2012; McGurk et al. 2004; Minzenberg et al. 2004; Pae, 2013; Tracy et al. 1998]. The effects of the muscarinergic antagonism had not been investigated thoroughly in a clinical setting at the initiation of the study.
Sertindole and olanzapine are both atypical antipsychotics [Nielsen and Nielsen, 2009], with differences in receptor affinities, especially with sertindole not showing any marked affinity for the muscarinergic receptor whereas olanzapine has a high affinity and an antagonizing effect [Correll, 2010]. In addition, Inhibitors,research,lifescience,medical sertindole does not show a tendency to induce Parkinsonism in clinical trial treated patients [Seeman and Tallerico, 1998], thereby excluding the need for concomitant anticholinergic drugs. In this study we aimed to investigate the effects of sertindole and olanzapine Inhibitors,research,lifescience,medical on cognition in patients diagnosed with schizophrenia, utilizing a computerized cognitive test battery. Material and methods Design The study is a 12-week, double-blind randomized head-to-head study in which all participants are randomized to either sertindole or olanzapine. Participants were recruited in Denmark and Sweden, but due to poor recruitment in the Swedish center (one participant) only data from Denmark are reported. Primary outcome was change in cognition as measured by the CANTAB test battery (Cambridge Cognition Ltd, Inhibitors,research,lifescience,medical Bottisham, Cambridge, UK) [Lowe and Rabbitt, 1998; Sahakian and Owen, 1992].
Participants were randomized 1:1 to receive either sertindole or olanzapine. The initial dose of sertindole was 4 mg, which was increased by 4 mg every fourth day until 16 mg was reached. Treatment doses of sertindole were between Inhibitors,research,lifescience,medical 16 and 24 mg. The dose of 24 mg was only used in exceptionally cases, as the risk of QTc prolongation is dose dependent. The initial dose of olanzapine was 10 mg and the flexible dose range was between 10 and 20 mg. All participants were treated with a tablet of sertindole or an identical placebo tablet, and an Inhibitors,research,lifescience,medical encapsulated olanzapine tablet or a dummy tablet, so participants were either on sertindole or olanzapine throughout the study period. Block size randomization was conducted by the pharmacy
Carnitine dehydrogenase by computer and randomization block size was variable. Disclosure of blinding was done after reporting of PANSS values to the pharmacy. Participants Men and women, between the ages of 18 and 65 years, diagnosed with an International Classification of Diseases, 10th revision diagnosis of schizophrenia F20.0–F20.3 and F20.9 (paranoid, hebephrenic, catatonic, undifferentiated or unspecified subtypes) were eligible for participation [World Health Organization, 1992]. Patients were excluded if an electrocardiogram showed QTc prolongation or if QT prolongation over 500 ms was shown after initiation of study drugs. Before inclusion, normal levels of potassium or magnesium were required, as well as a negative pregnancy test for women. All women were required to use a safe form of birth control.