Effects Of Antipsychotic Treatment Research Articles

Efficacy and dropout rates of antipsychotic medications for methamphetamine psychosis: A systematic review and network meta-analysis

BackgroundThis study aimed to compare the treatment effects of different antipsychotics for methamphetamine psychosis (MAP). MethodsClinical Trials, Cochrane Library, Pubmed, Scopus, and Web of Science were searched for short-term, randomized controlled trials (RCTs) from the inception to June 15, 2020. Standardized mean differences (SMDs) and odds ratios (ORs) were aggregated using random-effects pairwise comparisons and frequentist network meta-analyses (NMAs). Primary outcomes of interest were the main psychotic symptoms and dropout rates. We also rated the quality of NMA estimates. ResultsThis NMA included six RCTs of 395 patients with MAP. Six studied antipsychotics were aripiprazole, haloperidol, olanzapine, paliperidone extended-release, quetiapine, and risperidone. Risperidone is the most frequently studied antipsychotic, being investigated in four trials. Low quality of evidence was available to determine the efficacy of those antipsychotics for main psychotic symptoms. Aripiprazole was significantly inferior to olanzapine (SMD = 1.36, 95 % CI = 0.46–2.26), quetiapine (SMD = 1.13, 95 % CI = 0.28–1.98), haloperidol (SMD = 0.87, 95 % CI = 0.14–1.60), and paliperidone extended-release (SMD = 0.60, 95 % CI = 0.06–1.14). Olanzapine and quetiapine were superior to risperidone (SMD = -1.09, 95 % CI = -1.89 to -0.28 and SMD = -0.86, 95 % CI = -1.61 to -0.11, respectively). The dropout rates were not significantly different among the studied antipsychotics. ConclusionsThis analysis suggests that olanzapine or quetiapine may be a preferred antipsychotic for MAP, although the evidence for this was rated low-quality due to the high risk of bias or indirectness/intransitivity.

5-HT2A receptor-mediated Gαq/11 activation in psychiatric disorders: A postmortem study

Objectives Serotonin-2A (5-HT2A) receptors play an important role in the regulation of many brain functions that are disturbed in patients with such psychiatric diseases as mood disorders and schizophrenia. The objective of this study was to evaluate 5-HT2A receptor-mediated signalling pathway through Gαq/11 activation in psychiatric patients by using post-mortem brain samples. Methods Functional activation of Gαq/11 proteins coupled to 5-HT2A receptors was determined by means of [35S]GTPγS binding/immunoprecipitation assay in post-mortem prefrontal cortex of psychiatric patients diagnosed as bipolar disorder (BP), major depressive disorder (MDD), and schizophrenia, and individually matched controls. The effects of antipsychotic treatment as well as suicide were also analysed. Results There was no significant difference in maximum percent increase (%Emax) or slope factor among the four groups. The negative logarithm of concentration eliciting the half-maximal effect (pEC50) was significantly reduced in BP and schizophrenia patients as compared to controls. These alterations were attributable to antipsychotic medication. The pEC50 values in ‘non-suicide’ group of schizophrenia, but not in ‘suicide’ group, were significantly reduced as compared with controls. Conclusions Altered 5-HT2A receptor-mediated signalling pathway through Gαq/11 proteins in prefrontal cortex might be apparently involved in pathophysiology and pharmacotherapy of BP and schizophrenia. In schizophrenic patients, these alterations as a result of successful treatment with antipsychotic agents may help in prevention of suicidal behaviour.

Increased behavioral and neuronal responses to a hallucinogenic drug after adolescent toluene exposure in mice: Effects of antipsychotic treatment

Toluene has been characterized as a non-classical hallucinogen drug through activation of 5-HT2A receptors and antagonism of NMDA receptors. It remains unclear whether psychotic symptoms after long-term and intense toluene exposure are associated with abnormalities in 5-HT2A receptor function. The present study examined whether the responses to a hallucinogenic 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) were altered in a mouse model of toluene psychosis. Male NMRI mice were subchronically treated with toluene during adolescence. Reciprocal social interaction test and novel object recognition test were conducted to confirm the persistent behavioral deficits in adulthood. Subsequently, DOI-induced head twitch, c-Fos and Egr-2 expression, field potentials in the medial prefrontal cortex (mPFC), and the levels of 5-HT2A, 5-HT1A and mGlu2 receptors in the mPFC were monitored. Toluene exposure during adolescence produced social and memory impairments and enhanced DOI–induced behavioral, molecular and electrophysiological responses, but did not change the levels of 5-HT2A, 5-HT1A or mGlu2 receptors in the mPFC. Moreover, the effects of haloperidol and risperidone on the behavioral deficits and hyper-responsiveness to DOI after adolescent toluene exposure were compared. When administered after adolescent toluene exposure, risperidone could reverse social withdrawal, cognitive impairment and hypersensitivity to DOI, whereas haloperidol was only beneficial for social withdrawal. These findings suggest that increased functionality of 5-HT2A receptors may play a critical role in solvent-induced psychosis and recommend the antipsychotics with more selective 5-HT2A receptor antagonism as the first-line treatment for solvent-induced psychosis.

The effect of combined antipsychotic antidepressant treatment in experimental depression

The effect of combined antipsychotic antidepressant treatment in experimental depression

Investigation of DRD2 and HTR2A mRNA Expression in Two Therapeutic States of Antipsychotic Polypharmacy and Aripiprazole Monotherapy in the Peripheral Blood of Patients With Schizophrenia

Objectives: Schizophrenia is a severe psychiatric disorder that has profound effects on both individuals and the community. Notwithstanding the suggestion for treating schizophrenia with a minimum dose of drugs, antipsychotic polypharmacy increases the patient’s care costs and drug interactions. Aripiprazole reduces the metabolic side effects of antipsychotic polypharmacy treatment. DRD2 and HTR2A can serve as predictors for response to treatment in schizophrenic patients. The purpose of this survey was to measure the DRD2 and HTR2A genes expression in the peripheral blood samples using Real-Time Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Methods: A total of 19 patients with a long history of schizophrenia who received at least two types of antipsychotics with daily doses of more than 500 mg of chlorpromazine were entered into the study. The response rates to the treatment based on scores in the Brief Psychiatric Rating Scale (BPRS) questionnaire and DRD2 and HTR2A expression were compared between antipsychotic polypharmacy status and 6 months after monotherapy with aripiprazole. Results: The levels of DRD2 expression decreased significantly after the intervention. The mean changes in HTR2A expression and the BPRS questionnaire and also the relationship between changes in DRD2 and HTR2A expression and changes in BPRS score after the intervention were not significant. Discussion: The conversion of the antipsychotic polypharmacy state to monotherapy with aripiprazole has been accompanied by a significant decrease in DRD2A expression. These genes can be used for evaluating the response rate of schizophrenia treatments in the future.

One-year Outcome of First vs. Later Episode Schizophrenia: A Real-world Naturalistic Study

ObjectiveThe aim the study was to calculate remission, recovery and relapse rates in first episode patients with schizophrenia (FES) vs. patients at a later phase (non-FES).MethodsThirty-two FES and 101 non-FES patients took part in the study. The assessment included testing at baseline and at 1 year with the Positive and Negative Syndrome Scale (PANSS), Calgary Depression scale, State-Trait Anxiety Inventory (STAI), Udvalg for Kliniske Undersøgelser (UKU) scale, Simpson Angus, and General Assessment of Functioning (GAF) subscale. The statistical analysis included chi-square test and analysis of covariance.ResultsAt baseline 15.62% FES vs. 10.89% non-FES patients were in remission; none of FES vs. 2.97% non-FES patients were in recovery. At endpoint, the respective figures were 12.50% vs. 25.00% and 3.12% vs. 3.96%. None of the differences in rates was significant between the two groups except from the percentage of patients being under medication (higher in the non-FES group). Baseline PANSS negative subscale (PANSS-N) was the only predictor of the outcome at endpoint.ConclusionThe current study reported very low rates of remission and recovery of patients with schizophrenia without any differences between FES and non-FES patients. One possibility is that the increased antipsychotic treatment compensates for the worsening of the illness with time. An accumulating beneficial effect of antipsychotic treatment suggested that early lack of remission is not prognostic of a poor outcome.

Effects of Chronic Pharmacological Treatment on Functional Brain Network Connectivity in Patients with Schizophrenia

Schizophrenia is characterized by the dysfunction of various brain networks. Previous studies suggested that pharmacological treatments for schizophrenia induce functional changes in localized brain regions. However, the effects of antipsychotic treatments on brain networks associated with symptom improvement are still elusive. The elucidation of antipsychotic-induced functional brain changes is essential for the development of biologically informed treatment strategies. Forty-five healthy controls and 44 patients with schizophrenia underwent resting-state fMRI scans at baseline. The patients underwent a second scan after 6 weeks of antipsychotic treatment. At baseline, patients exhibited a significant decrease in functional connectivity of the cingulate gyrus in the default mode network compared to healthy controls, and this decrease was negatively correlated with symptom severity. Clinical improvements were observed after 6 weeks treatment, accompanied by an increase in functional connectivity of the cingulate gyrus in the default mode network and the inferior parietal lobule in the executive control network. The changes in functional connectivity of the inferior parietal lobule were significantly correlated with symptom improvement. These longitudinal neuroimaging findings suggest that schizophrenia might be an outcome of the disruption of the optimal balance of brain networks, and reestablishing this balance through antipsychotic treatment may result in clinical symptom improvement.

Influence of the use of atypical antipsychotics in metabolic syndrome.

ABSTRACTObjectivesTo describe the possible relationship between the use of antipsychotic drugs and the presence of metabolic syndrome. Other objectives are to list the main side effects of antipsychotic treatment, and to determine if there is any pharmacological treatment that can contribute towards counteracting metabolic syndrome.Material and methodA narrative bibliographic review was carried out of the following databases: PubMed, Cochrane, CINAHL, IBECS, LILACS and HealthCare. Preference in the selection process was given to clinical trials and systematic review articles or review articles and some articles that were considered relevant because of their content. The time period was limited to between January 2014 and November 2019. The languages were English and Spanish. Repeated articles and those that were not related to the objectives were rejected. The search criteria were: “antipsychotic AND metabolic syndrome”; “schizophrenia AND metabolic syndrome”; “bipolar disorder AND metabolic syndrome”; “metabolic syndrome AND suicide NOT disorder”; “metabolic syndrome AND prisons”; “metabolic syndrome AND prolactin”.Results24 articles were selected out of the 510 that were consulted. The relationship between atypical antipsychotics and metabolic syndrome was evident. Other anticholinergic, antidopaminergic effects, extrapyramidal syndromes, neuroleptic malignant syndrome, hypotension, arrhythmias, sedation, hypovitaminosis D, increased prolactin, sexual dysfunction, sleep disturbances, etc. are also highlighted. Pharmacological associations with other drugs were also found.DiscussionThere is a relationship between the use of atypical antipsychotics and weight gain, lipid disorders, glucose and high blood pressure. There are some associated drugs that decrease some symptoms (ranitidine, topiramate, metformin, melatonin, modafinil). Patients taking this type of medication should be monitored and encouraged to lead healthy lifestyles.

Low-Dose Quetiapine Causing Agranulocytosis and Leucopenia in a Patient with Benign Neutropenia: A Case Report

Low white blood cell (WBC) counts and agranulocytosis are a relatively rare side effect of atypical antipsychotic treatment. Often, quetiapine is used as an adjunctive medication to help with sleep and mood in some patients. Many times, it is prescribed at lower doses when targeting this mechanism of action, especially when used in combination with antidepressants. The following case highlights the importance of understanding the potential risks in prescribing quetiapine in patients who have underlying genetic susceptibility towards low white blood cell counts.

Association study between HTR2A rs6313 polymorphism and early response to risperidone and olanzapine in schizophrenia patients.

Antipsychotic drugs are the preferred choice for schizophrenia treatment; however, response is highly variable. In the context of the search for predictors of antipsychotic treatment effectiveness, the evaluation of response within 2 weeks has been indicated to predict long-term outcome. Moreover, a focus on symptomatological domains could be helpful to better characterize antipsychotic response, identifying more specific predictors. Pharmacogenetic studies have indicated a role for rs6313 in the serotonin receptor gene HTR2A in affecting response to antipsychotics, with heterogeneous results. With the aim to test for the first time the application of a dimensional approach for the evaluation of early response, we carried out a genetic association study between rs6313 and antipsychotic response in two groups of schizophrenia patients in monotherapy with risperidone (n = 121) and olanzapine (n = 100). Patients were evaluated at the baseline and after 1 and 2 weeks of treatment. When comparing early responders versus early nonresponders, no association was detected for the two drugs separately, whereas by taking into consideration the two drugs together it was observed that carriers of the T allele had a higher response probability compared to noncarriers. Considering 2-week improvements, changes in PANSS total scores, subscores and in PANSS Emsley's symptomatological dimensions were associated with rs6313 for both risperidone and olanzapine. Moreover, the repeated measures analysis indicated an association of rs6313 with the disorganized thought dimension for risperidone, and with the depressive and anxiety dimensions for olanzapine. These data add support to the hypothesis that the HTR2A gene is involved in antipsychotic treatment outcome.

Real-world effectiveness of antipsychotic treatment in psychosis prevention in a 3-year cohort of 517 individuals at clinical high risk from the SHARP (ShangHai At Risk for Psychosis).

Antipsychotics are widely used for treating psychosis, but it is unclear whether they can also prevent psychosis. This study attempted a longitudinal evaluation of antipsychotics under real-world conditions in China to evaluate their effect on the rate of conversion to psychosis in individuals with a clinical high risk (CHR) of psychosis. A total of 517 CHR individuals were recruited between 2011 and 2016 and followed up for 3 years. Among these, 450 (87.0%) individuals completed follow-up, 108 (24.0%) showed conversion to psychosis and 309 (68.7%) received antipsychotics. The main outcome was conversion to psychosis. The sample was further stratified according to the severity of positive symptoms. Patients who did not receive antipsychotics showed a lower conversion rate than those who did (17.7% vs 26.9%; odds ratio [OR] = 0.660, 95% confidence interval [CI] = [0.442, 0.985], p = 0.035). In mild CHR cases, antipsychotic treatment was more likely to be associated with conversion to psychosis, compared with the no-antipsychotics group, with no such difference observed in severe CHR cases. Among those who received antipsychotics, monotherapy or low-dose treatment was associated with lower conversion rates. Our results did not favor any specific type of antipsychotics and suggested that a very small subgroup of CHR individuals with severe positive and general symptoms but mild negative symptoms may benefit from antipsychotic treatment. Administration of antipsychotics to CHR patients is potentially harmful with no preventive benefits. We do not recommend antipsychotic treatment for CHR individuals, which is practiced widely in China, and strongly advise caution if these drugs are used.

T45. THE EFFICACY AND HETEROGENEITY OF ANTIPSYCHOTIC RESPONSE IN SCHIZOPHRENIA: A META-ANALYSIS

BackgroundAntipsychotics are more effective than placebo in reducing symptoms in schizophrenia. However, response to treatment appears to vary, and as such it has been proposed that different subtypes of schizophrenia exist, defined by treatment-response. This has not been formally examined using meta-analysis.MethodsRandomised controlled trials comparing placebo and antipsychotics for the acute treatment of schizophrenia published between January 1 1950 and November 30, 2018 were examined. Mean change and variance of change in symptoms were extracted from each study, alongside publication year, participant age and gender, baseline symptom severity, antipsychotic dose, and use of placebo lead-in. Relative variability of symptomatic improvement in antipsychotic-treated individuals compared to placebo-treated individuals was quantified using coefficient of variation ratio (CVR). Mean difference in symptom change was quantified using Hedges’ g. The significance of potential moderating factors was assessed using meta-regression and sensitivity analyses. In addition, individual patient data from two clinical trials (N=522) was examined in terms of both the distribution of total symptom change, and the variability of individual symptoms and symptom factors.Results11,006 articles were identified. 66 met inclusion criteria, reporting on 17,202 participants. Compared with placebo, antipsychotic-treated patients demonstrated both greater symptomatic improvement (g=0.47, p<0.001) and reduced variability in symptomatic improvement (CVR=0.86, p<0.001). Lower variability in antipsychotic-response was associated with studies including younger patients (z=3.07, p=0.002), those published earlier (z=3.98, p<0.001), with higher dose treatments (z=-2.62, p=0.009), and greater mean-difference in symptom-change (z=-5.70, p<0.001). In the individual patient data antipsychotic treated patients did not show significantly increased variability for any individual symptom, and there was no evidence of a bimodal distribution of response.DiscussionCompared to placebo, in addition to a greater mean change, antipsychotic treatment shows lower variability of change in total, positive, and negative symptoms. This is contrary to the hypothesis that there exists a subtype of antipsychotic non-responsive schizophrenia, instead providing evidence for a relatively homogeneous effect of antipsychotic treatment in improving symptoms of schizophrenia.

S155. DIETARY PATTERNS AND OBESITY IN INDIVIDUALS WITH SCHIZOPHRENIA

BackgroundIt is well established that individuals with schizophrenia, compared to the general population, have reduced lifespan of up to 20–25 years. High mortality rates in schizophrenia is mainly attributed to physical illnesses which include cardiovascular diseases and diabetes. Obesity is a major risk factor for these diseases and is highly prevalent in the schizophrenia population. Although the mechanisms underlying weight gain in schizophrenia is unclear, it is generally accepted that the high obesity rate is a result of various factors which include metabolic effects of antipsychotic treatment, inadequate physical activity and unhealthy diets. This study aimed to (i) examine dietary practices of individuals with schizophrenia in comparison to the general population and (ii) to examine dietary practice correlates with Body Mass Index (BMI) classification of overweight/obese.MethodsA sample of 107 community-dwelling individuals with schizophrenia were enrolled in this cross-sectional study. Height and weight were taken, and BMI was calculated. A 24-hour food recall which allows derivation of nutritional information, and the Dietary Practices Questionnaire (DPQ) which examines dietary habits, were administered based on participants’ usual diet. Dietary information was compared against the general Singapore population based on the National Nutrition Survey 2010 and the National Health Survey 2010. Logistic regression was performed to study the relationship between dietary practice and BMI status; the model was adjusted for age, gender, antipsychotic medication and energy intake.ResultsNutritional information reported by participants showed that the total daily energy (1895.3kcal ± 684), macronutrient intake (protein: 68.6g ± 35, carbohydrate: 251.8g ± 104.8 and total fat: 67.5g ± 31.8) and dietary fibre intake (16.1g ± 9.0) was lower than both the recommended Singapore guidelines and intake of the general population. In terms of dietary habits, participants were often eating out and frequented fast food places as much as the general population, and do not usually skip breakfast. The proportion of participants who do not consume sweet desserts (32.7% vs 14.9%) and deep-fried food (21.5% vs 9.6%) were higher than the general population, however the proportion of individuals reporting no intake of sweetened drinks was higher in the latter (20.6% vs 54.6%). The proportion of overweight/obese participants (Male: 70%, Female: 66%) was about twice that of the general population (Male:46.6%, Female: 33.8%). Based on the dietary habits explored, participants who did not consume deep-fried food were less likely to be overweight/obese compared to those who do (OR: 0.3, 95% CI:0.09–0.82, p=0.02).DiscussionDespite potential inaccuracies due to recall or social desirability bias, the results seem to suggest that individuals with schizophrenia were below the recommended energy intake; their nutritional intake and dietary habits were either similar or lower/poorer than the recommended guidelines or the general population. Consumption of deep-fried food was the only dietary habit identified as a potential factor towards overweight/obesity. Despite this, the rate of overweight/obese individuals with schizophrenia were high. As overweight/obesity is the result of imbalance between energy intake and expenditure, future research should explore other lifestyle factors such as physical activity, in addition to dietary practices.

Association of MTHFR 677C > T genetic polymorphism with extrapyramidal side effects of antipsychotic treatment

Several studies have revealed a positive association between methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphism 677C > T and schizophrenia. In T-allele carriers the functional activity of MTHFR is reduced contributing to hyperhomocysteinemia development, methionine deficiency and as a consequence - redox dysregulation and the alteration of dopamine synthesis. The aim of this study was to investigate the association of MTHFR677C > T with the severity of extrapyramidal side effects of antipsychotics in schizophrenia. The average score on the Simpson-Angus scale (SAS) in a group of patients with MTHFR 677 T-allele (n = 30; 13.27 ± 5.10, M ± SD) was statistically significantly higher (t = −2.40; p = 0.02) than in the comparison group of wild genotype MTHFR 677 CC carriers (n = 31; 9.84 ± 6.03, M ± SD), confirming the working hypothesis about a possible association of the MTHFR677 T-allele carriage with the development of extrapyramidal side effects of antipsychotics.

Characteristics of gray matter alterations in never-treated and treated chronic schizophrenia patients

Though gray matter deficits have been consistently revealed in chronic treated schizophrenia, it is still not clear whether there are different brain alterations between chronic never treated and treated patients. To explore the different patterns of gray matter alterations among chronic never treated patients and those treated with monotherapy, we recruited 35 never-treated chronic schizophrenia patients with illness durations ranging from 5 to 48 years, 20 illness duration-matched risperidone monotherapy and 20 clozapine monotherapy patients, and 55 healthy controls. GM (surface area, cortical thickness, and cortical volume) measures were extracted and compared using ANCOVA across the four groups followed by post hoc tests. Relative to controls, both treated and never-treated chronic schizophrenia patients showed reduced GM mainly involving the bilateral medial and rostral middle frontal, left banks superior temporal sulcus, left fusiform, and left pericalcarine cortex and increased in the left cuneus. Compared with the untreated patient group, the two treated groups showed reductions mainly in the bilateral prefrontal, temporal, and left inferior parietal lobules. The clozapine monotherapy patients demonstrated more severe decreases in the bilateral prefrontal cortex and left cuneus and less severe decreases in the left ventral temporal lobe than risperidone monotherapy patients. These findings provide new insights into the long-term effects of antipsychotic treatment on gray matter alterations in schizophrenia patients. Furthermore, the characteristic findings of reductions in the inferior parietal lobule might be specific for long-term antipsychotic treatment, which could be a possible target for medication development in the future.

MON-675 Ziprasidone Induced Diabetic Ketoacidosis

Introduction: Atypical antipsychotics are known to cause increased risk of type 2 Diabetes Mellitus (DM2), dyslipidemia, and weight gain (metabolic syndrome). Clozapine, a commonly used anti-psychotic, is known to cause Diabetic Ketoacidosis (DKA), but literature has rarely shown an association of DKA with Ziprasidone. Case: A 42-year-old African American female presented with two weeks of polyuria, polydipsia, 23-pound weight loss, blurriness of vision, and dry mouth. Before the presentation, she had been drinking several drinks with high sugar content. Her medications included Ziprasidone (Geodon), Trileptal, and Cogentin for her bipolar disorder. She was started on Ziprasidone in 2007, changed to Brand name Geodon in 2014. Except for dry mouth, her exam was unremarkable. Labs were significant for blood glucose of 1114 mg/dL, bicarbonate of 18mmol/L, beta-hydroxybutyrate of 3.33 mmol/L, serum osmolality of 334 mOsm/kg. She was diagnosed with new-onset diabetes mellitus presenting as diabetic ketoacidosis. Her mother was diagnosed with DM2 in her 40s. She ha difficult to control blood sugars despite aggressive hydration and required regular insulin drip for 3 days for her anion gap to close. Managing her BGs was challenging. Discussion: Clozapine and olanzapine are the common atypical antipsychotics that can cause DKA1, 2. To our knowledge, Ziprasidone is associated with hyperglycemia within days of starting the drug and HHS but not with DKA. For atypical antipsychotic associated DKA, risk factors include the duration of antipsychotic therapy, polypharmacy with multiple antipsychotic agents, non-Caucasians, obesity and pre-diabetes2, 3. Proposed mechanisms include peripheral insulin resistance, alteration of pancreatic beta-cell function by inhibiting 5-HT1A/2A/2C and alpha 2 adrenergic receptors1-3. However, there is no explanation of why few people develop complications while others do not. There is hypothesis regarding leptin gene polymorphisms of receptors that may play a role4. While starting patients on Ziprasidone, close monitoring of blood glucose is necessary before initiation and regular follow up thereafter3.1. Henderson DC. Atypical antipsychotic-induced diabetes mellitus: How strong is the evidence? CNS Drugs. 2002.2. Vuk A. Diabetic ketoacidosis associated with antipsychotic drugs: Case reports and a review of literature. Psychiatr Danub. 2017.3. Schwenkreis P. Atypical antipsychotics and diabetes mellitus. World J Biol Psychiatry. 2004.4. 1. Reynolds GP. Metabolic side effects of antipsychotic drug treatment - pharmacological mechanisms. Pharmacol Ther. 2010.

Editorial introductions

Editorial introductions

5-Hydroxytryptamine Receptors and Tardive Dyskinesia in Schizophrenia

BackgroundTardive dyskinesia (TD) is a common side effect of antipsychotic treatment. This movement disorder consists of orofacial and limb-truncal components. The present study is aimed at investigating the role of serotonin receptors (HTR) in modulating tardive dyskinesia by genotyping patients with schizophrenia.MethodsA set of 29 SNPs of genes of serotonin receptors HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B, and HTR6 was studied in a population of 449 Caucasians (226 females and 223 males) with verified clinical diagnosis of schizophrenia (according to ICD-10: F20). Five SNPs were excluded because of low minor allele frequency or for not passing the Hardy-Weinberg equilibrium test. Affinity of antipsychotics to 5-HT2 receptors was defined according to previous publications. Genotyping was carried out with SEQUENOM Mass Array Analyzer 4.ResultsStatistically significant associations of rs1928040 of HTR2A gene in groups of patients with orofacial type of TD and total diagnosis of TD was found for alleles, and a statistical trend for genotypes. Moreover, statistically significant associations were discovered in the female group for rs1801412 of HTR2C for alleles and genotypes. Excluding patients who used HTR2A, respectively, HTR2C antagonists changed little to the associations of HTR2A polymorphisms, but caused a major change of the magnitude of the association of HTR2C variants. Due to the low patient numbers, these sub-analyses did not have significant results.ConclusionWe found significant associations in rs1928040 of HTR2A and for rs1801412 of X-bound HTR2C in female patients. The associations were particularly related to the orofacial type of TD. Excluding patients using relevant antagonists particularly affected rs1801412, but not rs1928040-related associations. This suggest that rs1801412 is directly or indirectly linked to the functioning of HTR2C. Further study of variants of the HTR2C gene in a larger group of male patients who were not using HTR2C antagonists is necessary in order to verify a possible functional role of this receptor.

Susceptibility of male wild type mouse strains to antipsychotic-induced weight gain

While both men and women gain weight as a side effect of antipsychotic (AP) treatment, studies in mice have found only female mice are susceptible to weight gain. Therefore, to we set out to identify a strain of male mice that gain significant weight in response to APs which could better model AP-induced weight gain observed in humans. These studies determined that male Balb/c mice developed late onset olanzapine-induced weight gain. Patients often take APs for many years and thus understanding AP-mediated changes in food intake, energy expenditure and body weight regulation is particularly important.

Effects of antipsychotic treatment on haematological parameters of psychotic patients in tertiary care hospital of India

Introduction/Aim of study: Use of some antipsychotic agents results in haematological changes like leukopenia, neutropenia, thrombocytopenia, anaemia, Leukocytosis, thrombocytosis which may present a major problem for the management of psychotic patients. Material and Methods: Twenty four patients on therapy with antipsychotic drugs for a minimum period of three months were recruited for study for haematological changes at tertiary care Hospital of India. The study was conducted between March and august, 2019. Results: Out of 24 cases, 1 patient developed neutropenia (4.16%), and 01 patient developed anaemia (4.16%) within 3 month of treatment without any haematological disease. Conclusion: The significant reduction in blood cell count observed associated with antipsychotic agents especially neutropenia. An appropriate monitoring strategy should be used for clozapine and other antipsychotic drug to minimize the adverse drug reaction and early shift of treatment. Keywords: Antipsychotic drugs, Haematological parameters, Neutropenia.