotonin increases this risk. For this reason, all medications must be discussed with your doctor.
Symptoms of serotonin syndrome include:
Restlessness or agitation Irregular heartbeat
High blood pressure Nausea
Vomiting Overactive reflexes

Tardive Dyskinesia

Tardive dyskinesia is a disease that causes involuntary muscle movements similar to Parkinson's disease. It is known to be a side effect of antipsychotic drugs. In some cases, it is irreversible.

Symbyax Lawsuits

Pregnant women who take this drug may have children born with birth defects. In fact, a number of lawsuits were already filed by the families of children born with SSRI-related birth defects. Some families may wish to file Symbyax lawsuits. Some of the devastating defects included in these lawsuits are: PPHN, spina bifida, anencephaly (missing part of the brain or skull) club foot and cleft palate. The families of these children say drugmakers failed to adequately warn of these risks.