May 03, 2006

Mixed Results for Early Schizophrenia Treatment with Antipsychotic Meds

In the past decade schizophrenia researchers have been experimenting with a number of different strategies to prevent or delay the development of full-blown schizophrenia - as research suggests that it is becoming possible to more accurately identify people who are at high risk for development of schizophrenia (see the Early Schizophrenia Screening Test). At we encourage all avenues of research into prevention and delay of schizophrenia and hope that much more money will be invested in this area going forward to speed up the pace of research in this vital area.

The key strategies that the researchers are currently evaluating for prevention or delay of schizophrenia include the following:

1. Psycho-social treatments for family and the individual showing early signs of schizophrenia. (See the following story on the Maine PIER program that is reporting over 50% schizophrenia prevention / delay rates - but this group's results have not yet been reported or published in peer-reviewed journals so we have to be cautious about accepting them - read more in this story: "Nipping Madness in the Bud".

2. New non-medication therapies - such as Glycine treatment, Sarcosine/N-Methyl-Glycine treatment, - in fact there are studies that focused on these two areas right now - see Glycine in schizophrenia prevention, and N-Methyl-Glycine in schizophrenia prevention.

3. The use of anti-psychotic medications used as early treatment for possible prevention of schizophrenia is also an area that has been an area of increasing research.

Today's news report is on one such study focused on using antipsychotic medications in people who are showing the early signs of schizophrenia - a study sponsored by the National Institute of Mental Health and Eli Lilly corporation, titled "Randomized, Double-Blind Trial of Olanzapine Versus Placebo in Patients Prodromally Symptomatic for Psychosis".

In what some people are calling a bold and controversial treatment strategy: in this study the researchers were prescribing anti-psychotic drugs to young people who are at high risk for schizophrenia but who have not yet developed the full-blown symptoms.

The hope of this research is that while exposing some to drugs unnecessarily, preemptive treatment may help others ward off or even prevent psychosis, sparing them the agonizing torment that full-blown schizophrenia frequently brings.

The results from a study just recently published in the May Issue of The American Journal of Psychiatry suggests that for young people who clearly seem to be developing early signs of schizophrenia, treatment with the antipsychotic drug olanzapine appears to lower or delay the rate of conversion to full-blown psychosis, according to an article by Yale School of Medicine researcher Dr. Tom McGlashan).

The New York Times story on this research, noted:

"The long-awaited study, which was financed by Eli Lilly and the National Institute of Mental Health, raised more questions than it answered, experts said.

''The positive result was only marginally significant, and the negative result was clear,'' said Dr. Thomas McGlashan, a professor of psychiatry at Yale and the study's lead author. ''This might discourage people, and legitimately so, from using this drug for prevention because of the weight gain, but hopefully it won't discourage study'' of other drugs.

The findings are preliminary since 60 patients began the study and 17 completed it. Despite the long recruitment period and multiple study sites, participation was limited by the low incidence of pre-psychotic, or “prodromal,” symptoms in the general population.

“Delay of the onset of the most severe symptoms of schizophrenia appears to have occurred because of the early recognition and treatment of these persons,” said Robert Freedman, M.D., editor-in-chief of The American Journal of Psychiatry. “This enabled them to be better connected with treatment and to cope better with this devastating illness.”

The study, “The Prevention Through Risk Identification, Management, and Education (PRIME),” was conducted in two U.S. cities and two Canadian cities during 1998-2003. Senior author of the study was Thomas McGlashan, M.D., professor in the Department of Psychiatry at Yale.

The New York Times further noted:

"''Unfortunately, the study's numbers are so small that it cannot be decisive on the key issue, which is whether it's prudent to treat people early when there are uncertainties about the diagnosis and given the effect of stigma and adverse effects,'' said Dr. William Carpenter, director of the Psychiatric Research Center at the University of Maryland, who was not involved in the study.

The study was plagued by recruitment problems from the beginning, in 1997. Mild, psychosis-like symptoms are rare in adolescents, and families often wait until symptoms are pronounced before seeking treatment, Dr. McGlashan said. Good candidates trickled in slowly; and the researchers added several recruitment sites along the way to increase the numbers of people in the study"

The participants were mostly adolescents. The individuals or their parents sought treatment because the adolescents had symptoms resembling those of psychosis, but less severe. Symptoms included occasional periods of persecutory thoughts, abnormal sensory experiences such as hearing unusual sounds, and brief periods of incoherent thoughts, among other symptoms. Earlier studies suggest that many of these individuals would eventually develop the full symptoms of schizophrenia—persistent paranoia, auditory hallucinations and disability.

The participants were randomly assigned for one year to olanzapine, a drug often used to treat schizophrenia, or placebo, and then were observed for an additional year after treatment was stopped.

During the year of treatment the olanzapine group had greater improvement in prodromal symptoms with conversion to full psychosis in 16 percent of the olanzapine patients and 38 percent of the placebo patients. In following year, after the treatment was discontinued, the rates of conversion to psychosis did not differ and symptoms increased for the patients previously treated with olanzapine.

Research into the early detection and treatment of schizophrenia has become important to determine whether psychosis and/or some of its disabilities can be prevented. Recent investigations have examined whether a long duration of untreated psychosis leads to a poorer outcome after treatment begins. Clinical trials to determine whether schizophrenia can be delayed or prevented are now possible due to improvements in antipsychotic medications and in identification of high-risk individuals.

Weight gain is a frequent side effect of olanzapine, although it does not cause body tremors as did the first generation of antipsychotic medications. The patients in the PRIME study who took olanzapine gained an average of 19 pounds. Increases in glucose and cholesterol levels are also common in patients taking antipsychotic medications, but the patients in this study did not develop these symptoms.

Source: "Randomized, Double-Blind Trial of Olanzapine Versus Placebo in Patients Prodromally Symptomatic for Psychosis".


Many people still feel early medication will help to create better outcomes long term for the majority of people. The criticisms of the study aren't the only way to see it, as the results are not conclusive. Weight gain may reflect a need for better overall care, or that other medications should have been tried. Hopefully more studies of the type will be done, but they have several intrinsic problems - 1. many people have some early signs of the illness but won't go on to develop the illness. the signs can be due to drug abuse or other mental illnesses than schizophrenia. 2. some people have first episodes or early symptoms, and don't develop clear or consistent symptoms for up to 10 years, causing early treatment result studies to be inaccurate unless the study does followup for an extended period after the main part of the study.

Posted by: slc at May 11, 2006 09:08 AM

very interesting site. would like to see subject search box.

Posted by: George Miller at November 23, 2007 08:41 AM

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