Effects Of Atypical Antipsychotics Research Articles

Effects of typical or atypical antipsychotics on cognitive symptoms of the patients with schizophrenia

Effects of typical or atypical antipsychotics on cognitive symptoms of the patients with schizophrenia

Neurocognitive effects of atypical antipsychotics in patients with first-episode schizophrenia

Introduction: Cognitive impairment is a core feature of schizophrenia. The effects of atypical antipsychotics on the cognitive functions of patients with first-episode schizophrenia have not been comprehensively investigated so far. This study aims to compare neurocognitive effects of risperidone, olanzapine, and aripiprazole for first-episode schizophrenia.Methods: The study was a multicenter, randomized, open-label clinical trial. 546 patients were randomly divided into three medication groups, and followed up for 1 year. Cognitive performance was evaluated with a neuropsychological test battery. The Clinical trials.gov ID of the study is NCT01057849.Results: At 6 months, treatment resulted in significant improvements in all three groups in most cognitive domains except verbal learning and memory. At 12 months, three treatment groups had further improvements in three cognitive domains, but visual learning and memory performance dropped back to baseline.Conclusion: All three atypical antipsychotics tested in the study can potentially improve cognitive performance in first-episode schizophrenia, but no significant difference in the degree of improvement was found between drugs.

Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics

SummaryAccumulating evidence suggests that a disruption of early brain development, in which insulin-like growth factor-2 (IGF-2) has a crucial role, may underlie the pathophysiology of schizophrenia. Our previous study has shown that decreased serum IGF-2 was correlated with the severity of psychopathology in patients with schizophrenia. Here we conducted a prospective observation trial to investigate the effects of atypical antipsychotics on serum IGF-2 level and its relationship with clinical improvements in schizophrenia patients. Thirty-one schizophrenia patients with acute exacerbation and 30 healthy individuals were recruited in this study. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and serum IGF-2 levels were determined using ELISA. We found that schizophrenia patients with acute exacerbation had lower serum IGF-2 levels than control individuals at baseline (P<0.05). After 2 months of atypical antipsychotic treatment, a significant improvement in each PANSS subscore and total score was observed in patients (all P<0.01), and the serum IGF-2 levels of patients were significantly increased compared with those at baseline (203.13±64.62 vs. 426.99±124.26 ng/mL; t =−5.044, P<0.001). Correlation analysis revealed that the changes of serum IGF-2 levels in patients were significantly correlated with the improvements of negative symptoms (r=−0.522, P=0.006). Collectively, our findings demonstrated changes of serum IGF-2 response to improvements of negative symptoms in schizophrenia patients treated with atypical antipsychotics, suggesting that serum IGF-2 might be a treatment biomarker for schizophrenia.

Blood plasma proteomic modulation induced by olanzapine and risperidone in schizophrenia patients

Antipsychotics are the main line of treatment for schizophrenia. Even though there are significant rates of medication drop out due to side effects and limited response of approximately 50% of patients. This is likely due to incomplete knowledge in how these drugs act at the molecular level. To improve treatment efficacy during the critical early stages of schizophrenia, we aimed to identify molecular signatures at baseline (T0) for prediction of a positive response to the atypical antipsychotics olanzapine and risperidone after 6 weeks (T6) treatment. Blood plasma samples were processed and analyzed by label-free quantitative shotgun proteomics using two-dimensional nano-liquid chromatography, coupled online to a Synapt G2-Si mass spectrometer. Data were obtained in MSE mode (data-independent acquisition) in combination with ion-mobility (HDMSE). We were able to identify a potential panel of proteins that might predict a positive outcome to olanzapine and risperidone treatment. The proteins found to be differentially abundant between T0 and T6 in good responders compared to poor responders were analyzed in silico for enrichment pathways and found to be mostly involved with immune system functions. This data can contribute to better understand the biochemical signaling mechanisms peripherally triggered by antipsychotic medication and eventually used to develop surrogate biomarker tests to help improve treatment outcomes and guide development of new treatment approaches. SignificanceThe application of proteomics to the study of the atypical antipsychotic effects on the blood plasma proteome from schizophrenia patients could help in the search for new targets to improve the current therapies, as well as in the development of new therapeutic strategies. In this original article, we provided clues that atypical antipsychotics might be associated with good response by modulating proteins that play a role in inflammation and/or immune system pathways. In addition, the proteins with differential abundance found in the comparison between good and poor responders at the baseline might compose a signature for prediction of response effectiveness.

Effects of Atypical Antipsychotics on Neuroactive Vitamins in Patients With Schizophrenia.

In schizophrenia, neuroactive vitamins A/D/E play vital neuroprotective roles in its pathophysiological processes. During medical treatment, atypical antipsychotics, including aripiprazole, amisulpride, olanzapine, and paliperidone, were widely used at present. However, their impact on vitamin metabolism in vivo remained unclear. In this study, we conducted a case-control research to investigate the impacts of antipsychotics on vitamin metabolism. Schizophrenic patients (n = 163), who were divided into 5 groups (aripiprazole group, amisulpride group, olanzapine group, paliperidone group, nonmedication group) according to their different medication patterns, and healthy controls (n = 75) were involved. The concentrations of vitamin A/D/E and antipsychotics were measured using liquid chromatography-tandem mass spectrometry methods. Compared with healthy controls, significantly lower vitamin D and E concentrations were found in the nonmedication group after covariance analysis adjusting for age, sex, albumin, bilirubin, triglyceride, and cholesterol. We found that aripiprazole could affect vitamin D concentrations in vivo, and a positive correlation between aripiprazole concentrations and vitamin D concentrations (r = 0.319, P = 0.025) was observed in aripiprazole group. Such result revealed the very first observation for the influence of atypical antipsychotics medication toward vitamin status in vivo. Our study showed that low concentrations of vitamin D and E in vivo could be associated with schizophrenia, suggesting that hypovitaminosis may lead to a vulnerability to schizophrenia. More importantly, aripiprazole may potentially benefit the patients through improving their vitamin D status in vivo.

T196. THERAPEUTIC MANAGEMENT IN MULTIPLE SCLEROSIS AND SCHIZOPHRENIA SPECTRUM DISORDERS DUAL DIAGNOSIS

BackgroundMultiple sclerosis has been suggested as a potential vulnerability factor for schizophrenia and other psychotic disorders, and there is a hypothesis about a common etiology in a subgroup of schizophrenia and multiple sclerosis [1]. Immune-related single-nucleotide polymorphisms have been associated with schizophrenia and genetic pleiotropy between schizophrenia and multiple sclerosis has been reported, but not between bipolar disorder and multiple sclerosis (at the level of major histocompatibility complex) [2]. As new data about the involvement of genetically-determined immune factors in the susceptibility to schizophrenia appear (e.g., variants of complement factor 4 possibly linked to synaptic pruning during brain development) [3] the interest for finding therapeutic targets within the immune system for psychotic disorders is also increasing.MethodsThree patients diagnosed with both schizophrenia spectrum disorders (schizophrenia n=2, or schizoaffective disorder, depressive type n=1), female, mean age 43.7, with a history of psychotic disorder for at least one year, were monitored during 6 months using Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), Clinical Global Impressions – Severity (CGI-S), Columbia-Suicide Scale for Schizophrenia (CSSRS), Calgary Depression Scale (CDS), Multiple Sclerosis Severity Scale (MSSS), and the Extrapyramidal Symptom Rating Scale (ESRS). None of these patients presented other organic or psychiatric co-morbidity, and they were on active treatment for their multiple sclerosis throughout the 6-month duration of psychiatric evaluation. All patients were initiated on a new antipsychotic, because of the lack of efficacy of the previous agents, or due to their lack of therapeutic adherence. A patient was initiated on olanzapine 15 mg/day, while the other two received risperidone 4 mg/day. The antipsychotic doses were flexible during the 6 months of the treatment, with olanzapine between 10 and 20 mg daily, and risperidone between 3–6 mg daily. The initial PANSS mean score was 92.2, with a GAF of 35.3 and a CGI-S of 5.1.ResultsAll patients reached the week 24 visit of their evaluation, and the overall tolerablity of the antipsychotic treatment was good. All patients had lower PANSS scores at week 24 (the mean decrease was -25.6 points compared to baseline), higher GAF scores (+27.7 points), and lower CGI-S (-2.5 points). CSSRS did not change significantly during the 6 months, the score remained at minimum value, and the CDS scores also remained constantly under 3. ESRS recorded transient increments, but at week 12 they were not significantly increased reported at the baseline values, and no corrective medication was recommended throughout the 6 months for extrapyramidal symptoms. MSSS mean score did not change significantly at week 12 compared to its baseline values.DiscussionAtypical antipsychotics are efficient and well tolerated in patients with schizophrenia and multiple sclerosis dual diagnosis. The positive effects of atypical antipsychotics maintained during the 6 months of monitoring and they had no significant impact over the multiple sclerosis symptoms.ReferencesArneth BM. Multiple sclerosis and schizophrenia. Int J Mol Sci 2017;18(8):1760.Andreassen OA, Harbo HF, Wang Y, et al. Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci. Mol Psychiatry 2015;20(2):207–14.Kroken RA, Sommer IE, Steen VM, et al. Constructing the immune signature for schizophrenia for clinical use and research; an integrative review translating descriptives into diagnostics. Front Psychiatry 2018;9:753.

A typical antipsychotic treatment induced gradually expanding white matter alterations in healthy individuals with persistent auditory verbal hallucinations—an artificially controlled pilot study

Objective The aim of this study was to explore the effects of atypical antipsychotics (AaPs) on brain white matter (WM) tracts in healthy individuals with auditory verbal hallucinations (Hi-AVHs). Methods We analyzed neuroimaging, AVH symptoms, and cognitive assessment data obtained from 39 Hi-AVHs who reported being distressed by persistent AVHs and volunteered to receive AaP treatment. We used tract-based spatial statistics (TBSS) and t tests to explore AaP pharmacotherapy effects on AVH symptoms and brain WM alterations in Hi-AVH subjects. Results TBSS and t tests revealed WM alterations after AaP treatment, relative to pretreatment observations. Although AaPs alleviated AVH symptoms, WM alterations in these subjects expanded over 8 months of AaP treatment, encompassing most major WM tracts by the end of the observation period, including the corpus callosum, arcuate fasciculus, cortico-spinal tracts, anterior commissure, and posterior commissure. Conclusions The worsening of AaP-associated WM alterations observed in this study suggest that AaPs may not be a good choice for the treatment of Hi-AVHs despite their ability to alleviate AVHs.

Budget impact analysis of long acting injection for schizophrenia in Japan

Aims: To estimate the budgetary impact of providing additional reimbursement for long acting injections for schizophrenia patients in psychiatric hospital settings in Japan to improve patient outcomes in schizophrenia.Methods: Budget impact analysis of change in reimbursement policy using a prevalence-based model over a five-year time horizon. The results are reported as net change in expenditure and consequent cost/savings in Japanese yen at the time of analysis.Results: The budget impact analysis shows that an increase in reimbursement for LAIs could lead to cumulative savings of an estimated 36.6 billion JPY over five years. These savings result from a decrease in hospitalization costs and an increased usage of LAI (assumed to be 10%). Based on the sensitivity analysis, the saving estimates are most sensitive to change in market share of generic and branded oral antipsychotics.Limitations: Historical data were used to estimate the future costs of drug and hospitalization; however, it is not the best predictor of future, hence a source of potential bias. A good level of treatment adherence with oral antipsychotics was assumed, which is generally not the case; therefore, we might have overestimated the effectiveness of oral atypical antipsychotics. Additionally, the drug cost due to reimbursement might have also been overestimated because in clinical setting, the increase of LAI use may not have reached 10% of the market share. Lastly, patients’ behavior was derived from models, which may have loosely approximated the reality.Conclusions: An additional reimbursement for the use of LAI in schizophrenia patients is likely to be cost neutral/cost saving and should be considered as a policy option to improve patient outcomes and budget sustainability.

A comparative study of effectiveness, safety and cost effectiveness of olanzapine, risperidone and aripiprazole therapy in schizophrenia

Background: Schizophrenia is the most common psychotic disorder and responsible for approximately half of long-term psychiatric hospitalizations. Antipsychotic medications reduce the psychotic symptoms and prevent relapses. The choice of drug for treatment of schizophrenia depends on many issues, including effectiveness, cost, side-effect burden, availability, and tolerability. Many studies have compared antipsychotic drugs with one another, but no broad consensus has been reached. Our study compares the clinical effectiveness, safety and cost effectiveness of atypical antipsychotics in our setting.Methods: This was an observational, prospective study in which schizophrenia patients receiving either olanzapine, risperidone or aripiprazole were enrolled. Patients were followed up for 3 months. Evaluation of effectiveness was done by analysing mean reduction in PANSS score. Analysis of ADRs was done using WHO causality scale and Hartwig and Siegel severity scale. Cost analysis was done by comparing all three groups in term of cost range of antipsychotic drugs per improvement in PANSS score during the study period.Results: In the present study, the average dose of antipsychotic drugs received by a patient per day was 8.83±2.98 mg in olanzapine group, 4.76±1.12 mg in risperidone group and 20.43±8.5 mg in aripiprazole group. Mean reduction in PANSS score from baseline to 12 weeks was 23.79% in olanzapine group, 25.41% in risperidone group and 24.65% in aripiprazole group. Conclusions: All the groups were equally effective in reduction in PANSS score while risperidone was the most cost effective.

Plasma levels of 3-methoxy-4-hydroxyphenylglycol levels, number of hospitalization and cognitive function predicts the cognitive effect of atypical antipsychotic monotherapy in patients with acute schizophrenia.

Although the effects of atypical antipsychotics with regard to improving neurocognitive function are not sufficiently high. The present study applied an atypical antipsychotic monotherapy for patients with acute schizophrenia to (1) examine the percentage of patients who respond well to this treatment, (2) explore the factors that predict response (e.g. the improvement of neurocognition), and (3) identify the factors associated with improved neurocognitive function. We studied 40 patients with acute schizophrenia who had received atypical antipsychotic monotherapy for 24 weeks. The following parameters were evaluated at baseline and 24 weeks after the start of treatment: psychotic symptoms, neurocognitive function, and blood biological markers including homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, and brain-derived neurotrophic factor. Marked improvements in neurocognitive function were noted in 7.5%-25% of patients. The factors that significantly predicted neurocognitive function improvement were the frequency of hospitalization (verbal memory and verbal fluency), 3-methoxy-4-hydroxyphenylglycol (verbal fluency and executive function), and verbal memory (working memory). Approximately 20% of the patients showed good response to treatment with antipsychotics. Frequency of hospitalization, 3-methoxy-4-hydroxyphenylglycol level, and other parameters predicted responsiveness to these drug therapies. Thus, it might be useful to apply these factors to predict responses to treatment.

Whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects.

BackgroundStroke/thromboembolic events, infections, and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events.MethodsWhole transcriptome signatures were generated for SH‐SY5Y cells treated with amisulpride, risperidone, and volinanserin using RNA sequencing. Bioinformatic analysis was performed that scored the association between antipsychotic signatures and expression data from 415,252 samples in the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) repository.ResultsAtherosclerosis, venous thromboembolism, and influenza NCBI GEO‐derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (eg, brain derived neurotrophic factor [BDNF], platelet derived growth factor receptor [PDGFR]‐beta, tumor necrosis factor [TNF], transforming growth factor [TGF]‐beta, selenoamino acid metabolism, and influenza infection).ConclusionsThese findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.

P.364 Assessment of memory-guided saccade parameters to reveal short-term atypical anti-psychotic treatment effects in schizophrenia

P.364 Assessment of memory-guided saccade parameters to reveal short-term atypical anti-psychotic treatment effects in schizophrenia

Assessment of Long Term Metabolic Effects of Atypical Antipsychotics in Schizophrenia Patients

Abstract Background and aims. Patients with schizophrenia have a shorter life expectancy than normal population partially due to the metabolic side effects of antipsychotic treatment. The aim of this study is to evaluate the long-term evolution of the metabolic syndrome in chronic schizophrenia patients on fixed second generation antipsychotics (SGA). Material and method. The components of metabolic syndrome were evaluated repeatedly in a minimum 6 months and maximum 2 years follow-up period. The presence of metabolic syndrome (MetS) and metabolic risk scores (cMetS) according to National Cholesterol Education Program Adult Treatment Panel III were calculated and compared in time. In the prevalence, incidence and normalization logistic regression studies included all the known risk factors together with the follow-up period. Finally, all these rates were compared depending on the type of SGA. Results. Only cMetS, waist circumference and diastolic blood pressure presented significant increase in the follow-up period which was in average 385.5 days. The prevalence of MetS at base-line was 39.4%, which increased to 48.5% after the follow-up period. The calculated incidence of 30% was associated with a 23.1% rate of normalization. Logistic regression studies revealed as independent risk factors the age and base-line cMetS/weight for incidence and for normalization. In the aripiprazole group the normalization rate exceeded the incidence rate (33.3% vs 20%). Conclusions. The results emphasize the highly dynamic character of the metabolic syndrome even in chronic schizophrenia patients with fixed SGA regimen. The normalization of MetS is a possibility that should not ignored. The age and weight continue to remain independent risk factors, thus close monitoring in elderly and strict weight control plan are necessary. Aripiprazole showed better safety profile, but more extensive studies are required for definitive conclusions.

Long-acting atypical antipsychotics in schizophrenia: A systematic review and meta-analyses of effects on functional outcome.

Impairment in psychosocial function is common in schizophrenia. Long-acting injectable atypical antipsychotics are thought to enhance psychosocial function by boosting adherence. However, no systematic review has examined the effects of long-acting injectable atypical antipsychotics on psychosocial function in clinical trials. We searched major databases including Medline/PubMed, PsychINFO, EMBASE, CINAHL, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and Clinical Trial Registries for randomised controlled trials that compared long-acting injectable atypical antipsychotics to placebo, oral antipsychotic medications or long-acting injectable atypical antipsychotics for all years till 2018, with no language limits. We performed a systematic review of findings on change in psychosocial function and its predictors in the included reports. Data on change in psychosocial functioning were meta-analysed using a random-effects model. A total of 26 studies were included in systematic review, and 19 studies with 8616 adults, 68.1% males were meta-analysed. Long-acting injectable atypical antipsychotics were superior to placebo (standardised mean difference = 0.39; 95% confidence interval = [0.32, 0.47]; p < 0.001; I2 = 0%; 9 studies) and oral antipsychotic medications (standardised mean difference = 0.16; 95% confidence interval = [0.01, 0.31]; p = 0.04; I2 = 77%; 10 studies) for improved psychosocial function and superiority was maintained in short- and long trials. Poor psychosocial function was predicted by longer treatment duration, severe symptoms, poor cognition and poor insight. Functioning was assessed by either a single or a combination of measures, but was not the primary outcome in most studies. Other sources of bias include poor blinding and reporting of randomisation. Long-acting injectable atypical antipsychotics are beneficial for recovery of psychosocial function in comparison with placebo, but the magnitude of superiority over oral antipsychotic treatment was small. Severe psychopathology at baseline predicted poor psychosocial function. Future effectiveness trials in which post-randomisation involvement is kept to a minimum, and psychosocial function is included as primary outcome a priori, are needed to capture the real-world impact of long-acting injectable atypical antipsychotics and to address methodological biases.

Assessment of Reported Comparative Effectiveness and Safety of Atypical Antipsychotics in the Treatment of Behavioral and Psychological Symptoms of Dementia

Atypical antipsychotics offer modest effectiveness compared with placebo but with serious safety risks, including a boxed warning for the risk of death in the treatment of behavioral and psychological symptoms of dementia (BPSD). Their comparative effectiveness and safety are not fully known. To assess the relative benefits and safety of atypical antipsychotics in the treatment of BPSD shown in randomized clinical trials using network meta-analysis. PubMed/MEDLINE, Embase, PsychINFO, and Cochrane Library were searched from their inception until May 31, 2018. Key terms included dementia and atypical antipsychotics. Randomized clinical trials comparing any atypical antipsychotic with another atypical antipsychotic or with placebo were included in the analysis. Two independent reviewers used a standardized data extraction and quality assessment form. Random-effects network meta-analyses were performed. Effect sizes were reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with 95% CIs. In addition to ORs, the surface under the cumulative ranking curve (SUCRA) was ascertained, which represents the percentage of the effectiveness or safety for each treatment compared with a hypothetical treatment that would be ranked first without uncertainty. The primary effectiveness outcome assessed was the Neuropsychiatric Inventory (NPI); secondary effectiveness outcomes were the Brief Psychiatric Rating Scale (BPRS) and Cohen-Mansfield Agitation Inventory (CMAI). The primary safety outcomes were death and cerebrovascular adverse events (CVAEs). Secondary safety outcomes were extrapyramidal signs/symptoms; somnolence/sedation; falls, fracture, or injury; and urinary tract infection/incontinence. Seventeen studies (5373 patients) were included. The mean (SD) age of all participants was 80.8 (3.1) years, and most were women (3748 [69.8%]). Compared with placebo, aripiprazole was associated with improvement in outcomes on the NPI (SMD, -0.17; 95% CI, -0.31 to -0.02), BPRS (SMD, -0.20; 95% CI, -0.35 to -0.05), and CMAI (SMD, -0.30; 95% CI, -0.55 to -0.05); quetiapine was associated with improvement in outcomes on the BPRS (SMD, -0.24; 95% CI, -0.46 to -0.01), and risperidone was associated with improvement in outcomes on the CMAI (SMD, -0.26; 95% CI, -0.37 to -0.15). Differences between atypical antipsychotics were not significant for effectiveness, death, or CVAE. Compared with placebo, risperidone (OR, 3.85; 95% CI, 1.55-9.55) and olanzapine (OR, 4.28; 95% CI, 1.26-14.56) were associated with increased risk of CVAEs. The SUCRA estimated relative ranking of treatments suggested that aripiprazole might be the most effective and safe atypical antipsychotic and that olanzapine provides the least benefit overall; however, these results should be interpreted with caution where point estimates (OR and SMD) show that there is no statistically significant difference. This network meta-analysis supports the existence of a trade-off between the effectiveness and safety of atypical antipsychotics in the treatment of BPSD and confirms that a single most effective and safe treatment option does not exist. Clinicians should individualize the assessment of safety risks against expected benefits when prescribing these medications to patients with dementia.

C-Fos expression response to olanzapine, amisulpride, aripiprazole, and quetiapine single administration in the rat forebrain: Effect of a mild stress preconditioning

Antipsychotics have been shown to stimulate different forebrain areas, whereas some of them are sensitive to stress. In the present study, effect of a single administration of olanzapine (OLA), amisulpride (AMI), aripiprazole (ARI), and quetiapine (QUE) on the activity of cells in the striatal dorsolateral (stDL) area, the periventricular zone (peVZ), the septal ventrolateral (seVL) nucleus, and the accumbens nucleus shell (shACC) and core (coACC) was investigated in male rats preconditioned with a mild stress complex (CMS) for 20 days. The objective of the study was to extend the anatomical-functional knowledge on the mechanism of selected antipsychotics with the goals: 1) to analyze the ability of the selected antipsychotics to induce c-Fos protein expression in the above mentioned forebrain structures and to map the pattern of their topography and 2) to find out whether longer-lasting mild stress preconditioning may modify the impact of the selected antipsychotics on the activity of cells in the forebrain areas in adult rats. Ten groups of rats were used. CMS complex contained five stressors: cage crowding, air-puff noising, wet bedding, predator stress, and forced swimming. AMI (20 mg/kg), OLA (5 mg/kg), QUE (15 mg/kg), and ARI (10 mg/kg/b.w.) were administered intraperitoneally and 90 min later the animals transcardially perfused by fixative. c-Fos was visualized by ABC complex. In unstressed animals, OLA and ARI elevated c-Fos expression in all areas studied, AMI and QUE in all areas except stDL, seVL and coACC, shACC FL-2 (shACC posterior level), respectively. CMS potentiated the effect of AMI in coACC, and QUE in shACC FL-2 and suppressed the effect of AMI in peVZ, and ARI in peVZ and seVL. The present data provide new insights into activity of cells in response to CMS challenge, which might be helpful in understanding the diverse clinical effects of atypical antipsychotics.

Impact of the CYP2D6 phenotype on hyperprolactinemia development as an adverse event of treatment with atypical antipsychotic agents in pediatric patients.

Treatment with atypical antipsychotics is today the election therapy for different types of psychosis, but there is a high incidence of endocrine and metabolic disturbances. One of the major enzymes involved in the metabolism of antipsychotics is CYP2D6. Depending on the existing CYP2D6 alleles, the metabolic capacity of the enzyme may vary from very low to very high, so that patients can be grouped into four phenotypic groups: slow, intermediate, extensive (normal), and fast metabolizers. The aim of the study is to find a relationship between the individual intervariability of CYP2D6 and the incidence of hyperprolactinemia as side effect of atypical antipsychotics. A total of 81 patients with schizophrenia or bipolar disorders, median age 15.74 ± 4years, were enrolled in the study and prescribed the following atypical antipsychotics: risperidone, aripiprazole, and olanzapine. They were evaluated at 6, 12, and 18months after the initiation of treatment. Using the TaqMan Genotyping Assay, it has been identified the presence of the CYP2D6*4 allele in 28 patients, representing 34.56% of the total of 81 patients in the study, and CYP2D6*3 allele was identified in 15 patients and the presence of CYP2D6*41 to 11 patients. The allele CYP2D6*5 has not been present to the study patients. The study group has 44 patients which are extensive metabolizers (54%), 34 intermediate metabolizers (42%), and 3 poor (slow) metabolizers (4%). For the slow and intermediate metabolizers, atypical antipsychotics determined a significant increase of prolactinemia with high risk of adverse events.

Cost/effectiveness of aripiprazole vs. olanzapine in the long-term treatment of schizophrenia

Introduction/Objective. Although effectiveness of atypical antipsychotics in patients with schizophrenia is mostly similar, there are significant differences in adverse effects rate and treatment costs, making comparison of their cost/effectiveness ratios essential for optimal drug choice. The aim of this study was to compare cost/effectiveness of aripiprazole and olanzapine in long-term treatment of schizophrenia. Methods. A four-state, three-month cycle Markov model was built to compare aripiprazole and olanzapine. The model assumed that patients who relapse on treatment with both aripiprazole and olanzapine are further treated with clozapine. The perspective of the National Health Insurance Fund was chosen, and the period covered by the model was 10 years. The model results were obtained after Monte Carlo microsimulation of a sample with 1,000 virtual patients. Both multiple one-way and probabilistic sensitivity analysis was made. Results. After base-case analysis aripiprazole was dominated by olanzapine, as net monetary benefit was negative (-390,341.96 ?} 29,131.53 RSD) and incremental cost/effectiveness ratio (ICER) was above the willingness-to-pay line of one Serbian gross domestic product per capita per quality-adjusted life year (QALY) gained. Multiple one-way and probabilistic sensitivity analysis confirmed results of the base case simulation. Conclusion. Olanzapine has more beneficial cost/effectiveness ratio than aripiprazole for long-term treatment of schizophrenia in Serbian milieu.

Efekti tipičnih i atipičnih antipsihotika na kognitivne funkcije kod pacijenata sa psihotičnim poremećajima

Introduction: Although before, the prioritization of positive and negative symptoms of schizophrenia over neurocognitive impairment was of the highest importance, recent scientific achievements suggest that the disrupted neurocognitive functions are the core clinical feature of schizophrenia. Both general and specific cognitive functions are impaired. Earlier studies promoted atypical antipsychotics as the ones with the pro-cognitive effect, but an increasing number of recent studies do not demonstrate their superiority on neurocognitive improvement over typical antipsychotics. Aim: The aim of this study was to compare the effects of atypical antipsychotics and a combination of typical and atypical antipsychotics on cognitive functions in patients with psychotic disorders. Furthermore, the effects on gender and duration of disorder on the cognitive functioning of patients on different types of antipsychotic therapy were evaluated, as well as the effect of anticholinergic biperiden in patients receiving combined antipsychotic therapy. Subjects and Methods: This academic IV phase quasi-experimental clinical study included 50 hospitalized patients at the Clinic for Psychiatry at the Clinical Center of Vojvodina, who were divided into two groups of 25 subjects-one consisted of patients who had been on treatment with atypical antipsychotics for six weeks at least, while the second group included patients who had been on combined therapy with typical and atypical antipsychotics for minimum of six weeks. Within the second group, two subgroups could have been recognized; one with 12 patients who were co-medicated with anticholinergic biperidine, whilst the rest of 13 patients were using only combined antipsychotic therapy. All patients' cognitive functions were tested using the Mini-Mental State Examination (MMSE) and the results have been analyzed and compared using t-test. Results: There were no statistically significant difference in cognitive functioning between patients using atypical or combined antipsychotic therapy (p>0.05). There is no statistically signifi cant effect on gender or duration of disorder on cognitive functioning in the two compared groups (p>0.05). There is a statistically significant negative effect on cognition due to the co-medication with biperiden during combined antipsychotic therapy (p<0.05). Conclusions: Atypical antipsychotics did not show superiority in the improvement of neurocognitive functions over combined therapy with atypical and typical antipsychotics. Further investigations should be carried out in order to determine the exact effect of antipsychotics on cognitive functions.

The effect of atypical antipsychotics on hormonal and biochemical parameters in patients with schizophrenia

Objective of this research is to study the effect of atypical antipsychotics on hormonal and biochemical parameters in patients with schizophrenia. Materials and methods . A comprehensive clinical, psychopathological and laboratory examination of 96 patients with schizophrenia (F20 according to ICD-10) who were hospitalized in the Department of Endogenous Disorders of the Scientific Research Institute of Mental Health of the Tomsk Scientific Research Center and received second-generation antipsychotics, was carried out. The Positive and Negative Syndromes (PANSS) scale (in the adapted Russian version of SCI-PANSS) was filled for a psychometric assessment of the severity and dynamics of schizophrenia symptoms in all patients upon admission to hospital and at discharge after 4 weeks. The laboratory study included determination of the concentration of total cholesterol (TC), triglycerides (TG), high density lipoproteins (HDL), glucose, insulin and cortisol in blood serum with the calculation of lipoproteins with low (LDL) and very low (VLDL) density, atherogenic index (IA) ) and insulin resistance (HOMA-IR). Statistical data processing was performed using the standard application package SPSS Statistic (V. 17.) for Windows. Differences were considered statistically significant at p ≤0.05. Results . The pronounced effect of four-week treatment with atypical antipsychotics on the metabolism of glucose [glucose (p <0.001) and HOMA-IR (p=0.036)] was established. A statistically significant increase in TC (p=0.005), TG (p <0.001), VLDL (p <0.001), IA (p <0.001) and TG/HDL (p <0.001) after four weeks of treatment with atypical antipsychotics. No statistically significant changes in hormone levels were established. Conclusions . The results demonstrate the pronounced effect of a four-week treatment with atypical antipsychotics on glucose metabolism, a change in glucose level and insulin resistance index. A typical atherogenic change in the serum lipid spectrum is shown. These indicators are laboratory markers of the risk of cardiovascular disease and diabetes, and therefore careful monitoring of metabolic disorders in patients with schizophrenia is necessary.