National Research Center
for Women & Families

For patients who suffer from depression or anxiety, it's hard to know which medication is best. It seems everyday a new "wonder drug" is introduced, often costing 10 or 20 times as much as older medications. Things become even more confusing when doctors prescribe medications "off label," which means that the FDA has approved the drug as safe and effective for a specific use, but the doctor is prescribing it for another use which is not FDA approved.

Seroquel is such a drug. Manufactured by AstraZeneca and approved by the FDA to treat psychotic conditions such as schizophrenia and psychosis (such as hallucinations) that are sometimes associated with bipolar disorder (manic depression), Seroquel is the company's second biggest moneymaker, with sales over $3 billion dollars in 2006. There aren't that many schizophrenics or people with bipolar illness with psychosis to support such widespread use. Most prescriptions for the drug are "off label"-- for anxiety and depression. Despite its huge sales, Seroquel often causes rapid weight gain, and may also have serious adverse effects such as diabetes, hyperglycemia, pancreatitis, and sudden death.

The FDA is considering whether to approve Seroquel for depression and anxiety, and their major question is: do the benefits outweigh the risks? In her testimony at the FDA's public meeting on this topic on April 8, 2009, NRC president Dr. Diana Zuckerman concluded that the risks are too great, saying "These side effects are considered acceptable for schizophrenia treatment but should not be considered acceptable for depression or anxiety, since there are other, safer alternatives."

This is especially true since Seroquel's effectiveness is very modest. The benefits are statistically significant in several studies conducted by AstraZeneca (but not all of them). In fact, the patients on placebo ("sugar pills" that look just like medication) are improving greatly in these studies - almost as much as those taking Seroquel. Most of the improvement for patients is apparently due to the placebo effect: when depressed or anxious patients take a new pill, they tend to get better, even if the pill has no active ingredients that work. The drug itself appears to add little benefit. The difference between depression scores for patients taking Seroquel is just slightly better than the scores for the patients taking the placebo. These differences are sometimes statistically significant, but that doesn't mean they are meaningful improvements to the patients. In fact, Seroquel doesn't have any ingredients that are targeted to reduce depression or anxiety. Instead, patients taking Seroquel tend to feel "knocked out" - they tend to fall asleep. That may improve their scores on an anxiety scale or depression scale (since anxious and depressed people often have trouble sleeping) but it doesn't mean the patient actually feels less anxious or depressed.

The bad news is that in addition to those modest benefits there are numerous side effects. The Seroquel patients are significantly more likely to drop out of the study because of side effects (such as drowsiness or weight gain) than the placebo patients. Since the studies that AstraZeneca used to prove the safety and effectiveness of Seroquel for depression and anxiety are short-term (6-8 weeks), they cannot realistically measure long-term adverse effects. Patients who take drugs for depression don't usually stop after 6 weeks or 8 weeks. Many will take drugs for many months or many years. In addition to diabetes and the above-mentioned risks, patients who take Seroquel are at risk of developing tardive dyskinesia, a condition that causes uncontrolled movements, such as grimacing, tongue protrusion, and lip smacking. There is a lack of effective treatments for these symptoms and stopping the drug after the problems have started usually doesn't work. The nonprofit organization that educates people about movement disorders such as tardive dyskinesia, is clear about the importance of avoiding drugs that can cause this disorder; they say: "every effort should be made to limit the use of these drugs to those patients for whom no other treatment options are available." Drugs that can cause tardive dyskinesia should therefore never be given to anyone with depression or anxiety unless every other, safer drug has already been tried and failed.

Again, Seroquel is being widely prescribed for patients who could be treated at least as effectively with safer, less expensive medications. Consumers need to be their own advocates because even if a prescription drug label warns to try other medications first, many doctors tend to overlook that warning, especially when drug companies spend billions of dollars for advertisements, speeches, medical articles, and personal meetings to "educate" doctors about how effective the drug is.

The most alarming reason AstraZeneca should prohibit the use of Seroquel off label is the danger of sudden death. Although relatively rare, this risk is unacceptable for a drug used to treat depression or anxiety, since safer alternatives are available. At the FDA's April 2009 public meeting on Seroquel, family members testified about how their loved ones, veterans of the Iraq war, had died after being prescribed Seroquel from the VA for post traumatic stress disorder (PTSD). Commented Harold S. White, who lost his son under questionable circumstances: "In my research, I have found at least 51 military men have died in their sleep in the past six years, 35 in the last three years." He added that it "was always the same story," with perfectly healthy people dying suddenly after taking the drug. Cassandra Harper testified that "the doctors and nurses (at Walter Reed) should be given more information on the drugs they prescribe and possible side effects/interactions."

All medications for schizophrenia have serious side effects, but the disease is so devastating that those side effects may be acceptable. However, that is not true for the treatment of depression, anxiety, or insomnia, for adults or children. The National Research Center for Women & Families believes that it is not appropriate to prescribe Seroquel for anxiety, depression, or insomnia, unless the company can conclusively prove that the drug does not increase the risk of diabetes, tardive dyskensia, or sudden cardiac death. Since the company has clearly shown its unwillingness to do that research, it is the job of the FDA to demand it, keeping Seroquel off the market for those expanded uses unless conclusive research indicates that Seroquel is as safe as alternative treatments. And, it is the responsibility of physicians to not prescribe Seroquel when safer alternatives exist, which seems to be true for all uses except possibly schizophrenia and psychosis.