Effects Of Atypical Antipsychotic Medications Research Articles

Effect of Atypical Antipsychotic Medications on the Risk of Obstructive Sleep Apnea in Individuals With Schizophrenia

Background and Objective Weight gain and obesity could be side effects of taking atypical antipsychotic medications. They are major risk factors for obstructive sleep apnea. The purpose of this study was to investigate effects of atypical antipsychotic medications on the risk of obstructive sleep apnea in individuals with schizophrenia and control groups.Methods In this cross-sectional study, 123 patients with schizophrenia and 107 participants were selected from hospital staff and students using purposive sampling. Data were collected using structured clinical interview and Berlin questionnaires.Results Results showed that the risk of obstructive sleep apnea was significantly higher in individuals with schizophrenia. Age, body mass index, and phases of schizophrenia showed meaningful relationships with the duration of taking atypical antipsychotic medications with the risk of obstructive sleep apnea. However, the type of atypical antipsychotic medications did not have a significant relationship with the risk of obstructive sleep apnea.Conclusions Patients with schizophrenia treated with atypical antipsychotic medicationshave a higher risk of obstructive sleep apnea.

Increasing Monitoring and Management of Side Effects from Atypical Antipsychotic Medications in Children with Developmental Disabilities

Background: Behavior difficulties such as irritability, aggression, and repetitive and challenging behaviors are common in children with Autism Spectrum Disorder (ASD) and other developmental disabilities (DD). Atypical antipsychotic medications (AAPM) are currently first-line pharmacological agents for treatment of these behaviors. However, there are significant associated adverse effects of AAPM in children, including excessive weight gain, abnormal involuntary movements, and laboratory abnormalities. A recent chart review of children with ASD treated with AAPM revealed that 40% had overweight or obesity (OW/OB). Problem: Despite significant long-term health risks, the Division of Developmental and …

P.1.006 - Chronic administration of clozapine increases the level of serotonin 5-HT1A receptor heterodimerisation with 5-HT2A or D2 receptors in the mouse cortex

Background and Aims It is well established that dopamine D2 receptors and serotonin 5-HT1A and 5-HT2A receptors play an important role in neurotransmission and that alterations in their functioning are implicated in many psychiatric disorders, including schizophrenia. Only since the 1990s has there emerged an appreciation of the effects of atypical antipsychotic medications, which can be beneficial for the negative (cognitive) symptoms via combined action at dopamine as well as serotonin and other classes of neuroreceptors [1]. In recent years, various lines of evidence have revealed the formation of physiologically active GPCR heteromers in the plasma membrane [2,3]. GPCR heteromers offer a novel set of drug targets because the functional association of heteroreceptors, which are partners in the complex, can result in pharmacological and functional properties distinct from those of the monomers (and homomers). Clozapine (CLZ), an antipsychotic drug currently used in the clinic but still being the object of basic studies designed to search for its unique molecular features, has been also shown to act via various heterodimers [4]. Therefore, in the present study, we investigated whether atypical antipsychotic drug, CLZ, and typical drug, haloperidol (HAL), administered to mice acutely or repeatedly affected the formation of heterodimers of dopamine D2–5-HT1A receptors as well as 5-HT1A–5-HT2A receptors in the mouse brain cortex. Materials and Methods Mice C57Bl/6J were treated CLZ in two doses; however, HAL was administered in one dose. In line with our previous behavioral studies, we used ketamine to induce cognitive deficits in mice [5]. To visualize co-localization D2–5-HT1A receptors and 5-HT1A–5-HT2A receptors in the mouse brain immunohistochemistry was used. Proximity ligation assay (PLA) was used to accurately visualize, for the first time, GPCR heterodimers in the native tissue. Data were analyzed using two-way analysis of variance (ANOVA) with Bonferroni post-test to compare all groups of the experiments. Results Our study confirmed the co-localization of D2–5-HT1A and 5-HT1A–5-HT2A receptors in the mouse brain cortex. Low-dose clozapine (0.3 mg/kg) administered repeatedly increased the level of D2–5-HT1A heterodimers in the mouse prefrontal and frontal cortex ([F(2,22)] = 4.630; p Conclusion Our results provide interesting evidence that antipsychotic drugs have effect on the level of D2–5-HT1A as well as 5-HT1A–5-HT2A receptors heterodimerization, which may represent a novel, interesting therapeutic target for many psychiatric disorders.

Genome-Wide Association Study Suggested the PTPRD Polymorphisms Were Associated With Weight Gain Effects of Atypical Antipsychotic Medications.

Antipsychotic-induced weight gain (AIWG) is a serious concern in therapy with antipsychotic medications. To identify single nucleotide polymorphisms (SNPs) associated with AIWG, we conducted a genome-wide association study (GWAS) for antipsychotic treatment. The discovery cohort consisted of 534 patients with schizophrenia, who underwent 8-week treatment with antipsychotics and were genotyped using the Illumina Human 610-Quad BeadChip. The independent replication cohort consisted of 547 patients with schizophrenia, treated with similar antipsychotics, and genotyped using the Sequenom MassARRAY platform. Two hundred and thirty-six drug-naive patients treated with risperidone or quetiapine were analyzed independently. Additionally, we conducted pathway and expression analyses using several public bioinformatics databases. After correction for age and gender, the top 2 genome-wide significant SNPs with AIWG were located in the PTPRD gene (protein tyrosine phosphatase, receptor type D, 9p24-p23; rs10977144, P GWAS = 9.26E-09; rs10977154, P GWAS = 4.53E-08). The third most significant SNP was in the GFPT2 gene (glutamine-fructose-6-phosphate amidotransferase 2, 5q35.3; rs12386481, P GWAS = 1.98E-07). These results were validated in the replication cohort (rs10977144, P Replication = 4.30E-03; rs10977154, P Replication = 6.33E-03; rs12386481, P Replication =7.65E-03). These results were also verified in those patients initially exposed to risperidone and quetiapine (rs10977144, P = 1.97E-05; rs10977154, P = 2.04E-05; rs12386481, P = 1.97E-04). Pathway analyses showed that AIWG may involve in multiple pathways related to metabolic processes. Moreover, PTPRD mRNA might be highly expressed in brain regions, and the SNPs (rs10977144, rs1097154) also showed significant expression quantitative trait locus effects. Our findings indicate that PTPRD polymorphisms might modulate AIWG.

Predictors of Effect of Atypical Antipsychotics on Speech.

Background:Most of the studies have looked into the effect of typical antipsychotics on speech secondary to tardive dyskinesia.Aims:This study was aimed to explore the factors predicting the effect of atypical antipsychotic medications on the production of speech.Materials and Methods:One hundred and forty patients on stable regimen of three or more months on risperidone (92), olanzapine (28), aripiprazole (14), and clozapine (6) were recruited for the study. Speech was assessed by maximum phonation duration task, s/z ratio, diadochokinetic task, acoustic analysis and Frenchay Dysarthria Assessment (FDA). Extrapyramidal symptoms (EPS) were assessed by Simpson Angus scale.Statistical Analysis:Spearman correlation analysis was carried out to find the association between speech parameters and continuous variables. Effect of EPS, duration and dose of antipsychotic treatment on speech parameters was compared using Mann-Whitney test.Results:The risperidone group differ from other antipsychotics groups significantly in s/z ratio (0.07), FDA-total (0.23) and FDA-reflex (0.25). People who took antipsychotic for more than 2 years had lower score of FDA-palate (P = 0.042), and FDA-respiratory (P = 0.04) and higher values in noise-harmonic ratio (P = 0.011) and maximum /fundamental frequency (MFF) for males (P = 0.02). Effect of EPS was seen on MFF for males (spearman correlation coefficient = 0.34) and on almost all sections of FDA (spearman correlation coefficients = -0.2 to -0.33).Conclusion:Both duration of use and propensity of atypical antipsychotics to cause EPS can influence the speech performance of the patients. This information can be useful, particularly in people with the requirement of high quality speech.

Improving Model Specifications When Estimating Treatment Effects across Alternative Medical Interventions

Objective: The purpose of this paper is to critique the list of independent variables commonly used in observational research and test the impact of variables for prior use and treatment history on estimates of treatment effects. Methods: Using data from the California Medicaid program, this study generated a series of OLS estimates of the effect of atypical antipsychotic medications on costs and duration of therapy to illustrate the impact of alternative model specifications on treatment effects. The first sequence of estimates consisted of six model specifications, the last of which included variables reflecting the type of episode defined according to prior treatment history and compliance. The second sequences repeated the specification of the first 6 models but were carried out separately by episode type to examine the heterogeneity of treatment effect. The second sequence of models documented the impact of additional drug history variables. Results: Estimates of the impact of atypical antipsychotic use on total costs and duration on initial drug were statistically significant in the first 6 models. Estimates changed significantly when dummy variables indicating prior use of inpatient service and nursing home care were included in the model specification. Estimated effects changed substantially when prior total cost was included in cost analysis, or when prior treatment duration was included in duration analysis. Significant variation also existed in estimated effects across episode types, and it was particularly pronounced before controlling for prior cost/duration. Conclusion: It is important to add prior measures of the outcome variable to control for unobserved bias in retrospective studies. Also, the accuracy and utility of results to clinicians can be improved significantly if analyses are performed by episode type.

Atypical antipsychotics for psychosis in adolescents

Atypical antipsychotics for psychosis in adolescents

The Effectiveness of Treatments for Cocaine Dependence in Schizophrenic Patients: A Systematic Review

Objectives:To evaluate and compare the effectiveness of available treatments for cocaine dependence in schizophrenic patients. Method: We searched articles published between May 2002 and June 2012 in the following databases: Scopus, Pubmed and Web of Knowledge. The key words utilised were “schizophrenia”, "dementia praecox", "schizophrenic disorder", "cocaine related disorder", "cocaine abuse", "cocaine addiction", "cocaine dependence", “treatment”, “therapeutic”, and "drug therapy”. Selection of studies and data extraction: Original articles in English, Portuguese and Spanish were selected. Controlled, double-blind and open-label studies involving only human subjects were included in this review.Data Synthesis:We found studies on typical and atypical antipsychotics and one monoamine transporter antagonist. There were few indications of the effectiveness of atypical antipsychotic medications for the treatment of cocaine dependence in patients with schizophrenia.Conclusions:We suggest that further studies be conducted with atypical antipsychotic medicationsand greater methodological strictness, including using a placebo group in the studies, so that health professionals can determine the real effectiveness of this class of medication for the treatment of cocaine dependence in schizophrenic patients.

Psychosis, Agitation, and Antipsychotic Treatment in Dementia

Psychosis, Agitation, and Antipsychotic Treatment in Dementia

The Effectiveness of Treatments for Cocaine Dependence in Schizophrenic Patients: A Systematic Review

To evaluate and compare the effectiveness of available treatments for cocaine dependence in schizophrenic patients. We searched articles published between May 2002 and June 2012 in the following databases: Scopus, Pubmed and Web of Knowledge. The key words utilised were "schizophrenia", "dementia praecox", "schizophrenic disorder", "cocaine related disorder", "cocaine abuse", "cocaine addiction", "cocaine dependence", "treatment", "therapeutic", and "drug therapy". Original articles in English, Portuguese and Spanish were selected. Controlled, double-blind and open-label studies involving only human subjects were included in this review. We found studies on typical and atypical antipsychotics and one monoamine transporter antagonist. There were few indications of the effectiveness of atypical antipsychotic medications for the treatment of cocaine dependence in patients with schizophrenia. We suggest that further studies be conducted with atypical antipsychotic medicationsand greater methodological strictness, including using a placebo group in the studies, so that health professionals can determine the real effectiveness of this class of medication for the treatment of cocaine dependence in schizophrenic patients.

Five things to know about...weight gain induced by psychotropic agents.

Although particular attention has been paid to the effects of atypical antipsychotic medications on weight gain, most antipsychotic agents, mood stabilizers and antidepressants have been associated with weight gain.[1][1] Clinical trials may underestimate relevant weight gain for several reasons.

Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-Label Uses in Adults: A Systematic Review and Meta-Analysis

Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-Label Uses in Adults: A Systematic Review and Meta-Analysis

Immune system and glucose metabolism interaction in schizophrenia: A chicken–egg dilemma

Impaired glucose metabolism and the development of metabolic syndrome contribute to a reduction in the average life expectancy of individuals with schizophrenia. It is unclear whether this association simply reflects an unhealthy lifestyle or whether weight gain and impaired glucose tolerance in patients with schizophrenia are directly attributable to the side effects of atypical antipsychotic medications or disease-inherent derangements. In addition, numerous previous studies have highlighted alterations in the immune system of patients with schizophrenia. Increased concentrations of interleukin (IL)-1, IL-6, and transforming growth factor-beta (TGF-β) appear to be state markers, whereas IL-12, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and soluble IL-2 receptor (sIL-2R) appear to be trait markers of schizophrenia. Moreover, the mononuclear phagocyte system (MPS) and microglial activation are involved in the early course of the disease. This review illustrates a "chicken-egg dilemma", as it is currently unclear whether impaired cerebral glucose utilization leads to secondary disturbances in peripheral glucose metabolism, an increased risk of cardiovascular complications, and accompanying pro-inflammatory changes in patients with schizophrenia or whether immune mechanisms may be involved in the initial pathogenesis of schizophrenia, which leads to disturbances in glucose metabolism such as metabolic syndrome. Alternatively, shared underlying factors may be responsible for the co-occurrence of immune system and glucose metabolism disturbances in schizophrenia.

The effect of atypical antipsychotic medications in individuals with anorexia nervosa: A systematic review and meta‐analysis

Given that atypical antipsychotic medications have been increasingly prescribed for improving weight gain in anorexia nervosa (AN), we conducted a systematic review and meta-analyses to estimate the influence of atypical antipsychotics on BMI, eating disorder, and psychiatric symptoms in individuals with AN. Independent reviewers selected studies and extracted study characteristics, methodologic quality, and outcomes for the intention-to-treat group from randomized clinical trials comparing the effect of atypical antipsychotic use to placebo or an active control treatment on BMI. Compared with placebo, atypical antipsychotics were associated with a nonsignificant increase in BMI (weighted mean difference, WMD = 0.18, 95% CI: -0.36, 0.72; I(2) = 26%) and a nonsignificant effect on the drive for thinness and body dissatisfaction. Compared with placebo or active control, these medications led to an increase in anxiety and overall eating disorder symptoms. However, there was a significant reduction over placebo or active control on level of depression.

Neuronal correlates of appetite regulation in patients with schizophrenia: Is there a basis for future appetite dysfunction?

BackgroundGiven the undesired metabolic side effects of atypical antipsychotic medication it is important to understand the neuronal basis related to processing of appetite regulation in patients affected by schizophrenia. MethodsHere we used functional magnetic resonance imaging (fMRI) to assess brain activity in response to food cues and neutral stimuli in twenty patients with schizophrenia and eleven healthy individuals. In addition to clinical and dietary habits assessments, we collected, in patients, measurements of fasting glucose, ghrelin, leptin, insulin, prolactin and lipids blood concentration and we correlated the cerebral activity with clinical and metabolic measures. ResultsBoth groups engaged a common neuronal network while processing food cues, which included the left insula, primary sensorimotor areas, and inferior temporal and parietal cortices. Cerebral responses to appetitive stimuli in thalamus, parahippocampus and middle frontal gyri were specific only to schizophrenic patients, with parahippocampal activity related to hunger state and increasing linearly over time. Antipsychotic medication dosage correlated positively with a cognitive measure reflecting food cravings, whereas the severity of the disease correlated negatively with a cognitive measure indicating dietary restraint in eating habits. These cognitive variables correlated, in turn, with parahippocampal and thalamic neuronal activities, respectively. ConclusionsWe identified a specific neural substrate underlying cognitive processing of appetitive stimuli in schizophrenia, which may contribute to appetite dysfunction via perturbations in processing of homeostatic signals in relation to external stimuli. Our results also suggest that both antipsychotic medication and the disease severity per se could amplify these effects, via different mechanisms and neuronal networks.

Errors in Text and Figure in: Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-Label Uses in Adults: A Systematic Review and Meta-analysis

Errors in Text and Figure in: Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-Label Uses in Adults: A Systematic Review and Meta-analysis

P-287 - Atypical antipsychotics for psychosis in adolescents

Introduction Schizophrenia often presents in adolescence (13–18 years), is more likely to have a poor prognosis and young people are also more prone to adverse effects. Clearer guidance is needed in order to plan treatment for early onset cases more effectively. Objectives We aimed to evaluate effects of atypical antipsychotic medications for psychosis in adolescents. Search methods We searched the Cochrane Schizophrenia Group's Register. References of all identified studies were inspected for further trials. Methodology All relevant RCTs that compared atypical antipsychotic medication with pharmacological or non-pharmacological interventions in adolescents with psychosis were included. We reliably selected, quality assessed and extracted data from trials. Results There were 13 RCTs with a total of 1112 participants. Adolescents improved more on standard dose of risperidone (1.5 – 6.0 mg) against low dose of risperidone (0.15 – 0.6 mg) (1 RCT, n = 255, RR 0.54 CI 0.38 to 0.75). Participants on clozapine were three times more likely to have drowsiness as compared to haloperidol (1 RCT, n = 21, RR 3.30 CI 1.23 to 8.85, NNH 2 CI 2 to 17). Lesser number of adolescents on atypical antipsychotics left the study due to adverse effects (3 RCTs, n = 187, RR 0.65 CI 0.36 to 1.15) than on typical antipsychotics. Authors' conclusions There is no convincing evidence that atypical-antipsychotic medications are superior over typical antipsychotic medications. There is some evidence to show that adolescents respond better to standard-dose as opposed to lower dose of medications. Larger, more robust, trials are required.

Cognitive Effects of Atypical Antipsychotic Medications in Patients With Alzheimer's Disease: Outcomes From CATIE-AD

Cognitive Effects of Atypical Antipsychotic Medications in Patients With Alzheimer's Disease: Outcomes From CATIE-AD

Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-Label Uses in Adults

Atypical antipsychotic medications are commonly used for off-label conditions such as agitation in dementia, anxiety, and obsessive-compulsive disorder. To perform a systematic review on the efficacy and safety of atypical antipsychotic medications for use in conditions lacking approval for labeling and marketing by the US Food and Drug Administration. Relevant studies published in the English language were identified by searches of 6 databases (PubMed, EMBASE, CINAHL, PsycInfo, Cochrane DARE, and CENTRAL) from inception through May 2011. Controlled trials comparing an atypical antipsychotic medication (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, asenapine, iloperidone, or paliperidone) with placebo, another atypical antipsychotic medication, or other pharmacotherapy for adult off-label conditions were included. Observational studies with sample sizes of greater than 1000 patients were included to assess adverse events. Independent article review and study quality assessment by 2 investigators. Of 12 228 citations identified, 162 contributed data to the efficacy review. Among 14 placebo-controlled trials of elderly patients with dementia reporting a total global outcome score that includes symptoms such as psychosis, mood alterations, and aggression, small but statistically significant effects sizes ranging from 0.12 and 0.20 were observed for aripiprazole, olanzapine, and risperidone. For generalized anxiety disorder, a pooled analysis of 3 trials showed that quetiapine was associated with a 26% greater likelihood of a favorable response (defined as at least 50% improvement on the Hamilton Anxiety Scale) compared with placebo. For obsessive-compulsive disorder, risperidone was associated with a 3.9-fold greater likelihood of a favorable response (defined as a 25% improvement on the Yale-Brown Obsessive Compulsive Scale) compared with placebo. In elderly patients, adverse events included an increased risk of death (number needed to harm [NNH] = 87), stroke (NNH = 53 for risperidone), extrapyramidal symptoms (NNH = 10 for olanzapine; NNH = 20 for risperidone), and urinary tract symptoms (NNH range = 16-36). In nonelderly adults, adverse events included weight gain (particularly with olanzapine), fatigue, sedation, akathisia (for aripiprazole), and extrapyramidal symptoms. Benefits and harms vary among atypical antipsychotic medications for off-label use. For global behavioral symptom scores associated with dementia in elderly patients, small but statistically significant benefits were observed for aripiprazole, olanzapine, and risperidone. Quetiapine was associated with benefits in the treatment of generalized anxiety disorder, and risperidone was associated with benefits in the treatment of obsessive-compulsive disorder; however, adverse events were common.

The effect of atypical antipsychotics on pituitary gland volume in patients with first-episode psychosis: A longitudinal MRI study

Background Pituitary volume is currently measured as a marker of hypothalamic-pituitary-adrenal hyperactivity in patients with psychosis despite suggestions of susceptibility to antipsychotics. Qualifying and quantifying the effect of atypical antipsychotics on the volume of the pituitary gland will determine whether this measure is valid as a future estimate of HPA-axis activation in psychotic populations. Aims To determine the qualitative and quantitative effect of atypical antipsychotic medications on pituitary gland volume in a first-episode psychosis population. Method Pituitary volume was measured from T1-weighted magnetic resonance images in a group of 43 first-episode psychosis patients, the majority of whom were neuroleptic-naïve, at baseline and after 3 months of treatment, to determine whether change in pituitary volume was correlated with cumulative dose of atypical antipsychotic medication. Results There was no significant baseline difference in pituitary volume between subjects and controls, or between neuroleptic-naïve and neuroleptic-treated subjects. Over the follow-up period there was a negative correlation between percentage change in pituitary volume and cumulative 3-month dose of atypical antipsychotic ( r = − 0.37), i.e. volume increases were associated with lower doses and volume decreases with higher doses. Conclusions Atypical antipsychotic medications may reduce pituitary gland volume in a dose-dependent manner suggesting that atypical antipsychotic medication may support affected individuals to cope with stress associated with emerging psychotic disorders.