April 07, 2006

CATIE II - Schizophrenia Treatment Study Update

A government study (CATIE 2) comparing treatments for chronic schizophrenia found that an older drug (Clozapine/Clozaril) performed better than three new treatments, but it also highlighted the drug's dangerous side effects.

The national clinical trial comparing clozapine with other new-generation antipsychotic medications for the treatment of chronic schizophrenia has shown that people who switched to clozapine from their first medication because it failed to manage symptoms adequately, were twice as likely to continue treatment as patients who switched to other antipsychotic medications. A companion study found that for people who switched to new-generation antipsychotic medications other than clozapine, those who took olanzapine and risperidone continued taking their medication longer than people taking quetiapine and ziprasadone. The results of the trial, which was funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health, were published in two papers in the April 2006 issue of the American Journal of Psychiatry.

The results of CATIE — Clinical Antipsychotic Trials of Intervention Effectiveness — offer the 2.4 million adults in the United States with chronic schizophrenia and their doctors information that can help tailor treatments to the individual needs of patients. In phase 2 of this study, 543 people were studied in 57 different treatment sites to provide guidance to help doctors determine what to do next when patients need to change medications, a common occurrence in treating schizophrenia. Research has shown that patients who consistently receive treatment do much better than those who stop taking their medications, so finding the right treatment is crucial.

The lead investigators for the two studies in phase 2 of CATIE were Jeffrey A. Lieberman, M.D., of Columbia University and the New York State Psychiatric Institute; Scott Stroup, M.D., of the University of North Carolina at Chapel Hill; and Joseph McEvoy, M.D., of Duke University. These studies were the next step for patients who did not do well on their first medication in phase 1 of the trial, results of which were published in the New England Journal of Medicine in September 2005.

Phase 2 of CATIE compared the medications, called "atypical antipsychotics," with each other in two different groups of participants. In one group, patients who had stopped taking a phase 1 medication because symptoms were not adequately relieved were randomly assigned to get one of four medications: clozapine, olanzapine, quetiapine, or risperidone. In that group, clozapine was the most effective. Forty-four percent of the patients who changed to clozapine stayed on it for the rest of the 18-month study, compared with 18 percent of patients who had changed to the other medications. On average, patients stayed on clozapine for 10 months, while patients on any of the other medications stayed on them for only 3 months.

Not all patients can or want to take clozapine, because it may cause serious side effects in some people, including inflammation of the heart muscle, and agranulocytosis, which is a dangerous drop in levels of white blood cells that are part of the immune system. As a result, patients taking clozapine require close monitoring. Although the patients who took clozapine in this study tolerated it fairly well overall, one person developed agranulocytosis.

There were other phase 1 patients who had stopped taking their medication because of side effects or because they told their doctors they wanted to change medications. These patients, as well as patients who wanted more symptom relief but didn't want to take clozapine, took part in a different phase 2 medication trial. In this part of the trial, clozapine was not included, and ziprasidone, the newest of the atypical medications available in the early stages of CATIE, was compared with the other three (olanzapine, quetiapine, or risperidone). Ziprasidone is known to have very different side effects, and it does not usually cause weight gain, as the other medications do.

Overall, patients in this phase 2 group stayed on risperidone seven months and on olanzapine just over six months, compared to four months on quetiapine and less than three months on ziprasidone. Until phase 2 was completed, neither patients nor researchers knew which medications were given, unless it was clozapine, because of the need for close monitoring. None of the patients were given a placebo — "blank" pill — for comparison.

Future CATIE reports will address a number of topics, such as cost-effectiveness, quality of life, and predictors of response, and will provide a more detailed picture of the interaction between patient characteristics, medications, and outcomes. CATIE is part of an overall NIMH effort to conduct "practical" clinical trials that address public health issues important to people affected by major mental illnesses in real-world settings.

The Wall Street Journal reported that:

"Joseph P. McEvoy, associate professor of psychiatry at Duke University Medical Center and lead author of the clozapine study, said he hoped the results would lead more psychiatrists to consider using the drug [Clozapine/Clozaril] for patients who don't respond to other medicines. He estimated 2% of U.S. schizophrenia patients take the medicine now. The study found the median time for patients to discontinue clozapine was 10.5 months, compared with 3.3 months for quetiapine (sold as Seroquel by AstraZeneca PLC), 2.8 months for risperidone (sold as Risperdal by Johnson & Johnson), and 2.7 months for olanzapine (sold as Zyprexa by Eli Lilly & Co.)."

For more information on CATIE phase 2, visit:

Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE): NIMH Study To Guide Treatment Choices for Schizophrenia
Questions and Answers About the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness Study (CATIE) — Phase 2 Results

For more information on CATIE phase 1, visit:

NIMH Study To Guide Treatment Choices for Schizophrenia
Questions and Answers About the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness Study (CATIE) — Phase 1 Results


It's CATIE phase 2, not "CATIE II"

Big difference, actually.

Posted by: Mark at April 11, 2006 08:43 AM

Very interesting information to me,i have also shizophrenia, and
i also have took this medicine and i have to say newest a typical drugs have worse side effects, like weight gein, but they improve my emotion, my negative symptoms so you have decide to have bad side effects and good emotion state or less side effekt

Posted by: roger at April 16, 2006 12:15 AM

I am already ALOT overweight and Equetro, Abilify and Lamitcal has made me gain ANOTHER 15 lbs. Is there anything else that I can take besides Clozaril? Does anyone have to get their blood drawn for 6 months every week like me?

Posted by: Yammer at May 2, 2006 09:50 AM

My son is used Clozaril for 1 year at a dozage of 400 mg/per day The drug is very good except side effects. The worst effect ist the sleepness. My son is unable to get up early in the moorning. This affects the moorning leesons. Does anyone have any comment on that? Is there any other drug overcome this side effect?

Posted by: ilker at May 17, 2006 07:00 AM

Hi Ilker,

THere is a drug called Modafinil that many people in our discussion areas have said helps a great deal with the sleepiness. Here is alink for more information:



Posted by: szadmin at May 17, 2006 11:36 AM

Dear szadmin,
Thans for your advice. I wonder what happens if modafil is used together with clozapine as both medice related with dopamine level of the brain.

Posted by: ilker at May 18, 2006 05:23 AM

Hi Ilker,

There have been a number of studies on modafinil use in schizophrenia - and there are no indications that I saw that the modinafil had any interaction with the anti-psychotic medications - but I'm not a doctor - so best if you discuss this with a doctor.

They are not consistent - some show a moderately strong positive effect, some studies show no effect. For a small number of people it appears that there may be a negative effect. To learn more - you might try going to www.pubmed.org
and search on "modafinil schizophrenia"

Here are two studies that you'll see:

Patients with schizophrenia experience cognitive impairments associated with hypofunctioning of the frontal cortex. Modafinil, a novel wake-promoting agent, works through the sleep-wake centers of the brain to activate the cortex. This 4-week, open-label, pilot study evaluated adjunct modafinil in patients with schizophrenia or schizoaffective disorder. Eleven patients received once-daily oral doses of modafinil (100 mg/day, days 1-14; 100 or 200 mg/day, days 15-28) in addition to antipsychotic therapy. Modafinil significantly improved patients' global functioning as assessed by a blinded clinician (week 2, P = 0.026; week 4, P = 0.012) and the investigator (week 3, P = 0.035). Modafinil significantly improved overall clinical condition, with 64% and 82% of patients rated as clinically improved at week 4 by a blinded clinician and the investigator respectively. Eighty-nine percent of patients considered themselves to be clinically improved. Modafinil significantly improved fatigue (P = 0.025, week 3) and tended to improve cognitive functioning scores. Control of positive symptoms was well maintained. Treatment-emergent adverse events included dry mouth (n = 2) and hallucinations (n = 2). One patient discontinued the study because of hallucinations that were considered to be possibly related to inadequate antipsychotic therapy. Although preliminary, these results suggest modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition, and reduces fatigue in patients with schizophrenia or schizoaffective disorder. Additional controlled studies are warranted.

OBJECTIVE: To assess the effects of modafinil on fatigue, symptoms, attention, working memory, and executive functioning in schizophrenia patients treated with psychotropic medications. METHOD: Twenty-four patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder (10 men and 14 women) were randomly assigned to modafinil up to 200 mg a day (N = 13) or placebo (N = 11) as an adjunct therapy in an 8-week, double-blind, placebo-controlled study. Data were collected from May 18, 2001 to September 11, 2003. RESULTS: Four subjects terminated the study early, including one because of worsening of psychosis during the first week taking modafinil. In the modafinil (N = 10) and placebo (N = 10) groups, fatigue improved significantly over time (p

Posted by: szadmin at May 18, 2006 10:06 AM

My brother is considering changing from clozaril and lamictal because it makes him sleepy, he is considering switching onto "Abilify", does anyone have experience of abilify and how do you find it?

Posted by: MK at June 29, 2006 01:08 PM

does anyone have any idea on psychoanalytically oriented psychotherapy for schizophrenia patients ?

Posted by: ilker at July 5, 2006 01:59 AM

I take depakote for seizures that I had over 8 months ago. I also take 1mg Haldol and 300 mg Seroquil for shizophrenia. I have no emotions at all. I am like a zombie. I also take Lexapro for depression. Does anyone have any ideas.

Posted by: christie ewart at February 6, 2007 07:27 PM

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