Antipsychotics Raise Stroke Risk In Dementia Patients
5 CommentsBy Ed Silverman // August 29th, 2008 // 8:04 am
People taking antipsychotics are nearly twice as likely to have a stroke compared to those not on the meds, according to a study in the British Medical Journal. And the risk is higher - about 3.5 times - for men and women with dementia, which means doctors should only prescribe such medicine to these patients as a last resort, the researchers said
Previously, stroke risk associated with older antipsychotic drugs was unclear but the study showed both old and new treatments carry increased risk. “The risks associated with antipsychotic use in patients with dementia generally outweigh the potential benefits, and in this patient group, use of antipsychotic drugs should be avoided whenever possible,” the researchers wrote.
The researchers looked at the medical records of nearly 7,000 men and women and recorded the incidence of stroke among those who at some point had taken antipsychotics. They found that they were 1.7 times more likely to have a stroke and that the risk was much higher if people had dementia.
The most common older meds included a drug class called phenothiazine and older generics: haloperidol and benperidol. The most widely used newer drug in the study was Johnson & Johnson’s Risperdal. Other newer drugs in the study included Lilly’s Zyprexa, Sanofi-Aventis’ Solian and AstraZeneca’s Seroquel.
The researchers did not look at why people with dementia are at greater risk but one possibility may be that vascular causes of certain types of dementia may be involved, Douglas tells Reuters. “We don’t know why this extra risk associated with antipsychotics is even greater in people with dementia.”
Daniel Haszard
Zyprexa has generated a lot of bad press for Eli Lilly and they still have unresolved Zyprexa settlement claims.
Eli Lilly is ‘reaping the whirlwind’ for aggressive marketing of Zyprexa that has caused suffering and deaths.
Zyprexa is being avoided by doctors they aren’t prescribing it for new patients at all anymore.
Salmon
The claims made by this study should be interpreted cautiously.
The presumed mechanism behind stroke with antipsychotics is via effects on serotonin and serotonin receptors, which are primarily effects of ‘atypical’ rather than ‘conventional’ antipsychotics. Thus the results showing more strokes with ‘atypicals’ is consistent with this. However if you look at table 1 in the article it’s primarily a comparison of risperidol (81%) with a lessor amount of olanzapine (Zyprexa 18%) compared primarily with an unknown mixture of ‘phenothiazines’. Of of the ‘atypicals’ I would expect risperidone to be much less likely to cause problems compared to olanzapine. In addition, when you look at the ‘conventional’ antipyschotics 20% are claimed to be butyrophenone (haloperidol and benperidol) yet benperidol is really structurally a mixture of a butyrophenone and an atypical that’s similar to risperidol and which is structurally similar to serotonin.
Thus at least one and possibly more drugs may have been misclassified structurally and pharmacologically.
Lastly the study only examined up to 6 months which may be OK for effects on platelet aggregation, however stroke is more than just platelet aggregation and serotonin effects on blood vessel wall thickness may take more than one year. In fact if you look at the FDA slides on Vioxx which causes these effects on blood vessel thickness the plots of increased risk for different drugs only begin to separate after 1 year. So 6 months is clearly insufficient.
A similar study was recently published in the Aug 6th issue of the Journal of the American Geriatric Association. It looked at death due to cardiopulmonary events, and claimed no difference between ‘conventional’ and ‘atypical’ antipsychotics. Yet 25% of the ‘conventional’ antipsychotics were really ‘atypicals’ and again this study only looked at usage up to 6 months. This study was published by the group at Harvard which is closely associated with Beiderman.
On June 16th the FDA also came out claiming no differences between ‘atypicals’ and ‘conventional’ antipsychotics yet again many of the drugs listed by FDA as ‘conventional’ were really ‘atypicals’ by both structure and pharmacologic effect and some are considered drugs of last resort because they’re so dangerous.
All 3 of these reports have received significant press. I believe that there may be a campaign underway to confuse the issue of the lack of safety of ‘atypicals’ as compared to ‘conventional’ antipsychotics. By doing this it will not only confuse the issue almost everyone and will allow FDA to have a series of special advisory meetings to delay and obfuscate the issue so as to protect sales. This would be a useful tactic if companies marketing ‘atypicals’ and especially the -apines i.e. Clozapine, Lilly (olanzapine), and others that may come to market shortly. Were afraid that the toxicity of these agents were about to made a public issue.
Salmon
Salmon
Lets watch who tries to shoot me down this time.
Also if you go over to Shearlings got Plowed Blogsite and look at the structure of the nonsedating antihistamines loratadine (Claritin) and Descloratadine (Clarinex) (Shearing Plough) you’ll see that the structures are extremely similar to olanzapine and clozapine. Also parts of the structure are remarkably similar to parts in olanzapine that I previously pointed out on Shearlings got Plowed may be involved in worsening hepatotoxicity in the presence of Hepatitis C and the basis for SP’s and Vertex’s new Hep C drugs.
If you look at the summary basis of the approval at Drug@FDA.gov you’ll see that for Descloratadine there were significant cardiac toxicity during development. They explain this away by claiming that in the presence of a CYP3A4 inhibitor they don’t see it even though the exposures to the parent and metabolite go up.
This is an absurd argument as it may mean that there’s a toxic metabolite produced by 3A4/5 and an inhibitor would thus be protective. This and the high incidence of hypospadias may be partly behind FDA wanting to get pediatric OTC cough and cold meds off the market.
I also know the reviewer listed on the review for descloratadine and she was recently forced out of the FDA. I wonder if her review of this Schering Plough drug had anything to do with the attempt to fire her.
Salmon
Susan
I know families who have lost their (young - twenties and thirties) to olanzapine, including my son to profound hyperglycemia. Causes of death include profound hyperglycemia, pancreatitis, and suicide. The sorrow is always much greater and never ending when one loses a child. But what is happening with those with dementia amounts to genocide, and highlights the penultimate failure of the FDA and the Bush Administration to regulate a dirty industry.
Salmon
I’m sorry Susan.
I believe that the effects in the elderly will also be seen in children. I think it will just take longer as I believe the elderly are just at greater risk due to normal changes in physiology with aging. So instead of seeing problems after several months or a year it may take years until we start seeing children dying due to cardiac problems.
Salmon