Uninterrupted therapy ensures optimal outcome
Catie shows patients stayed longer with olanzapine than other drugs
Staying on medication does more than relieve schizophrenia patients of symptoms and offers benefits over the long term.
"The traditional measure of clinical efficacy is symptom change," said Dr. Richard Keefe, associate professor of psychiatry and behavioral sciences at the Duke University Medical Center in Durham, North Carolina. "But one of the most important things about the treatment of schizophrenia is that patients who stay on their medication for whatever reason do much better in the long term than those who are treated intermittently or who discontinue their medication."
In a symposium organized by the Philippine Psychiatric Association and Eli Lilly Philippines, Keefe presented results of the Clinical Antipsychotic Trials of Intervention Effectiveness (catie), which assessed the effectiveness of various antipsychotics.
Catie enrolled 1,460 patients with schizophrenia and randomized them into one of five different treatment arms-olanzapine (7.5 mg/day), quetiapine 200 mg/day), risperidone (1.5 mg/day), ziprasidone (40 mg/day), and perphenazine (eight mg/day). The participants were between 18 and 65 years, diagnosed with schizophrenia (based on dsm-iv criteria), and did not have first-episode or treatment-resistant schizophrenia.
The primary outcome measure was all-cause treatment discontinuation, which was a combination of factors relating to tolerability and efficacy as well as input from both clinician and patient. Secondary outcomes looked at the specific reasons for discontinuation, the traditional psychopathology involved, safety profiles, adherence to treatment, quality of life, neurocognition scores, and other comorbidities.
Longest with olanzapine
The primary results showed little difference in discontinuation among treatment groups, but as time wore on, patients on olanzapine began to discontinue at a slower rate than the rest. Looking at pairwise comparisons, olanzapine was better at keeping patients on medication compared with quetiapine, and significantly better than risperidone. The difference with perphenazine was not statistically significant, but olanzapine patients still stayed longer on average (9.2 v. 5.6 months).
Differences in discontinuation rates for lack of efficacy showed statistical significance. Olanzapine patients discontinued at a significantly lower rate than those on quetiapine, risperidone, and perphenazine. But while the difference was largest against ziprasidone, it was not statistically significant, probably due to the power differences among treatment comparisons.
Hospitalization rate due to exacerbation was lowest among patients on olanzapine (10 percent). Added Keefe: "Remember that patients on olanzapine were actually on olanzapine for a significantly longer period of time. Quite a difference between the drugs on this important clinical outcome."
Discontinuation rates due to intolerability were not significantly different across treatments, although risperidone appeared relatively more tolerable than the other antipsychotics. Olanzapine patients were likely to discontinue due to weight or metabolic effects, while those on perphenazine discontinued more for extrapyramidal symptoms.
Weight gain was significantly higher and more frequent in olanzapine-treated patients than the rest, especially compared with those on ziprasidone and perphenazine, who actually lost weight. But Keefe clarified: "Because olanzapine patients were on the drug longer, they had more opportunity to gain weight."
Number to treat
Most clinical epidemiologists believe number needed to treat (nnt) as "the least misleading and most clinically useful measure of treatment effectiveness" (Gray, 2004). nnt is expressed as one over the absolute risk reduction, which measured by subtracting the experimental event rate from the control event rate. "For example, if nnt equals five, [then it] means for every five patients treated with the experimental treatment, there would be one more response if the control treatment had been used."
The catie results showed the nnt for all-cause discontinuation rates involving olanzapine was 10 against risperidone, six against quetiapine, seven against ziprasidone, and nine versus perphenazine. This means that in terms of nnt, olanzapine was most effective in preventing treatment discontinuations.
In terms of hospitalization rates, nnt for olanzapine was five against perphenazine, three against quetiapine, seven against risperidone, and four against ziprasidone.
"Olanzapine was the most effective in terms of the rates of discontinuation and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone," concluded Keefe. "Olanzapine, however, was associated with greater weight gain and increases in glucose and lipid metabolism. In the future, we are going to see if the effectiveness of these drugs can be determined by the cognitive improvement that was found early on in the treatment." M
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