Typical Antipsychotics Research Articles

Prescribing changes for bipolar patients discharged from two public psychiatric hospitals in Taiwan, 2006–2019

BackgroundFor bipolar disorder, a severe, recurring mental disorder, pharmacotherapy is a cornerstone of effective treatment. The purpose of this study was to investigate prescribing changes among patients with bipolar disorder discharged from two public psychiatric hospitals in Taiwan over a 14-year period. MethodsPatients with bipolar disorder discharged from the two study hospitals between 2006 and 2019 (n = 9071) were included in the analysis. Prescribed drugs for the treatment of bipolar disorder, including mood stabilizers (i.e., lithium, valproate, carbamazepine, and lamotrigine), any antipsychotics (i.e., second- and first-generation antipsychotics; SGAs & FGAs), and any antidepressants, were examined. Complex polypharmacy was defined as the use of 3 or more agents among the prescribed drugs. Temporal trends of each prescribing pattern were analyzed using the Cochran-Armitage Trend test. ResultsThe prescription rates of SGAs, any antidepressants, antidepressant monotherapy, antidepressants without mood stabilizers, and complex polypharmacy significantly increased over time, whereas the prescription rates of any mood stabilizers, lithium, carbamazepine, FGAs, and antidepressants plus mood stabilizers significantly decreased. LimitationsTreatment allocation is not randomized in a retrospective study. The diagnoses of bipolar disorder were based on clinical judgments. This was a hospital-based study. ConclusionsSubstantial prescribing changes took place during the study period. The decreased use of lithium and the increased use of antidepressants were not in accordance with the evidence-based treatment and recommendations in treatment guidelines. Therefore, long-term outcomes of prescribing changes should be explored in the future.

Trends in the utilization of psychotropic medications in China from 2018 to 2021

Background: Monitoring psychotropic medicine consumption trends can provide information on the extent of pharmacological interventions for mental disorders and availability of psychotropic medicines. Objectives: This study aimed to illustrate the trends in psychotropic drug utilization in China’s hospitals. Methods: We retrospectively analyzed the aggregated monthly psychotropic procurement records of 1009 hospitals from 31 provinces in China from January 2018 to September 2021. Total psychotropic medicine consumption included the sales of antipsychotics, antidepressants, anxiolytics, mood stabilizers, and sedatives or hypnotics. Information, including generic name, procurement amount, dosage form, strength, purchase time, and geographical data, was collected. Population-weighted psychotropic utilization was expressed in defined daily dose per 1000 inhabitants per day (DDD/1000/day). Results: Psychotropic medicine sales increased from 4.5 DDD/1000/day in Q1 2018 to 6.4 DDD/1000/day in Q3 2021; total utilization in China’s hospitals increased by 42.2%. The use of each class of psychotropics showed a gradually increasing trend. Antidepressants were the most consumed psychotropics, accounting for 48.4% of the total psychotropic utilization (3.1/6.4 DDD/1000/day), followed by sedatives or hypnotics (31.3%; 2.0/6.4 DDD/1000/day) and antipsychotics (15.6%; 1.0/6.7 DDD/1000/day). Among all sub-classes of psychotropics, a most significant growth in DDD per 1000 inhabitants per day was seen for selective serotonin reuptake inhibitors (1.2–1.9 DDD/1000/day), whereas the consumption of typical antipsychotics (from 0.1 to 0.09 DDD/1000/day) and tricyclic antidepressants (from 0.05 to 0.03 DDD/1000/day) decreased during the study period. Psychotropic utilization substantially increased between Q1 2018 and Q3 2021 in regions with different economic levels. In Q3 2021, total psychotropic utilization in secondary and tertiary hospitals was 9.4 DDD/1000/day and 6.0 DDD/1000/day, respectively. Sedatives or hypnotics in secondary hospitals accounted for the largest proportion of utilized psychotropics (43.6%; 4.1/9.4 DDD/1000/day), whereas antidepressants were the most commonly used psychotropic in tertiary hospitals (50.0%, 3.0/6.0 DDD/1000/day). Conclusion: This study showed that despite increases in psychotropic medication use, the consumption of medicines is still much lower than in other countries and regions internationally. With reference to the estimated prevalence of corresponding mental disorders, our study illustrates that a large treatment gap for mental health problems exists in China. In addition, the wide use of psychotropics with weak clinical evidence raises serious concerns regarding rational use. Greater efforts are needed to increase the availability of psychotropic medicines and to facilitate proper psychotropic use.

Antipsychotic-induced movement disorders: integrative review

Objective: To identify movement disorders induced by antipsychotics. Methods: We selected clinical trials from MEDLINE and LILACS databases without publication date restriction. Studies of antipsychotics as a pharmacological intervention, compared or not to other interventions were included (combined treatments were not included). The primary outcome was movement disorders. Two independent reviewers analyzed the studies and summarized them in an electronic spreadsheet. We assessed the quality of the selected studies using the PEDro scale. Results: Five studies were included in this review. In these studies, it was possible to identify the main psychiatric symptoms and their severity, as well as dyskinetic movements. When a reduction in dyskinetic movements was observed in treatments with both atypical and typical antipsychotics, there were adverse effects. Those included excessive sedation, loss of body mass, vomiting, and leukocytopenia. Conclusion: This study verified the findings in literature on the effects of antipsychotics, including the type of medication, dosage, and form of administration, as well as instruments used to assess the outcome related to movement disorders. It was not possible to determine the best therapeutic dose for managing the disorders due to the significant distinction in dosages and medications. All five studies had some effect related to the drug use or its withdrawal.

Praktyka preskrypcyjna w zakresie leków przeciwpsychotycznych w schizofrenii w latach 2013–2018 na podstawie danych Narodowego Funduszu Zdrowia

The aim of the study was to analyse the prescribing pattern of antipsychotic drugs in patients with schizophrenia during the years 2013-2018. Schizophrenia is analysed as one of the diseases with the highest rate of Disability-Adjusted Life Years - DALY. In this study, the unitary data of the National Health Fund (NFZ) reported in the years 2013-2018 were used. Adult patients were identified by their Personal Identification Number (PESEL), and the antipsychotics were identified by the European Article Number (EAN). The study included 209,334 adults who were diagnosed with F20 to F20.9 (according to ICD-10) and were prescribed at least one antipsychotic within a year. The active substances of prescribed antipsychotic medication have been divided into typical (first generation), atypical (second generation) and long-acting injectable antipsychotics (both first and second generation). The statistical analysis contains descriptive statistics for selected sections. A linear regression, one-way analysis of variance and t-test were used in the study. All statistical analyses were performed using R, version 3.6.1 and Microsoft Excel. In the years 2013-2018, the number of patients in the public sector diagnosed with schizophrenia increased by 4%. The largest increase was recorded among persons diagnosed with other schizophrenia (F20.8). In the analysed years, the number of patients who were prescribed second-generation oral antipsychotics increased significantly as well as the number of patients who were prescribed long-acting antipsychotics, especially the secondgeneration agents (risperidone LAI, olanzapine LAI). The most prescribed first-generation antipsychotics included: perazine, levomepromazine and haloperidol with a downward trend for each; and the most common second-generation drugs included: olanzapine, aripiprazole and quetiapine. A noteworthy finding was an extremely high increase in the frequency of prescribing haloperidol in the form of depot. Extending the study to include information on applied prescriptive practice in the private sector would provide a fuller picture of the studied phenomenon.

Should antipsychotics be used for the management of agitation and psychosis in dementia?

SUMMARYAgitation and psychosis are two common distressing symptoms of dementia. The results of this issue's Cochrane Corner review suggest that, if a pharmacological approach is required, the use of risperidone and other atypical antipsychotics for the purpose of managing these symptoms seems questionable. Furthermore, typical antipsychotics, haloperidol in particular, might have a greater impact on agitation and psychosis than already recognised. This commentary critically appraises the evidence on the efficacy of typical and atypical antipsychotics for agitation and psychosis in dementia.

Second-Generation Antipsychotics' Effectiveness and Tolerability: A Review of Real-World Studies in Patients with Schizophrenia and Related Disorders.

Despite methodological limitations, real-world studies might support clinicians by broadening the knowledge of antipsychotics’ (APs) effectiveness and tolerability in different clinical scenarios and complement clinical trials. We conducted an extensive literature search in the PubMed database to evaluate the effectiveness and tolerability profiles of second-generation antipsychotics (SGAs) from real-world studies to aid clinicians and researchers in selecting the proper treatment for patients with schizophrenia and related disorders. The present review evidenced that SGAs demonstrated superior effectiveness over first-generation antipsychotics (FGAs) in relapse-free survival and psychiatric hospitalization rate and for treating negative symptoms. Persistence and adherence to therapy were higher in SGAs than FGAs. Most studies concluded that switching to long-acting injectables (LAIs) was significantly associated with a lower treatment failure rate than monotherapy with oral SGAs. Considerable improvements in general functionality, subjective well-being, and total score on global satisfaction tests, besides improved personal and social performance, were reported in some studies on patients treated with LAI SGAs. Clozapine was also associated with the lowest rates of treatment failure and greater effectiveness over the other SGAs, although with more severe side effects. Effectiveness on primary negative symptoms and cognitive deficits was rarely measured in these studies. Based on the data analyzed in the present review, new treatments are needed with better tolerability and improved effectiveness for negative, affective, and cognitive symptoms.

Tardive Dyskinesia and Long-Acting Injectable Antipsychotics: Analyses Based on a Spontaneous Reporting System Database in Japan.

Objective: This study compared the reporting frequency of tardive dyskinesia (TD) between long-acting injectable antipsychotics (LAI-APs) and the equivalent oral antipsychotics (O-APs), LAI first-generation antipsychotics (LAI-FGAs) and LAI second-generation antipsychotics (LAI-SGAs), and individual LAI-APs.Methods: The Japanese Adverse Drug Event Report was used in this study, and data were obtained from April 2004 to February 2021. Patients who received LAI-APs available in Japan (LAI haloperidol, LAI fluphenazine, LAI aripiprazole, LAI risperidone, and LAI paliperidone) or the equivalent O-APs were included in this study. We calculated the adjusted reporting odds ratios (aRORs) to compare the reporting frequency of TD.Results: A total of 8,425 patients were included in the study. TD was reported significantly less frequently with LAI paliperidone than with oral paliperidone (aROR [95% confidence interval (CI)] = 0.13 [0.05-0.36]). Other LAI-APs were associated with a numerically lower reporting frequency of TD than the equivalent oral SGAs. The reporting frequency of TD associated with LAI-SGAs was significantly lower than that of LAI-FGAs (aROR [95% CI] = 0.18 [0.08-0.43]). All LAI-SGAs were significantly associated with a lower reporting frequency of TD than that of LAI fluphenazine (aROR [95% CI]: LAI aripiprazole, 0.11 [0.04-0.35]; LAI risperidone, 0.09 [0.03-0.32]; LAI paliperidone, 0.02 [0.005-0.09]). and LAI haloperidol, 8.58 [1.85-39.72]). LAI fluphenazine was significantly associated with a higher reporting frequency of TD than LAI haloperidol (aROR [95% CI] = 8.58 [1.85-39.72]). The reporting frequency of TD associated with LAI paliperidone was significantly lower than that with LAI aripiprazole (aROR [95% CI] = 0.18 [0.05-0.73]).Conclusions: Compared to O-APs, LAI-APs, particularly LAI-SGAs, may be associated with a lower risk of TD.

Extrapyramidal Symptoms and Novel Antipsychotic Drugs

One of the challenges of antipsychotic medication is the occurrence of Extrapyramidal Symptoms. These cannot be easily eliminated considering the pathophysiology of schizophrenia and the established mechanism of action of classical antipsychotics. The antipsychotics help improve symptoms of schizophrenia by binding to dopamine receptors in the central nervous system and blocking dopamine. This prevents the basal ganglia from getting enough dopamine. Many drugs used in the treatment of mental disorders such as the neuroleptics and antidepressants adversely affect extrapyramidal system function, resulting in symptoms such as tremors and muscle rigidity collectively known as extrapyramidal symptoms. Treatment generally involves lowering the dose or trying a different antipsychotic but drugs may also be used specifically to treat symptoms. This review examines the attempt to eliminate extrapyramidal symptoms by generations of antipsychotic medications and their comparative efficacy in the treatment of schizophrenia. A wide internet search was carried out using keywords and phrases that include; Antipsychotics, Typical Antipsychotics, Atypical Antipsychotics, Dopaminergic, Extrapyramidal symptoms, comparative efficacy of Antipsychotics and Adverse Effect of Antipsychotics. This will further reinforce knowledge and prescription patterns for antipsychotic medications.

Temporal Trends Over Two Decades in the Use of Anticholinergic Drugs Among Older Community-Dwelling People in Helsinki, Finland.

BackgroundKnowledge of the adverse effects of drugs with anticholinergic properties (DAPs) has increased in recent decades. However, research on the temporal trends of the clinical use of DAPs is still sparse.ObjectivesThe aim of this study was to investigate the temporal trends of DAP use over two decades in the older community-dwelling population and to explore the medication classes contributing to the use of DAPs.MethodsThe study involved random samples of ≥ 75-year-old community-dwelling Helsinki citizens in 1999, 2009, and 2019 from the Helsinki Ageing Study. A postal questionnaire inquired about their health, functioning, and medications. The medications were categorized as DAPs according to Duran’s list. In addition, we grouped DAPs into various medication groups.ResultsThe prevalence and burden of DAPs on Duran's list showed a decreasing trend over the years. In 1999 the prevalence was 20% and the burden 0.35, in 2009 they were 22% and 0.35, respectively, and in 2019 they were 16% and 0.23, respectively. There were no differences in how the 75- and 80-year-olds used DAPs compared with those aged 85 years and older. The proportion of typical antipsychotics, benzodiazepines, hypnotics, urinary antispasmodics, and asthma/chronic obstructive pulmonary disease medications decreased, whereas the proportion of atypical antipsychotics, antidepressants, strong opioids, and antihistamines increased. In particular the use of mirtazapine increased—to 3.9% in 2019. In 2019 the three most prevalent groups of DAPs were antidepressants (7.4%), opioids (2.7%), and antihistamines (2.4%).ConclusionsThe decrease in the use of DAPs on Duran's list is a welcome change. Although the use of old, strong DAPs has decreased, new DAPs have simultaneously emerged. Physicians need continuous education in prescribing DAPs and more recent information on the use and effects of DAPs is needed in order to decrease their exposure among the rapidly growing older population.

GAMBARAN KEJADIAN EKSTRAPIRAMIDAL SINDROM PADA PASIEN TERAPI ANTIPSIKOTIK TIPIKAL DI RUMAH SAKIT JIWA ACEH

The use of antipsychotics in schizophrenic patients often causes side effects in the form of Extra Pyramidal Syndrome (EPS), namely the presence of uncontrolled muscle movement disorders such as seizures, shaking and so on. The incidence of EPS is more common with the use of typical antipsychotics than atypicals. This study aims to see the incidence of EPS in inpatients with schizophrenia at the Aceh Mental Hospital located in Banda Aceh in 2020. The population in this study were all inpatients who were given typical antipsychotics. While the research sample was 399 samples collected from medical record data of inpatients in 2020, so the study was retrospective with a cross sectional approach. Data collected in the form of patient identity (gender, age), drug therapy (typical antipsychotics) and the incidence of EPS. The results showed that schizophrenic patients who received typical antipsychotic therapy who were hospitalized at the Aceh mental hospital in 2020, were 324 men (81.2%) and 75 women (18.8%), with the highest age range being at 36-45 years amounting to 202 people (50.6%). Typical antipsychotic therapy used in the form of combination of typical-typical and typical-atypical drugs, namely clozapine-trifluperazine (40.6%), chlorpromazine-risperidone (20.3%), haloperidol-chlorpromazine-trifluperazine (16%), haloperidolchlorpromazine (7%), and haloperidol-trifluperazine (5%). The incidence of EPS that occurred was 113 people (28.3%), with the highest number of EPS occurring from the administration of haloperidol-chlorpromazine-trifluperazine combination antipsychotic therapy, which was 61 people (15.3%).

An Updated Analysis of Psychotropic Medicine Utilisation in Older People in New Zealand from 2005 to 2019.

Psychotropic medicine utilisation in older adults continues to be of interest because of overuse and concerns surrounding its safety and efficacy. This study aimed to characterise the utilisation of psychotropic medicines in older people in New Zealand. We conducted a repeated cross-sectional analysis of national dispensing data from 1 January, 2005 to 31 December, 2019. We defined utilisation using the Anatomical Therapeutic Chemical classification defined daily dose system. Utilisation was measured in terms of the defined daily dose (DDD) per 1000 older people per day (TOPD). Overall, the utilisation of psychotropic medicines increased marginally by 0.42% between 2005 and 2019. The utilisation increased for antidepressants (72.42 to 75.21 DDD/TOPD) and antipsychotics (6.06-19.04 DDD/TOPD). In contrast, the utilisation of hypnotics and sedatives (53.74-38.90 DDD/TOPD) and anxiolytics decreased (10.20-9.87 DDD/TOPD). The utilisation of atypical antipsychotics increased (4.06-18.72 DDD/TOPD), with the highest percentage change in DDD/TOPD contributed by olanzapine (520.6 %). In comparison, utilisation of typical antipsychotics was relatively stable (2.00-2.06 DDD/TOPD). The utilisation of venlafaxine increased remarkably by 5.7 times between 2005 and 2019. The utilisation of zopiclone was far greater than that of other hypnotics in 2019. There was only a marginal increase in psychotropic medicines utilisation from 2005 to 2019 in older adults in New Zealand. There was a five-fold increase in the utilisation of antipsychotic medicines. Continued monitoring of psychotropic medicine utilisation will be of interest to understand the utilisation of antidepressants and antipsychotic medicines during the coronavirus disease 2019 pandemic year.

Associations between the number of antipsychotics prescribed and metabolic parameters in Japanese patients with schizophrenia.

There is little evidence on the effects of antipsychotic polypharmacy on metabolic parameters in patients with schizophrenia. Thus, this cross-sectional study explored the associations between the number of antipsychotics prescribed and metabolic parameters in Japanese patients with schizophrenia. We obtained metabolic parameter data from 19,675 patients with schizophrenia. Of these, 1380 (7.0%), 8422 (42.8%), 6326 (32.2%), and 3547 (18.0%) were treated with none, one, two, and three or more antipsychotics, respectively. We compared eight metabolic parameters among the four groups using univariate analyses. We then performed multiple regression analysis to assess the effect of the number of antipsychotics prescribed on metabolic parameters after controlling for the effects of age, sex, type of care (outpatient/inpatient), chlorpromazine-equivalent dose, and antipsychotic type (aripiprazole, olanzapine, and risperidone). There were significant differences in body mass index (BMI), systolic and diastolic blood pressure (dBP), total cholesterol, low-density lipoprotein cholesterol, and triglycerides among the four groups. The multiple regression analysis showed that the number of antipsychotics prescribed was significantly correlated with BMI and dBP (standardized regression coefficient = 0.031 and 0.026, respectively). Our results suggested that the number of antipsychotics prescribed adversely affects BMI and dBP. Clinicians should avoid inappropriate antipsychotic polypharmacy, especially polypharmacy involving three or more antipsychotics.

Mapping the Knowledge of Antipsychotics-Induced Sudden Cardiac Death: A Scientometric Analysis in CiteSpace and VOSviewer.

The drugs on the market for schizophrenia are first-generation and second-generation antipsychotics. Some of the first-generation drugs have more side effects than the other drugs, so they are gradually no longer being applied clinically. Years of research have shown that the risk of sudden cardiac death in psychotic patients is associated with drug use, and antipsychotic drugs have certain cardiotoxicity and can induce arrhythmias. The mechanism of antipsychotic-induced sudden cardiac death is complicated. Highly cited papers are among the most commonly used indicators for measuring scientific excellence. This article presents a high-level analysis of highly cited papers using Web of Science core collection databases, scientometrics methods, and thematic clusters. Temporal dynamics of focus topics are identified using a collaborative network (author, institution, thematic clusters, and temporal dynamics of focus topics are identified), keyword co-occurrence analysis, co-citation clustering, and keyword evolution. The primary purpose of this study is to discuss the visual results, summarize the research progress, and predict the future research trends by bibliometric methods of CiteSpace and VOSviewer. This study showed that a research hotspot is that the mechanisms of cardiotoxicity, the safety monitoring, and the assessment of the risk-benefit during clinical use of some newer antipsychotics, clozapine and olanzapine. We discussed relevant key articles briefly and provided ideas for future research directions for more researchers to conduct related research.

Antipsychotic utilization patterns in pregnant women with psychotic disorders: a 16-year population-based cohort study.

Despite growing concern about reproductive safety of antipsychotics, there is a paucity of research specifically assessing prenatal antipsychotic prescribing practices for psychotic disorders. This population-based cohort study identified women aged 15-50years with diagnosis of psychotic disorders, who delivered their first and singleton child between 2003-2018 in Hong Kong, with an aim to examine temporal trends and predictors of prenatal antipsychotic use as well as antipsychotic utilization patterns before and during pregnancy. Data were retrieved from territory-wide medical-record database of public healthcare services. Of 804 women, 519 (65%) redeemed at least one prescription for antipsychotics during pregnancy. Older age at conception (25-34years: OR 2.12 [95% CI 1.22-3.67]; 35-50years: 2.52 [1.38-4.61]; 15-24years as reference category) and antipsychotic treatment within 12months pre-pregnancy (24.22 [16.23-36.16]) were significantly associated with prenatal antipsychotic use. Second-generation-antipsychotic (SGA) use during pregnancy increased over 16-year study period, while prenatal first-generation-antipsychotic (FGA) use showed declining trend. Overall antipsychotic and SGA use progressively decreased across pre-pregnancy and trimesters of pregnancy. Further analyses on antipsychotic use trajectories revealed that 87.4% (n = 459) of 529 women receiving antipsychotics in 12-month pre-pregnancy redeemed antipsychotic prescription during pregnancy, and 63.4% (n = 333) continued antipsychotic treatment throughout pregnancy. Only 7.5% of the cohort (n = 60) commenced antipsychotics in pregnancy. This is one of the few studies evaluating real-world prenatal antipsychotic utilization among women with psychotic disorders. Future research delineating risk conferred by illness-related factors and antipsychotic exposure on adverse maternal and fetal outcomes is warranted to facilitate treatment guideline development.

Association of Antipsychotic Dose With Survival of Advanced Cancer Patients With Delirium.

Delirium is common in patients with advanced cancer, and antipsychotics are widely used for its management. We aimed to explore the association of the antipsychotic dose with survival of terminally ill cancer patients with delirium. A secondary analysis of a multicenter prospective observational study was conducted. We enrolled adult advanced cancer patients who developed delirium and received antipsychotics at 14 palliative care units in Japan between September 2015 and May 2016. Hazard ratios of survival after starting antipsychotics between groups with different oral chlorpromazine equivalent doses: low: <100 mg, moderate: 100-200 mg, high: ≥200 mg, were calculated with adjustment for potential confounders using Cox regression. The antipsychotic dose-specific mortality risk was estimated with smooth splines. Of 453 patients enrolled, 422 patients were analyzed. The median antipsychotic dose was 92.6 mg: low-dose (N=231), moderate-dose (122), and high-dose (69). The median survival of all patients was 11 days. Compared with the low-dose group, the high-dose group showed a significantly shorter survival (HR: 1.46, 95%CI: 1.08-1.98). Smooth splines demonstrated that HR continuously increased as the antipsychotic dose increased. In patients treated with atypical antipsychotics, the high-dose group showed a significantly shorter survival than the low-dose group (HR: 2.86), while in patients treated with typical antipsychotics, survival was not significantly different (0.99). Higher doses of antipsychotics were associated with increased mortality in terminally ill cancer patients with delirium. To minimize the potential mortality risk, antipsychotics should be started at low doses and titrated carefully.

A two-year follow-up study on the first manic episode due to mood-incongruent psychosis.

Mood-incongruent psychosis during bipolar disorder has been associated with poor outcomes. However, it remains unknown whether this is secondary to persistent affective or psychotic symptoms or both. Sixty-eight patients with bipolar disorder between the ages of 16 and 45 were recruited during their first psychiatric hospitalization for mania. These patients were evaluated using structured and semi-structured clinical interview then followed longitudinally. Outcomes during the first twenty-four months of follow-up were compared between patients with mood-incongruent psychosis and those without (i.e., patients with mood-congruent psychosis or no psychosis) during the index manic episode. Specifically, ratings of the percent of weeks during follow-up with the duration of mood incongruent psychotic symptom, any psychotic symptom, affective syndromes, and scores of global outcomes were compared. Comparing the 24-month follow-up results between the two groups, patients with mood incongruent psychotic symptoms had a lower global functional rating scale, efficacy index, while the duration of mood incongruent psychotic symptom, any psychotic symptom, and complete affective symptom showed statistically significant differences between the two groups. There were also statistically significant differences between the two groups in the duration of mood stabilizers, and antidepressants use, typical antipsychotics, and atypical antipsychotics. Partial correlation analysis reveals the scores of the global assessment of functioning scale (GAF) after 24 months showed a significant negative correlation with the length of time of incongruent psychotic symptoms. Still, the correlation was intermediate (correlation coefficients less than 0.5，r2 =-0.471, P<0.001). Mood-incongruent psychosis that occurs during the first manic episode appears to predict an increased likelihood of persistent psychotic symptoms during the subsequent twenty-four months. This persistence of psychosis is associated with a worse overall course of illness than patients without mood-incongruent psychosis. These results apply to a relatively short outcome period, and the sample size is relatively small.

Quetiapine Add-On Therapy May Improve Persistent Sleep Disturbances in Patients with PTSD on Stabile Combined SSRI and Benzodiazepine Combination: A One-Group Pretest-Posttest Study.

To assess potential benefits of quetiapine for persistent sleep disturbances in patients with posttraumatic stress disorder (PTSD) on stable combined SSRI and benzodiazepine therapy, who previously failed to respond to various benzodiazepine and non-benzodiazepine hypnotic adjuvant treatment as well as to first-generation antipsychotic add-on treatment. Fifty-two male PTSD outpatients on stable combination treatment with SSRI and benzodiazepines, with persistent sleep disturbances not responding to prescription of zolpidem, flurazepam, nitrazepam, promazine, and levopromazine, were assessed for sleep disturbances improvements after prescription of quetiapine in the evening. Each patient met both ICD-10 and DSM-IV criteria for PTSD. Psychiatric comorbidity and premorbidity were excluded using the Mini-International Neuropsychiatric Interview (MINI). Improvement on the CAPS recurrent distressing dream item, reduction in the amount of time needed to fall asleep, prolongation of sleep duration, and reduction in average number of arousals per night in the last 7 days before the assessment period were used as efficacy measures. All sleep-related parameters improved significantly at the end of a five-week follow-up: sleep duration increased by one hour (p<0.001), sleep latency decreased by 52.5 minutes (p<0.001), median number of arousals per night decreased from two to one (p<0.001), CAPS recurrent distressing dream item median decreased from five to four (p<0.001), and the number of patients dissatisfied with their sleep quality and quantity decreased from 45 to two (p<0.001). Quetiapine prescribed in the evening may be successful therapy for persistent sleep disturbances in patients with PTSD and generally good response to an SSRI and benzodiazepine combination, who previously failed to respond to some of the usual hypnotic medication or addition of first-generation antipsychotics: zolpidem, flurazepam, nitrazepam, promazine, and levopromazine.

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.

Impact of childhood trauma on antipsychotic effectiveness in schizophrenia spectrum disorders: A prospective, pragmatic, semi-randomized trial

Antipsychotic medications are generally effective in ameliorating psychotic symptoms in schizophrenia spectrum disorders (SSDs). Identifying predictors associated with poor treatment response is important for a personalized treatment approach. Childhood trauma (CT) may have a general and differential effect on the effectiveness of different types of antipsychotics in SSDs. The Bergen-Stavanger-Trondheim-Innsbruck (BeSt InTro) study is a pragmatic, researcher-initiated, semi-randomized trial. The present study aimed to investigate symptom change (the Positive and Negative Syndrome Scale) from baseline to 1, 3, 6, 12, 26, 39 and 52 weeks of antipsychotic treatment (amisulpride, aripiprazole and olanzapine) by group (CT/no CT). Participants (n = 98) with diagnoses within the schizophrenia spectrum (F20–29 in the International Classification of Diseases — 10th Revision) were randomized to receive amisulpride, aripiprazole or olanzapine, and for this study categorized into groups of none and low CT, and moderate to severe CT according to thresholds defined by the Childhood Trauma Questionnaire Short-Form manual. CT in SSDs predicted an overall slower treatment response and less antipsychotic effectiveness after 26 weeks of treatment, which was statistically nonsignificant at 52 weeks. Secondary analyses showed a differential effect of CT related to type of antipsychotic medication: patients with SSDs and CT who received olanzapine showed less antipsychotic effectiveness throughout 52 weeks of treatment. The intention-to-treat and per-protocol analyses were convergent. Our findings indicate that in patients with SSD and CT, delayed response to antipsychotics could be expected, and a longer evaluation period before considering change of medication may be recommended.

Possible involvement of apoptosis in the antipsychotics side effects: A mini-review.

Antipsychotics are used in the treatment of schizophrenia and other psychiatric disorders. Generally, they are divided into typical and atypical ones, according to the fact that atypical antipsychotics induce fewer side effects and are more effective in terms of social and cognitive improvements. Their pharmacological effects are mediated via broad range of receptors that consequently influence different cellular signalling pathways. Antipsychotics produce undesirable side effects that range from relatively minor to life threatening. In vitro and in vivo studies have pointed to neurotoxic effect exerted by some antipsychotics and have shown that apoptosis might play role in some side effects induced by antipsychotics, including tardive dyskinesia, weight gain, agranulocytosis, osteoporosis, myocarditis, etc. Although cumulative data have suggested safety of atypical antipsychotics use during pregnancy, some of them have been shown to induce apoptotic neurodegenerative and structural changes in fetal brains with long-lasting impact on cognitive impairment of offspring. Typical antipsychotics seem to be more cytotoxic than atypical ones. Recently, epidemiological studies have shown lower incidence of cancer in schizophrenic patients that suggest the ability of antipsychotics to suppress risk of cancer development. Some antipsychotics have been reported to inhibit cancer cell proliferation and induce their apoptosis. Therefore, antipsychotics apoptotic effect may be used as a tool in the treatment of some types of cancer, especially in combinatorial therapies. In this mini-review, we focused on pro- and antiapoptotic or 'Dr. Jekyll and Mr. Hyde' effects of antipsychotics, which can be involved in their side effects, as well as their promising therapeutic indications.