Typical Antipsychotic Drugs Research Articles

TRATAMENTO FARMACOLÓGICO DA ESQUIZOFRENIA: PASSADO, PRESENTE E FUTURO

Schizophrenia is a chronic and severe psychiatric disorder characterised by the manifestation of positive and negative symptoms and/or cognitive dysfunction. Treatment typically includes psychotherapy, sociotherapy and pharmacological therapy, which consists of the use of typical and atypical antipsychotic drugs, as well as dopaminergic system stabilisers. Although they do not provide a cure, these treatments can reduce the intensity and frequency of symptoms, resulting in improved quality of life and a quicker reintegration into social life. Thus, the aim of the present study was to conduct a narrative literature review on the clinical evolution of antipsychotic use throughout history, as well as to discuss potential new drugs that are still in clinical research. Studies have shown that typical antipsychotics are effective in treating positive symptoms but have no impact on negative symptoms and can even exacerbate or provoke them. Additionally, they produce highly limiting side effects, such as movement disorders. Atypical antipsychotics, on the other hand, are capable of reducing both positive and negative symptoms, and they also present fewer side effects related to the extrapyramidal motor system. However, they tend to cause metabolic disturbances. Conversely, dopaminergic system stabilisers also treat both positive and negative symptoms, with side effects that are generally better tolerated, along with a lower propensity to cause weight gain and motor disturbances. It is worth noting that many patients are unable to tolerate the various adverse reactions of the available antipsychotics. Moreover, some patients are or become refractory to their therapeutic effects. Consequently, there is currently a focus on developing new agents that have different pharmacological targets. Some of these potential new drugs have shown efficacy in refractory patients, representing a potential paradigm shift in the treatment of the disorder.

Comparative Study of Effectiveness of Haloperidol Versus Olanzapine among Patients with Schizophrenia

Aim: To compare the efficacy of oral Typical Antipsychotic drug [Haloperidol] Group A versus oral Atypical Antipsychotic drug [Olanzapine] Group B in patients who met the criteria for schizophrenia. This study includes observe and compare the positive symptoms and negative symptoms in Group A and Group B by using PSYRATS scale and negative symptom assessment tool. Study Design: Prospective comparative observational study. Place and Duration of Study: The study was carried from April 2023 – September 2023 at Psychiatric Outpatient Department in the Government Medical College and Hospital, Nagapattinam. Methodology: The study sample comprised 60 patients [N=60], The 30 subjects were in Group A and 30 subjects were in Group B who met the SCID – DSM V criteria and also include criteria 1. Age between 22 – 65 years. 2. Subject should have Minimum mental state examination [MMSE] score between 25 – 30. Paired and Unpaired t test was performed to observe statistical significance. Results: Out of 60 patients Olanzapine was associated with a mean baseline to endpoint improvement of ( -22.77) versus a Mean change of ( -14.39) in Haloperidol. Olanzapine [Group B] had higher mean difference than Haloperidol [Group A]. Conclusion: By using PSYRATS scale and Negative symptom assessment tool, Olanzapine treated group were numerically better than the Haloperidol treated group in both Negative and Positive Symptoms.

Oral discomfort and health behavior of patients with typical vs. atypical antipsychotic drugs.

Psychiatric patients suffer from oral diseases and side effects of antipsychotic medication. In particular, the typical antipsychotic drugs may cause severe hyposalivation with subsequent oral symptoms. We therefore aimed to compare oral health behavior and oral side effects of in-hospital patients taking typical vs. atypical antipsychotic drugs with the hypothesis that the former drugs cause more oral pain than the newer drugs. This cross-sectional questionnaire and interview study investigated subjective oral symptoms and their health behavior in 170 hospitalized psychiatric patients, comparing those taking typical vs. atypical antipsychotic drugs. Cross-tabulations and chi-square tests were used for analyses. Persistent oral pain lasting throughout the day was reported by 46% in the typical, and 5% in the atypical antipsychotic group patients, respectively. In both groups, the pain was mainly in the tongue and buccal mucosa and was described as a burning sensation. A significantly higher prevalence of xerostomia was reported in the typical antipsychotic medication group (66%) compared with the atypical antipsychotic medication group (53%, p<0.01). Self-assessed dental health was assessed as poor by two-thirds of the patients of whom 69% reported toothbrushing once daily. Approximately half of them reported having had a visit to a dentist within the previous year. Of the women 28%, and of the men 17%, respectively, had received professional consultations for oral symptoms. The current results on psychiatrically hospitalized patients emphasize the need for awareness of oral discomfort and its subsequent effects on the quality of life in this challenging patient group. Focus should also be placed on a wide range of support encouraging the patients to maintain good daily oral hygiene and seek professional dental help when needed.

Formulation, in vitro and in vivo evaluation of olanzapine nanoparticles dissolving microneedles for transdermal delivery

Olanzapine (OLZ) is classified as a typical antipsychotic drug utilized for the treatment of schizophrenia. Its oral bioavailability is 60% due to its low solubility and pre-systemic metabolism. Hence, the present work aims to formulate and evaluate OLZ nanoparticles dissolving microneedles (MNs) for transdermal delivery to overcome the problems associated with drug administration orally. OLZ nanoparticles were prepared by the nanoprecipitation method. The optimized OLZ nanoparticle formula was utilized for the fabrication of dissolving MNs by loading OLZ nanodispersion into polydimethylsiloxane (PDMS) micromould cavities, followed by casting the polymeric solution of polyvinylpyrrolidone(PVP-K30) and polyvinyl alcohol (PVA) to form MN matrix. The results revealed that the optimized OLZ nanoparticle formula (NP-5) exhibited particle size 115.76±5.45 nm, entrapment efficiency 78.4±5.46, and zeta potential -19.01±1.6 mV. The results of MNs revealed that MN-4 exhibits a high drug content of 98.52%, and ex vivo permeation through rabbit skin exhibited that MN-4 permeates more effectively than a simple patch by approximately 5.16 fold. In vivo pharmacokinetics study revealed that the area under curve AUC 0-∞ of MN-4 was 6054.56±376 ng. h/ml as compared with AUC0-∞ of marketed OLZ tablet was 3975.77±373 ng. h/ml. It can be concluded that the dissolving MN-4 patch is considered a promising formula to overcome the problems associated with drug administration orally and could improve drug bioavailability, in addition to the ease of administering the medication to schizophrenic patients.

Preparation and Optimization of Olanzapine as Transdermal Nanoparticles Delivery System

Background: The treatment of schizophrenia typically involves the use of olanzapine (OLZ), a typical antipsychotic drug that has poor oral bioavailability due to its low solubility and first-pass effect. Objective: To prepare and optimize OLZ as nanoparticles for transdermal delivery to avoid problems with oral administration. Methods: The nanoprecipitation technique was applied for the preparation of eight OLZ nanoparticles by using different polymers with various ratios. Nanoparticles were evaluated using different methods, including particle size, polydispersity index (PDI), entrapment efficiency (EE%), zeta potential and an in vitro release study. The morphology was evaluated by a field emission scanning electron microscope (FESEM) and an atomic force microscope (AFM). We also perform differential scanning calorimetry (DSC). Results: Characterization studies of OLZ nanoparticles showed that OLZ-6 was the best formula with a particle size of 115.76 nm, a PDI of 0.24, a high EE% of 78.4%, and a high zeta potential of -19.01 mV. The in vitro release of OLZ was higher than that of other formulations. FESEM reveals the spherical shape of the nanoparticles, and AFM screening confirms that the OLZ-6 size is comparable to what the Zeta sizer finds. The DSC results confirm the purity of OLZ and the compatibility between the drug and polymer. Conclusions: OLZ-6, as a transdermal delivery system, is a promising formula to overcome the problems associated with oral drug administration and could enhance its bioavailability.

The effect of cognitive impairment based on Mini-Mental State Examination (MMSE) on suicidal tendency in patients with schizophrenia: A large cross-sectional study

BackgroundThe effect of cognitive function on suicidal tendency in patients with schizophrenia is still inconclusive. This study aimed to explore the effect of cognitive impairment on suicidal tendency in schizophrenia patients and the risk factors of suicidal tendency in schizophrenia patients with cognitive impairment. MethodsA total of 988 subjects were recruited for this study and finally 517 patients were included in the statistical analysis. Sociodemographic information was collected for each subject. Mini-Mental State Examination (MMSE) was used to assess patients' cognitive functioning. In addition, the Positive and Negative Syndrome Scale (PANSS) positive subscale, Insomnia Severity Index (ISI), and Beck Scale for Suicide Ideation (BSI) were used to assess psychotic symptoms, severity of insomnia, and intensity of suicidal ideation, respectively. ResultsSchizophrenia patients with cognitive dysfunction were significantly less likely to develop suicidal tendencies than those without cognitive dysfunction (P < 0.05, OR = 0.58, 95%CI: 0.39–0.81). In patients with cognitive impairment, those with suicidal tendency had substantially higher scores on BSI, ISI, EC, PD, IRI, F1, and PANSS positive subscale, and took more types of antipsychotic drugs than those without suicidal tendency (all P < 0.05), and the results of binary logistic regression analysis showed that, PANSS positive subscale score (B = 0.06, p = 0.04, OR = 1.07, 95%CI: 1.00–1.13) was a risk factor for suicidal tendencies. ConclusionsOur findings suggest that schizophrenia patients with cognitive dysfunction are significantly less likely to develop suicidal tendencies. Moreover, positive symptom is a risk factor for suicidal tendencies in schizophrenia patients with cognitive dysfunction.

Prenatal aripiprazole induces alterations of rat placenta: a histological, immunohistochemical and ultrastructural study.

Antipsychotic drugs (APDs) are used to treat many psychiatric illnesses as schizophrenia. Typical antipsychotic drugs (TAPDs) are being used; however, they have many side effects. Atypical antipsychotic drugs (AAPDs) are newer medications with known fewer side effects. Aripiprazole (ARI) is an AAPD, recommended by healthcare providers, even during pregnancy. It can cross the placental barrier and enter fetal circulation, so it might be possible that ARI can adversely impair normal placental development and growth, if it is given prenatally. ARI was applied orally to pregnant female rats in two doses (3& 6mg/kg body weight). On gestation day 20, the mothers were sacrificed, and the placentas were removed and processed for general histological and electron microscopic evaluations. Immunohistochemistry was done using anti-PCNA (proliferating cell nuclear antigen), anti-Bax (for apoptosis) and anti-vascular endothelial growth factor alpha (VEGFA). Morphological evaluation revealed degenerative changes in the placenta as dark nuclei, vacuolization, and cyst formation. Ultra-structurally, there was degeneration of cellular components including organelles and nuclei. These changes were found in different cells of the basal and labyrinth zones and were dose dependent. Immunohistochemistry revealed upregulation of Bax and VEGFA and downregulation of PCNA. Prenatal administration of the AAPD, ARI to pregnant female rats resulted in histological changes in the placenta. Additionally, there was a decrease in cellular proliferation and increase in apoptosis, and vascular impairment. This indicates placental atrophy and dysgenesis and might suggest possible teratogenic effects to ARI, which needs further evaluation.

DEVELOPMENT, OPTIMIZATION AND IN VITRO CHARACTERIZATION OF HALOPERIDOL NANOCRYSTALS USING 32 FACTORIAL DESIGN

Objective: The main aim of the present study was to improve the dissolution rate of Haloperidol nanocrystals and thereby increase their bioavailability. Haloperidol is a typical antipsychotic drug and it is used to treat schizophrenia as well as acute mania and mixed states associated with bipolar disorder. Haloperidol falls into the Biopharmaceutics Classification System (BCS-II) class of drugs (poorly soluble aqueous and highly permeable) and has poor bioavailability. Methods: The present study involves the preparation and optimization of Haloperidol nanocrystals by the anti-solvent precipitation method using Polaxomer407 and polyvinyl pyrrolidone K30 (PVP K30). The prepared nanocrystals were evaluated for various parameters like particle size, zeta potential, % drug content, % yield, surface morphology, drug-excipient compatibility studies (Fourier-transform infrared spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC)), and in vitro dissolution studies. Results: Nine preparations were done and the best preparation amongst them was selected for further studies. F7 preparation containingpolaxomer407 and PVP K30 was selected as optimized preparation based on their evaluation parameters. 32 factorial design was used in the preparation. The particle size of the F7 nanocrystals was 300.2±2.7 nm and the zeta potential-36.3±3.2 mV. The % yield was in the range of 63.62±0.3%-98.21±0.8 %. The drug content of various preparations was found to be in the range of 58.46±0.8%-93.54±0.5 %. In vitro dissolution studies showed the highest % drug release for F7(91.54±0.03%) in 10 h. Conclusion: F7 preparation was found to be having acceptable characteristics and thus selected as optimized preparation.

Correlation analysis and gender differences of cognitive function based on mini-mental state examination (MMSE) and suicidal tendency in patients with schizophrenia

BackgroundThe aim of this study was to investigate the correlation and gender differences between cognition and suicidal tendency in patients with schizophrenia.MethodsA total of 554 patients with schizophrenia were recruited. The Mini-Mental State Examination (MMSE), Positive and Negative Syndrome Scale (PANSS), Interpersonal Reactivity Index (IRI), Toronto Alexithymia Scale (TAS), and Insomnia Severity Index (ISI) were used to assess clinical symptoms.ResultsIn male patients, MMSE score and the incidence of suicidal tendency were correlated (P = 0.04, OR = 1.06, 95%CI: 1.00–1.12). Among patients with cognitive dysfunction, IRI score (P = 0.01, OR = 1.04, 95%CI: 1.01–1.06), and types of antipsychotic drugs (P < 0.01, OR = 3.97, 95%CI: 1.76–8.97) in male patients were associated risk factors for suicidal ideation. Among patients without cognitive dysfunction, PANSS positive subscale score (P = 0.03, OR = 1.06, 95%CI: 1.01–1.11), and PANSS general psychopathology score (P = 0.02, OR = 1.05, 95%CI: 1.01–1.08) were associated risk factors for suicidal ideation in male patients and PANSS positive subscale score (P < 0.01, OR = 1.15, 95%CI: 1.05–1.26) were associated risk factors for suicidal ideation in female patients.ConclusionsThere were significant gender differences in the correlation between cognitive functioning and suicidal ideation in patients with schizophrenia. Cognitive function may play an important mediating role in other factors on suicide.

Bacillus Calmette-Guérin Vaccine Attenuates Haloperidol-Induced TD-like Behavioral and Neurochemical Alteration in Experimental Rats.

Tardive dyskinesia (TD) is a hyperkinetic movement disorder that displays unusual involuntary movement along with orofacial dysfunction. It is predominantly associated with the long-term use of antipsychotic medications, particularly typical or first-generation antipsychotic drugs such as haloperidol. Oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis are major pathophysiological mechanisms of TD. The BCG vaccine has been reported to suppress inflammation, oxidative stress, and apoptosis and exert neuroprotection via several mechanisms. Our study aimed to confirm the neuroprotective effect of the BCG vaccine against haloperidol-induced TD-like symptoms in rats. The rats were given haloperidol (1 mg/kg, i.p.) for 21 days after 1 h single administration of the BCG vaccine (2 × 107 cfu). Various behavioral parameters for orofacial dyskinesia and locomotor activity were assessed on the 14th and 21st days after haloperidol injection. On the 22nd day, all rats were euthanized, and the striatum was isolated to estimate the biochemical, apoptotic, inflammatory, and neurotransmitter levels. The administration of the BCG vaccine reversed orofacial dyskinesia and improved motor function in regard to haloperidol-induced TD-like symptoms in rats. The BCG vaccine also enhanced the levels of antioxidant enzymes (SOD, GSH) and reduced prooxidants (MDA, nitrite) and pro-apoptotic markers (Cas-3, Cas-6, Cas-9) in rat brains. Besides this, BCG treatment also restored the neurotransmitter (DA, NE, 5-HT) levels and decreased the levels of HVA in the striatum. The study findings suggest that the BCG vaccine has antioxidant, antiapoptotic, and neuromodulatory properties that could be relevant in the management of TD.

Racial disparities in emergency department utilization among patients with newly diagnosed depression

ObjectiveTo test the hypothesis that racial and ethnic minorities have increased emergency department visit rates, despite being established with a primary care provider. MethodsIn this retrospective cohort study, ED visits without hospital admission in a 12-month period among patients with a new primary care provider-issued diagnosis of depression were assessed. Electronic medical record (EMR) data was obtained from 47 family medicine clinics in a large Michigan-based healthcare system. General linear regression models with Poisson distribution were used to predict frequency of ED visits. ResultsA total of 4159 patients were included in the analyses. In multivariable analyses, Black / African American race was associated with an additional 0.90 (95% CI 0.64, 1.16) ED visits and American Indian or Alaska Native race was associated with an additional 1.39 (95% CI 0.92, 1.87) ED visits compared to White or Caucasians (null value 0). These risks were only exceeded by patients who received a prescription for a typical antipsychotic drug agent. ConclusionDespite being established patients at primary care providers and having follow-up encounters, Black / African American and American Indian or Alaska Native patients with depression were considerably more likely to seek ED treatment compared to White/Caucasian patients with depression.

Augmentation therapy with serotonin1A receptor partial agonists on neurocognitive function in schizophrenia: A systematic review and meta-analysis

BackgroundIn a previous meta-analysis, the use of serotonin1A(5-HT1A) receptor partial agonists of the azapirone class as an add-on therapy was associated with beneficial effects on positive symptoms and attention/processing speed in schizophrenia patients. This meta-analysis builds on that study by examining the effects of adjunctive treatment with 5-HT1A partial agonists in improving other domains of neurocognitive function in schizophrenia patients. MethodsA literature search was performed from 1987 to May 2023 to identify randomized controlled trials. The standardized mean difference (SMD) with 95 % confidence intervals (CI) was calculated when there were two or more studies. Four studies, involving 313 patients, met the inclusion criteria and were used in the analysis. Results5-HT1A partial agonists (buspirone or tandospirone) did not have a significant effect on verbal learning (SMD = 0.08, 95 % CI = −0.31 to 0.47) or working memory (SMD = 0.15, 95 % CI = −0.09 to 0.39). Regarding executive functions (Wisconsin Card Sorting Test), positive but non-significant results were seen with the category number (SMD = 0.26, 95 % CI = −0.81 to 1.32), while non-significant effects were noted for percent preservation errors (SMD = −0.10, 95 % CI = −0.53 to 0.33). ConclusionsThe absence of any significant benefits in the cognitive domains studied here may have been due to the variance in the concomitant medication (typical vs atypical antipsychotic drugs), the level of cognition at baseline, or other factors. Further studies with various types of 5-HT1A agonists are warranted to examine the potential cognitive efficacy of stimulating these receptors.

Usage and cost-effectiveness of anti-psychotics in psychiatry OPD among various clinical conditions: A prospective observational study in a tertiary care center.

Psychotropic medications are prescription drugs that are commonly used to control some symptoms associated with many different types of mental ill health. Although they cannot cure a patient illness, they can assist with the management of some extremely distressing symptoms and this in turn can facilitate individuals in leading a more fulfilled life. This study attempts to collect the demographic details of the outpatient in the psychiatric department and to describe the usage, prescribing trends and cost-effectiveness of antipsychotics in psychiatry OPD among various clinical conditions to older and younger patients with psychiatry disorders. This study was a prospective observational study, conducted over a period of 6 months from November 2021 to April 2022 in the Department of Psychiatry, Chidambaram Government Medical College and Hospital, a 1400 bedded multi-specialty tertiary care teaching hospital, Tamil Nadu Dr. M.G.R. Medical University Chennai, Tamil Nadu. The recruitment of subjects was carried out with the help the physicians who had the knowledge of patient's history and caregivers consenting to the study protocol and patients with case sheets carrying antipsychotics prescription. A total number of 150 cases were enrolled in this study. All psychiatric OPD cases were studied and the results were taken. Based on the inclusion and exclusion criteria, 93 were the anti-psychotics prescribed cases and 57 were the non-anti-psychotics prescribed cases. Out of 93 patients, 69.89% (65 patients) were male and 30.10% (28 patients) were female. Out of non-psychotic 57 patients, 27 were male patients and 30 were female patients. Out of the 93 OPD patients, 40% of the patients have psychological based symptoms followed by 17% of patients have behavioral symptoms. 86.02% of patients received atypical antipsychotic medications in comparison with 36.55% of patients received the typical antipsychotic medications. In this study, we had observed the usage and types of anti-psychotic drugs to control and minimize the different psychotic symptoms among the OPD patients. Maximum antipsychotics studied were cost-effective and cheaper in Pradhan Mantri Bhartiya Janaushadhi Pariyojana (PMBJP) as compared to Intas, Torrent, Sun, Linux, Cipla, Abbott, Alkem, and Sanofi.

Histone deacetylase 1 regulates haloperidol-induced motor side effects in aged mice

BackgroundAntipsychotic drugs prescribed to elderly patients with neuropsychiatric disorders often experience severe extrapyramidal side effects. Previous studies from our group suggest that changes in histone modifications during aging increase the risk for antipsychotic drug side effects, because co-administration of antipsychotics with class 1 histone deacetylase (HDAC) inhibitors could mitigate the severity of motor side effects in aged mice. However, which HDAC subtype contributes to the age-related sensitivity to antipsychotic drug side effects is unknown. MethodsIn this study, we overexpressed histone deacetylase type 1(HDAC1) in the striatum of 3-month-old mice and knocked down HDAC 1 in the striatum of 21-month-old mice by microinjection of AAV9-HDAC1-GFP or AAV9-CRISPR/Cas9-HDAC1-GFP vectors. Four weeks after the viral-vector delivery, the typical antipsychotic drug haloperidol was administered daily for 14 days, followed by motor function assessments through the open field, rotarod, and catalepsy behavioral tests. ResultsYoung mice with overexpressed HDAC1 showed increased cataleptic behavior induced by haloperidol administration, which is associated with the increased HDAC1 level in the striatum. In contrast, aged mice with HDAC1 knocked down rescued locomotor activity, motor coordination, and decreased cataleptic behavior induced by haloperidol administration, which is associated with decreased HDAC1 level in the striatum. ConclusionsOur results suggest that HDAC1 is a critical regulator in haloperidol-induced severe motor side effects in aged mice. Repression of HDAC1 expression in the striatum of aged mice could mitigate typical antipsychotic drug-induced motor side effects.

Duration of Hospitalization According to the Type of Treatment in Patients Diagnosed With Schizophrenia: A Retrospective Cross-sectional Study

Background: Schizophrenia is a complex mental disorder with the most severe and devastating effect on a person’s life. Given that schizophrenia treatments have different effects on the duration of hospitalization and reduction of positive and negative symptoms, we decided to conduct a study to evaluate the duration of hospitalization according to the type of treatment in patients diagnosed with schizophrenia in Ebn-e-Sina hospital in Bandar Abbas. Materials and Methods: In this retrospective descriptive cross-sectional study, the files of 75 patients with schizophrenia admitted to the psychiatric ward of Ebn-e-Sina hospital in 2019-2020 were included after obtaining the approval of the ethics committee. A group of patients was treated with electroconvulsive therapy (ECT) and typical antipsychotic drugs, and another with ECT and atypical antipsychotic medications until the acute phase of the disease subsided. The patient’s file information was summarized and arranged in a checklist prepared by the researcher and then statistically analyzed using SPSS version 22.0. Results: The patients’ most commonly received treatment was typical and atypical antipsychotic medications combined with ECT (60.0%), followed by combination therapy (29.30%), atypical antipsychotic medications (8.00%), and typical antipsychotic medications (2.70%), respectively. Considering the specific objectives of this study, it was found that the mean length of hospital stay in the 4 treatment groups was significantly different (P=0.006). Conclusion: The duration of hospitalization in the combined with ECT group was significantly longer compared to the others.

Pharmacoeconomical affordability of antipsychotic drugs for patients with mental disorders in the structure of dementia at the regional level

Objective. To analyze the pharmacoeconomical affordability of antipsychotic drugs (APD) in patients with mental disorders in the structure of dementia at the level of the Gomel region of the Republic of BelarusMaterials and methods. The study used data from the State Register of Medicines of the Republic of Belarus (2022); Clinical Protocol for providing medical care to patients with mental and Behavioral Disorders (2010); website data https://myfin.by about the average pension amount and the minimum subsistence budget of the Gomel region for 2022; data from «State Register of Medicines of the Republic of Belarus» website. For the analysis, the price list for medicines (drugs) of the largest pharmacy chains in Belarus was used, which included the state pharmacies of the Gomel UP «Pharmacy» and commercial pharmacies of the well-known brands in Belarus «ADEL» and «Dobrya Leki». Parameters such as the price affordability of the APD and 4 availability coefficients (Cd) were determined, allowing to correlate the average cost of antipsychotic drugs packaging and the cost of the average daily dose of antipsychotic drugs with the consumer income, as well as the total affordability coefficient (Cd total.).Results. According to all criteria, the most economically affordable drug from the group of typical APD was the generic Haloperidol–Ozone (Ozon, Russia), and the least affordable from the group of atypical ones was the generic Olanzapine (Belmedpreparaty, Republic of Belarus).Conclusion. There is a large selection of APD on the pharmaceutical market of the Gomel region. Generic APD predominate on sale, which are more affordable compared to the original APD. But one should not forget about the advantages of the original drugs – efficiency, safety, innovativeness, reproducibility of the effect and strict quality control, confirmed in clinical trials. However, the genetic drug Olanzapine (Belmedpreparations, RB) is not in any way more superior in terms of affordability, but even inferior to some drugs. This study allowed us to establish that in the Gomel region of the Republic of Belarus, a patient with dementia is provided with a wide choice of APD and the ability to determine the criteria for preference when buying a specific drug.

Risperidone Induced Parkinsonism: A Rare Case Report

The present case report narrates the case of a 60-year-old woman with a past medical history of schizophrenia, who exhibited parkinsonism symptoms subsequent to the administration of risperidone - a typical antipsychotic drug that impacts dopamine and serotonin levels. The patient presented with pill-rolling tremors, bradykinesia, rigidity, and weakness in the left upper limb, and was diagnosed with Parkinsonism following a physical examination by a physician. The patient was subsequently referred to a neurologist, who recommended switching from risperidone to Riscon Plus, a medication that combines risperidone with Trihexyphenidyl, an anticholinergic drug that improves muscle control and reduces stiffness. This case report emphasizes the significance of vigilant monitoring for the symptoms of Parkinsonism in individuals consuming dopamine-blocking drugs and the possible advantages of shifting to alternate treatments that can alleviate such undesirable consequences.

Assessment of Plasma Glucose and Lipid Profile Dysregulation among Patients on Antipsychotics in Sokoto

Background: Antipsychotic drugs used in the treatment of psychotic disorders have been implicated in negative effects on the blood glucose and lipid profile levels of patients. Methods: We studied the anthropometric parameters and then the plasma glucose and lipid profile levels of one hundred and seventy-two (172) patients between the ages of 18 and 45 years; who are on various oral antipsychotics. Also, forty (40) treatment-naïve psychiatric patients and forty (40) healthy controls were included in the study. The results were analysed using standard methods. Results: The mean plasma glucose level was significantly higher (p&lt;0.05) in psychiatric patients on oral antipsychotic drugs compared to controls. The mean plasma glucose level of treatment-naïve psychiatric patients was also significantly higher (p&lt;0.05) compared to that of healthy controls. Furthermore, there was a significant increase in plasma glucose levels of patients on second-generation antipsychotic drugs compared to those on first-generation antipsychotic drugs. The lipid profile of patients on antipsychotic drugs showed a similar trend. There were significant increases in the plasma levels of Total Cholesterol (TC), Low-Density Lipoprotein (LDL), Triglycerides (TG) and a significant decrease in the plasma level of High-Density. However, the plasma TG levels were significantly higher in the typical antipsychotic drugs group. Lipoprotein (HDL) levels of individuals that were on antipsychotics were significantly decreased when compared to healthy controls Conclusion: The lipid profile and plasma glucose concentration were altered by oral antipsychotic drugs in Sokoto, Nigeria. Therefore, it may be clinically expedient to vigorously assess the plasma glucose and lipid profile levels of all patients that are on oral antipsychotic drugs and interventions planned as appropriate. Keywords: Antipsychotic drugs, lipid profile, glucose, Cholesterol, Lipoprotein

Association of In Utero Antipsychotic Medication Exposure With Risk of Congenital Malformations in Nordic Countries and the US

Psychiatric disorders are common among female individuals of reproductive age. While antipsychotic medication use is increasing, the safety of such medications in pregnancy is an area with large evidence gaps. To evaluate the risk of first-trimester antipsychotic exposure with respect to congenital malformations, focusing on individual drugs and specific malformation subtypes. This cohort study used data from nationwide health registers from the 5 Nordic countries and the US and spanned 1996 to 2018. The Nordic cohort included all pregnancies resulting in singleton live-born infants, and the US cohort consisted of publicly insured mothers linked to their live-born infants nested in the nationwide Medicaid Analytic eXtract. Data were analyzed from November 2020 to April 2022. One or more first-trimester dispensing of any atypical, any typical, and individual antipsychotic drugs. Any major congenital malformation and specific malformation subtypes previously suggested to be associated with antipsychotic exposure in utero: cardiovascular malformations, oral clefts, neural tube defects, hip dysplasia, limb reduction defects, anorectal atresia/stenosis, gastroschisis, hydrocephalus, other specific brain anomalies, and esophageal disorders. Propensity score stratification was used to control for potential confounders. Pooled adjusted estimates were calculated using indirect standardization. A total of 6 455 324 unexposed mothers (mean maternal age range across countries: 24-31 years), 21 751 mothers exposed to atypical antipsychotic drugs (mean age range, 26-31 years), and 6371 mothers exposed to typical antipsychotic drugs (mean age range, 27-32 years) were included in the study cohort. Prevalence of any major malformation was 2.7% (95% CI, 2.7%-2.8%) in unexposed infants, 4.3% (95% CI, 4.1%-4.6%) in infants with atypical antipsychotic drug exposure, and 3.1% (95% CI, 2.7%-3.5%) in infants with typical antipsychotic drug exposure in utero. Among the most prevalent exposure-outcome combinations, adjusted relative risks (aRR) were generally close to the null. One exception was olanzapine exposure and oral cleft (aRR, 2.1 [95% CI, 1.1-4.3]); however, estimates varied across sensitivity analyses. Among moderately prevalent combinations, increased risks were observed for gastroschisis and other specific brain anomalies after atypical antipsychotic exposure (aRR, 1.5 [95% CI, 0.8-2.6] and 1.9 [95% CI, 1.1-3.0]) and for cardiac malformations after chlorprothixene exposure (aRR, 1.6 [95% CI, 1.0-2.7]). While the association direction was consistent across sensitivity analyses, confidence intervals were wide, prohibiting firm conclusions. In this study, considering the evidence from primary and sensitivity analyses and inevitable statistical noise for very rare exposure-outcome combinations, in utero antipsychotic exposure generally was not meaningfully associated with an increased risk of malformations. The observed increased risks of oral clefts associated with olanzapine, gastroschisis, and other specific brain anomalies with atypical antipsychotics and cardiac malformations with chlorprothixene requires confirmation as evidence continues to accumulate.

Development and Evaluation of a Physiologically Based Pharmacokinetic Model for Predicting Haloperidol Exposure in Healthy and Disease Populations.

The physiologically based pharmacokinetic (PBPK) approach can be used to develop mathematical models for predicting the absorption, distribution, metabolism, and elimination (ADME) of administered drugs in virtual human populations. Haloperidol is a typical antipsychotic drug with a narrow therapeutic index and is commonly used in the management of several medical conditions, including psychotic disorders. Due to the large interindividual variability among patients taking haloperidol, it is very likely for them to experience either toxic or subtherapeutic effects. We intend to develop a haloperidol PBPK model for identifying the potential sources of pharmacokinetic (PK) variability after intravenous and oral administration by using the population-based simulator, PK-Sim. The model was initially developed and evaluated to predict the PK of haloperidol and its reduced metabolite in adult healthy population after intravenous and oral administration. After evaluating the developed PBPK model in healthy adults, it was used to predict haloperidol–rifampicin drug–drug interaction and was extended to tuberculosis patients. The model evaluation was performed using visual assessments, prediction error, and mean fold error of the ratio of the observed-to-predicted values of the PK parameters. The predicted PK values were in good agreement with the corresponding reported values. The effects of the pathophysiological changes and enzyme induction associated with tuberculosis and its treatment, respectively, on haloperidol PK, have been predicted precisely. For all clinical scenarios that were evaluated, the predicted values were within the acceptable two-fold error range.