August 08, 2004

An initial trial of 4 new possible meds for schizophrenia

Meltzer HY, et al., Placebo-Controlled Evaluation of Four Novel Compounds for the Treatment of Schizophrenia and Schizoaffective Disorder. Am J Psychiatry 2004; 161:975,984.

This article is about a trial of 4 new types of antipsychotic medications at the beginning of their testing on people with schizophrenia. As the mechanism of schizophrenia is only partially understood, there is still room to discover new activities in the brain that may contribute to the symptoms that are visible on the outside. Traditionally, antipsychotic medications have focused on the neurotransmitter dopamine which is a chemical in the brain that when too abundant in particular areas can cause hallucinations, delusions and other symptoms. Newer antipsychotics have become more focused in certain dopamine receptors and have also targeted other neurotransmitters receptor sites in order to help minimize side effects. The medications in this study all target new receptors in the brain and work in ways significantly differently than the medications currently on the market. Each of these receptors are like keyholes in which a molecule called a neurotransmitter is the key that helps turn on or turn off various activity in brain cells. They naturally exist in the brain for various purposes but can be altered in schizophrenia and therefore may be targets for new medications. Of the 4 medications in this trial, one targets a cannabinoid receptor, another works on a specific type of serotonin receptor, another works at a neurokinin receptor and the last works as a blocker of the neurotensin receptor.

To study these medications, the authors of the study compared these new compounds to haloperidol (Haldol) and to a sugar pill or placebo. Ultimately, 2 of the medicines (the one that worked on the neurokinin receptor and the serotonin receptor drug) worked as well as haloperidol in certain aspects and will warrant further study. Neither drug worked better than Haldol though each may ultimately have subtle benefits that might make them more useful in particular patients. Also, they may have fewer side effects than Haldol, however longer term studies will need to be done in order better estimate side effect profiles. It is encouraging that in this study, none of the drugs studied had any more side effects than placebo.

This study is encouraging because it shows that there are new molecules being tested to treat schizophrenia. While none of these are a magic bullet, two of the four medicines will be further studied and may make contributions to the armamentarium we have to treat schizophrenia. Despite these advances, much more testing will be needed on these medications, both in terms of safety and effectiveness, before they will be ready to come to market.

This trial was sponsored by Sanofi-Synthelabo Research which developed each of these medicines.

link to the article on pubmed

Author: Jacob Ballon


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