Typical Antipsychotic Drugs Research Articles

Olanzapine Use in Schizophrenia and the Modulation of Its Response by Genetic Variations

Schizophrenia is a chronic disease with diverse psychopathology and multiple phases of illness. Consequently, numerous factors must be considered when assessing the benefits of a given treatment over short- and long-term periods. Olanzapine is an atypical antipsychotic reported to be effective without producing many of the disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs. Despite the fact that olanzapine is still associated with a known risk of metabolic side effects, including weight gain, many clinicians continue to prescribe olanzapine for the treatment of schizophrenia with the expectation of additional therapeutic antipsychotic efficacy relative to other first-line atypical antipsychotics. This review focuses on the epidemiology, pathogenesis, and treatment of schizophrenia with special emphasis on the role of olanzapine in the treatment of schizophrenia. Genetic variants associated with the therapeutic efficacy and adverse effects of olanzapine are reviewed and those with the potential to act as a clinical predictor of therapeutic response and/or adverse effects are discussed. Recommendations are made for the use of some of these genetic variants in clinical medicine.

Neuroleptic Malignant Syndrome: Typical Antipsychotic Drugs Versus Atypical Antipsychotic Medications

Introduction: Neuroleptic malignant syndrome is an idiosyncratic reaction and a severe disorder caused by an adverse reaction to drugs with dopamine receptor- antagonist properties and is characterized by a tetrad of rigidity, fever, altered mental status, and autonomic instability. In the present assessment, typical or conventional antipsychotics have been contrasted with atypical antipsychotics with respect to recorded cases of neuroleptic malignant syndrome among a sample of nonwestern psychiatric inpatients. Methods: For assessment, all the cases with a diagnosis of neuroleptic malignant syndrome during the last sixty-two months, after exclusion of other conceivable differential diagnoses, were incorporated in the current retrospective, record-based evaluation. The clinical diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. The valuation of independent variables was analyzed by ‘Compression of proportions. Statistical significance is defined as p value ≤0.05. Results: Amongst 19814 psychiatric inpatients, in the course of sixty-two months, eighteen cases received the diagnosis of neuroleptic malignant syndrome. As said by the findings, neuroleptic malignant syndrome was meaningfully more frequent among males, in comparison with females, and it was importantly more prevalent among cases suffering from schizophrenia, in comparison with bipolar disorder. Also, the highest risk of neuroleptic malignant syndrome was found in the age group of 30-39. In the current assessment, only one of the patients, who had received haloperidol, died due to aspiration pneumonia and respiratory failure, and the most prevalent symptom was fever, which was observable in one hundred percent of cases. In addition to a similar clinical profile, ‘Compression of proportions’ did not show any significant difference between the conventional (typical) antipsychotics versus the atypical antipsychotic medications with respect to the occurrence of neuroleptic malignant syndrome. Conclusion: As said by the findings, no significant difference was evident between the typical antipsychotic drugs versus the atypical antipsychotic medications, with respect to incidence and clinical profile of neuroleptic malignant syndrome.

Enhancement of Haloperidol Binding Affinity to Dopamine Receptor via Forming a Charge-Transfer Complex with Picric Acid and 7,7,8,8-Tetracyanoquinodimethane for Improvement of the Antipsychotic Efficacy.

Haloperidol (HPL) is a typical antipsychotic drug used to treat acute psychotic conditions, delirium, and schizophrenia. Solid charge transfer (CT) products of HPL with 7,7,8,8-tetracyanoquinodimethane (TCNQ) and picric acid (PA) have not been reported till date. Therefore, we conducted this study to investigate the donor–acceptor CT interactions between HPL (donor) and TCNQ and PA (π-acceptors) in liquid and solid states. The complete spectroscopic and analytical analyses deduced that the stoichiometry of these synthesized complexes was 1:1 molar ratio. Molecular docking calculations were performed for HPL as a donor and the resulting CT complexes with TCNQ and PA as acceptors with two protein receptors, serotonin and dopamine, to study the comparative interactions among them, as they are important neurotransmitters that play a large role in mental health. A molecular dynamics simulation was ran for 100 ns with the output from AutoDock Vina to refine docking results and better examine the molecular processes of receptor–ligand interactions. When compared to the reactant donor, the CT complex [(HPL)(TCNQ)] interacted with serotonin and dopamine more efficiently than HPL only. CT complex [(HPL)(TCNQ)] with dopamine (CTtD) showed the greatest binding energy value among all. Additionally, CTtD complex established more a stable interaction with dopamine than HPL–dopamine.

Development and Characterization of Transdermal Patch of Modified form of Brexpiperazol

Aim: Brexpiprazole (BPZ) is a typical antipsychotic drug used for the treatment of schizophrenia and depression. It is classified under BCS class-II with low aqueous solubility and high intestinal permeability. In the present investigation, a solid dispersion of BPZ was prepared to improve the solubility. A transdermal patch was optimized using the central composite design to control the delivery of BPZ.
 Place and Duration of Study: The formulation was prepared and characterized at K. B. Institute of Pharmaceutical Education and Research, Gandhinagar, Gujarat, India during January 2021 to September 2021.
 Methodology: A solid dispersion of BPZ was prepared using PEG 6000.A transdermal patch of BPZ was prepared and optimized using central composite design. Independent variables were fixed as ratio of RLPO: RSPO=2:1 (X1) and conc. of plasticizer (Triacetin) %W/W of polymer (X2). Dependent variables were fixed as folding endurance% (Y1) and cumulative % drug release at 24, 48, 72 and 96 hrs respectively (Y2-Y5) for the optimization of transdermal patch of SD of BPZ. Optimized formulation was characterized fully for its safety and efficacy using ex- vivo permeation study, skin irritation study and stability study.
 Result: The tensile strength of optimized patch was 2.1±0.045 Kg/cm2. The thickness and hardness of patch was 0.0478±0.025 and 80.54±2.64gm/mm. The moisture content and moisture uptake values were 5.2%±0.36 and 6.21±0.24% respectively. Drug content was found to be 99.41±2.64%. The flux value obtained from BRX-SD-TP was 0.06 µg/cm2h. The flux was very proximal to the desired flux value. Prepared formulation was non-irritant and stable.
 Conclusion: From the findings it can be concluded that BRX-SD-TP was successfully developed for treatment of Schizophrenia.

HALLUCINATION IN PATIENTS WITH BORDERLINE PERSONALITY DISORDER

In modern practice, hallucinations found in patients with borderline personality disorder (BPD) are often identified as ‘pseudohallucinations’ to state the suspicion that they do not qualify as true hallucinations. In the interest of Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for BPD, it is stated that during times of tremendous stress, transient ideation of paranoid or dissociative symptoms may occur. BPD is defined as a mental health disorder with remarkable impulsivity, instability of mood and interpersonal relationships, along with suicidal behavior that can complicate medical treatment. It is crucial to identify this diagnosis to plan for further treatment. The existence and severity of hallucinations in BPD patients are closely related to posttraumatic stress disorder (PTSD), prior childhood adversities, as well as current adult life stressor. Auditory verbal hallucinations (AVH) were reported to be the most commonly observed types of hallucinations in patients with BPD. Similarities of the AVH characteristics between BPD patients and those with schizophrenia make it hard to diagnose and manage the hallucinations in BPD patients. Pharmacological management including both typical and atypical antipsychotic drugs may be beneficial in order to treat hallucinations in these patients, however, low-dose antipsychotics are preferred due to its adverse reaction. Psychotherapy such as cognitive behavior therapy (CBT) and non-invasive brain stimulation techniques may be helpful as well. Questioning patient’s psychotic symptoms in an untrue or “made-up” form is rarely advantageous and may leads to undesired therapeutic alliance dismissal. Keywords: hallucination, borderline personality disorder, depression.

Evaluation of the Salivary Flow in Patients with Schizophrenia. A Literature Review

Schizophrenia is a chronic psychiatric disease that affects approximately 1% of the global population. Schizophrenia is characterised by positive, negative and cognitive symptoms. The etiological factors of this psychiatric illness are not fully deciphered, but the most incriminated are genetic factors and environmental risk factors. The treatment of schizophrenia has the role of reduction the duration and intensity of episodes and consists in the administration of typical or atypical antipsychotic drugs, antiparkinsonian, anxiolytic, sedatives or antidepressants. Of these, some of the drugs may have side effects that modify patients' salivary flow rates. Xerostomy is a subjective sign characterized by a dry mouth sensation and is caused by hypofunction of the salivary glands. According to a series of studies, xerostomia can be an adverse effect of typical antipsychotic medication as well as antiparkinsonian medication. Sialorrhea is caused by hyperfunction of the salivary glands and is characterized by an increased secretion of saliva. This side effect is especially noticeable during the night sleep. Alteration of salivary function creates increased discomfort to the schizophrenic patient, which causes him to give up regular medication. The aim of this study is to review the literature on the link between schizophrenia, the treatment of schizophrenia and impaired salivary function.

Neuroleptic Induced Parkinsonism and Catatonia- A Case Report

<h3>Introduction</h3> Neuroleptic induced Parkinsonism (commonly called EPS or extrapyramidal sideeffect) is commonly associated with use of both typical and atypical antipsychotic drugs. They may present with immobility, staring and rigidity. Catatonia is a psychomotor syndrome which is often overlooked by medical providers who consider it under the realm of psychiatric disorders such as Catatonic Schizophrenia and Depression. There are 2 subtypes described - Retarded and excited. It is also seen in various medical conditions including neurological, infectious, metabolic or drug-induced conditions and appears to be a resultant final syndrome after a cascade of events similar to the Delirium.Identifying Catatonia is very important as it is a risk factor for the development of Neuroleptic Malignant Syndrome (NMS) which carries a 10% mortality rate with clinical features indistinguishable from Malignant Catatonia. <h3>Methods</h3> Mary is a 66 yr old female with a psychiatric diagnosis of Neurocognitive disorder, remote history of schizophrenia with last exacerbation about 10 years ago with no residual symptoms who was brought to the ED by family for new onset bizarre behavior with inability to take care of self. She presented combative and disorganized in the medical ED requiring IV Haldol for behavioral control. She was subsequently admitted to the medical service for management of poor oral intake. She was seen by the Psychiatry Consult service the next day and noted to have reduced facial expression and tremors and rigidity suggestive of Neuroleptic Induced Parkinsonism. Bush Francis Catatonia rating scale was administered and she was noted to have signs of mutism, waxy flexibility, mitgehen, negativism and automatic obedience. There were periods when she was lucid and responded to questions meaningfully with brief replies. There were no features of fever and autonomic instability ruling out NMS. The possibility of Neuroleptic induced Parkinsonism along with Neuroleptic induced Catatonia was considered and organic work up was advised. The lab results were not significant for any other metabolic syndromes with exception of mildly elevated CPK. CT head was negative. The possibility of retarded subtype of Delirium was considered but patient was mute and demonstrated many of the motor signs of Catatonia. Other differentials considered were NMS, Locked-in syndrome, Abulia and Vegetative state. Haloperidol was discontinued and Mary was started on Benztropine. Over the next 2 days, there was a gradual resolution of her symptoms of EPS as well as catatonia. Naranjo possibility scale indicated probable association of Haloperidol to Neuroleptic Induced Parkinsonism. The features of Catalonia also resolved without needing the use of Benzodiazepine. <h3>Results</h3> Patient with Neuroleptic induced parkinsonism may present with symptoms similar to catatonia. Patients with Neuroleptic induced parkinsonism are more interactive and cooperative as opposed to Catatonic patients who are often withdrawn and negativistic. Tremor, which is present in parkinsonism, is not a feature of catatonia. Posturing and Echophenomena are typically absent in parkinsonism. We need to be careful to differentiate freezing seen in Parkinsonism and not mistake it for posturing. We also need to differentiate the posturing and immobility of catatonic patients from dystonia. Some patient who are treated with antipsychotic drugs may develop signs consistent with both catatonia and parkinsonism. There are very few case reports of Neuroleptic induced Parkinsonism coexisting with Neuroleptic induced Catatonia as is seen in Mary. We need to use rating scales to help differentiate and chart these symptoms on a daily basis. The mainstay of treatment for Catatonia involves the use of Benzodiazepines. There have been few reports of anticholinergics being helpful in the management of Catatonia. <h3>Conclusions</h3> Neuroleptic induced Parkinsonism can rarely coexist with Neuroleptic induced catatonia. The distinction is important as it has crucial treatment implications and misdiagnoses may occur if one is not careful. Untreated Catatonia can progress to NMS and Malignant Catatonia which lie on a continuum. The clinical picture can be complicated when the patients have other medical comorbidities including Dementia.

Amisulpride withdrawal akathisia responding to aripiprazole with propranolol in first-onset psychosis: a case report

BackgroundAkathisia tends to develop as an early complication of antipsychotic treatment in a dose-dependent manner. Although withdrawal akathisia has been reported after the discontinuation or dose reduction of typical antipsychotic drugs, akathisia following atypical antipsychotic drug withdrawal remains a rare phenomenon.Case presentationA 24-year-old woman with an acute psychotic episode was admitted and initially treated with aripiprazole. The aripiprazole dose was titrated up to 30 mg/day over 9 days and maintained for the next 3 days; however, her psychotic symptoms persisted without change. She was switched to amisulpride, with the dose increased over 2 weeks to 1000 mg/day. Subsequently, although the patient’s psychotic episode subsided, her serum prolactin levels increased markedly. After discharge, the amisulpride dose was increased to 1200 mg/day owing to auditory hallucinations and was maintained with quetiapine (100–200 mg/day) and benztropine (1 mg/day) for 13 weeks. Given the potential for hyperprolactinemia as a side effect, the amisulpride dose was reduced to 800 mg/day concurrently with the discontinuation of benztropine; however, these changes resulted in severe restlessness without other extrapyramidal symptoms. The withdrawal akathisia disappeared over 2 weeks after switching to aripiprazole (10 mg/day) with propranolol (40 mg/day) and the patient’s prolactin levels had normalized after 6 months of aripiprazole monotherapy.ConclusionsThe present case highlights the potential for the development of withdrawal akathisia when the dose of amisulpride is tapered abruptly. Thus, a slow tapering and careful monitoring are recommended when switching from amisulpride to other antipsychotic drugs. Furthermore, this case suggests that changing the regimen to aripiprazole with propranolol may be a potential option for amisulpride withdrawal akathisia superimposed on pre-existing hyperprolactinemia.

Understanding the Effects of Antipsychotics on Appetite Control.

Antipsychotic drugs (APDs) represent a cornerstone in the treatment of schizophrenia and other psychoses. The effectiveness of the first generation (typical) APDs are hampered by so-called extrapyramidal side effects, and they have gradually been replaced by second (atypical) and third-generation APDs, with less extrapyramidal side effects and, in some cases, improved efficacy. However, the use of many of the current APDs has been limited due to their propensity to stimulate appetite, weight gain, and increased risk for developing type 2 diabetes and cardiovascular disease in this patient group. The mechanisms behind the appetite-stimulating effects of the various APDs are not fully elucidated, partly because their diverse receptor binding profiles may affect different downstream pathways. It is critical to identify the molecular mechanisms underlying drug-induced hyperphagia, both because this may lead to the development of new APDs, with lower appetite-stimulating effects but also because such insight may provide new knowledge about appetite regulation in general. Hence, in this review, we discuss the receptor binding profile of various APDs in relation to the potential mechanisms by which they affect appetite.

Medication Error : Haloperidol Toxicity In A Child With Intellectual Disability

Haloperidol is a typical antipsychotic drug used in the treatment of schizophrenia and mania in adults, and for hyperactivity, behavioural and movement disorders in children. A common adverse effect of this drug is the development of extrapyramidal symptoms due to the blockage of dopamine receptors. Here we report a case of haloperidol toxicity due to medication error.

Psychopharmacotherapy of late-stage hypochondriac conditions: frequency of use and effectiveness of drugs

To conduct a comparative analysis of psychopharmacotherapy effectiveness in hypochondriac disorders of late age and to identify the optimal combinations of drugs depending on the thymopathic (hypothymic and/or anxiety) components accompanying the main hypochondriac manifestation. One hundred and eight female inpatients, aged from 50 to 88 years, with leading hypochondriac symptoms of non-delusional level were enrolled in the study. All patients were examined clinically and psychopathologically using psychometric scales: the Montgomery-Asberg Depression Rating Scale, the Hamilton Anxiety Rating Scale, the hypochondria rating scale and the UKU side-effect rating scale. Based on the psychometric assessment, the patients were divided into the following groups: group 1 - subjects with hypochondriac symptoms without accented thymopathic component (n=18); group 2 - subjects with a high level of hypothymia (n=49); group 3 - subjects with a high level of anxiety (n=22); group 4 - subjects with a high level of both anxiety and depression (n=19). Hypochondriac disorder without a thymopathic component was treated with monotherapy with antipsychotic drugs in low therapeutic dosages or with a combination of antipsychotic drugs in low therapeutic dosages with tricyclic antidepressants in low and medium dosages. Hypothymic hypochondriac disorders were treated with antidepressants of mainly SSRIs group and of tricyclic structure in combination with typical and atypical antipsychotic drugs in low therapeutic dosages. In these patients monotherapy with antidepressants or a combination of different antidepressants was effective in rare cases only. Hypochondriac disorder with an anxiety component was significantly more often treated by complex therapy with the addition of anxiolytic drugs, as well as a combination of antidepressants with antiptychotic drugs. Mixed hypochondriac states were treated with a combination of antidepressants and antipsychotic drugs or complex therapy with the addition of an anxiolytic drug. Hypochondriac disorders of late age in most cases are accompanied by depressive and/or anxiety symptoms, which must be taken into account for improvement of diagnostic effectiveness and relevant selection of therapy.

Characteristics of antipsychotic drug-induced hypothermia in psychogeriatric inpatients.

Hypothermia is a potentially lethal adverse reaction to typical and atypical antipsychotic drugs (APD). Among predisposing factors are advanced age and comorbid somatic diseases. The aim of this study was to assess the incidence of hypothermia and quantify risk factors. Charts of N=3002 psychogeriatric inpatients were screened for incidence of hypothermia (body core temperature <35.0°C). The frequency of hypothermia was compared between patients treated with versus without APD and, within the sample of APD-treated patients, for (1) specific APD, (2) sex, (3) main diagnosis, and (4) age. N=54 cases (2.6%) of hypothermia occurred in APD-treated patients and 12 cases (1.3%) in non-APD-treated patients (p=0.024). In APD-treated patients, only male sex (p=0.038) and pipamperone were associated with a higher incidence of hypothermia (p=0.0017). Whereas the main diagnosis delirium showed a trend to significance, age did not correlate with hypothermia. Medication with pipamperone was associated with an increased risk of hypothermia. The advanced age of our sample might as well explain the high incidence of hypothermia within our sample and the failure to detect high age as a risk factor due to a ceiling effect.

Olanzapine: Association Between a Typical Antipsychotic Drug and Aortic Calcification.

Aims: This study concentrates on the relationship between antipsychotic drugs (APDs) and aortic calcification.Methods: All 56 patients with schizophrenia were divided into two groups according to aortic calcification index. APD equivalent dose was calculated via defined daily doses method.Results: In schizophrenia patients with higher aortic calcification index scores, APD equivalent doses were lower. APD equivalent dose was negatively related to aortic calcification index. Although equivalent APD dose in patients without olanzapine treatment was negatively related to aortic calcification index, it seems that equivalent APD dose did not associate with aortic calcification.Conclusion: Aortic calcification is negatively associated with APD dose in schizophrenia patients. Olanzapine seems to be vital to the relationship between aortic calcification and APD treatment.

Housing Temperature Influences Atypical Antipsychotic Drug-Induced Bone Loss in Female C57BL/6J Mice.

ABSTRACTAtypical antipsychotic (AA) drugs, such as risperidone, are associated with endocrine and metabolic side effects, including impaired bone mineral density (BMD) acquisition and increased fracture risk. We have previously shown that risperidone causes bone loss through the sympathetic nervous system and that bone loss is associated with elevated markers of thermogenesis in brown and white adipose tissue. Because rodents are normally housed in sub‐thermoneutral conditions, we wanted to test whether increasing housing temperature would protect against bone loss from risperidone. Four weeks of risperidone treatment in female C57BL/6J mice at thermoneutral (28°C) housing attenuated risperidone‐induced trabecular bone loss and led to a low‐turnover bone phenotype, with indices of both bone formation and resorption suppressed in mice with risperidone treatment at thermoneutrality, whereas indices of bone resorption were elevated by risperidone at room temperature. Protection against trabecular bone loss was not absolute, however, and additional evidence of cortical bone loss emerged in risperidone‐treated mice at thermoneutrality. Taken together, these findings suggest thermal challenge may be in part responsible for bone loss with risperidone treatment and that housing temperature should be considered when assessing bone outcomes of treatments that impact thermogenic pathways. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Blockade of the orexin 1 receptors in the nucleus accumbens’ shell reversed the reduction effect of olanzapine on motivation for positive reinforcers

Effort-based choice of high reward requires one to decide how much effort to expend for a certain amount of reward. Orexin is a crucial neuropeptide in the physiological aspect especially a variety of affective and cognitive processes. The nucleus accumbens (NAc) is a region of the neural system that serves effort-related high reward choices andthe Orexin 1 receptor (OX1R) is distributed extensively throughout the nucleus accumbens shell (AcbS). Olanzapine (OLZ), a typical antipsychotic drug, has a high affinity to D2 as an antagonist, and also partial agonistic-like action at D2 receptors has been reported. We examined the interaction of OLZ with the orexinergic receptor 1 in AcbS on effort- related high reward choice when two goal arms were different in the amount of accessible reward. The animals had to pass the barrier for receiving a high reward in one arm (HRA) or obtain a low reward in the other arm without any cost. Before surgery, all animals were selecting the HRA on almost every trial.During test days, the rats received local injections of either DMSO 20% /0.5 µl, as vehicle or SB334867 (30, 100, 300 nM/0.5 µl), as selective OX1R antagonist, within the AcbS. Other group received OLZ (32 µM/0.5 µl DMSO20%) / vehicle alone or 5 min after administration of SB334867 (300 nM/0.5 µl). The results showed that administration of OLZ in the AcbS alters rat’s preference for high reward. On the other hand, blocked of the OX1R (300 nM/0.5 µl) in this region could reverse the effect of OLZ, however, administration of the OX1R antagonists alone in the AcbS led to decreasing rat's preference for high reward. This result indicates that the orexin-1 antagonist might affect some effects of antipsychotic drugs.

Effects of perioperative interventions for preventing postoperative delirium: A protocol for systematic review and meta-analysis of randomized controlled trials.

Background:Postoperative delirium (POD) not only increases the medical burden but also adversely affects patient prognosis. Although some cases of delirium can be avoided by early intervention, there is no clear evidence indicating whether any of these measures can effectively prevent POD in specific patient groups.Objective:The aim of this meta-analysis was to compare the efficacy and safety of the existing preventive measures for managing POD.Methods:The PubMed, OVID (Embase and MEDLINE), Web of Science, and the Cochrane Library databases were searched for articles published before January 2020. The relevant randomized controlled trials (RCTs) were selected based on the inclusion and exclusion criteria. Data extraction and methodological quality assessment were performed according to a predesigned data extraction form and scoring system, respectively. The interventions were compared on the basis of the primary outcome like incidence of POD, and secondary outcomes like duration of delirium and the length of intensive care unit and hospital stay.Results:Sixty-three RCTs were included in the study, covering interventions like surgery, anesthesia, analgesics, intraoperative blood glucose control, cholinesterase inhibitors, anticonvulsant drugs, antipsychotic drugs, sleep rhythmic regulation, and multi-modal nursing. The occurrence of POD was low in 4 trials that monitored the depth of anesthesia with bispectral index during the operation (P < .0001). Two studies showed that supplementary analgesia was useful for delirium prevention (P = .002). Seventeen studies showed that perioperative sedation with α2-adrenergic receptor agonists prevented POD (P = .0006). Six studies showed that both typical and atypical antipsychotic drugs can reduce the incidence of POD (P = .002). Multimodal nursing during the perioperative period effectively reduced POD in 6 studies (P < .00001). Furthermore, these preventive measures can reduce the duration of delirium, as well as the total and postoperative length of hospitalized stay for non-cardiac surgery patients. For patients undergoing cardiac surgery, effective prevention can only reduce the length of intensive care unit stay.Conclusion:Measures including intraoperative monitoring of bispectral index, supplemental analgesia, α2-adrenergic receptor agonists, antipsychotic drugs, and multimodal care are helpful to prevent POD effectively. However, larger, high-quality RCTs are needed to verify these findings and develop more interventions and drugs for preventing postoperative delirium.

Worldwide antipsychotic drug search intensities: pharmacoepidemological estimations based on Google Trends data

Prescription patterns of antipsychotic drugs (APDs) are typically sourced from country-specific data. In this study, a digital pharmacoepidemiological approach was used to investigate APD preferences globally. Publicly available data on worldwide web search intensities in Google for 19 typical and 22 atypical APDs were temporally and spatially normalized and correlated with reported prescription data. The results demonstrated an increasing global preference for atypical over typical APDs since 2007, with quetiapine, olanzapine, risperidone, and aripiprazole showing the largest search intensities in 2020. Cross-sectional analysis of 122 countries in 2020 showed pronounced differences in atypical/typical APD preferences that correlated with gross domestic product per capita. In conclusion, the investigation provides temporal and spatial assessments of global APD preferences and shows a trend towards atypical APDs, although with a relative preference for typical APDs in low-income countries. Similar data-sourcing methodologies allow for prospective studies of other prescription drugs.

Sex differences in the association between serum BDNF and cognitive impairment in schizophrenia patients using various antipsychotics

BackgroundCognitive impairment is one of the core symptoms of schizophrenia patients. There are often various differences in the efficacy of different antipsychotics in the treatment of cognitive impairment by sex. The purpose of this study was to explore whether there are gender differences in the association between serum BDNF levels and cognitive performance in patients with schizophrenia taking different antipsychotics. MethodsWe used Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess the cognitive function of three groups of schizophrenia patients (420 on clozapine, 183 on risperidone, 215 on typical antipsychotic drugs) and 467 healthy controls. Positive and Negative Syndrome Scale (PANSS) was used to assess schizophrenia symptoms of patients. Enzyme-Linked ImmunoSorbent Assay was used to measure serum brain-derived neurotrophic factor (BDNF) levels. ResultsAmong the patients taking clozapine and typical antipsychotic drugs, the RBANS total score, immediate memory, attention, and delayed memory subscores in females were higher than those in males (all p < 0.05). The RBANS total score and the delayed memory subscores in female patients taking risperidone were higher than those in male patients (all p < 0.05). Significant correlation between BDNF and cognition only existed in male patients taking clozapine, male patients taking risperidone, and male and female patients taking typical antipsychotic drugs (all p < 0.05). ConclusionRegardless of antipsychotic effect, the cognitive function of female patients is better compared to that of male patients. For male patients, the association between BDNF and cognitive performance exists in each medication group. For female patients, this significant association was only shown in the typical antipsychotic group, but not in the clozapine and risperidone groups.

Association Between ApoA1 Gene Polymorphisms and Antipsychotic Drug-Induced Dyslipidemia in Schizophrenia.

PurposeDyslipidemia frequently occurs in schizophrenia patients treated with antipsychotic drugs (APDs), especially atypical APDs. Apolipoprotein A1 (ApoA1) plays a key role in lipid metabolism. The aim of this study was to investigate whether ApoA1 gene polymorphisms are associated with APD-induced dyslipidemia in schizophrenia patients.Patients and MethodsA total of 1987 patients with schizophrenia were enrolled in this study. Serum lipid profiles were determined with a biochemistry analyzer. Genotyping for the rs5072 polymorphism of ApoA1 was performed with TaqMan assay. Logistic regression analysis was carried out to evaluate the relationship between ApoA1 gene polymorphisms and APD-induced dyslipidemia. The effects of drug classification (typical vs atypical APD) and drug regimen (monotherapy vs combination therapy) on serum lipid levels were also analyzed.ResultsA significant association was found between rs5072 and triglyceride (TG) levels in the recessive model of the logistic regression analysis (adjusted odds ratio [OR]=1.50, 95% confidence interval [CI]: 1.03, 2.17; P<0.05). TG level was significantly higher in patients treated with combination therapy (1.03 (0.71, 1.51) mmol/l) compared to monotherapy (0.93 (0.67, 1.43) mmol/l) and was also associated with sex. There were significant differences in TG levels among the three genotypes of ApoA1 rs5072 (GG, GA, and AA) in the whole study population and in patients treated with atypical APDs.ConclusionThe ApoA1 rs5072 variant is associated with dysregulated TG metabolism in schizophrenia patients treated with APDs, which may increase susceptibility to dyslipidemia.

Effects of Psychostimulants and Antipsychotics on Serum Lipids in an Animal Model for Schizophrenia.

Schizophrenia (SCZ) treatment is essentially limited to the use of typical or atypical antipsychotic drugs, which suppress the main symptoms of this mental disorder. Metabolic syndrome is often reported in patients with SCZ under long-term drug treatment, but little is known about the alteration of lipid metabolism induced by antipsychotic use. In this study, we evaluated the blood serum lipids of a validated animal model for SCZ (Spontaneously Hypertensive Rat, SHR), and a normal control rat strain (Normotensive Wistar Rat, NWR), after long-term treatment (30 days) with typical haloperidol (HAL) or atypical clozapine (CLZ) antipsychotics. Moreover, psychostimulants, amphetamine (AMPH) or lisdexamfetamine (LSDX), were administered to NWR animals aiming to mimic the human first episode of psychosis, and the effects on serum lipids were also evaluated. Discrepancies in lipids between SHR and NWR animals, which included increased total lipids and decreased phospholipids in SHR compared with NWR, were similar to the differences previously reported for SCZ patients relative to healthy controls. Administration of psychostimulants in NWR decreased omega-3, which was also decreased in the first episode of psychosis of SCZ. Moreover, choline glycerophospholipids allowed us to distinguish the effects of CLZ in SHR. Thus, changes in the lipid metabolism in SHR seem to be reversed by the long-term treatment with the atypical antipsychotic CLZ, which was under the same condition described to reverse the SCZ-like endophenotypes of this validated animal model for SCZ. These data open new insights for understanding the potential influence of the treatment with typical or atypical antipsychotics on circulating lipids. This may represent an outcome effect from metabolic pathways that regulate lipids synthesis and breakdown, which may be reflecting a cell lipids dysfunction in SCZ.