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| |  Risperidone Is Superior to Standard Antipsychotics According to Studies CHICAGO, April 16, 1996 -- Data pooled from all double-blind, random-assignment studies with risperidone reveals that risperidone is superior to standard antipsychotic agents in overall efficacy and safety at its optimal dose of 6 mg, and at a mean of all effective risperidone doses from 6 to 16 mg -- the best and worst-case scenarios. The meta- analysis, conducted by John M. Davis, MD and Philip G. Janicak, MD of the University of Illinois, is published in the February issue of Psychiatric Annals. "The meta-analysis is extremely valuable for physicians who have not reviewed all of the data on risperidone," says Dr. Davis. "Some individual studies of risperidone are not statistically significant, but when data from all the studies are compiled and risperidone is compared to standard antipsychotic agents under the best and worst-case scenarios, it is clear that risperidone is substantially more effective and affects a wider variety of symptoms than conventional drugs." Risperidone (Risperdal(R), Janssen Pharmaceutica) was introduced in 1994 for the management of the manifestations of psychotic disorders. Risperidone is the first of a new class of antipsychotic agents that specifically block the dopamine (e.g., D2) as well as the serotonin (e.g., 5HT2) families of receptors. Conventional antipsychotics block primarily dopamine receptors. Clozapine also blocks 5HT2 and D2 receptors, in addition to a wide variety of other receptors; however, risperidone is the first antipsychotic to block those receptors and little else. The meta-analysis explores whether risperidone's additional 5HT2 blockade and targeted mechanism of action produces greater efficacy, a wider spectrum of efficacy, and an improved safety profile than standard antipsychotics. Improvement in Positive, Negative and General Symptoms While haloperidol is effective for positive symptoms (hallucinations, delusions, conceptual disorder), risperidone not only significantly improves positive symptoms, but also has a substantial effect on negative symptoms (blunted affect, social withdrawal) and general symptoms (poor impulse control, active social avoidance). Based on four studies of 382 patients, risperidone improved positive symptoms somewhat more than conventional neuroleptics, and was considerably more effective against negative and general symptoms than haloperidol (or other conventional neuroleptics). (See Table 1.) Superior Side Effect Profile An analysis of all the studies finds that risperidone causes substantially less acute extrapyramidal side effects (EPS) than conventional neuroleptics. EPS (uncontrollable muscle rigidity, tremors, and body shakes) are the most significant measurable adverse events in antipsychotic agents. It is possible (but unproven) that drugs that cause acute EPS also cause tardive dyskinesia (TD), EPS are also risk factors for TD, and acute EPS can create other serious problems, such as laryngeral dystonias, dystonic reactions, akathisia and akinesia. In addition to a lower incidence of EPS, risperidone does not cause varied problems such as: pigmentary retinopathy or ECG changes seen with thioridazine; lens and corneal opacities seen with chlorpromazine; the substantial anticholinergic side effects seen with chlorpromazine, thioridazine, and clozapine; seizures seen with clozapine and low-potency phenothiazines; agranulocytosis or aplastic anemia, and jaundice. Potential Cost Savings "Although there is little data to support the cost-effectiveness of risperidone, it is reasonable to assume that its superiority to standard drugs may result in cost savings," says Dr. Davis. "risperidone's greater efficacy in negative symptoms could help facilitate the social adjustment of patients into the community, allowing them to live in less restrictive environments and seek employment. The improvement in positive symptoms may result in fewer hospital readmissions and its relative freedom from adverse effects means a reduction in the cost of managing patients' therapy. Such savings could far outweigh the initial cost of this medication." Meta-Analytic Techniques Five studies of risperidone in schizophrenia patients were included in the meta-analysis -- the North American Collaborative Trial and International World Collaborative Study, sponsored by Janssen, and three flexible dose trials. The results of the five trials were combined and evaluated using two different meta-analytic techniques to explore the efficacy of risperidone compared to standard neuroleptics. The first meta-analytic technique (the Mantel-Haenszel method) is based on the number of patients who respond or do not respond to medication. The second method (Hedges and Olkin) is based on the mean improvement in the new drug group and in the standard drug group and their standard deviations. Regardless of a worst-case or best-case scenario, both meta-analyses revealed a statistically significant superiority for risperidone over conventional neuroleptics. (See Table 2.)
TABLE 1 Effect of Risperidone on Positive and Negative Symptoms Based on Four Studies of 382 Patients 6 mg dose vs standard neuroleptic
6 to 16 mg dose vs standard neuroleptic
TABLE 2 Risperidone Versus Standard Neuroleptics
* 6 mg dose risperidone chi square = 15.8
Risperidone Versus Standard Neuroleptics
*6 to 16 mg dose risperidone chi square = 10.8
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