2nd Generation Antipsychotics Research Articles

Anti-inflammatory effects of 2nd generation antipsychotics in patients with schizophrenia: A systematic review and meta-analysis

BackgroundSchizophrenia is a major psychiatric disorder with unknown aetiology. Recent evidence suggests a potential role for cytokines in its pathophysiology and that antipsychotic medication may alter this. While the aetiology of schizophrenia remains only partly understood, an altered immune function representing an important avenue of further discovery. In this systematic review and meta-analysis we focus on the specific effects of second generation antipsychotics risperidone and clozapine on inflammatory cytokines. MethodsA defined systematic search of PubMed and Web of Science databases was performed to identify relevant studies published between Jan 1900 and May 2022. After screening of 2969 papers, 43 studies (27 single-arm and 8 dual-arm) were included that consisted of a total of 1421 patients with schizophrenia in the systematic review. From these, twenty studies (4 dual-arm; 678 patients) had data available on which a meta-analysis could be carried out. ResultsOur meta-analysis showed a significant reduction of pro-inflammatory cytokines post-risperidone treatment in the absence of a similar association with clozapine. Subgroup analyses (First episode v chronic) demonstrated that duration of illness influenced the extent of cytokine alteration; risperidone treatment produced significant cytokine changes (lowered IL-6 and TNF-α) in chronic patients but not in first-episode psychosis (FEP) patients. ConclusionVarying treatment effects on cytokines can be observed by the use of different antipsychotic drugs. The cytokine alterations post-treatment are influenced by the specific antipsychotic drugs and patient status. This may explain disease progression in certain patient groups and influence therapeutic choices in the future.

The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos.

The effects of second-generation antipsychotics on prenatal neurodevelopment, apoptotic neurodegeneration, and postnatal developmental delays have been poorly investigated. Even at standard doses, the use of quetiapine fumarate (QEPF) in pregnant women might be detrimental to fetal development. We used primary mouse embryonic neurons to evaluate the disruption of morphogenesis and differentiation of ventral midbrain (VM) neurons after exposure to QEPF. The dopaminergic VM neurons were deliberately targeted due to their roles in cognition, motor activity, and behavior. The results revealed that exposure to QEPF during early brain development decreased the effects of the dopaminergic lineage-related genes Tyrosine hydroxylase (Th), Dopamine receptor D1 (Drd1), Dopamine transporter (Dat), LIM homeobox transcription factor 1 alfa (Lmx1a), and Cell adhesion molecule L1 (Chl1), and the senescent dopaminergic gene Pituitary homeobox 3 (Pitx3). In contrast, Brain derived neurotrophic factor (Bdnf) and Nuclear receptor-related 1 (Nurr1) expressions were significantly upregulated. Interestingly, QEPF had variable effects on the development of non-dopaminergic neurons in VM. An optimal dose of QEPF (10 µM) was found to insignificantly affect the viability of neurons isolated from the VM. It also instigated a non-significant reduction in adenosine triphosphate formation in these neuronal populations. Exposure to QEPF during the early stages of brain development could also hinder the formation of VM and their structural phenotypes. These findings could aid therapeutic decision-making when prescribing 2nd generation antipsychotics in pregnant populations.

Olanzapine in oncology palliative care.

Olanzapine is an effective antipsychotic drug used in psychiatry to treat psychoses, especially schizophrenia and schizoaffective disorders. It belongs to the 2nd generation antipsychotics, its mechanism of action ranks among multireceptor antagonists (MARTA); it affects the dopamine, serotonin, adrenaline, histamine, and muscarinic systems. The broad pharmacodynamic profile of olanzapine provides for a broad indication spectrum with a better adverse effect profile compared to conventional antipsychotics. It can be used in a number of situations to benefit cancer patients in palliative care as well as in the terminal stages of the disease. The review article presents possible indications for olanzapine in oncological palliative care. Apart from dealing with delirium and anxiety, indications for the use of antipsychotics in palliative medicine include the management of nausea, vomiting and loss of appetite. Olanzapine is an effective antiemetic in cancer patients with tumor-induced nausea and in antiemetic regimens for chemotherapy-induced nausea and vomiting. Olanzapine is an effective treatment for delirium, as effective as haloperidol, but with a lower toxicity profile. It increases appetite and can be used with advantage in patients with anorexia and weight loss. It is possible to use its anxiolytic and mood-stabilizing effects; in many situations, it can serve well as a co-analgesic, especially in the so-called total pain. It is proven to increase the quality of life of patients with advanced cancer. Due to its effect, simple dosage and a good safety profile, olanzapine is a useful drug for the routine clinical practice of an oncologist - a non-psychiatrist.

The risk of a blood pressure increase during treatment with selected psychotropic drugs

Arterial hypertension is the most common cardiovascular risk factor in the general population. Increased mortality from arterial hypertension affects all ethnicities and ages, including those with mental disorders. Most people with arterial hypertension suffer from the primary form of the disease. The aim of this article was to analyze the influence of psychiatric drugs on blood pressure. The articles for analysis were selected via the PubMed search engine in the Medline database using the names of individual drugs or a group of psychotropic drugs, the AND operator and the words “hypertension” or “blood pressure” or “cardiovascular system”. The articles were then selected and 44 references were selected for analysis. Selected articles were archived on April 9, 2021. Many medications with the potential to increase blood pressure are used to treat mental illness. These include venlafaxine, milnacipran, bupropion, esketamine, 1st and 2nd generation antipsychotics, tricyclic antidepressants and psychostimulants. In patients using psychotropic drugs that may increase blood pressure, attention should be paid to monitoring it during treatment.

A Case-control Study of Sexual Dysfunction and Serum Prolactin Levels in Patients with Psychotic Disorders

Introduction: Sexual functioning has remained widely neglected aspect of patient care for those suffering from severe mental disorders and has received little attention. Yet, it has been construed as one of the major factors contributing to nonadherence with antipsychotic medications. Aim: To study sexual dysfunction in patients with psychotic disorders and its clinical association with serum prolactin levels. Materials and Methods: This case-control study was conducted in the Department of Psychiatry at MGM Medical College and associated Mental Hospital, Indore, Madhya Pradesh, India, from 13th February 2020 to 21st January 2021. The study sample consisted of 200 subjects including 100 cases and 100 controls. The case group included patients with a diagnosis of psychotic disorders currently in remission for at least 1 month. Remission of the patients was ensured by Brief Psychiatric Rating Scale (BPRS) with a score of <4 on all items and <28 total score. Assessment of sexual dysfunction was done using Arizona Sexual Experience Scale (ASEX). The control group included healthy subjects aged between 18-65 years, either sex having active sexual partners with a score of < 3 on all the items of the General Health Questionnaire (GHQ-12). Collection of blood sample was done and serum was analyzed for prolactin levels using the Chemiluminescent Microparticle Immunoassay (CMIA) method. Statistical analysis was done using Statistical Package for the Social Sciences version 28.0 (SPSS) for windows. Results: The mean age of the case group was 39.9±7.457 years while that of the control group was 35.60±9.37 years. The number of male patients (71% and 73%) was higher than females (29% and 27%) in the control group and case group respectively. The difference between the two were statistically significant. The total number of cases who experienced sexual dysfunction came out to be 59 out of 100. Total 55.93% of those having sexual dysfunction were suffering from difficulty in sexual arousal, followed by difficulty with penile erection/vaginal lubrication (49.15%), orgasmic dysfunction (34.48%), and reduced sexual drive (23.72%). Among the cases, the mean serum prolactin level (14.14±10.60 ng/mL) was seen to be significantly higher (p-value <0.001) than the control group (9.46±6.05 ng/mL). Maximum serum prolactin level (29.00±9.95 ng/mL) was seen to be associated with usage of a combination of both 1st and 2nd generation antipsychotics. Conclusion: There was a significant prevalence of sexual dysfunction in psychotic patients and is associated significantly with elevated serum prolactin levels.

The association of dry eye syndrome and psychiatric disorders: a nationwide population-based cohort study

BackgroundSeveral previous studies reported a greater prevalence of dry eye syndrome (DES) among patients with psychiatric diseases. The aim of this study is to investigate the prevalence and risk factors of DES in patients with psychiatric disorders (PD) using nationwide population-based data in Taiwan.MethodsThis population-based cohort study retrospectively identified patients with PD from 1997 to 2011. Patients with both PD and DES served as the DES cohort, and PD patients without DES comprised the non-DES cohort. PD was defined as a diagnosis of PD (ICD-9-CM 290–319) made by psychiatrists only, with at least three consecutive outpatient visits or at least one inpatient visit. DES was defined as a diagnosis of DES (ICD-9-CM 375.15) and a prescription for an eye lubricant (anatomical therapeutic chemical code, ATC code: S01XA). The main outcome measures were the prevalence of DES in these patients and associated risk factors.ResultsA total of 75,650 patients with PD (3665 in the DES cohort and 71,985 in the non-DES cohort) were included in the final analysis. The majority of patients in the DES group were women (72.6%), compared the non-DES group (57.8%). The mean age of patients in the DES cohort was 62.2 ± 14.9, which was significantly older than those in the non-DES group (50.9 ± 17.5). The patients with DES had a significantly greater likelihood of having dementia, bipolar disorder, depression, and neurotic disorders. Conditional regression analyses revealed that patients with dry eye disease were more likely to have schizophrenia (OR = 1.34), bipolar disorder (OR = 1.9), depression (OR = 1.54), and neurotic disorders (OR = 1.62). In addition, patients with DES were more likely to use 1st generation anti-psychotics (OR = 1.28) and had a lower risk of using 2nd generation anti-psychotics (OR = 0.64).ConclusionThe study demonstrated that among PD patients, DES is highly prevalence in certain subtypes of PD, such as depression, bipolar disorder, and neurotic disorders, after adjusting for the comorbidities.

The Development of Psychiatric and Mental Health Nursing in Taiwan: Reflection From the Perspective of Recovery

Evidence-based nursing science has identified psychological recovery, partnership, and medication adherence as factors that have influenced the development of mental health care. This article discusses the process by which mental health care has developed from a medical / rehabilitation-focused model to a model that focuses on patient empowerment. The current model aims to assist patients to achieve self-awareness and to develop coping skills that enhance their motivation to transform. Medical advances have improved the control of psychiatric symptoms. Following the introduction of 2nd generation antipsychotics, patients were invited to establish decisions related to these prescription medications. Under the principles of patient-centered service, Taiwanese mental health professionals have changed their relationship with patients from a therapeutic model to a mutual-partnership model. Furthermore, investigations of the therapeutic care of patients with mental illness have used the needs of patients as their starting point and emphasized various aspects of patient and caregiver needs. Taiwanese mental health professionals are searching for a model of mental health care that is superior to the traditional operative framework of medical authority.

Indicators of treatment of schizophrenia in different stages of psychiatric care

Objective. To study indicators of treatment of schizophrenia in different stages of psychiatric care, to reveal prognostic factors of the dynamics of psychopathological symptoms in treatment of schizophrenia and to estimate the risk of schizophrenia relapse. Material and methods. Three hundreds of patients, aged 18-65 years, diagnosed with schizophrenia (ICD-10) were included in data analysis. Patients were stratified into 4 groups by the type of psychiatric care: inpatients (n=68), outpatients of day hospital (n=71), outpatients of psychoneurological dispensary rehabilitation department (n=75) and outpatients supervised by psychoneurological dispensary local doctor. Treatment characteristics (use of 1st and 2nd generation antipsychotics) of these groups were compared. Results and conclusion. The positive effect of modern antipsychotics on schizophrenia course, frequency of relapses and hospitalizations was identified. The results can help in improvement of psychiatric care due to wide implementation of 2nd generation antipsychotics.

Disentangling early sensory information processing deficits in schizophrenia

ObjectiveThe disentangling of early sensory information processing deficits and examination of their relationships to demographic and clinical factors are important steps for the validation of potential biomarkers and/or endophenotypes of schizophrenia. The aims of the present study were to characterize commonly used sensory event-related potential deficits, to determine whether they are (1) distinct from one another and (2) independently associated with important clinical characteristics. MethodsMMN, P3a and RON event-related potentials (ERP) were recorded from schizophrenia patients (SZ; n=429) and nonpsychiatric comparison subjects (NCS; n=286). Subgroup analyses on demographic and clinical variables were performed. ResultsSchizophrenia patients exhibited robust ERP deficits at frontocentral electrodes (MMN: d=1.10; P3a: d=0.87; RON: d=0.77), consistent with previous studies. Each ERP component uniquely accounted for variance in amplitude and schizophrenia deficits. Amplitude reductions occurred with increasing age in both NCS and SZ patients. A small subset of patients prescribed combinations of 1st and 2nd generation antipsychotics exhibited significantly reduced MMN amplitude relative to other medication-defined subgroups. ConclusionsMMN, P3a, and RON are dissociable deficits with distinct relationships to age and medication status in schizophrenia patients, potentially reflecting divergent pathophysiological processes. Reduced MMN in patients taking multiple antipsychotic medications appear to be attributable to greater severity of symptoms and functional impairments, rather than a medication effect. SignificanceIndependent information processing deficits in schizophrenia patients may differentially contribute to the commonly observed deficits in neurocognitive and psychosocial functioning.

P-1250 - Is this really schizofrenia?

Introduction A 34 year old man was referred to our unit for psychiatric evaluation. His psychomotor development was normal until the age of 12, when he started showing progressive loss of cognitive skills and finalized motor activity. Symptoms rapidly worsened and by the age of 20 his language and motor skills were severly compromised. Starting at age 17 he had been treated with both 1st and 2nd generation antipsychotics which did not lead to any changes in symptoms. Family history was negative for psychotic or neurological disorders. The mother had alcohol abuse disorder and the younger sister was diagnosed with generalized anxiety disorder. Method At the time of our evaluation patient was receiving 10 mg of Olanzapine. He was vigilant and passively cooperative to examination; he displayed physical immobility, waxy flexibilitas, stereotyped behaviour, camptocormia, echolalia, blunted affect and automatic and repetitive behaviour. Thought content was difficult to evaluate but he denied hallucinations or delusional thoughts. Results BP was normal, as well as brain MRI and PET. Screening for Wilson's disease, metabolic diseases and fragile X Syndrome were negatve. DAT scan was also performed and showed no abnormalities. Medication withdrawal didn’t lead to any changes in his status. Conclusions The patient's symtoms fulfill the criteria for drug resistant Catatonic Schizophrenia. However the early onset of symptoms, the rapid deterioration of cognitive abilities, the early and extensive motor imparment and the complete resistance to drug treatment make this an interesting case for discussion about differential diagnosis.

Effects of olanzapine and risperidone on lipid metabolism in chronic schizophrenic patients with long-term antipsychotic treatment: A randomized five month study

ObjectiveMetabolic syndrome and elevated lipids, related to cardiovascular risk factors, are more prevalent in schizophrenia and there has been much debate about the extent to which specific antipsychotics contribute more to the increased risk of developing hyperlipidemia and metabolic syndrome. Most studies have concentrated on fasting levels in patients recently started on medication. Randomized prospective studies of metabolic effects of 2nd generation antipsychotics using both fasting measures and provocative tests may provide results that are more informative. We present results of a randomized prospective study of lipid metabolism and metabolic syndrome in chronic schizophrenic patients using both fasting and post-prandial lipid measures. MethodHospitalized patients with chronic schizophrenia, most of whom had been treated with multiple antipsychotics in the past, were randomly assigned to treatment with a single antipsychotic, olanzapine or risperidone, for a period of 5months. At baseline and every treatment month thereafter, fasting levels of lipids, free fatty acid (FFA) and leptin were assessed. At baseline and end of month 2 of treatment patients had a fatty meal test (FMT) in which postprandial lipids were measured at several time points before and after meal ingestion. Weight was assessed monthly and waist measures were taken at baseline and month 5. Data was analyzed on 23 patients randomized to risperidone and 23 patients randomized to olanzapine. ResultsOverall, there were no differential drug effects on any fasting lipid measure and fasting triglycerides did not increase in olanzapine treated patients after 5months of treatment. However, at 2months of drug treatment the FMT revealed a significantly greater increase in triglycerides, and very low density (VLDL) cholesterol and triglycerides, in olanzapine compared to risperidone patients (Ps=.05–.01). There was no difference between treatments with olanzapine vs. risperidone on development of metabolic syndrome during the 5month treatment period. ConclusionsChronic schizophrenic patients treated for years with first and second generation antipsychotics may have developed tolerance to the effects of olanzapine on increasing fasting triglycerides and other lipids, but some underlying metabolic abnormalities may be revealed in postprandial tests of lipid metabolism. These findings suggest that the development of standardized tests and criteria for measurement of postprandial triglycerides and related lipid levels, in addition to fasting levels, may be helpful in identifying metabolic effects of olanzapine and other second generation antipsychotics in chronically treated schizophrenics. In some reports postprandial increases in triglycerides have been identified as important risk factors for cardiovascular disease, but the actual differential consequences of these lipid metabolic differences for development of atherosclerosis and cardiovascular disease in patients treated with different antipsychotics need more objective outcome measures to determine and quantify cardiovascular risk outcomes.

Are antidepressants warranted in the treatment of patients who present suicidal behavior?

The aim of the study was to ascertain the clinical course of patients admitted to a psychiatric intensive care unit (PICU) just after a suicide attempt (SA) and to evaluate the effectiveness of 2nd generation antipsychotics and mood stabilizers in these patients. We examined all the 129 patients discharged in a three-year period, who had been admitted after a SA and considered in the analysis the 82 cases non-transferred (in the first 72 h) to other PICUs for administrative or logistic reasons. Among them, 47 received a complete neuropsychiatric assessment. We distinguished between patients who had been treated with Antidepressants (AD) or not in the three months preceding hospitalization. We treated all patients with mood stabilizers and 2nd generation antipsychotics. Only one patient was treated with AD in the course of current hospitalization. Both cases treated and not treated with AD before admission improved significantly, especially in symptoms of anxiety and depression, as well as in suicidality. The suicidal risk abated without AD treatment. In patients with impending suicide risk, AD should not be considered standard treatment. Mood stabilizers and 2nd generation antipsychotics can be effective.

Comorbidity of Asperger's syndrome and Bipolar disorder

Background and objectiveAsperger's Syndrome (AS) is a pervasive developmental disorder that is sometimes unrecognized, especially in the adult psychiatric setting. On the other hand, in patients with an AS diagnosis, comorbid psychiatric disorders may be unrecognized in the juvenile setting. The aim of the paper is to show and discuss some troublesome and complex problems of the management of patients with AS and comorbid Bipolar Disorder (BD).MethodsThe paper describes three patients affected by AS and bipolar spectrum disorders.Results and conclusionMood stabilizers and 2nd generation antipsychotics were effective in the treatment of these AS patients with comorbid BD, while the use of antidepressants was associated with worsening of the mood disorder.It is of importance to recognize both the psychiatric diagnoses in order to arrange an exhaustive therapeutic program and to define specific and realistic goals of treatment.

2nd generation antipsychotics for refractory generalized anxiety disorder

2nd generation antipsychotics for refractory generalized anxiety disorder

Preliminary Findings in Switching from Parenteral Haloperidol to Oral Quetiapine Treatment in the Management of Acutely Agitated Patients

Agitation is a very common but complex clinical challenge to the hospital psychiatrist. A subset of agitated patients, threatening their life and that of others, unresponsive to verbal interventions, has to be medicated by parenteral administration. For this indication haloperidol is a well studied and routinely prescribed compound despite its limiting side effects. Therefore, switching to 2nd generation antipsychotics after successful treatment of the acute symptoms should be considered. Our prospective naturalistic study describes clinical practice in the management of acutely agitated patients. Fifteen acute agitated psychiatric patients requiring i.v. haloperidol treatment at admission were subsequently switched to oral quetiapine, remaining on this medication until their discharge. Age, gender, weight, diagnoses, dosages of haloperidol and quetiapine, serum concentration analysed by HPLC, duration of i.v. application, smoking behaviour and co-medications were registered. The patients (10 f) were mainly affected by schizophreniform (N=8), affective or schizoaffective (N=6) disorders. The mean age was 38.4 years (25–58), the mean body weight 71.2kg (55–103.5). Eight patients were identified as smokers. Haloperidol was prescribed for a mean duration of 5.8 days (2–11) in a mean dose of 24.6mg (15–30) reaching a mean serum concentration of 19.9 ng/ml (6–47) with a mean C/D ratio of 0.8 (0.3–1.57). Switching to quetiapine was based on clinical improvement. The mean dose of quetiapine was 573.3mg (300–800) resulting in a mean serum concentration of 267.6 ng/ml (57–520) and a mean C/D ratio of 0.5 (0.1–0.9). A subanalysis revealed that patients (N=8) initially treated with high doses of haloperidol (up to 30mg) were switched earlier to quetiapine (average 2 days) and discharged with smaller doses quetiapine of 525mg/d (300–800) than patients (N=7) medicated with haloperidol up to 20mg requiring a mean quetiapine doses of 671.5mg/d (500–800). Additionally smokers showed lower haloperidol but higher quetiapine serum concentration than non smokers. Since significantly more smokers were present in the group treated with high haloperidol doses, the opposite effects of nicotine on haloperidol and quetiapine will be discussed. Our results indicate that the initial dose of parenteral haloperidol has a clinical impact on the switching time to quetiapine and on the final doses of quetiapine.

S13.04 Czech and Slovak meeting on the WPA consensus statement on 2nd generation antipsychotics

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