October 11, 2004

Ziprasidone vs. Olanzapine (short term)

Randomized, Controlled, Double-Blind Multicenter Comparison of the Efficacy and Tolerability of Ziprasidone and Olanzapine in Acutely Ill Inpatients With Schizophrenia or Schizoaffective Disorder

George M. Simpson, M.D., Ira D. Glick, M.D., Peter J. Weiden, M.D., Steven J. Romano, M.D., and Cynthia O. Siu, Ph.D.

Am J Psychiatry 161:1837-1847, October 2004

This is a study that compares both the effectiveness and side effects of two second generation antipsychotics: Olanzapine (Zyprexa, by Eli Lilly) and Ziprasidone (Geodon, by Pfizer). The authors state that there have not been very many direct comparisons between the newer drugs but that each drug seems to have various side effects labeled on them.

The study was set up very well to help eliminate confounding variables (things that can alter a study other than what one is looking for.) It is a double-blind (neither the patient or the people working on the study know what drug the patient is on), randomized (anyone is equally likely to get one drug or the other), and it takes place throughout the US to help eliminate regional differences. The authors used a number of common rating scales to asses for changes in symptoms both positive symptoms and negative symptoms. They also looked at weight gain (body mass index), insulin levels (to see of increased risk of diabetes) and cholesterol levels. However, the authors only looked at 6 weeks worth of data so long-term implications of these data are hard to decipher and can only at best be inferred.

The results showed that both groups were the same with respect to the number of patients who dropped out of the study because the drug did not work. However, ultimately, a statistically significant number of patients dropped out from the ziprasidone group vs the olanzapine group, however the reasons are not made clear (lost to followup or withdrawn consent perhaps.) This may or may not be clinically meaningful. Having patients withdraw early from a study potentially can distort results and lead to statistical confusion and less accurate results depending on how the lost patients are tabulated.

The main results of the study showed that both drugs had approximately equal efficacy on treating the core symptoms of schizophrenia. Where thedifferences were seen was primarily in side effects. This is where the withdrawal of patients makes things difficult as well as the short duration of the study. The side effects looked at were weight gain, cholesterol changes and diabetes parameters. Many of these things take time to develop and while a change in six weeks is suggestive of future problem it does not necessarily speak to the long term significance. However, this study showed that olanzapine had a more serious side effect profile than ziprasidone which is something that many people have noted over recent years. They also showed that cardiac conduction defects often attributed to ziprasidone were not clinically seen here.

Overall, does this mean that olanzapine is a bad medication compared to ziprasidone? Well, this is one case where it is definitely helpful to see who sponsored this study: Pfizer, who makes ziprasidone (geodon) in the US. Ziprasidone has had a lower market share since coming onto the market several years ago. While there may be many reasons for this, perhaps this study was done to help bolster ziprasidone's position in the marketplace. Regardless of intention, data is data (statistical manipulation aside) and this is important information.

However, it cannot be denied that olanzapine does have severe metabolic side effects that should be considered when one starts on an antipsychotic. If someone you know is already on one of these or another, this study is not enough to warrant a change, especially if the medication is working. However, it does point out again the importance of maintaining a close eye on the overall health of someone with schizophrenia and not settling for merely the reduction of symptoms to be enough when one is taking care of such a patient.

This study was supported by Pfizer Inc. (maker of Geodon which is the tradename for ziprasidone).

Click here for a link to this study on PubMed

Author: Jacob Ballon


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