Clozaril — trying to rear it’s ugly head again

Finnish Researcher Claims Clozaril Safer Than Other Antipsychotics

By Philip Dawdy

A study is just out in The Lancet and it is making an interesting and somewhat bizarre claim: that the atypical antipsychotic Clozaril, long out of favor especially in the US due to safety problems, is in fact safer for people diagnosed with schizophrenia than are perphenazine, Seroquel, Risperdal and Zyprexa. All of these drugs have huge problems and sorting out which is safer is about like asking which brand of handgun kills fewer people. I’m also a bit surprised at how Reuters and Bloomberg have cast their stories on the study, but I’ll get to that in a minute.

Here’s Reuters:

“Clozapine was the first of a new generation of schizophrenia drugs, known as atypical antipsychotics. But its use has been restricted by health authorities because of safety concerns and patients taking it require regular blood tests.”Despite this, an analysis of 10 years’ records for 67,000 patients in Finland found that, compared to treatment with the first-generation drug perphenazine, the risk of early death for patients on clozapine was reduced by 26 percent.

“By contrast, mortality risk was 41 percent higher for those on Seroquel, known chemically as quetiapine; 34 percent higher with Johnson & Johnson’s Risperdal, or resperidone; and 13 percent higher with Eli Lilly’s Zyprexa, or olanzapine.

“‘We know that clozapine has the highest efficacy of all the antipsychotics and it is now clear, after all, that it is not that risky or dangerous a treatment,’ study leader Jari Tiihonen of the University of Kuopio said in a telephone interview.

“We should consider whether clozapine should be used as a first-line treatment option.'”

Let’s be clear about one thing: these drugs are not safe for many patients who take them or are forced to take them, so arguing about which one causes less early death is a bit specious, since they all cause early death in some patients.

In the Reuters article, the researcher claims that due to restrictions on Clozaril’s use in the UK and Europe (there are no official restrictions on it in the US, although its use is very limited here) many thousands of people diagnosed with schizophrenia died who would otherwise be alive if they had taken Clozaril. That’s a pretty fishy argument. While I don’t question what the Finnish data showed the Finnish researchers, that data doesn’t line up with experiences in America.

The FDA adverse events database shows 3,257 reports of death from Clozapine (most of the database information for that drug is under its generic name) and that database only goes back to the fourth quarter of 1997. There other deaths connected with Clozaril that occurred before late-2007, but I don’t know how many there were even though from about 1990 through 1995 was when Clozaril was being used the most in this country. It’s probably a safe bet that 1,000 or more people died before late-1997. So figure 4,200 or so deaths.

Here are totals from the FDA’s adverse events database for deaths tied to other antipsychotics:

Seroquel: 2,139.

Zyprexa: 3,442.

Risperdal: 2,827.

While I don’t know the ages of all the deaths, the fact that we’re seeing more deaths with Clozaril than with the other main antipsychotics in America makes me wonder about the efficacy of the Finnish data. It also makes me wonder about how many brain cells some of my colleagues in the media have because, as did Reuters, Bloomberg also cast this study as making the case that non-Clozaril use led to deaths and that this somehow all reopen discussions about using the drug.

Please.

Posted by Philip Dawdy at July 13, 2009 12:03 AM