SNAP-25 gene polymorphisms and weight gain in schizophrenic patients.

Drug induced weight gain is a serious side effect of several atypical antipsychotics. As genetic factors play an important role in the homeostasis of hunger/satiety we tried to replicate a preliminary previous finding about an impact of three polymorphisms in the synaptosomal-associated protein of 25kDa (SNAP-25; sites MnlI, TaiI and DdelI in the 3(')-UTR) on clinical response and antipsychotic induced weight gain. We genotyped 162 schizophrenic patients being treated in monotherapy with atypical antipsychotics and 312 healthy control subjects for the three polymorphisms in the SNAP-25 gene using PCR. PANSS scores and weight were measured weekly for a minimum of five weeks. We found significant associations between the TaiI and MnlI polymorphisms and serum triglyceride levels at baseline and for the DdelI polymorphism and weight gain. In conclusion our study can at least partly replicate the previous findings concerning the impact of SNAP-25 gene polymorphisms on weight gain during antipsychotic treatment.

T- and B-lymphocytes in patients with schizophrenia in acute psychotic episode and the course of the treatment.

Schizophrenia is associated with alterations of the immune system. There are, however, only limited data dealing with immune parameters in unmedicated schizophrenic patients and the course of these parameters during treatment. In this study, we monitored CD19+ (B)- and CD3+ (T)-lymphocytes in the course of antipsychotic treatment. Forty patients diagnosed with an acute exacerbation of schizophrenia were tested before and after 3 days, 2 weeks, 4 weeks and 3 months of treatment with antipsychotics. The percentages of CD19+- and CD3+ -lymphocytes were analysed by flow cytometry using fluorescence conjugated anti-CD19 and anti-CD3 antibodies. Twenty healthy volunteers served as controls. In the acute state of psychosis, a significant reduction of the CD3+ -lymphocyte subpopulation was observed, while the percentage of CD19(+)-lymphocytes was increased. Both subpopulations levelled to those of the control group in the course of treatment. As expected, the levels of the immune parameters did not change in the healthy controls during the course of the study. The observed alterations of the CD19+ - and CD3+ -lymphocytes in the acute state of psychosis especially in patients with the paranoid subtype of schizophrenia, and the "normalization" during the observation period are discussed under the aspect of the immune hypothesis of schizophrenia, in particular of the type-1/type-2 imbalance hypothesis.

Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics.

OBJECTIVE: In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome. METHOD: The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug. RESULTS: Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings. CONCLUSIONS: Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies.

Patients' acceptance of the deltoid application of risperidone long-acting injection.

OBJECTIVE: Recently risperidone long-acting injection (RLAI) was approved for alternative injection into the deltoid muscle in addition to the already established injection into the gluteal muscle. For the first time two different injection locations of a long-acting antipsychotic injection can be offered to patients. Their actual acceptance is of key interest. EXPERIMENTAL PROCEDURES: We surveyed 60 patients stabilized on gluteal RLAI therapy in our depot outpatient clinic. Participants were offered the possibility of switching to the alternative deltoid injection in a standardized manner. Prior to switching patients scored the extent of perceived pain and experienced level of shame through the present gluteal injection therapy on a 7-point-scale. Patients choosing to switch were followed up after three months and asked to report on their individual experience. RESULTS: Switching to the deltoid application was chosen by 34 out of 60 patients. Three months later 15 patients were still receiving deltoid injections. The main reason for their staying with the deltoid injection was improved practicability as reported by these patients and 13 out of 15 patients clearly preferred the new location over the gluteal application. The main reason for returning to the gluteal injection was the pain experienced through the injection in the deltoid. Patients' initial decision whether to switch was not correlated with either perceived pain or the experienced level of shame through the preceding gluteal injections. CONCLUSIONS: The application of RLAI in the deltoid muscle is viewed as an alternative to the injection in the gluteal muscle by a considerable number of patients. Nevertheless, some patients experience increased injection pain through this application location while others perceive the switch as beneficial in terms of practicability. Therefore offering both injection locations with their respective pros and cons should become standard in the RLAI treatment offered.

Long-term observation of patients successfully switched to risperidone long-acting injectable: A retrospective, naturalistic 18-month mirror-image study of hospitalization rates and therapy costs.

Abstract Objective. The aim of the present 18-month retrospective study was to assess the association between a continuous long-term treatment with risperidone long-acting injectable (RLAI) of at least 12 months and in-patient care of patients suffering of schizophrenia or schizoaffective disorder. Furthermore we wanted to assess the cost-effectiveness of a long-term treatment with RLAI. Methods. In a mirror-image design, data of 119 patients with schizophrenia and schizoaffective disorder who were switched to RLAI treatment were analyzed retrospectively. Hospitalization rates, the duration of inpatient treatment and the overall treatment costs were assessed 12 and 18 months after switching to RLAI and compared to the equivalent time preceding the switch. Results. After 12 and 18 months of RLAI treatment, the mean reduction of inpatient care was 27.4 and 38.4 days per patient, respectively, compared to the equivalent time period prior to switching to RLAI (Wilcoxon P < 0.001). The overall savings in drug and institutional-care costs were 21.1 and 21.9%, respectively. Conclusions. Patients receiving RLAI for at least 12 months showed a reduction in inpatient days and lower overall treatment costs.