New Antipsychotics No Better For First Episodes
9 CommentsBy Ed Silverman // March 28th, 2008 // 7:23 am
The so-called atypicals - including Abilify, Risperdal, Zyprexa, Seroquel and Geodon - have been hailed as more effective and easier to tolerate than the older and cheaper kind such as Haldol, which cause tremors and rigid muscles. But the new generation are no better at treating a first episode of schizophrenia, according to a study in The Lancet. Such findings are important because the atypicals are heavily promoted, widely prescribed and expensive.
The Dutch researchers studied 498 patients between 18 and 40 years old in Europe and Israel in an open trial lasting 12 months. The patients were randomly assigned to a low-dose version of Haldol, or a higher dose of one of four atypicals. They found that during the subsequent 12-month period, more patients taking Haldol discontinued treatment when compared with patients taking the other drugs.
However, the reductions in all symptoms were about the same for all groups. But when the researchers further analyzed the data according to sex, tendencies towards suicide, and substance abuse, they found no significant differences between the drugs. Despite a high continuation rate for several of the atypicals, the researchers wrote that “it cannot be concluded that second-generation antipsychotic drugs are more efficacious in the treatment of these patients.”
As an aside, many of the authors reported various ties to the drugmakers that sell atypicals. And funding for the study was provided by AstraZeneca, Pfizer and Sanofi-Aventis.
HorusCat
This is an interesting spin on what we already know: there is no difference in efficacy between the older antipsychotics and the newer ones. There may be a difference in “negative” symptoms–this is a hard parameter to measure.
What we do know is there is a difference in side effects between older and newer antipsychotics. Surely, a patient’s quality of life should enter into the equation when choosing a medication. Unfortunately, those suffering from schizophrenia don’t have many willing to speak up for them.
An interesting aspect of research occurring right now is whether or not the newer antipsychotics preserve function and prevent atrophy in the schizophrenic brain. Tantalizing preliminary research suggests that the first-break schizophrenic may have more to gain from using the atypicals than the chronic schizophrenic with many years of disease behind him.
Laurie
“Tantalizing preliminary research suggests that the first-break schizophrenic may have more to gain from using the atypicals than the chronic schizophrenic with many years of disease behind him.”
The preliminary has a lot of “could, may, and might” in those studies. And then one has to weigh the risk of diabetes vs a “possible” positive effect on brain mass. Then the definitive question of what does increase brain mass mean to function….
HorusCat
Laurie,
Of course there are a lot of “coulds, mays and mights” right now. Researchers are learning exponentially more about schizophrenia and brain function. Multiple genes and multiple neurotransmitters are involved; there may be different subsets of people who have different deficits. This is another area where pharmacogenomics may eventually be helpful. And it’s not a matter of increased brain mass, it’s a matter of decreasing atrophy. We know that the brain of a person with a 40 year history of schizophrenia looks far different than that of a person with no such history. I think it’s a really exciting time for researchers, and they are hoping for real breakthroughs.
Not all the atypicals have equal metabolic risks. And even those that do have usefulness. Someone with schizophrenia who is able to really function while taking Zyprexa may be willing to take the metabolic risk because he is so appreciative of the way he feels while taking the drug. The typicals carry risks, too. Tardive dyskinesia is a horrible thing to live with.
The atypicals are not perfect medicines. Researchers and doctors alike are frustrated with the limitations of the medications currently available. I think the common goal is to find a way for a person suffering from schizophrenia to live as fully and completely as possible–and to make that “as possible” as big as we can.
Jack2
Discontinuation Rate over 12 months:
Haloperidol: 63%
Quetiapine: 51%
Amisulpride: 32%
Ziprasidone: 31%
Olanzapine: 30%
….and that’s not positive data for the atypicals?!?
HorusCat
Jack2,
Thanks for chiming in. From what I can tell from conversations with doctors and patients, the atypicals are better-tolerated. Compliance is a huge issue with antipsychotics, as you probably know. (Compliance is a problem with all Americans, but it becomes really obviously a problem when the non-compliant person becomes delusional and paranoid in public!) The atypicals are better, but still… When Janssen came out with Consta, it was a big step forward for the long-acting injectibles, because it is much better tolerated than Haldol dec. From what I hear, the Lilly long-acting Zyprexa worked phenomenally well, but the side effects scared off the FDA. It is notoriously hard to formulate a long-acting antipsychotic. Pfizer tried with Geodon, but finally gave up.
I think our medications for schizophrenia are going to get better and better. For a relatively small portion of the population (1%), they chew up a lot of medical resources. Not only because antipsychotics are expensive, but because providing the ancillary support services that keep patients out of the hospital is expensive; and hospital stays really eat up the money.
Jack2
I just look at the data and think the FACTS in this study read like an advertisement for Zyprexa. Yet the editorial just jumps on the bandwagon that we need to rethink atypicals. Was there ever a concensus that atypicals worked better than typicals? Not to my knowledge. I think the concensus came down to better tolerability (less EPS), and maybe a stronger effect on negative symptoms (or less of a drug induced decline in negative symptoms). I think this study actually SUPPORTS the notion of better tolerability.
I didn’t read the whole study. Why no Risperdal? It’s practically the benchmark.
HorusCat
Jack2,
You know, if Zyprexa didn’t cause weight gain and possibly diabetes, it would take over the world. I hate to admit it, but it is a great drug. I don’t know where Risperdal is…but you know, it’s kind of in-between the typicals and the atypicals…
If you read my first post about atypicals perhaps offering more in the way of “neuro-protection,” then you might agree that it is worth investigating them further for more than just positive and negative symptom control.
Atlex
Despite what the authors state, they essentially conclude that atypicals do work better than older antipsychotics. Assuming atypicals and older antipsychotics work 50% (this number may or may not be accurate) of the time, out 100 patients taking an atypical, roughly 35 benefit (1/2 of the 70% that are adherent). For older antipsychotics, the number would be 19 to 25 (1/2 of the 37% to 50% who are adherent).
Jack2
Exactly Atlex.
Horus,
With the patent life running down on those atypicals (except maybe ziprasidone - I don’t really now), I don’t think you’ll see much more industry funded research on those drugs no matter how tantalizing. As a serotonin and dopamine antagonist I’d call Risperdal an atypical.