SS-09-01

Evaluating antipsychotics: Methodological challenges

W. Fleischhacker. Psychiatrische Univers. -Klinik Innsbruck, lnnsbruck, Austria

A broad range of study designs are employed to evaluate the pharmacotherapy in psychiatry. These range from small exploratory open studies via the gold standard of the randomized placebo-controlled clinical trial to large pragmatic naturalistic studies. Outcome criteria have traditionally focused on improvement of psychopathological symptoms and on the assessment of safety and tolerability issues. More recently additional outcomes, previously considered as "soft criteria", such as quality of life and social adjustment have gained importance. Various rating scales and assessment instruments are available to reliably quantify changes in the parameters described above. Ideally, the evaluation of psychiatric treatments should be based on studies of different design and scope to minimize the risk of misinterpretation. For instance, while any open clinical trial is subject to an observer bias, RCT's have been shown to lead to a selection bias, that may hamper the generalizability of the results obtained. An earlier use of non-inferiority trials, which have so far been used exclusively in post registration studies is also encouraged. As the focus of safety/tolerability assessment has shifted from a strong emphasis on extrapyramidal motor dysfunctions to non-motor adverse events such as metabolic and sexual dysfunctions, cardiac safety and others, clinical trials designs need to account for this by including more specific side effect rating scales and laboratory tests. In addition, subjective tolerability and compliance need to be assessed with more vigor. In conclusion, a modem evaluation of pharmacotherapy must go beyond traditional measures of psychopathological symptoms and include real life outcomes such as quality of life, psychosocial reintegration and the subjective perception of a drug's benefit/risk profile.

SS-09-02

Efficacy beyond the PANSS

H.-J. Mӧler. Ludwig-Maximilians-Universität Klinik für Psyehiatrie, Müinchen, Germany

With the advent of the second generation antipsychotics the concept of efficacy criteria has changed. In the time of traditional neuroleptics, efficacy in reducing positive symptoms was the primary and more or less single goal. Nowadays efficacy is also conceptualised in terms of negative symptoms and even depressive symptoms. A large amount of evidence is available that second generation antipsychotics are advantageous in this respect. However, there is even a focus on additional domains of efficacy, domains which are not primarily covered by applying the widely used standardised rating scales. Especially cognitive disturbances are seen as a major treatment goal in schizophrenia. There is evidence that second generation antipsychotics have more pronounced influences on these cognitive disturbances than traditional neuroleptics. These positive findings appear not to be mediated by differences in symptoms or side effects between second generation antipsyehotics and the traditional neuroIeptics. The subjective dimension of the patients themselves is increasingly also included as an outcome domain. Especially quality of life measurements are more and more frequently integrated as a part of the drug evaluation in schizophrenia research. Several results indicate that second generation antipsychotics are favourable compared to traditional neurolcptics in terms of quality of life. Although this does not appear to increase patient compliance to a great degree, as is demonstrated particularly by long-term studies, at least the principal acceptance of second generation antipsyehotics by patients is better than it used to be with the traditional neuroleptics.

SS-09-03

EUFEST: A randomized pragmatic long-term trial in first episode schizophrenia

R. Kahn, H. Boter. University Medical Center, GA Utrecht, Netherlands

Objective: Second generation antipsychotics have proven to be at least as effective as the earlier antipsychotics in treating schizophrenia and preventing relapse. Clinical trials have also persistently shown a lower incidence of extrapyramidal side effects with the newer agents. However, most of the studies comparing the second generation drugs with the older antipsychotics have been conducted in more or less chronic patients with schizophrenia. Another problem is even more pervasive: studies examining drug effects have mostly been conducted in highly selected samples, for instance excluding patients with concomitant drug abuse or patients who are aggressive, suicidal, or less likely to comply with the prescribed regimen. Thus, the generalizability of the studies assessing the efficacy of the newer, atypical antipsychotics is limited at best. Finally, it has been argued that the beneficial effects of the new antipsychotics would fail to materialize when compared with lower doses of first-generation antipsychotics. This issue, however, has not been tested in first-episode schizophrenia patients. The European First Episode Schizophrenia Trial (EUFEST) is developed to answer these questions. In an unselected group of 500 first-episode patients this open randomized clinical trial compares the treatment with regular doses of one of four second generation antipsychotics (amisulpride, quetiapine, olanzapine, and ziprasidone) to that of a low dose of haloperidol on lost of retention to allocated treatment in one year follow-up. Secondary outcomes are psychopathology, side effects, compliance, quality of life, patients' needs, and substance abuse. The study is currently running in 14 European countries involving 49 sites.

SS-09-04

Quality of life as an important outcome parameter

J. Bobes Garcia. University of Oviedo Med. Dept., Psychiatl T Area, Oviedo, Spain

Objective: The aim of this presentation is to assess the frequency of Obesity, Metabolic Syndrome and Cardiovascular Disease in Spanish population treated with atypical antipsychotics and haloperidol.

Methods: A retrospective, cross-sectional, multicenter study was carried out by 49 Spanish Psychiatrists (the CLAMORS Collaborative Group). 517 evaluable, consecutive outpatients meeting DSM-IV criteria for Schizophrenia, Schizophreniform or Schizoafective Disorder, and treated with haloperidol (n = 84), amilsupride (n =78), olanzapine (n = 106), quetiapine (n= 79), risperidone (n:81) and ziprasidone (n = 89) for at least 12 weeks, were recruited.

Results: The treatments with the highest number of patients with Obesity were quetiapine (52%) and amisulpride (51.5%), and the lowest ziprasidone (32,9%). The treatment with the highest number of patients with any component of Metabolic Syndrome were qutiapine for abdominal obesity (52,2%) and dyslipidemia (43.1%), and olanzapine for hipertrygliceridemia (46.5%), hypertension (54.3%) and glucose intolerance (21.0%). Finally, according to ATP-III, the treatments with the hightest number of patients with very high/moderate risk of Heart Disease were olanzapine (51.9%) and haloperidol (51.2%).

Conclusion: The frequency of Obesity and Metabolic Syndrome, and the risk of Heart Disease, was different according to the type of antipsychotic therapy.