Use Of Atypical Antipsychotic Drugs Research Articles

Associations between constipation risk and lifestyle, medication use, and affective symptoms in patients with schizophrenia: a multicenter cross-sectional study.

To investigate the association between lifestyle and atypical antipsychotic drug use in patients with schizophrenia and the risk of constipation and to assess the impact of anxiety and depressive symptoms on constipation risk. Cross-sectional convenience sampling was employed, and 271 participants aged 20-65 were enrolled. Data were collected via a structured questionnaire comprising participants' demographic data, medication information, dietary behavior assessment, and the Baecke Physical Activity Questionnaire, Beck Depression Inventory-II, and Beck Anxiety Inventory. IBM SPSS 24.0 with multivariate logistic regression was used for data analysis. We performed a subgroup analysis of anticholinergic drugs via multivariate logistic regression. In total, 180 participants had functional constipation; risk factors included female sex, anxiety symptoms, depressive symptoms, and quetiapine and aripiprazole use. Patients who drank more than 3,000cc of water daily or used risperidone were less likely to have functional constipation. Depressive and anxiety symptoms were risk factors even after adjusting for sex, use of anticholinergics and laxatives, consuming two servings of fruit, consuming three servings of vegetables, consuming more than 3,000cc of water daily, physical activity, medical comorbidity, chlorpromazine equivalent dose, and atypical antipsychotic use. Similar associations were found for two affective symptoms and functional constipation in the subgroup analysis of anticholinergic drugs. The prevalence of functional constipation in patients with schizophrenia was 66.4%. The risk factors included female sex, anticholinergics, aripiprazole, quetiapine, and depressive and anxiety symptoms. Risperidone users and those who drank 3000cc of water daily were less likely to have constipation.

Treatment of tardive dyskinesias with vitamin E: A case series

IntroductionTardive dyskinesia is usually persistent, irreversible involuntary movement of the tongue, lips, face, trunk and extremities in patients taking long-term dopaminergic antagonist drugs. Although it is mostly associated with the use of neuroleptics, cases of tardive dyskinesia existed before the discovery of these agents. Patients with schizophrenia and other neuropsychiatric disorders are particularly at risk for tardive dyskinesia because they are exposed to neuroleptics and anticholinergic agents for longer periods than healthy individuals. Free radicals are thought to be probably involved in the pathogenesis of tardive dyskinesia. Vitamin E is a fat-soluble antioxidant, and it is thought to be effective in the treatment of antipsychotic-associated tardive dyskinesia, as it has a cytotoxic free radical-binding effect.ObjectivesIn this poster presentation, it was aimed to evaluate the clinical results of the treatment of tardive dyskinesia with high-dose vitamin E in four inpatients with serious mental illness and long-term antipsychotic use. In addition, the treatment of tardive dyskinesia will be discussed in the light of current literature data.MethodsIn the case report, there are three patients with schizophrenia and one with mild mental retardation. They were treated with 1600 IU of vitamin E per day. The patients continued their vitamin E treatment for 90 days. The severity of tardive dyskinesia of the patients was measured by Abnormal Involuntary Movement Scale (AIMS).ResultsAt the end of the 90 day treatment, the AIMS measurements of the subjects decreased 72,7%, 73,3%, 72,2% and 80% respectively.Image:ConclusionsIn our clinic, we observed that patients using long-term typical antipsychotics were prescribed antipsychotics in unindicated situations or in high doses, patients with high risk for tardive dyskinesia were not taken into consideration when planning treatment, and we encountered cases of tardive dyskinesia despite the widespread use of atypical antipsychotic drugs in hospitalized patients. The use of benzodiazepines is restricted especially in elderly individuals due to their side effects and the risk of addiction in long-term use. Although the clinical importance of vitamin E is unknown, it is preferred because it can be used with a low risk of side effects, considering that it can prolong bleeding time. Although the results of a review of tardive dyskinesia treatment do not suggest that vitamin E reliably improves tardive dyskinesia symptoms, our experience shows that patients benefit from vitamin E treatment. In this regard, there is a need for studies that will be conducted with a large sample and compare the effectiveness of vitamin E with the treatments known to be effective in tardive dyskinesia.Disclosure of InterestNone Declared

Comparison of the Effect of Olanzapine, Haloperidol and Quetiapine on the Resolution of Individual Delirium Symptoms in ICU Patients: A Double-blind, Clinical Trial Study

Introduction: Considering that haloperidol is a first-generation antipsychotic drug known as the primary treatment for delirium, it causes extrapyramidal side effects, and olanzapine and quetiapine are second-generation antipsychotic drugs without extrapyramidal side effects. In this study, we compared the effects of olanzapine and quetiapine with haloperidol on the resolution of individual delirium symptoms.
 Materials and Methods: In a double-blind clinical trial study, 90 patients admitted to the ICU in three groups received haloperidol at a dose of 2.5 mg/day, while in the second group, patients received olanzapine at an amount of 2.5- 10.5mg/day. In the third group, they received quetiapine at a dose of 12.5 to 75 mg daily. Then, patients' sedation levels were measured according to RASS criteria, and their disease severity was evaluated according to APACHE II criteria.
 Results: During 15 work shifts in the first, second, third, seventh, and tenth days, sedation scores in all three groups decreased significantly (p-v <0.05), and all three drugs were effective in subsiding patients' agitation in 10 days. In the evening and night of the first day, the sedation score in the quetiapine group was higher than the other two groups; however, after the treatment period and in the work shifts of the seventh and tenth days, the patients in the quetiapine group had the lowest sedation score on the RASS scale. Also, after starting drug treatment in the three groups, the mean severity of the disease was significantly different in the three groups (p-v <0.05), so that on the third and seventh day, the olanzapine group had the lowest and the haloperidol group had the highest disease severity. But on the tenth day, the severity of the disease was lowest in the patients in the quetiapine group.
 Conclusion: As a result of this study, it was found that quetiapine, olanzapine, and haloperidol had the most significant effect in improving the sedation level of patients with delirium according to RASS criteria, respectively, and the use of atypical antipsychotic drugs had more favorable outcomes than typical ones in controlling patients' delirium.

Can atypical antipsychotic drugs cause hepatotoxicity?

IntroductionNeuropsychiatric drugs account for 16% of drugs that can lead to hepatotoxicity and psychiatric patients can have multiple comorbidities that can increase the incidence of liver disorders such as alcoholism, drug abuse and polymedication. The continuous use of atypical antipsychotic drugs (AAD) has raised questions over their tolerability over endocrine, metabolic and cardiovascular systems. They are also associated with mild elevation of aminotransferases and occasionally cause idiosyncratic liver injury with varying phenotypes. Hepatotoxicity is defined based on biological parameters such as elevation of alkaline phosphatase enzyme, SGPT, SGOT and GGT or clinical abnormalities (jaundice and hepatitis).ObjectivesThis work reviewed the current available evidence on the hepatic damage produced by AAD.MethodsNon-systematic review of the literature with selection of scientific articles published in the past 10 years; by searching Pubmed and Medscape databases using the combination of MeSH descriptors. The following MeSH terms were used: atypical antipsychotic drugs; hepatotoxicity; hepatic; Olanzapine; Clozapine; Risperidone; Aripiprazol; Paliperidone.ResultsAtypical Antipsychotic Drugs are generally well tolerated and hepatic alterations are in general very low or rare. The cases published were observed with Clozapine, Olanzapine and Risperidone. Atypical Antipsychotic drugs have a better profile than Chlorpromazine.ConclusionsIn conclusion, the hepatic injury generally occurs within the first weeks of treatment and is usually reversible with drug withdrawal. Hepatic check-ups may be relevant, especially in the beginning of treatment.DisclosureNo significant relationships.

Bipolar disorder, pregnancy, COVID-19: Electroconvulsive therapy is needed!

IntroductionTreating pregnant women with bipolar disorder is among the most challenging clinical endeavors. Patients and clinicians are faced with difficult choices at every turn, and no approach is without risk. Many primary mood stabilizers have been associated with risk of congenital malformations. In the last 15 years, there has been an increase of antepartum use of atypical antipsychotic drugs, many of which could be viable alternatives to mood stabilizers. Electroconvulsive therapy has been recommended as a safe and efficacious treatment of bipolar depressive and manic episodes in pregnant women.ObjectivesThis case presents a 24-year-old woman, with COVID-19 infection, that underwent an acute manic episode at her 20-weeks-pregnancy. The goal was to stabilize the patient by the use of electroconvulsive therapy.MethodsThe patient was admitted in isolation in the psychiatric ward. Treatment was started with olanzapine 20mg/d and lorazepam 4mg/d. The patient maintained psychotic agitation that required higher dosage, while on the second week of isolation the PCR test was negative. After six weeks of treatment severe manic symptoms continued and electroconvulsive therapy was started.ResultsShe received 10 electroconvulsive therapy sessions. The patient showed a substantial clinical improvement after the seventh administration. She gave birth at 37 weeks, with no complications during labor (Apgar 9/10).ConclusionsElectroconvulsive therapy has been shown as a suitable option for patients with severe psychiatric disorders in the pregnancy period, either medication resistant illness and psychotic agitation.DisclosureNo significant relationships.

Atypical Antipsychotics Augmentation in Patients with Depressive Disorder and Risk of Subsequent Dementia: A Nationwide Population-Based Cohort Study

While atypical antipsychotic medications are widely used for treating depressive disorders, their long-term effects on the risk of subsequent dementia have not been studied adequately. To investigate whether the risk of dementia differs according to the use of atypical antipsychotic drugs, and compare the effects of antipsychotic agents on dementia risk in individuals with late-life depressive disorders. A nationwide population-based retrospective cohort study was conducted using data from the National Health Insurance Service-Senior Cohort of South Korea. Atypical antipsychotic dosages were standardized using a defined daily dose, and the cumulative dosage was calculated. Participants were observed from January 2008 to December 2015. Cox proportional hazard regression analysis was used to estimate the hazard ratios. The cohort included 43,788 elderly adults with depressive disorders: 9,901 participants (22.6%) were diagnosed with dementia. Findings showed that atypical antipsychotics were prescribed to 1,967 participants (4.5%). Compared with non-users, users of atypical antipsychotics experienced a significantly higher risk for dementia with an adjusted hazard ratio (aHR) of 1.541 (95% confidence interval [CI], 1.415-1.678). A cumulative dose-response relationship was observed (test for trend, p < 0.0001). Among atypical antipsychotics, risperidone displayed the highest risk for dementia (aHR 1.767, [95% CI, 1.555-2.009]). In this study of elderly individuals with depressive disorders, atypical antipsychotic use was associated with a significantly higher risk of subsequent dementia. Healthcare professionals should be aware of this potential long-term risk. A limitation that should be mentioned is that we could not exclude patients with bipolar depression.

Ten-Year Risk of Cardiovascular Disease in Patients with Bipolar Disorder

Patients with bipolar disorder (BPD) are less likely to seek treatment for cardiovascular diseases (CVD) despite the two fold increased CVD-related death rate in BPD. The aim of this study was to evaluate the relationship between clinical variables, exercise characteristics and 10-year risk of CVD in patients with bipolar I disorder (BPD-I). The study was carried out with 106 euthymic BPD-I patients who were followed up at the Mood Disorders Centers of Bakırköy Hospital for Mental and Neurological Diseases and Selcuk University Faculty of Medicine. The physical activity status of the patients were evaluated with the Godin Leisure-Time Exercise Questionnaire (GLTEQ) and the prospective 10-year risk of CVD was assessed by the QRISK®2-2017 - CVD risk algorithm. Mean age of the patients were 39.5±8.6 years. The mean QRISK2 score of the patients was 3.64±0.46 %, which did not differ with respect to the gender. Patients' mean healthy heart age (QAGE) was 8.49±6.46 years ahead of their current age. There was a weak negative correlation between GLTEQ total score and QRISK2 score (r= 0.168), but this was not statistically significant. However, statistically significant positive correlations were determined between the categorical QRISK2 score and the disease age of onset (RR:1.18; 95%CI:1.09-1.28), treatment duration (RR:1.16; 95%CI:1.05-1.29) and the inclusion of atypical antipsychotic agents in the treatment received (RR:5.99; 95%CI:1.12-31.90). A strong positive correlation was determined in this study between the QRISK2 score and the use of atypical antipsychotic drugs in the treatment of the BPD-I patients. It is important to identify patients diagnosed with bipolar disorder with a high risk of developing CVD to review the psychiatric treatment and to encourage the patients for preventive approaches.

Polymorphic variants of xenobiotic metabolism genes and body mass index in schizophrenia patients receiving antipsychotic therapy

The use of atypical antipsychotic drugs has made metabolic disorders one of the most common side effect of pharmacotherapy for schizophrenic patients. The aim of this study was to assess the contribution of polymorphic variants of genes of the P450 cytochrome system to changes in body mass index in patients with schizophrenia. As a result of the study, we did not identify significant associations of genotypes and alleles of the studied polymorphic variants of the CYP2D6, CYP1A2, CYP2C19 genes with weight gain in patients with schizophrenia of Russian nationality of the Siberian region receiving antipsychotic therapy and can revealed neither protective nor predisposing effects. Metabolic syndrome and, increase in body weight especially, are complex side effect, and further studies is needed to increase successful exploration and identification of the genetic component and assess contribution.

The utilization and challenges of Japan's MID-NET® medical information database network in postmarketing drug safety assessments: A summary of pilot pharmacoepidemiological studies.

To examine the potential role of Medical Information Database Network (MID-NET® ), a newly established Japanese medical information database network, in postmarketing drug safety assessments through the characterization of its advantages and limitations in five pilot studies. The pilot studies were designed to address three major objectives in postmarketing drug safety assessments, ie, the examination of actual drug utilization, the impact of safety-related regulatory actions, and drug-associated risks. The five studies were conducted on the following topics: (a) utilization of codeine-containing products and its relationship with respiratory depression, (b) impact of a Dear Healthcare Professional letter on hypocalcemia incidence associated with denosumab (Ranmark® ) use, (c) risk of acute myocardial infarction associated with antidiabetic drug use, (d) risk of glucose metabolism disorders associated with atypical antipsychotic drug use, and (e) prospective monitoring of abnormal laboratory test results during new drug prescriptions. The pilot studies were successfully conducted and demonstrated the value of MID-NET® in postmarketing drug safety assessments. In particular, the ability to utilize laboratory test results as objective clinical indicators is a major advantage of this database. Potential limitations include a relatively small sample size and a lack of patient-level data linkages among hospitals. MID-NET® was confirmed to be a valuable database for postmarketing drug safety assessments. The use of laboratory test results to define clinical outcomes may allow more objective and accurate analyses to be conducted. These studies furthered our understanding of the characteristics of MID-NET® , including its advantages and limitations.

To Study the Correlation of Vitamin D and Metabolic Syndrome in Schizophrenia

ObjectivesSchizophrenia, a highly heterogeneous &amp; biological disorder of the brain, is associated with biochemical, metabolic &amp; cardiovascular derangements. Vitamin D is known to have the role as a neuro‐modulator/neuroprotection in the brain. Prevalence of metabolic syndrome in schizophrenia is very high &amp; it further increases with the use of atypical antipsychotic drugs. The present study is conducted to correlates the association between serum levels of vitamin D and parameters of metabolic syndrome in the patient of schizophrenia.MethodsVenous blood sample was collected from 50 adult schizophrenic patients. Serum vitamin D and parameters of metabolic syndrome like waist circumference, blood pressure (systolic as well as diastolic), fasting blood glucose (FBS), triglycerides (TG) and high‐density lipoprotein (HDL) was measured. An analysis was done using the SPSS version 20.0 for Windows (Chicago, Illinois, USA). Mean and the standard deviation is calculated for the continuous variables. Pearson's correlation was used to assess the relationship between vitamin D level and parameters of metabolic syndrome.ResultsSystolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBS) and triglycerides (TG) were found to have an inverse relation with serum vitamin D level. Vitamin D level was found in the deficient category (&lt;20 ng/dl) in most of the patients. Waist Circumference and high‐density lipoprotein (HDL) was found to have a direct correlation with vitamin D in the patient of schizophrenia of the population.ConclusionsThe study showed the possible clinical role of vitamin D level in initiating changes in the biochemical and physical parameters of metabolic syndrome in patients of schizophrenia even though the sample size is small. It might signify the role of Vitamin D in the pathogenesis of metabolic syndrome in schizophrenia.Support or Funding InformationThe present study is a part of my intramural project funded by All India Institute of Medical Sciences, Jodhpur, Rajasthan, IndiaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Antipsychotic Treatment Associated With Increased Mortality Risk in Patients With Dementia. A Registry-Based Observational Cohort Study

ObjectiveTo assess all-cause mortality patients with dementia treated with typical and atypical antipsychotic drugs (APDs). DesignRegistry-based cohort study. Setting and participantsA total of 58,412 patients diagnosed with dementia and registered in the Swedish Dementia Registry were included in the study. Of the study sample, 2526 of the patients were prescribed APDs. Of these, 602 patients were prescribed typical APDs and 1833 patients were prescribed atypical APDs. Ninety-one patients were prescribed both typical and atypical APDs. MeasurementsAll-cause mortality based on Swedish Cause of Death Register. Adjusted hazard ratios of mortality were calculated according to class of APDs (typical or atypical) prescribed. Final models were adjusted for age at dementia diagnosis, sex, Charlson comorbidity index, living arrangement, and Mini-Mental State Examination. ResultsIn the adjusted models, use of APDs at the time of dementia diagnosis was associated with increased mortality risk in the total cohort (hazard ratio = 1.4; 95% confidence interval 1.3–1.5). After stratifying for dementia types, increased mortality risks associated with APDs were found in patients with Alzheimer's disease, mixed dementia, unspecified dementia, and vascular dementia. Higher risk for mortality was found with typical APDs in patients with mixed and vascular dementia and with atypical APDs in patients with Alzheimer's disease, mixed, unspecified, and vascular dementia. Furthermore, in patients with Alzheimer's disease who had typical APDs, use lower risk of death emerged in comparison with patients with atypical APDs. Conclusions/ImplicationsBoth the use of atypical and typical APDs increased the risk of death in patients with dementia even after adjusting for differences in basic characteristics between groups. Although we cannot rule out the influence of residual confounding, these results would seem to add to studies suggesting caution in APD prescription for patients with dementia.

A Comparison of Pediatric and Adult Safety Studies for Antipsychotic and Antidepressant Drugs Submitted to the United States Food and Drug Administration

To examine the differences in the adverse drug reaction (ADR) profile of antipsychotic and antidepressant agents between pediatric and adult patients in studies submitted to the Food and Drug Administration (FDA) during the drug development process. Clinical trials in adult and pediatric patients were conducted by sponsors as part of the drug development programs for antipsychotic and antidepressant agents, and ADR information was collected as part of those trials and submitted to the FDA. Data collection was conducted by reviewing publicly available FDA-authored reviews and FDA-approved product labels for 10 drugs with an antipsychotic or an antidepressant indication from 2007 to2017. There were 308 drug and ADR combinations for the 10 drugs and drug combinations with 113 (36.7%) having a significantly different incidence in pediatric patients compared with adults. Sixty-eight (60.2%) of these ADRs had a significantly higher incidence in pediatric patients than in adults. Sedation was higher in 6 of the 10 drugs and drug combinations with risk differences ranging from 9.6 to 36.6%. This analysis indicates that there were significant differences between the pediatric and adult safety profiles of antipsychotic and antidepressant drugs. Sedation was the major ADR associated with the use of atypical antipsychotic drugs in pediatric patients. Clinicians caring for children should consider the ADR profile when prescribing antipsychotics and antidepressants in pediatric patients.

Quetiapine Induced Autoimmune Hemolytic Anemia in a Child Patient: A Case Report

Autoimmune hemolytic anemia is a disease characterized with destruction of erythrocytes as a result of antibody produce against patient’s own erythrocytes and anemia. Autoimmune hemolytic anemia can be roughly stratified into two groups according to serological features and secondary causes including drugs induced hemolytic anemia. Drugs induced autoimmune hemolytic anemia is very rare in pediatric patients. Even though hematological side effects such as leucopenia, agranulocytosis, eosinophilia, thrombocytopenic purpura and aplastic anemia might occur due to psychotropic drug use; to the best of our knowledge there is no autoimmune hemolytic anemia case due to quetiapine, an atypical antipsychotics, in literature. We hereby describe the first child case of autoimmune hemolytic anemia during quetiapine treatment.We also are pointing out that one should keep in mind serious hematological side effects with atypical antipsychotic drug use with this case report.

PND2 - Risk of Death from the Use of Atypical Antipsychotic Drugs for the Treatment of Neuropyschiatric Symptoms of Dementia: A Network Meta-Analysis

The aim of this study is to assess the comparative risk of death from the use of atypical antipsychotics in the treatment of behavioral and psychological symptoms of dementia. This systematic review and network meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Electronic and hand searches for relevant studies were performed from PubMed, Embase, Cochrane library, Clinicaltrials.gov and PsychInfo databases until September 2017. The inclusion criteria were defined as follows: (1) randomized, placebo-controlled trial; (2) adult patients with dementia using atypical antipsychotics; (3) reporting death outcome; (4) minimum follow-up period of 6 weeks. The network meta-analysis was performed using a random effects model. A total of 15 trials comparing four atypical antipsychotics (aripiprazole, olanzapine, quetiapine and risperidone), enrolling 4,076 participants were included. The network meta-analysis revealed that there is no statistically significant difference for the risk of death in using any of the atypical antipsychotics when compared with placebo and to each other [OR, (95%CI): aripiprazole vs placebo, 1.61 (0.39,6.65); olanzapine vs placebo, 1.70 (0.72,4.01); quetiapine vs placebo, 1.59 (0.72,3.52) and; risperidone vs placebo, 1.26 (0.67,2.35); risperidone vs aripiprazole, 0.78 (0.17,3.68); risperidone vs olanzapine, 0.74 (0.30,1.82); risperidone vs quetiapine, 0.79 (0.30,2.08)]. Based on Surface Under the Cumulative Ranking Curve (SUCRA), placebo was ranked as the best treatment approach (81.5%); followed by risperidone (57.8%); followed by aripiprazole (40.3%) followed by quetiapine (37.4%); then olanzapine (33.0%). According to the network meta-analysis, when compared with each other and when compared to placebo, there is no statistically significantly risk of death from the use of atypical antipsychotics. Cumulative ranking probabilities suggests that risperidone is the safest treatment approach after placebo.

New Trends in the Treatment of Schizophrenia.

This article are to describe current trends in the treatment of schizophrenia and the most interesting new approaches to optimizing outcome and fostering the development of new schizophrenia treatments. Increasing utilization of diverse types of atypical antipsychotic drugs (AAPDs), e.g. clozapine- type serotonin (5-HT)2A and weak dopamine (DA) D2 antagonist, amisulpride, a D2/D3/5-HT7 antagonist, and cariprazine, a D3 partial agonist with additional neurotransmitter targets, is occurring as their advantages in efficacy, especially for cognitive impairment and mood symptoms, and side effects are becoming appreciated. Typical APDs, e.g. haloperidol, are diminishing in favor because of their EPS, especially, tardive dyskinesia (T D) and appreciation that reducing D2 receptor stimulation is not the only means to treat psychosis. Some of the mechanisms inherent in various AAPDs, e.g. 5-HT2A inverse agonism, and D3 receptor partial agonism, are now recognized as effective treatments for psychosis. A new focus on treating the cognitive impairment associated with schizophrenia (CIAS) has emerged via mechanisms such as stimulation of acetyldraline receptor with muscarinic and nicotinic receptor agonists, but demonstrating their efficacy in trials is proving elusive. Pharmacogenetic strategies which may lead to personalized treatment of schizophrenia are emerging but have not yet succeeded in being widely reimbursable. Transcranial stimulation and cognitive enhancement therapy are more common but more evidence for their efficacy is needed. The heterogeneity of the pathophysiology of the various domains of schizophrenia requires a diversity of treatments that are best met by the expert use of AAPDs at the current time. Pharmacogenetic efforts are consistent with new evidence that multiple genes are involved in the risk for schizophrenia and the effectiveness of AAPDs.

Neuroleptic malignant syndrome in a patient with stable dose of olanzapine

Neuroleptic malignant syndrome (NMS), a potentially fatal consequence due to typical neuroleptics, has been described so far. In the past few years, there has been increased use of atypical antipsychotic drugs. Cases of NMS related to atypical neuroleptics, such as olanzapine, are less common in spite of increasing cases reported in literatures. Here, we report a case of NMS in a patient with bipolar affective disorder on maintenance treatment with 5 mg olanzapine for the last 7 year. He was successfully treated with bromocriptine and discharged in stable condition in 10 days.

Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney

ABSTRACTThe use of atypical antipsychotic drugs (APD) was reported to be associated with adverse effects on the kidneys. Thus, the aim of this study was to examine whether APD exerted their adverse effects by interfering with the renal antioxidant defense system. Male 3-mo-old Wistar rats were treated for 28 d with ziprasidone (ZIP), clozapine (CLO), or sertindole (SER) using a daily dose recommended for antipsychotic drug therapy. The expression and activities of antioxidant enzymes superoxide dismutase (SOD) type 1 and type 2, catalase (CAT), glutathione reductase (GR), and glutathione S-transferases (GSTs) activity were measured in the kidneys. Changes in the kidneys were also evaluated histologically. Ziprasidone, CLO, and SER reduced renal SOD type 1 and type 2 activities. Decreased CAT activity was observed only in SER-treated rats. An inhibition in GR activity and increased activity of GST was found only after treatment with CLO. Histological analysis showed dilatation of proximal tubules in kidneys with all three drugs. In conclusion, data indicate that redox disturbances may contribute to renal morphologic alterations in proximal tubules in rats treated with all APD.

H3 histamine receptor antagonist pitolisant reverses some subchronic disturbances induced by olanzapine in mice.

The use of atypical antipsychotic drugs like olanzapine is associated with side effects such as sedation and depression-like symptoms, especially during the initial period of the use. It is believed that the occurrence of these undesirable effectsis mainly the result of the histamine H1receptors blockade by olanzapine. In addition, use of olanzapine increases the level of triglycerides in the blood, which correlates with growing obesity. The aim of this study was to investigate the influence of pitolisant – H3 histamine antagonist - on subchronic olanzapine-induced depresion-like symptoms, sedation and hypertriglicerydemia. Forced swim test was conducted to determinate depressive-like effect of olanzapine and antidepressive-like activity during the co-administered pitolisant. The test was performed after the first and fifteenth day of the treatment of the mice. The spontaneous activity of the mice was measured on the fourteenth day of the treatment with a special, innovative RFID-system (Radio-frequency identification system) – TraffiCage (TSE-Systems, Germany). Triglyceride levels were determined on the sixteenth day of the experiment after 15 cycles of drug administration. Daily olanzapine treatment (4 mg/kg b.w., i.p., d.p.d) for 15 days significantly induces sedation (p < 0.05) and prolongs immobility time in forced swim tests (FST) in mice (p < 0.05); and also elevates the level of triglycerides (p < 0.05). Administration of pitolisant (10 mg/kg b.w., i.p.) subsequentto olanzapine normalizes these adverse effects. This study presents a promising alternative for counteracting some behavioral changes and metabolic disturbances which occur in the early period of treatment with antipsychotic drugs.

Prevalence of neuroleptic-induced movement disorders: an 8-year follow-up study in chronic schizophrenia inpatients

Background: Atypical antipsychotic drug use by schizophrenia patients in Estonia increased from 32% in 2004 to 61% in 2009.Aims: To assess the prevalence of neuroleptic-induced movement disorders in the Estonian institutionalized population of schizophrenia patients twice over a period of eight years, before and after introduction of atypical antipsychotic drugs using DSM-IV criteria.Methods: DSM-IV criteria and specific rating scales were used to evaluate the prevalence of neuroleptic-induced movement disorders among 72 patients who participated in the study in 2009 compared to 99 patients who participated in 2001.Results: Despite increased use of atypical antipsychotics in the study population (up to 30% from 20%), the proportion of movement disorder-free population remained the same over 8 years – 38.9% in 2001 versus 38.4% in 2009. There were significant intra-individual fluctuations. Use of a typical antipsychotic resulted in an almost seven times higher risk of tardive dyskinesia after 8 years. Doses of antipsychotic drugs had no effect on the severity of neuroleptic-induced movement disorders.Conclusions: Unfortunately, in 18% of patients the switch of medication from typical to atypical did not change the overall prevalence of neuroleptic-induced movement disorders in the group. The long-term benefit of atypical antipsychotics requires further research in patients who are treated with antipsychotics for years.

Effects of risperidone treatment on the expression of hypothalamic neuropeptide in appetite regulation in Wistar rats

Although the use of atypical antipsychotic drugs has been successful in the treatment of schizophrenia, they can cause some complications in the long-term use, including weight gain. Patients using these drugs tend to disrupt treatment primarily due to side effects. The atypical antipsychotic mechanism of action regulates a number of highly disrupted neurotransmitter pathways in the brains of psychotic patients but may also cause impairment of neurohormonal pathways in different brain areas. In this study, we investigated the circulating levels of hypothalamic neurohormones, which are related to appetite regulation; neuropeptide Y (NPY); alpha melanocyte stimulating hormone (α-MSH); cocaine and amphetamine regulated transcript (CART); agouti-related peptide (AgRP); and leptin in male Wistar rats, which were treated with risperidone, a serotonin antagonist, for four weeks. Alterations in the mRNA expression levels of these candidate genes in the hypothalamus were also analyzed. We hypothesized that risperidone treatment might alter both hypothalamic and circulating levels of neuropeptides through serotonergic antagonism, resulting in weight gain. Gene expression studies revealed that the mRNA expression levels of proopiomelanocortin (POMC), AgRP, and NPY decreased as well as their plasma levels, except for NPY. Unexpectedly, CART mRNA levels increased when their plasma levels decreased. Because POMC neurons express the serotonin receptor (5HT2C), the serotonergic antagonism of risperidone on POMC neurons may cause an increase in appetite and thus increase food consumption even in a short-term trial in rats.