Side Effects Of Antipsychotics Research Articles

The effect of spinach-derived thylakoids on anthropometric parameters and metabolic profile in antipsychotic treatment: A case report

Background: Antipsychotics is the first line, evidence-based treatment of schizophrenia and other primary psychotic disorders. Metabolic adverse effects are common, including body weight gain, hypertension and metabolic syndrome. There is still no safe treatment for these adverse effects, except from lifestyle changes. Studies of thylakoids have shown body weight loss and improved metabolic parameters in overweight women. Case report: A 53-year old female with a history of unspecified nonorganic psychosis, treated with Quetiapin and Topimax (Topiramat), was given a supplement of 5g thylakoids daily for 12 weeks. She reported a rapid decrease of sweet craving and loss of body weight was observed. Conclusion: We report a successful treatment with thylakoid supplements of the metabolic side effects of antipsychotics in a female adult with a history of body weight problems and sweet craving. Further investigation and larger studies are needed. A safe treatment of metabolic side effects could increase quality of life for patients in need of antipsychotic treatment.

Chapter 25 - The use of melatonin to mitigate the adverse metabolic side effects of antipsychotics

Antipsychotic drugs are efficacious first-line treatments for many individuals diagnosed with a psychiatric illness. However, their adverse metabolic side-effect profile, which resembles the metabolic syndrome, represents a significant clinical problem that increases morbidity and limits treatment adherence. Moreover, the mechanisms involved in antipsychotic-induced adverse metabolic effects (AMEs) are unknown and mitigating strategies and interventions are limited. However, recent clinical trials show that nightly administration of exogenous melatonin may mitigate or even prevent antipsychotic-induced AMEs. This clinical evidence in combination with recent preclinical data implicate the circadian system in antipsychotic-induced AMEs and their mitigation. In this chapter, we provide an overview on the circadian system and its involvement in antipsychotic-induced AMEs, as well as the potential beneficial effect of nightly melatonin administration to mitigate them.

Low-Dose Ziprasidone in Combination with Sertraline for First-Episode Drug-Naïve Patients with Schizophrenia: A Randomized Controlled Trial

Background: Many patients with SCZ discontinue antipsychotics, frequently due to dose related multiple and severe adverse effects. This clinical trial was designed to investigate the efficacy, safety, and tolerability of adding sertraline to ziprasidone in order to substantially reduce its dose and potential side effects in first-episode and drug-naive (FEDN) patients with SCZ. Methods: This 24-week randomized, double-blinded controlled clinical trial randomly allocated 452 FEDN SCZ patients to receive a usual dose of ziprasidone (control group) or half the dose of ziprasidone in combination with sertraline (ZS group). Treatment outcome included the Positive and Negative Syndrome Scale (PANSS), the Hamilton Depression Rating Scale (HAMD), CGI-Severity (CGI-S) and the Personal and Social Performance Scale (PSP) at baseline and weeks 2, 4, 8, 12 and 24. Findings: Repeated measures ANCOVA showed significant treatment by time interactions on the PANSS negative symptom, general psychopathology and total scores, as well as CGI-S, HAMD and PSP scores (all p<0.05). Furthermore, the ZS group had greater reductions in PANSS negative symptoms, general psychopathology and total scores (all p<0.05) and greater increases in the PSP total score (p<0.01) than the control group. Importantly, adverse effects were lower in the ZS than control group. The reduction in PANSS, CGI-S or HAMD scores was not correlated with the increase in PSP. Sex and duration of disease predicted PSP improvement from baseline to week 24 in the ZS group. Interpretation: Our FEND patients with SCZ were effectively treated for their psychotic and depressive symptoms while experiencing significantly fewer adverse effects using half the usual ziprasidone dose when combined with sertraline. The implications for long term improved retention and compliance with treatment using this combination therapy are substantial for introducing them to life saving chronic care that will be optimally effective and minimally aversive due to antipsychotic side effects including cardiac problems. Trial Registration: The clinical trial was registered with ClinicalTrials.gov (ClinicalTrials.gov Identifier NCT04076371). Funding: Funding for this study was provided by the CAS Pioneer Hundred Talents Program. Declaration of Interest: None to declare. Ethical Approval: The study protocol was approved by the Institutional Review Board of First Hospital of Shanxi Medical University

Comprehensive assessment of exposure to clozapine in association with side effects among patients with treatment-resistant schizophrenia: a population pharmacokinetic study.

Background:There have been scarce data on the distribution of clozapine concentrations in comparison with the recommended range (350–600 ng/ml) or their relationship with side effects among patients with treatment-resistant schizophrenia. Furthermore, no studies have assessed the association between side effects and overall exposure to the drug by calculating the 24-h area-under-curve (AUC).Methods:In- and outpatients with schizophrenia or schizoaffective disorder (ICD-10) who were receiving a stable dose of clozapine for ⩾2 weeks were included. Side effects were assessed using the Glasgow antipsychotic side-effects scale for clozapine (GASS-C). Using two collected plasma samples, plasma clozapine and norclozapine concentrations at peak and trough and their 24-h AUC were estimated using population pharmacokinetic models.Results:A total of 108 patients completed the study (mean ± SD age, 43.0 ± 10.1 years; clozapine dose, 357.5 ± 136.9 mg/day); 33 patients (30.6%) showed estimated trough concentrations of clozapine within the recommended range (350–600 ng/ml) whereas the concentrations were higher and lower than this range among 37 (43.5%) and 28 (25.9%) patients (%), respectively. There were no significant correlations between estimated peak or trough concentrations or 24-h AUC of both clozapine or norclozapine, and GASS-C total or individual scores. No significant differences were found between GASS-C total or individual item scores between the patients with estimated trough concentrations of clozapine of >600 ng/ml and the other subjects.Conclusion:The results suggest that clozapine or norclozapine concentrations are not linked directly to the extent of side effects experienced in clozapine-treated patients with treatment-resistant schizophrenia while the cross-sectional study design limits the interpretation of any causal relationships. These findings indicate that side effects associated with clozapine may occur at any dose or concentration.

Potential Antipsychotic Side Effects and Adverse Events of Assisted Living Residents With Dementia

This presentation provides the findings from a descriptive study examining the potential adverse events and side effects of antipsychotic medications prescribed to assisted living (AL) residents with dementia drawn from interviews with family members and chart review on 238 AL residents, from 91 AL communities in seven US states. We found that 85% of family reported that medication had been administered for agitation or aggression, 93% of the sample experienced at least one potential side effect, and 19% experienced five or more. The most common potential side effects were neurologic/psychological effects (89% of residents), and somnolence during the day (81%). Six percent of the sample experienced at least one potential adverse event. This work implies a need for caution when prescribing antipsychotics to older adults with dementia in AL. Medication management efforts should extend to monitoring AL residents for potential side effects and adverse events from specific psychoactive medications.

Psychoactive Prescribing in Assisted Living

More than 800,000 older adults reside in almost 30,000 assisted living (AL) communities across the country, 42% of who have moderate or severe dementia. As many as 97% of persons with dementia display symptoms of distress such as agitation or anxiety, and 69% of AL communities provide medications to treat this distress. Unfortunately, the psychoactive medications that are prescribed are often ineffective, contraindicated, and may cause serious adverse events including mortality. Especially concerning is the use of antipsychotic medications, which carry a black-box warning for persons with dementia. This symposium will present data from a seven state study of 250 AL communities and the 13,600 individuals who reside there. The first speaker will discuss the prevalence of psychoactive prescribing in AL overall and by medication type, and community characteristics that relate to use (e.g., staffing, resident case-mix). The second presentation will focus on the use of pro re nata (PRN) psychotropic medications, to examine the extent to which use is situational. The third speaker will address the use of off-label antipsychotic medications, and typologies of AL communities that differentiate use. The fourth speaker will discuss the prevalence of potential antipsychotic side-effects and adverse events, and also family member knowledge of medication use. The final speaker will compare the use of antipsychotic and antianxiety prescribing in proximate AL communities and nursing homes, to examine the extent to which local prescribing patterns may influence use. All five presentations of this symposium convey important issues for practice, policy, and future research.

The interaction of folate cycle enzyme genes and the risk of extrapyramidal side effects of antipsychotics

Personalized medicine means the selection of therapy for patients, taking into account the assessment of genetic risk factors for side effects. A number of studies show that folate metabolism disorders, including single nucleotide polymorphisms (SNPs) in the genes of folate-metabolizing enzymes, are more frequently detected in schizophrenic patients than in the general population. The role of SNPs of the key folate cycle enzymes in developing the extrapyramidal side effects of antipsychotics has not yet been studied, although there is evidence of their association with other movement disorders.Objective: to analyze the association between the carriage of SNP alleles of MTHFR 677C&gt;T, MTR 2756A&gt;G, and MTRR 66A&gt;G and the severity of extrapyramidal side effects of antipsychotics in patients with schizophrenia.Patients and methods. The investigation included 61 patients with schizophrenia (according to the criteria for ICD-10 Code F20). All the patients took antipsychotics for at least 7 hospital days were examined using real-time polymerase chain reaction (PCR) with allele-specific primers, followed by detection for the carriage of SNP alleles of MTHFR 677C&gt;T, MTR 2756A&gt;G, and MTRR 66A&gt;G. The standardized Simpson–Angus scale (SAS) was used to evaluate the severity of extrapyramidal symptoms; the PCR test results were unknown during their examination.Results and discussion. In the patients carrying a low-functional 677 T allele in the gene of the key folate cycle enzyme MTHFR, the severity of extrapyramidal side effects of antipsychotics was statistically significantly higher than in the carriers of the wild-type genotype: 13.27±5.10 versus 9.84±6.03 SAS scores, respectively (t=-2.40; p=0.020). In addition, the carriage of the wild allele A of SNP in the MTRR 66A&gt;G gene (F=3.83; p=0.0283; pcorr.=0.043) is associated with the severity of extrapyramidal symptoms. There was a direct moderate correlation of the number of risk alleles at two loci with the total SAS score (r=0.51; p=0.00017).Conclusion. The polymorphic allele of MTHFR 677T and the wild allele of MTRR 66A can be regarded as risk alleles for the development of extrapyramidal side effects of antipsychotics.

Heightened sensitivity of people with Alzheimer’s disease to the side effects of antipsychotic drug amisulpride may be mediated through an interaction with glucose transporter 1 at the blood‐brain barrier

AbstractBackgroundAmisulpride is an atypical antipsychotic which antagonises dopamine (D2, D3) receptors in vitro and in vivo (Schoemaker et al., 1997). Older people, particularly those with dementia are more susceptible to antipsychotic side effects, including amisulpride (Reeves et al., 2017). Clinical and basic science research suggested that blood‐brain barrier (BBB) disruption underpins this heightened sensitivity by increasing central drug access (Sekhar et al., 2019; Harwood et al., 1994). The current study examines healthy and Alzheimer’s disease (AD) physiology to further understand this increased sensitivity.MethodWe investigated the BBB transport of amisulpride in 5xFamilial Alzheimer’s mouse model (5xFAD), and in age‐matched wild type mice (WT, C57/BL6) (12‐15 months old). 5xFAD mice express human amyloid precursor protein and presenilin 1 transgenes with five AD‐linked mutations, they develop Aβ plaques and cognitive impairments (Oakley et al., 2006). All experiments were performed according the Animal Scientific Procedures Act (1986) and Amendment Regulations 2012. Anaesthesia was applied via intraperitoneal injection of medetomidine hydrochloride and ketamine mixture. The mice were perfused with artificial plasma, containing [3H]amisulpride (6.5 nM) and [14C]sucrose (9.4 μM). Brain amyloid plaques were confirmed in 5xFAD mice by transmission electron microscopy. In silico molecular docking using AuDock Vina and GOLD software identified transporters of interest for our model substrate. Amisulpride was considered a substrate for a given transporter, if it had free energy binding lower than ‐5 kcal/mole and high chem score.ResultCompared to WT (n=6), the 5xFAD (n=7) mice had increased striatal [3H]amisulpride uptake of 79% (t=1.975, df=11, p=0.0370). The [14C]sucrose (passive permeability measure) permeability was not significantly changed. Preliminary in silico analysis suggested that amisulpride is a substrate for glucose transporter 1 (GLUT1) and a very weak substrate for multidrug and toxin extrusion transporter (MATE2) (Table 1).ConclusionIn silico studies suggested amisulpride interacts with BBB solute carrier (SLC) transporters: organic cation transporter (OCT1), plasma membrane monoamine transporter (PMAT), MATE1 (Sekhar et al., 2019), GLUT1 and MATE2, but not with the adenosine triphosphate binding cassette (ABC) transporter P‐glycoprotein. The increased brain permeability to amisulpride in 5xFAD mice suggests altered BBB transporter function, possibly due to SLC transporter expression changes associated with AD.

S2004 A Hard Pill to Swallow: Oropharyngeal Dysphagia Secondary to Antipsychotics

INTRODUCTION: Dysphagia can be anatomically categorized as either oropharyngeal or esophageal based on where and when the patient endorses difficulty swallowing and oropharyngeal dysphagia secondary to antipsychotic medications is often overlooked. Antipsychotics, especially the first generation, have been classically associated with extrapyramidal symptoms such as dystonia, akathisia, tremors and tardive dyskinesia. Dysphagia is an uncommon side effect of antipsychotics which can lead to choking, asphyxiation, or even aspiration pneumonia. Antipsychotic medications block the D2 receptors in the nigrostriatal pathway which are also hypothesized to regulate motor neurons responsible for complex muscle movements such as swallowing. Here, we present a case of severe dysphagia leading to failure to thrive in an adult after initiation of a first-generation antipsychotic. CASE DESCRIPTION/METHODS: A 69-year-old male with a history of schizoaffective disorder who presented with a one-month history of difficulty swallowing. Three days before this symptom, he was started on Haloperidol for his schizoaffective disorder. He complained of difficulty in initiating a swallow, pointing towards his neck region, which was soon followed by coughing and choking with both solid and liquid food. He stopped eating and drinking due to the overwhelming fear of choking leading to significant weight loss and cachexia. His physical examination was significant for temporal wasting, bradykinesia, cogwheel rigidity and diffuse hyperreflexia. Labs were unremarkable. A barium swallow revealed a difficulty in initiation of swallow, aspiration of thin barium with no spontaneous cough and poor pharyngeal constriction. CT soft tissue/neck revealed no evidence of extrinsic compression and MRI brain was done to rule out a stroke. An upper endoscopy was not performed as the barium swallow provided sufficient information to clinch the diagnosis. The patient’s antipsychotics were discontinued, and his nutritional status had to be optimized with NG tube feedings. After two weeks, the patient was transitioned to a liquid diet and discharged from the hospital. DISCUSSION: Antipsychotic-related oropharyngeal dysphagia is an uncommon side effect; however, it has been reported in case reports. It is important to identify this side effect, especially in elderly patients or patients with pre-existing anatomical or functional changes as it can lead to complications such as asphyxiation and aspiration pneumonia contributing to mortality.Figure 1.: Barium swallow study showing heavy pooling of barium in vallecula and pyriform sinuses.Figure 2.: Barium swallow revealing poor pharyngeal constriction leading to aspiration of thin barium without coughing.

Profile of Leptin Levels in Schizophrenic patients Receiving Antipsychotic Therapy in Prof. Dr. HB Saanin Hospital Padang

Weight-gain is one of the antipsychotic side effects, and it can increase the risk factor of metabolic syndrome. Several studies relate it to increase leptin levels. This research was conducted to determine the profile of leptin levels in schizophrenic patients who were receiving antipsychotic therapy at Prof. DR. HB Saanin Mental Hospital. The research was conducted from November 2019 to January 2020 on schizophrenic patients who were taking antipsychotic drugs. This research was conducted on 50 samples by using consecutive sampling techniques. Data analysis using univariate are presented in geometric mean and CI 95%. Moreover, a Comparison of leptin levels between groups was performed by T-test and one-way ANOVA. The average leptin level from 50 samples of schizophrenic patients was 5.12µg/ml (CI 95%=3.32-7.90). The highest average leptin level is from the 46-55 year age group which is 11.32µg/ml (CI 95% =5.24 - 24.42), female is 13.29µg/ml (CI 95%=5.84-30.26), BMI ≥30kg/m2 is 12.84µg/ml (CI 95%=4.31-38.23), subjects with above-average waist circumference is 5.54µg/ml ( CI 95%=3.45-8.90), and the atypical group of drugs is 6.08µg/ml (IK 95%=3.41-10.84). Increasing levels of leptin occur in schizophrenic patients who were 46-55 y.o, female BMI ≥30kg/m2, above-average waist circumference, and receiving atypical antipsychotics.

Identification of Antipsychotic Side Effects with Glassgow Antipsychotic Side-Effect Scale (GASS)

Schizophrenia is ranked 4th of the top 10 diseases that burden worldwide. If the population of Indonesia reaches 200 million, it estimates that around two million have Schizophrenia. Based on Data from the World Health Organization (WHO), it estimates that around 24 million people worldwide have schizophrenia.2 the American Psychiatric Association (APA) were reported the incidence of Schizophrenia in the United States is about 1% of the adult population with a total of more than 2 million people. Schizophrenic patients were treated by antipsychotic agents that act to inhibit dopamine receptors, especially D2, and also inhibit adrenergic acetylcholine receptors and serotonin 5-HT2A. It can manifest side effects like extrapyramidal syndrome, amenorrhea, drowsiness, and others. This research aims to the identification of antipsychotic side effects with Glasgow Antipsychotic Side-effect Scale (GASS). 100 schizophrenics in HB. Saanin Mental Hospital were participating in this descriptive study after fulfilling the criteria of inclusion and exclusion. This study used the GASS questionnaire to interview subjects who were signing informed consent and get an explanation about this study. In this study, 92% of subjects reported mild side effects. The frequent complaints were extrapyramidal effects, sedation and CNS effects, anticholinergic effects, and weight gain (93%,80%,70 0% and 70% respectively). We found women complained of the side effects more often (16.38 ± 5.275) than men (12.58 ± 5.484) significantly with the value P = 0.001. Gass instruments can use screening antipsychotic side effects. This study concludes the most side effects complaints being extrapyramidal and drowsiness, and women more commonly found side effects than men.

Profile of recipients of holistic health counselling in a psychiatric OPD in South India.

Persons with mental illness (PwMI) are prone to weight gain as a side effect of antipsychotics. Health counselling on diet, physical activity, medication adherence, expressed emotions and technology use, by health professionals, can help in managing these side-effects. The aim of this study was to identify the pre-counselling profile of the subjects such as body mass index (BMI), diet, physical activity, medication adherence, expressed emotions and technology use among PwMI; to attend the Holistic Health Clinic as part of follow-up services in the psychiatry Outpatient Department (OPD) as well as to find correlation and association between the study variables. The study involved a cross-sectional descriptive design based on convenience sampling. The sample consists of 56 patients who are receiving antipsychotics under symptom control (self-reported) and were overweight. Data were collected with a patient assessment proforma and analysed using SPSS-22. The patients referred to the holistic health counselling (HHC) had abnormal weight and BMI. The mean and SD of weight was 74.48 ± 14.07 and BMI 29.51 ± 5.15. All the participants received counselling on diet, 87.5% on physical activity, 62.5% on sleep hygiene, 55.4% on medication adherence, 8.9% on family emotional climate and only 5.4% on healthy use of technology. Weight has shown significant relation with gender (male = 80.84 ± 17.71, female = 71.09 ± 10.52, t = -2.52, p = .015) and near to significant relationship (χ2 = 7.685, p = .053) with educational status. Patients receiving second-generation antipsychotics (SGA) have lesser extra pyramidal side-effects; however, they are more prone to gain weight. Proper screening and counselling during the follow-up visit in the outpatient setting can help in identification, prevention and management of the obesity-related metabolic syndrome and cardiovascular disease (CVD), and motivate them to adopt healthy behaviours.

Antipsychotic Drugs and Peripheral Edema: A Review

Antipsikotikler, şizofreni ve bipolar bozukluk gibi çeşitli psikiyatrik bozuklukların tedavisinde uzun yıllardır kullanılmaktadır. Distoni, tardif diskinezi, akatizi, sedasyon, kilo artışı, aritmi antipsikotiklerin bazı yan etkilerindendir. Periferik ödem antipsikotiklerin bir diğer önemli yan etkisidir. İnterstisyel alanda normalde bulunması gerekenden daha fazla sıvı bulunması olarak tanımlanabilecek periferik ödemin hem birinci kuşak antipsikotikler hem de ikinci kuşak antipsikotiklerle ilişkisi bildirilmiştir. Bu yan etkinin olası mekanizmalarını açıklamak için aşırı duyarlılık ve vazodilatasyon, doz-cevap ilişkisi, doz artırım hızı ve alerjik reaksiyon modelleri oluşturulmuştur. Hasta konforunu bozan bu yan etkinin ayırıcı tanısı ve olası risk faktörlerinin belirlenmesi önem arz etmektedir. Bu hastalar, multidisipliner bir yaklaşımla ele alınmalı ve müdahalede geç kalınmamalıdır. Hasta ve yakınlarının bu yan etkiye karşı uyarılması gerekmektedir.

The impact on functioning of second-generation antipsychotic medication side effects for patients with schizophrenia: a worldwide, cross-sectional, web-based survey

BackgroundIt is well established that the different antipsychotics used for schizophrenia symptoms differ substantially in their side effects. However, relatively little is known about the impact of these side effects on functioning from the patient’s perspective. We aimed to understand how key side effects of second-generation antipsychotics impact the functioning and quality of life (QoL) of patients with schizophrenia.MethodsThis is a cross-sectional, web-based survey of patient-reported side effect burden of antipsychotic drugs in adults with schizophrenia. The survey was deployed in the United States, Canada, Australia, Spain, Italy, Norway, and Denmark. It included sociodemographic and clinical questions, the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), and the Glasgow Antipsychotic Side-Effect Scale (GASS). Eight pre-defined key side effects classified as activating (“Shaky hands or arms,” “Restlessness,” and “Difficulty sleeping”), sedating (“Sleepy during the day”, “Feeling drugged or like a zombie,” and “Feeling dizzy/Fainted”) or other side effects (“Problems enjoying sex” and “Gaining weight”), and additional questions related to impacts on function and quality of life were asked.ResultsIn total, 435 participants (mean age: 38 years, 53.8% female) were included. The total Q-LES-Q-SF score indicated overall medium satisfaction with their quality of life (score of 44.3; possible range 14–70). The most prevalent side effects were “Sleepy during the day” (83.2%), “Difficulty sleeping” (74.7%), “Dry mouth” (63.9%), “Problems enjoying sex” (53.4%) and “Gaining weight” (52.4%). Women reported the side effects of “Sleepy during the day”, “Problems enjoying sex” and “Gaining weight” more frequently than men. Key side effects impacted physical, social, occupational and psychological aspects of functioning. Patients with key side effects often felt frustrated by their experiences. Total Q-LES-Q-SF score showed a significant inverse correlation with the score of pre-defined groups of side effects indicating worse QoL in association with more severe key side effects in these patients.ConclusionStable patients with schizophrenia taking second-generation antipsychotics live with many side effects, including activating and sedating side effects, sexual side effects, and weight gain. Presence of these side effects is associated with substantial impacts across all aspects of daily functioning and lower quality of life and satisfaction.

Family Support is the Key to Compliance with the Treatment of Relapsing Schizophrenia Patients

Introduction: One problem in treating schizophrenia patients is relapse. The previous study results state that the biggest factor causing relapse is non-compliance with taking medication. This non-compliance with taking medication is influenced by several factors, including patient sociodemography, drug side effects, and family support. The purpose of this study was to determine the factors associated with medication adherence in Schizophrenia patients who were undergoing rehospitalization in an inpatient installation at RSJD in one city in Central Java, Indonesia.Methods: This study is a descriptive correlational analytic study with a cross-sectional approach. The population in this study were Schizophrenia patients who were undergoing re-hospital in the inpatient installation. Thirty-six samples were taken with the consecutive sampling method. The research instruments used were a socio-demographic questionnaire, family support questionnaire, Medication Adherence Rating Scale (MARS), and Glasgow Antipsychotic Side-effect Scale (GASS). Data analysis using descriptive analysis and chi-square test.Results: There is a relationship between family support for relapse in schizophrenia patients (p = 0.023).Conclusion: Researchers suggest that the hospital improves the treatment of family motivation to provide good support to patients to reduce the rate of re-hospitalization.

Prise en charge des comorbidités cardio-vasculaires chez les jeunes patients souffrant d’une psychose débutante : état des lieux et perspectives thérapeutiques

Patients with psychiatric disorders have a decrease in their life expectancy. Excess mortality of patients with schizophrenia was demonstrated by a meta-analysis in the late 1990s and has not decreased for the past 30years. A recent meta-analysis including nearly 250,000 patients with schizophrenia found an average decrease in life expectancy of 14.5years (CI95: 11,2–17,8), more important for men than for women: 15.9 (CI95: 13,8–18,0) vs 13.6 (CI95: 11,4–15,8). A closer look at the somatic comorbidities, including metabolic syndrome, and investigation of causes of death of these patients highlighted already well-known factors, namely late diagnosis and insufficient treatment of physical diseases, side effects of antipsychotics, unhealthy lifestyle (poor diet, smoking, excessive alcohol consumption and lack of exercise), and higher risk of suicide and accident. Concerning ultra-high risk (UHR) patients, a 2016 meta-analysis of 47 studies evaluated the cardiovascular risk factors. They reported a higher prevalence of smoking in UHR (odds ratio 2,3) and a lower level of physical activity associated with a normal BMI (Body Mass Index) compared to the control population. A meta-analysis about patients with a first episode of psychosis (FEP) found reduced total and LDL cholesterol levels and an increased triglyceride level compared to the control population. One study found alteration of the fasting plasmatic levels of glucose and insulin, as well as insulin resistance in FEP patients, compared to controls albeit the HbA1c level was not significantly different. A meta-analysis reported a prevalence of metabolic syndrome of 10 % in FEP or drug naïve patients versus 35 % and 20 % in treated and untreated patients with chronic schizophrenia respectively. Somatic comorbidities usually appear during the first two years of the disease. Some interventions have proven their efficacy in reducing the occurrence of metabolic syndrome and other cardiovascular risk factors. For instance, metformin, a treatment for type 2 diabetes that is allowed from the age of 10, has shown benefits in children and adolescents receiving second-generation antipsychotics in a recent meta-analysis, with a mean weight loss of 3.23kg (IC95 % −5.59 −0.86) after 16 weeks. Dietary-hygienic interventions are also effective in reducing cardiovascular risk. Other interventions such as omega-3 supplementation, vitamin D, N-acetylcysteine, and fasting have not proven to be effective. Comprehensive care programs have been developed to promote somatic care in psychiatric patients, such as the Canadian HeAL (Healthy Active Lives) program. These programs are more effective when proposed from the beginning of the disease and the introduction of antipsychotics. In this review, because there is no French recommendation, we translate a tool for the prescription of metformin and the Canadian recommendations from the HeAL program. Generalization of these programs to all young psychotic patients could improve their life expectancy and reduce the overall mortality. Prevention of cardiovascular risk factors and cardio-metabolic monitoring of treatments must be part of the standard of care in early psychosis. These programs aim at providing patients with the quality of somatic and mental care they are entitled to. This requires the involvement of all stakeholders, including patients and their families but also psychiatrists and other caregivers.

Reliability of the Glasgow Antipsychotic Side-effects Scale for Clozapine Japanese version (GASS-C-J).

The purpose of this study was to develop the Glasgow Antipsychotic Side effects Scale for Clozapine Japanese version (GASS-C-J) and examine its reliability to assess clozapine-related side effects. We developed the GASS-C-J using forward and backward translation. Semantic equivalence of the GASS-C-J to the GASS-C was confirmed by the original author. We then administered the GASS-C-J twice to 109 patients on clozapine treatment at two psychiatric hospitals in Japan. We assessed the internal consistency and test-retest reliability of the GASS-C-J using Cronbach’s alpha and weighted kappa coefficient, respectively. We also examined if discrepancies in each GASS-C-J item score between the first and second rating were correlated with items of the Brief Evaluation of Psychosis Symptom Domains (BE-PSD). The Cronbach’s alpha coefficient of the GASS-C-J at the first and second rating was 0.78 (95% CI: 0.72 to 0.84) and 0.82 (95% CI: 0.76 to 0.88), respectively. The weighted kappa coefficient of individual and total GASS-C-J item scores ranged from 0.45 to 0.88. Some symptom domains were correlated with discrepancies in specific items of the GASS-C-J: psychotic symptoms and nausea/vomiting (rs = 0.27), thirst (rs = 0.31), and appetite/weight gain (rs = 0.27); disorganized thinking and urinary incontinence (rs = 0.26); depression/anxiety and myoclonus (rs = 0.25), hypersalivation (rs = -0.27), and blurred vision (rs = -0.22). These findings demonstrate that the GASS-C-J can be used in clinical and research settings as a reliable scale to assess clozapine-related side effects.

Clinical validation of the self-reported Glasgow Antipsychotic Side-effect Scale using the clinician-rated UKU side-effect scale as gold standard reference.

Antipsychotics are key for the treatment of psychotic and several non-psychotic disorders. Unfortunately, antipsychotic medications are associated with side effects, which may reduce quality of life and treatment adherence. Therefore, regular screening of antipsychotic side effects is essential. The Glasgow Antipsychotic Side-effect Scale is a patient self-report scale developed for this purpose. However, the Glasgow Antipsychotic Side-effect Scale has only been validated against another self-report side effect measure, which is suboptimal. We aimed to validate the Glasgow Antipsychotic Side-effect Scale using the clinician-rated Udvalg for Kliniske Undersøgelser side-effect rating scale as the gold standard reference. 81 antipsychotic-treated outpatients with schizophrenia-spectrum disorders (age = 42±13 years; males = 43%, schizophrenia = 77%, illness duration: median = 11 years) completed the Glasgow Antipsychotic Side-effect Scale and were subsequently scored on the Udvalg for Kliniske Undersøgelser by trained raters. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for paired Glasgow Antipsychotic Side-effect Scale and Udvalg for Kliniske Undersøgelser items. Sensitivity of Glasgow Antipsychotic Side-effect Scale items ranged from 33-96%, with 19 (86%) having >75% sensitivity. Lowest sensitivity emerged for "nocturnal enuresis" (33%), "galactorrhea" (50%) and "hyperkinesia" 14-99%, with 14 items (64%) having >75% specificity, being lowest for "asthenia" (14%), "polyuria/polydipsia" (35%), "sedation" (41%), "akathisia" (53%), "dystonia" (65%), "hyperkinesia" (68%), "hypokinesia" (70%) and "accommodation" (70%). Positive predictive value ranged from 7-85%, with six items (27%) having a positive predictive value >75%. Negative predictive value ranged from 40-98%, with 21 items (95%) having a negative predictive value >75%. The mean time to complete the Glasgow Antipsychotic Side-effect Scale was 4±2 minutes. The Glasgow Antipsychotic Side-effect Scale demonstrated satisfactory validity as a self-rated tool for antipsychotic side effects and may aid measurement-based care and decision-making.

M201. MODERATORS OF WEIGHT GAIN IN RANDOMIZED CONTROLLED TRIALS OF SCHIZOPHRENIA – A META-REGRESSION ANALYSIS

BackgroundWeight gain is an important side effect of antipsychotics. Meta-analyses of randomized controlled trials indicate differences between the multiple antipsychotics in propensity to cause weight gain. However, antipsychotic-associated weight gain, in randomized controlled trials as well as in real life situations, might also depend on population characteristics and treatment-related factors.As a preparatory work for a systematic review and network-meta-analysis on metabolic side effects of antipsychotics (presented in another poster at this conference), we conducted a meta-regression analysis of potential moderators of weight gain.MethodsWe selected acute phase short-term, acute phase long-term as well as relapse prevention studies (all found by systematic reviews conducted by our group in the past) from our database of randomized controlled trials of antipsychotics in schizophrenia.We conductedi) meta-regression-analyses based on pairwise meta-analysis of the mean difference (MD) in change in weight (kg) between patients exposed to antipsychotics and placebo, andii) meta-regression-analyses based on single-arm meta-analysis of the change in weight (kg).We examined the moderators baseline weight, study duration, percentage women, and publication year.We conducted the analyses for all drugs pooled, placebo and per individual drug. For presentation of the results we focus on the drugs aripiprazole, haloperidol, quetiapine, olanzapine, and risperidone, because these are popular drugs in clinical practice, they differ in their receptor-binding profiles and multiple studies are available for these drugs.We conducted the analysis in R using the commands metacont, metagen and metareg from the package meta.ResultsThe dataset comprises 603 randomized controlled trials with 141 584 patients that examined 40 different antipsychotics. Trial duration varied between 3 and 156 weeks (median 8 weeks). 168 studies with 49 670 patients reported on change in body weight.We found no effect of baseline weight on antipsychotic-associated weight gain, however on placebo, lower baseline weight was associated with more weight loss.Moreover, on antipsychotics, higher percentage of women was associated with less weight gain, and, on placebo, higher percentage of women was associated with more weight loss.Longer study duration was not associated with increased weight gain. On placebo, longer studies were associated with more weight loss.There was no effect of publication year.DiscussionSurprisingly, we found no moderating effect of baseline weight and study duration on weight gain. However, our data suggests that men and women could have different risk of weight gain. Moreover, weight loss after switching to placebo might be higher in women and patients with less baseline weight. For interpretation, it must be noted that meta-regressions are observational evidence and thus prone to confounding. In addition, the scatter plots, presented on the poster, need to be considered to judge the robustness and magnitude of the moderated effects. Additional meta-regressions (planned to present on the poster) should address further potential moderators, such as antipsychotic dose, ethnicity, previous antipsychotic exposure and dropout rates.

S205. A TRANSLATIONAL HOMER 1A-BASED NETWORK APPROACH: IMAGING HOW HALOPERIDOL MODULATES GLUTAMATE SYSTEM FUNCTIONAL CONNECTIVITY

BackgroundSchizophrenia has been conceptualized both as synaptic plasticity and a functional connectivity disorder. Data on brain connectivity can be rendered in the form of network models. In our study we want to evaluate a particular kind of the structural and functional interaction between region of interest (ROI) relevant to schizophrenia pathophysiology: we evaluated the expression of Immediate Early Gene (IEG), Homer1a (H1a), in the different ROI and its functional interaction after Haloperidol (antipsychotic drug) acute administration. H1a is an IEG expressed in an activity-dependent manner, coding for a protein involved in the activity-induced reorganization of glutamatergic synapses.MethodsSprague-Dawley rats were randomly assigned to two treatment groups (n=23), receiving vehicle (NaCl 0.9%; VEH) or haloperidol 0.8 mg/kg (HAL) i.p. injection. H1a induction was evaluated using in situ hybridization. Signal intensity analysis was performed in 34 ROIs in the cortex, in the caudate-putamen and the nucleus accumbens. Student’s t-test was used to detect treatment effects. A signal correlation analysis was performed, computing all possible pairwise Pearson correlations among ROIs separately in the two groups. Using significant correlations, two networks were created for HAL and VEH groups, and their network, node, and edge properties were assessed.ResultsBonferroni-corrected Student’s t-tests revealed statistically significant differences between the two treatment groups. Haloperidol significantly induced Homer1a gene expression compared to vehicle in all ROIs of the striatum (dmCP: p<.0001, t=9.089, df=44; dlCP: p<.0001, t=10.684, df=44; vlCP: p<.0001, t=10.870, df=44; vmCP: p<.0001, t=9.760, df=44; AcCo: p<.0001, t=8,573, df= 44; AcSh: p<.0001, t=6.615, df=44), a result that is consistent with our previous observations. No significant statistical differences were detected among cortical ROIs explored. Correlations between dmCP-AcSh, dlCP-AcSh, vlCP-AcCo, vlCP-AcSh and vmCP-AcSh were significantly different between the VEH and the HAL group (p<.01); correlations between I-vlCP and dlCP-AcCo were also significantly different between the two treatment groups (p<.05); the I-dlCP and I-vmCP showed a trend towards significance.DiscussionHaloperidol acute administration led to a modification of the gene expression pattern in the brain regions considered herein, and consequently to differential functional connectivity. The observed disruption in the functional correlations of the nucleus accumbens may play a role in the affective, motivational and emotional consequences of haloperidol administration, with the loss of functional correlations with the lateral subregions of the caudate-putamen being potentially more relevant to the motor side-effects of haloperidol. These functional connectivity changes are potentially related to neural activity and synaptic plasticity within the glutamate system and may play a role in antipsychotic therapeutic and side effects. As far as we know, this is the first network analysis study on after haloperidol acute treatment of a gene deeply correlated to dendritic spine architecture.