A large study funded by NIH's National Institute of MentalHealth (NIMH) provides, for the first time, detailed informationcomparing the effectiveness and side effects of five medications — bothnew and older medications — that are currently used to treat peoplewith schizophrenia. Overall, the medications were comparably effectivebut were associated with high rates of discontinuation due tointolerable side effects or failure to adequately control symptoms. Onenew medication, olanzapine, was slightly better than the other drugsbut also was associated with significant weight-gain and metabolicchanges. Surprisingly, the older, less expensive medication used in thestudy generally performed as well as the newer medications. The study,which included more than 1,400 people, supplies important newinformation that will help doctors and patients choose the mostappropriate medication according to the patients' individual needs. Thestudy results are published in the September 22 issue of the NewEngland Journal of Medicine.
"The study has vital public healthimplications because it provides doctors and patients with much-neededinformation comparing medication treatment options," said NIMH DirectorThomas R. Insel, M.D. "It is the largest, longest, and mostcomprehensive independent trial ever done to examine existing therapiesfor this disease."
Schizophrenia, which affects 3.2 millionAmericans, is a chronic, recurrent mental illness, characterized byhallucinations, delusions, and disordered thinking. The medicationsused to treat the disorder are called antipsychotics. Previous studieshave demonstrated that taking antipsychotic medication is far moreeffective than taking no medicine, and that taking it consistently isessential to the long-term treatment of this severe, disablingdisorder. Although the medications alone are not sufficient to cure thedisease, they are necessary to manage it.
In the CATIE (ClinicalAntipsychotic Trials of Intervention Effectiveness) trial, researchersdirectly compared an older medication (perphenazine), available sincethe 1950s, to four newer medications (olanzapine, quetiapine,risperidone, and ziprasidone), introduced in the 1990s. The purpose ofthe study was to learn whether there are differences among the newermedications and whether the newer medications hold significantadvantages over the older medications; these newer medications known asatypical antipsychotics, cost roughly 10 times as much as the oldermedications.
The size and scope of the trial, with more than1,400 participants at 57 sites around the country, its 18-monthduration, and its inclusion of a wide range of patients in a variety oftreatment settings ensure that the findings are reliable and relevantto the 3.2 million Americans suffering from schizophrenia.
At thebeginning of the study, patients were randomly assigned to receive oneof the five medications. Almost three quarters of patients switchedfrom their first medication to a different medication. The patientsstarted on olanzapine were less likely to be hospitalized for apsychotic relapse and tended to stay on the medication longer thanpatients taking other medications. However, patients on olanzapine alsoexperienced substantially more weight gain and metabolic changesassociated with an increased risk of diabetes than those studyparticipants taking the other drugs.
Contrary to expectations,movement side effects (rigidity, stiff movements, tremor, and musclerestlessness) primarily associated with the older medications, were notseen more frequently with perphenazine (the drug used to represent theclass of older medications) than with the newer drugs. The oldermedication was as well tolerated as the newer drugs and was equallyeffective as three of the newer medications. The advantages ofolanzapine — in symptom reduction and duration of treatment — over theolder medication were modest and must be weighed against the increasedside effects of olanzapine.
Thus, taken as a whole, the newermedications have no substantial advantage over the older medicationused in this study. An important issue still to be considered isindividual differences in patient response to these drugs.
Severalfactors, such as adequacy of symptom relief, tolerability of sideeffects, and treatment cost influence a person's willingness andability to stay on medication.
"There is considerable variationin the therapeutic and side effects of antipsychotic medications.Doctors and patients must carefully evaluate the tradeoffs betweenefficacy and side effects in choosing an appropriate medication. Whatworks for one person may not work for another," said Jeffrey Lieberman,M.D., CATIE's Principal Investigator and Chair of The Department ofPsychiatry, Columbia University and Director of the New York StatePsychiatric Institute.
The CATIE study was led by Lieberman, andco-Principal Investigators Scott Stroup, M.D. (University of NorthCarolina at Chapel Hill), and Joseph McEvoy, M.D. (Duke University).CATIE was carried out by researchers at 57 sites across the country,including private and public mental health clinics, Veteran's HealthAdministration Medical Centers, and University Medical Centers, wherepeople with schizophrenia received their usual care.
This NewEngland Journal of Medicine article is the first to report outcomesfrom the CATIE schizophrenia trial, and addresses many of the primaryquestions from the study. Future reports will address a multitude oftopics (e.g., cost-effectiveness of the medications, quality of life,predictors of response) and will provide a more detailed picture of theinteraction between patient characteristics, medication, and outcomes.The information from the CATIE study will inform new approaches forimproving outcomes in schizophrenia.
CATIE is part of an overallNIMH effort to conduct "practical" clinical trials that address publichealth issues important to those persons affected by major mentalillnesses in real world settings.
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