By: Helen Buttery
Winter 2005-06, Vol 9 No 2
New is not necessarily improved. At least not when it comes to antipsychotic drugs used to treat people diagnosed with schizophrenia, according to the results of a study published in the New England Journal of Medicine. The study, funded by the National Institute of Mental Health in Bethesda, Maryland, is the largest clinical trial of its kind. Instead of a controlled study seeking government safety and approval standards, the research focused on how well drugs already on the market work in the real world.
The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) involved almost 1,500 people taking antipsychotics, and compared the overall effectiveness of newer, second-generation antipsychotics – olanzapine, quetiapine, risperidone and ziprasidone – with one of their first-generation predecessors, perphenazine.
“New is not always better,” says Dr. Robert B. Zipursky, clinical director of the Schizophrenia Program at the Centre for Addiction and Mental Health in Toronto, and vice-chair of Research at the University of Toronto Department of Psychiatry. The study found olanzapine to be moderately more effective, with the remaining antipsychotics, including the first-generation drugs, not far behind.
For Zipursky, this confirms what he and his collegues in the Schizophrenia Program have suspected for years: “This study reinforces the view that the newer drugs are no more efficacious in controlling the symptoms of schizophrenia.”
However, Zipursky cautions, the findings do not mean that the older antipsychotics are reasonable equals when it comes to treatment. Physicians and clients must evaluate the tradeoffs between efficacy and side-effects in choosing the appropriate medication. What works well for one person may not work for another. “The side-effects are different and the likelihood that people will stop the medications differed across medications, with individuals being less likely to discontinue treatment with olanzapine,” says Zipursky.
The unique design of the study allowed researchers to make these distinctions. “This study represents a significant shift in the design of pharmacological clinical trials in schizophrenia,” says Dr. Donald Addington, head of the Regional Clinical Department of Psychiatry at the Calgary Health Region, and head of the University of Calgary Department of Psychiatry. “The agenda has been directed by a government agency, which is interested in the clinical benefits to patients and the costs to the health system.” Ultimately this may have implications for how clinicians view these drugs.
Unlike common drug trials, which test the efficacy of drugs and are sponsored by pharmaceutical companies seeking registration with Health Canada or, in the United States, the Food and Drug Administration, this government-sponsored study sought to determine the drugs’ effectiveness. Efficacy and effectiveness are two completely different things.
Efficacy studies (often designed as placebo-controlled studies) occur under controlled experimental conditions to determine whether a drug works. For instance, a study may examine 250 men with schizophrenia in their 30s with no other health conditions – not a realistic sample of the population taking these drugs. To correct this, the CATIE study set out to determine the effectiveness of the drugs – that is, whether they worked under real-life conditions. “Some patients will have heart disease and some won’t; some will be old and some will be young. All of those confounding variables are eliminated in a tight placebo-controlled study,” explains Addington.
With all of their individual traits, participants stuck with olanzapine slightly longer than the rest of the medications. Before 18 months, the rate of discontinuation for olanzapine was 64 per cent, whereas the average for all medications was 74 per cent. The rate at which participants stopped their medications may seem high, but Addington says the rate is quite typical among people with schizophrenia. He attributes this trend to what is often a lack of insight into the need to adhere to treatment, a typical scenario with other complicated drug programs used to treat other long-term conditions like diabetes. “It’s a normal human desire not to be stuck with a complicated treatment regime,” he says.
Still, olanzapine did have the lowest discontinuation rate, leading researchers to conclude that it is the most effective of the medications. “This conclusion is interesting because olanzapine is associated with heavy weight gain and is the most expensive, so obviously it has some overall balancing benefits to receive that kind of outcome,” says Addington.
But the fact that the results did not vary significantly among medications constitutes a worthwhile lesson for clinicians: Clients are individuals – what works comes down to a client’s prerogative, not the newest or even the most effective drug. Addington warns against a cookie-cutter approach to prescribing medications. Clinicians need to work with individual clients to see how medication works for them. Addington remembers a client with a family history of diabetes. Since olanzapine caused him to gain weight, he went off of it. “Different people have different values,” says Addington. “It’s not just about treating schizophrenia; it’s about treating the person.”
The findings do not mean that the older antipsychotics are reasonable equals when it comes to treatment. Physicians and clients must evaluate the tradeoffs between efficacy and side-effects in choosing the appropriate medication. What works well for one person may not work for another.