Rethinking Antipsychotics - Part II
In an earlier blog I noted that there may be a sea change in how psychiatry thinks about prescribing new-generation (atypical) antipsychotics such as Zyprexa and Risperdal.
Originally approved for treating schizophrenia, over the last several years the FDA has approved their use for treating short-term mania. Zyprexa also has a long-term indication.
(Seroquel and a combination Zyprexa-Prozac pill known as Symbyax also have an FDA indication for treating bipolar depression.)
In recent years, atypicals have moved up to a first choice option in various treatment guidelines in treating patients in the initial phase of their mania. These are generally your 911 situations - where the patient poses a clear threat to himself and others and where pharmaceutical overkill is acknowledged as best practice.
Long-term treatment is far more problematic. Owing to the risk of tardive dyskinesia (chronic muscular spasms), the American Psychiatric Association does not recommend its long-term use for mania unless there is a valid clinical reason. Right from the very beginning, patients complained to their deaf psychiatrists about the weight gain side effects. A 1997 study found that patients on Zyprexa gained 27 pounds in one year, and a 1999 study found a nine-pound gain on the drug over 10 weeks.
In medical practice, a seven-percent weight gain from baseline is considered clinically significant. In 2001, the US Surgeon General declared an obesity epidemic, reporting that approximately 300,000 US deaths a year are associated with obesity and overweight compared to more than 400,000 deaths a year from cigarette smoking.
With weight gain comes diabetes risk. In 2002, studies appeared documenting diabetes risk in patients on atypicals. In 2003, a joint panel of the American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity issued a consensus statement advising that doctors screen and monitor their patients on atypicals, including taking blood samples and other measures.
In 2003, the drug companies added a diabetes warning to their product labeling.
With weight gain also comes cardiac risk, depression risk, and a host of potential medical problems. According to endocrinologist Judith Korner MD PhD of Columbia University at a session of the 2004 American Psychiatric Association's annual meeting, "Obesity hits every organ system in the body."
But an $18 billion a year worldwide market in atypicals indicates that psychiatrists were paying far more attention to the carefully-rehearsed sales pitches of well-groomed pharmaceutical detailers than to either their own patients, scientific studies, drug labeling, or medical common sense.
According to an article in PLoS this year, the drug industry spent $15.7 billion on promoting prescriptions drugs in the US in 2000, $4.8 billion spent on detailing. According to the article, trainee drug reps are told: "When you're out to dinner with a doctor, the physician is eating with a friend. You are eating with a client." Reps then use "the friendship" to request favors in the form of prescriptions.
Late last year, the NY Times reported that Eli Lilly suppressed information concerning Zyprexa's links to obesity and elevated blood sugar. According to Lilly's own internal documents, sales reps were instructed to play down in conversations with doctors information which showed 30 percent of patients on the drug gain 22 pounds or more after a year on the drug, with some reporting gains of 100 pounds or more.
This year, the FDA slapped AstraZeneca on the wrist for misstatements about Seroquel and diabetes and other risks, and Pfizer for claiming that Geodon was more effective than the old generation Haldol.
Recently, psychiatrists have begun owning up to the fact that they may risk killing their patients by placing their patients on weight-gaining antipsychotics long term. The impetus came from a currently ongoing series of NIMH-underwritten series of trials involving patients with schizophrenia taking antipsychotics, known as CATIE.
The early results for the most part indicate no major surprises, namely that the new generation of antipsychotics are no more effective than the old generation of antipsychotics, and that some of the new antipsychotics cause a hell of a lot of weight gain. Over the long-term, virtually all the patients dropped out of the trials.
These findings were so old-hat that I did not bother to report it in my email Newsletter.
The true news value in the CATIE studies was only that the psychiatrists themselves interpreted the studies as news. This became evident at last year's APA annual meeting, and came in loud and clear at this year's APA. "Am I a Psychiatrist ... or an Endocrinologist?" read the title to one industry-supported symposium. "Antipsychotics and Metabolic Risk: A Clinical Issue at the Forefront of Contemporary Psychiatry," read one of the talks from this symposium.
Were psychiatrists finally starting to wake up?
Yes, there may be valid clinical reasons to place patients on antipsychotics over the long term. But antipsychotics, new or old, are basically dumb meds. They block dopamine in all the dopamine systems of the brain, not just where they are needed, resulting in a high cost of doing business. A study reported in the American Journal of Psychiatry this year actually found that 12 patients with schizophrenia felt worse, not better, on antipsychotics.
Dumb meds call for smart meds strategies. Unfortunately, past performance indicates that psychiatrists have only been about as knowledgeable as what drug reps tell them. Maybe that is changing. At the very least, psychiatrists can start by listening to their patients