Seroquel XR is approved to treat depression, but should you take it?

Published: December 2009

Antidepressants can be a lifeline for the 18 million Americans a year who feel overwhelmed by sadness and despair. Yet more than half of the people who take those medications continue to suffer stubborn depressive symptoms.

In such cases doctors can increase the dose, switch to another antidepressant, or recommend psychotherapy. But these days more and more patients instead receive a second drug to boost the partial effects of the first. And to that end doctors are increasingly prescribing powerful medications whose primary domain has been the treatment of psychosis. Several of these antipsychotic medications, including quetiapine (Seroquel), have become particularly popular for use in treating depression.

Known as atypical or second-generation antipsychotics, quetiapine and others in this class are approved by the Food and Drug Administration (FDA) to treat schizophrenia and, in most cases, bipolar disorder. But their off-label use for depression, anxiety, and other non-psychotic disorders has become so widespread that antipsychotic medications are now the top revenue-producing class of drugs in the U.S. Three of them-aripiprazole (Abilify), olanzapine (combined with an antidepressant and sold as Symbyax), and now the extended-release version of quetiapine (Seroquel XR)-recently gained FDA approval for the treatment of depression that hasn't responded to an antidepressant alone. With quetiapine as the most recent addition to the list, is it a good idea to add this drug to your antidepressant treatment regimen?

What is the evidence that it works?

Most of the evidence for the use of quetiapine to treat depression consists of short-term studies. That's why an FDA advisory committee in 2009 voted not to recommend it as a stand-alone treatment for depression, citing concerns about potential long-term risks in a large population, especially when safer drugs are available.

But the committee found enough evidence in two six-week trials to recommend quetiapine for limited use as an add-on drug for "resistant depression." Those studies found that depressed patients who took quetiapine plus an antidepressant had significantly reduced symptoms compared with those who received a placebo plus an antidepressant.

"The majority of experts on the committee acknowledged that it is effective," says Wayne K. Goodman, M.D., chairman of the committee and professor and chairman of the department of psychiatry at the Mount Sinai School of Medicine in New York. "But the overarching issue with this class of drugs is safety. Physicians should be aware of the side effects and try other options first."

What are the risks?

Metabolic problems. Chronic use may cause weight gain and increases in cholesterol, triglycerides, and blood-sugar levels, which are components of metabolic syndrome - a disorder that increases the risk of diabetes, heart disease, and stroke.

Movement disorders. Long-term use may lead to repetitive, uncontrollable movements of the face, tongue, and other parts of the body, and those symptoms (tardive dyskinesia) may be irreversible.

Sudden cardiac death. A large 2009 study, published in The New England Journal of Medicine, suggests that users of some atypical antipsychotics, including quetiapine, may have a greater risk of cardiac arrest than nonusers.

Black-box warning (the most serious kind issued by the FDA). Children, teenagers, and young adults who use quetiapine for depression may have an increased risk of suicidal thinking, and older adults undergoing treatment for dementia may have an increased risk of death.

Other safety concerns. Quetiapine may increase the risk of cataracts, reproductive and sexual problems, speech impairment, and hypothyroidism (underactive thyroid). It may temporarily lower your white blood cell count, increasing the risk for infection.

Common side effects. They include drowsiness, dizziness, dry mouth, constipation, and abdominal pain.

What precautions can you take?

Before starting treatment, you should have a fasting blood-sugar and lipid profile, and your doctor should record your weight. "Establishing that baseline is the standard of practice for using atypical antipsychotics," says Michael E. Thase, M.D., professor of psychiatry at the University of Pennsylvania School of Medicine. You should be monitored regularly for changes during treatment. CU medical advisers also suggest having a blood count and thyroid function test before starting treatment.

  • Call your doctor immediately if you develop diabetic symptoms such as extreme thirst or hunger, frequent urination, blurred vision, or weakness.
  • Discontinue the medication and see a doctor if you experience high fever, sweating, unstable blood pressure, or muscle rigidity, which may signal a rare but potentially fatal reaction.
  • Have your eyes checked for cataracts before and periodically during treatment.
  • Use the drug with caution if you have cardiovascular disease or a history of heart attack or seizures.
  • Don't drive or operate machinery until you know how the medication affects you.
  • Men who experience a prolonged, painful, or unwanted erection should discontinue the drug and contact their physician.
  • Antipsychotic drugs can affect your body's ability to regulate temperature, so use care during vigorous exercise or exposure to extreme heat.
  • Tell your doctor if you are pregnant or planning to become pregnant. Don't breast-feed while taking quetiapine.
  • Tell your doctor what prescription and nonprescription drugs or supplements you take.
  • Avoid long-term use of antipsychotics as add-ons for depression. "I would try to wean patients off in six to 12 months," Goodman says.

What other options can you try?

Most people who need an antidepressant should start with a selective serotonin reuptake inhibitor (SSRI) or another type of "second-generation" antidepressant. If that doesn't provide adequate benefit after four to eight weeks, your doctor will likely increase the dosage or switch you to another SSRI or a different type of antidepressant. Studies suggest that about 30 percent to 40 percent of people don't respond fully to treatment with an initial antidepressant, so it's not uncommon to try three or even four different medicines before finding one that works. Also, some studies have found—and many experts believe—that antidepressants often work best in combination with talk therapy lasting at least several months.

If those measures don't provide relief, adding another drug, such as a second antidepressant, is often the next step.

If depression remains even after those treatments, an atypical antipsychotic may be considered, but we recommend it only as a last resort, given its potential for serious side effects. However, if you have severe symptoms, your physician may suggest it earlier in the process. One thing to note is that many people who begin taking these types of medications stop using them because of the unpleasant or bothersome side effects. If you reach the point of considering Seroquel XR or any other atypical antipsychotic to treat your depression, Consumer Reports medical advisers suggest that you consult with a psychiatrist to help manage these medications.

Bottom line. Quetiapine and other atypical antipsychotics may complement the effects of antidepressants, but they're expensive and can cause significant side effects that require careful monitoring. Our advice: Talk with your doctor about all available treatments for your depression. If first-line medications aren't effective or you can't tolerate them, consider quetiapine only after its risks and benefits have been thoroughly explained to you.

Editor's Note:

These materials were made possible by a grant from the state Attorney General Consumer and Prescriber Education Grant Program, which is funded by a multistate settlement of consumer fraud claims regarding the marketing of the prescription drug Neurontin (gabapentin). 

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