Thursday, January 15, 2009

The News we Feared?

January 15, 2009, 9:03 am
Newer Antipsychotic Drugs Double Heart Risk, Just Like Older Meds
Posted by Sarah Rubenstein
The prevailing wisdom that the latest generation of antipsychotics is safer than older medicines takes a hit in the current issue of the New England Journal of Medicine.
A study comparing the drugs finds: Patients taking the newer group of drugs, called atypicals, are twice as likely to suffer sudden cardiac failure and death as nonusers. They’re just as likely to suffer those problems as if they were taking the older antipsychotics. The risk of death wasn’t high, though, at 3% for a patient treated for 10 years, as the New York Times explains it.
Sales of atypical antipsychotics have grown sharply in recent years, reaching $13 billion through the first 11 months of 2008, according to IMS Health, as quoted by the WSJ. The atypicals are supposed to help patients avoid side effects associated with the older meds, including involuntary, sometimes irreversible tremors and tics and increased risk of sudden cardiac death.
An accompanying editorial argues that use of the atypical drugs in children and elderly patients should be “reduced sharply.” (See more on risks in the Alzheimer’s patients and children.)
Jerry Avorn, a Harvard Medical School professor who has criticized drugmakers’ marketing practices and who co-authored the editorial, questioned the marketing of atypical antipsychotics as a safer alternative to older, more conventional medicines. “Now we understand that they have their own problems that are quite substantial,” he told the WSJ.
The atypical drugs used in the study were AstraZeneca’s Seroquel, Eli Lilly’s Zyprexa, Johnson & Johnson’s Risperdal and Novartis’s Clozaril. The “typical” drugs used for comparison were haloperidol and thioridazine, both generics. A Lilly spokesman told the WSJ the study provides information physicians should consider when prescribing such drugs, but added that Zyprexa has helped millions with serious mental illnesses regain control of their lives.

As reported by The Wall Street Journal Health Blog - 1/15/09


  1. Hey Kids! Lilly is paying $1.4 billion (that's billion with a "b") and pleading guilty to selling Zyprexa off-label! Now that's worth posting!

  2. When I read these types of studies, I wonder if the effect can always be attributed to the drug. In other words, is it true that these psychiatric drugs cause an increase in heart-risk, or is it that individuals with psychiatric problems are at a higher risk for heart problems? I think that people fail to realize sometimes that it’s very difficult to tease out causation over correlation.

  3. Nathan,

    You should check the labeling first.

    Antipsychotics do cause all sorts of cardiac toxicities, and the risk is different for different drugs. It's extremely high for thioridazine, quietiapine, and clozapine. You've said in other posts that you're a chemist who works in drug development on if I recall pharmacologic effects. You should understand that the risk may be different for different drugs and there are different dose responses at different receptors for even a single drug. Plus effects may be different depending on metabolite profiles and drug interactions. While underlying cardiac disease may contribute and may be higher in the population using these drugs that's all the more reason to be cognizant of different degrees of toxicities with different drugs.

    A person who understands the nuances should have no problem designing an epidemiological study in such a way to have a very good chance to show a predetermined outcome.


  4. Harpsky,

    Yeah, I read that interesting news. We'll get the story up. As I recall, this was a False Claims Act suit brought by a whistleblower, while damages will go to several states, etc.

    On a much more personal note, my sister died of sudden cardiac death while on Clozaril. Given the other drugs she was taking , it is difficult to know what caused what. But that's two out of five of my ow immediate family members who died as a result of rx drugs prescribed appropriately (my mother on Oraflex).

    Personally, I have been rx'd Vioxx and Propulsid (did't take either after I read label - luckily Vioxx was post label change). I understand odds are that all would have been fine. But, personally, I will emulate my father (and hope for enough of his genes), who rarely took anything more than an aspirin throughout his mostly happy and healthy ninety-eight years.

    Best to all.

  5. Belated response to Nathan - My sister was 54 and had no CV risks revealed by thorough exams up to the time of her death. I don't believe anyone has found an association between schizophrenia and CV risk more generally. She was in excellent health, did aerobics several days per week, and had successfully quit smoking many years earlier. Despite her illness, she was a successful artist and was about to have studio showings of her work.

    I agree that causality is always a difficult, sometimes impossible, call. The "reasonable person" criterion, supported by relevant studies which do provide odds, are relevant.

  6. I've gotten a copy and taken a look at the article and the editorial. Actually it's not too bad but there's a couple of important pieces of info that I'm having trouble finding. So I'll need to spend some time with the article. That said there are a number of caveats and it addresses a very limited type of cardiac toxicity. So it doesn't really address the types of chronic cardiac and cardiopulmonary toxicities I'm concerned with especially in special populations or in the presence of other drugs such as SSRIs, certain inducers and inhibitors, or lithium. I think it's a good beginning and begins to address some questions I had in my mind, but not all of them. If it were me I would have several very specific questions that I would want answers to on this study and on specific drugs so that I could write appropriate labeling for use.



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