About a year ago, patients began trooping into the office of UCLA psychiatrist Andrew Leuchter, asking whether an antipsychotic drug called Abilify "might be right for them." Few appeared to be delusional, plagued by hallucinations or suffering fearsome mood swings. Mostly, they were depressed or anxious, and frustrated by the pace of their recovery.
Leuchter wondered what was up: Depressed patients didn't usually seek out drugs used to quell psychiatry's most disturbing symptoms.
What was up, he soon discovered, was spending on a new advertising campaign touting Abilify as an "add-on" treatment for depression. For the first time since the arrival of a new generation of antipsychotic medications -- six drugs called the "atypicals" because they work differently from the earlier generation of antipsychotic drugs -- the makers of one, Abilify, had been granted the legal right to market to a vast new population of patients beyond those with schizophrenia or bipolar disorder.
This week, a Food and Drug Administration advisory panel recommended that the agency should grant the makers of a second atypical antipsychotic drug -- Seroquel XR -- similar latitude. The drug giant AstraZeneca wants permission to market the drug as a treatment for depression or anxiety that has not yielded to antidepressants alone.
But this time, it wasn't quite so easy a sell. The panel did say the drug was safe and effective for such purposes when used with other drugs, recommending approval for its use as an "add-on" treatment. But the panel recommended against the drug as a stand-alone treatment. And this time, the panel -- echoing an issue expressed by the FDA in convening the meeting -- cited safety concerns about the drugs' use in a greatly expanded population of patients.
Mounting research has made clear that the atypical antipsychotics are not only less safe than originally thought; they are not, on balance, any safer or more effective than older drugs for schizophrenia. And for the population of depressed or anxious patients that some are now proposed to treat, studies suggest the benefits are extremely modest.
The accumulated findings on the larger group of drugs had prompted the FDA to ask its advisory panel whether expanding the population of patients taking Seroquel XR would be wise. Like other members of this class of drugs, Seroquel has been linked to weight gain extreme enough to cause diabetes and to an often irreversible disorder characterized by involuntary tics and jerking movements.
As for Abilify, Sonia Choi, a Bristol-Myers Squibb spokeswoman, said the company "is continually monitoring the safety of Abilify, including the metabolic data, as part of our regular practice and is committed to disclosing clinical trials results" on the medication as they become available.
The concerns expressed by the FDA and its advisory panel, many public health experts say, come too late. In less than a decade, physicians have embraced the broad use of the atypical antipsychotics to treat mental disorders far less severe than schizophrenia and bipolar disorder -- afflictions such as anxiety, sleep difficulties, depression, attention deficit disorder and autism. First prescribed almost exclusively to adults, the drugs are now often used in the treatment of adolescents and kids as young as 2.
The sales of atypical antipsychotics have skyrocketed in recent years, propelling overall sales of antipsychotic drugs past all other classes, to $14.6 billion in 2008, according to IMS Health, a private firm that tracks drug trends. In 2008, 50 million prescriptions for antipsychotics, mostly the new ones, were filled in the U.S. -- a 5% hike in one year alone.
In the process, the spreading use of these costly drugs is raising -- for the nation as well as individual patients -- the rates and the risks of weight gain, diabetes, strokes, fatal heart attacks, an array of movement disorders and potentially, suicide, according to a wide range of critics.
"This is very worrisome; frankly I have serious concerns about these drugs," says Dr. Steven Nissen, who is chairman of the Cleveland Clinic's cardiovascular medicine department and serves as an ad hoc advisor for FDA panels. Studies point to a "very questionable balance between efficacy and safety" for the class, he said. But that message, he said, has been lost in an apparent "marketing bonanza" for the companies that make the medications. A recent report by the consulting firm Decision Resources found the makers of the atypicals spent $993 million in 2006 to promote the drugs to doctors and patients.
That's not to say the drugs haven't helped people.