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Schizophrenia is a chronic mental illness that requires lifelong antipsychotic treatment. Therapy discontinuation, often due to poor adherence, increases the risk of relapses after both first and subsequent psychotic episodes. Long-acting injectable (LAI) antipsychotic drugs (APDs) have been introduced to increase therapeutic adherence, reducing blood-level variability compared to corresponding oral preparations. To compare the effectiveness of three LAI-APDs: aripiprazole (Apr) prolonged release once monthly (OM) haloperidol decanoate (Hal-D) and paliperidone palmitate (PP-OM). We retrospectively collected data for all patients with schizophrenia or other psychoses (n=217) treated with the three LAI-APDs for the first time from January 1, 2012 to October 31, 2016: n=48 with Apr-OM, n=55 with Hal-D, and n=114 with PP-OM. After 6 and 12 months of LAI treatments, we assessed clinical and functioning improvement, urgent consultations, psychiatric hospitalizations, adverse effects, and dropout. We compared urgent consultations and psychiatric hospitalizations required by the same patient 6 and 12 months before and after LAI implementation. Data were statistically analyzed. The three LAI groups differed significantly only for \"need for economic support from social service\" (more frequent in the Hal-D group) and \"schizoaffective disorder\" (prevalent in the Apr-OM group). Apr-OM was prescribed at the maximum dose required by the official guidelines, whereas the other two LAIs were prescribed at lower doses. After 6 and 12 months' treatment with the three LAI-APDs, we registered similar and significant reductions in both urgent consultations and psychiatric hospitalizations ( <0.001) and overlapping clinical and functioning improvement-scale scores ( <0.001), and 14.28% of patients dropped out, with no difference among the three LAI-APDs. Different kinds of adverse effects, though similar for number and severity, were reported in the three LAI groups. Our results suggest that both first- and second-generation LAI-APDs represent important therapeutic options, useful for improving schizophrenia's clinical course and its economic burden. Our study, which offers a wide and comprehensive observation of real-world clinical settings, combined an effectiveness evaluation through mirror analysis performed for each individual patient to a subsequent comparison among the three LAI-APDs, allowing us a more complete evaluation of clinical efficacy.

SummaryOur systematic review and meta-analysis of observational studies indicated that the use of antipsychotics was associated with a nearly 1.5-fold increase in the risk of fracture. First-generation antipsychotics (FGAs) appeared to carry a higher risk of fracture than second-generation antipsychotics (SGAs).IntroductionThe risk of fractures associated with the use of antipsychotic medications has inconsistent evidence between different drug classes. A systematic review and meta-analysis was conducted to evaluate whether there is an association between the use of antipsychotic drugs and fractures.MethodsSearches were conducted through the PubMed and EMBASE databases to identify observational studies that had reported a quantitative estimate of the association between use of antipsychotics and fractures. The summary risk was derived from random effects meta-analysis.ResultsThe search yielded 19 observational studies (n = 544,811 participants) with 80,835 fracture cases. Compared with nonuse, use of FGAs was associated with a significantly higher risk for hip fractures (OR 1.67, 95% CI, 1.45–1.93), and use of second generation antipsychotics (SGAs) was associated with an attenuated but still significant risk for hip fractures (OR 1.33, 95% CI, 1.11–1.58). The risk of fractures associated with individual classes of antipsychotic users was heterogeneous, and odds ratios ranged from 1.24 to 2.01. Chlorpromazine was associated with the highest risk (OR 2.01, 95% CI 1.43–2.83), while Risperidone was associated with the lowest risk of fracture (OR 1.24, 95% CI 0.95–1.83).ConclusionsFGA users were at a higher risk of hip fracture than SGA users. Both FGAs and SGAs were associated with an increased risk of fractures, especially among the older population. Therefore, the benefit of the off-label use of antipsychotics in elderly patients should be weighed against any risks for fracture.

Diabetes mellitus occurs in schizophrenia patients at higher rates than in the general population. Reasons for this elevated risk are poorly understood and have not been examined prospectively in antipsychotic-naïve, first-episode patients. This study aims to determine which antipsychotics are associated with diabetes development in antipsychotic-naïve schizophrenia patients. All antipsychotic-naïve patients diagnosed with schizophrenia in Denmark between 01 January 1997 and 31 December 2004, followed until 31 December 2007, allowing for ⩾3 years follow-up, unless death or diabetes onset occurred. Risk factors for the time to diabetes onset were assessed, including antipsychotics taken for at least 180 defined daily doses in the first year after first antipsychotic prescription (‘initial treatment’). Risk factors for diabetes incidence were assessed, including antipsychotic use within 3 months before diabetes onset or study end (‘current treatment’). Of 7139 patients, followed for 6.6 years (47 297 patient years), 307 developed diabetes (annual incidence rate: 0.65%). Time to diabetes onset was significantly shorter in patients with higher age (hazard ratio (HR): 1.03, confidence interval (CI): 1.02–1.03) and those with ‘initial’ treatment of olanzapine (HR: 1.41, CI: 1.09–1.83), mid-potency first-generation antipsychotics (FGAs) (HR: 1.60, CI: 1.07–2.39), antihypertensive (HR: 1.87, CI: 1.13–3.09), or lipid-lowering drugs (HR: 4.67, CI: 2.19–10.00). Significant factors associated with diabetes within 3 month of its development included treatment with low-potency FGAs (odds ratio (OR): 1.52, CI: 1.14–2.02), olanzapine (OR: 1.44, CI: 1.98–1.91), and clozapine (OR: 1.67, CI: 1.14–2.46), whereas aripiprazole was associated with lower diabetes risk (OR: 0.51, CI: 0.33–0.80). In addition to general diabetes risk factors, such as age, hypertension, and dyslipidemia, diabetes is promoted in schizophrenia patients by initial and current treatment with olanzapine and mid-potency FGAs, as well as by current treatment with or low-potency first-generation antipsychotics and clozapine, whereas current aripiprazole treatment reduced diabetes risk. Patients discontinuing olanzapine or mid-potency FGA had no increased risk of diabetes compared with patient not treated with the drugs at anytime.

Purpose of Review The purpose of this review was to assess and present the findings up to this date on the efficacy of antipsychotics in the treatment of generalized anxiety disorders (GAD), social anxiety disorders (SAD), panic disorders (PD), and obsessive-compulsive disorders (OCD), mostly based on published randomized controlled trials (RCTs) or on open-label studies when RCT were lacking. Recent Findings Quetiapine could be recommended in patients with GAD. The efficacy of aripiprazole in two open-label studies on patients with antidepressant-refractory GAD should be assessed in RCTs. Despite preliminary positive results in open studies, there are currently no strong evidence for the effectiveness of antipsychotics in refractory SAD and in refractory PD. Conversely, risperidone and aripiprazole can be used for the treatment of refractory OCD as augmentation agents to antidepressants. Summary Contrary to SAD and PD, this review found evidence for the use of second-generation antipsychotics in GAD and OCD. Otherwise, first-generation antipsychotics cannot be recommended in anxiety disorders and OCD.

Treatment discontinuation is a major challenge in routine clinical settings. Despite poor adherence to antipsychotic medication, long acting injectable (LAI) formulations are an underutilized option in psychotic disorders. Recently, an earlier and broader use of LAIs has been emphasized. However, few studies have evaluated the factors associated with LAI antipsychotic discontinuation in ordinary clinical practice. The main purpose of the present study was, therefore, to identify the factors associated with LAI discontinuation in a real-world setting. Patients in treatment with LAI antipsychotics were recruited. A Cox regression analysis was applied considering a 12-month follow-up period. Moreover, a Kaplan-Meier survival analysis was applied to compare the single treatment LAI antipsychotic groups in terms of time to discontinuation. Our analysis showed an LAI discontinuation rate at 12 months, corresponding to 28.8%, with olanzapine and aripiprazole having a longer time to discontinuation compared to zuclopenthixol. The results of the present study can help clinicians with their choice of LAI antipsychotic according to patients’ characteristics and in a context of precision medicine. Increasing knowledge about factors affecting discontinuation of LAI antipsychotics can improve the prescribing practices of these compounds. Individualized approaches may ameliorate long-term patients’ treatment adherence, thus preventing the long-term disability caused by psychotic disorders.

Background: Schizophrenia is a burdensome illness which virtually affects all aspects of the patient’s life. There is a lack of national level data from India on prescription pattern of Antipsychotics Polypharmacy and other drugs combination in the treatment of Schizophrenia. Aim and Objectives: To evaluate Prescription pattern of Antipsychotic Polypharmacy in schizophrenia. Methodology: The medication records of patients admitted from August 2006 to May 2007 were reviewed to evaluate the prescription pattern of antipsychotics poly pharmacy, Demography of the patients like age, sex, were also evaluated. Results: The medical records of 139 schizophrenic patients were reviewed, out of 139 patients 30.93% (n = 43) patients received combination therapy. In combination therapy 28.77% (n=40) were prescribed two antipsychotics and 0.007% (n= 3) were prescribed three antipsychotic drugs. The average age was 34.4±11.9 years. F 20.0 Paranoid schizophrenia received maximum prescriptions for combination therapy 18.71% (n=26). Comparison of adjunct medication showed Anxiolytics and Anticholinergics 17.26% (n=25) received maximum prescriptions for combination therapy A total of 20.86% (n=29) received combination of Second Generation Antipsychotics SGA + First Generation Antipsychotics FGA, maximum patients 18 was in the combination of Haloperidol + Resperidone. Conclusion: The present study revealed an increasing trend of polypharmacy among schizophrenia patients admitted in a tertiary care hospital. The present study demonstrate the rate of antipsychotic polypharmacy is relatively low in India

Background First-generation antipsychotics (FGAs) are associated with a range of adverse events which can significantly reduce patients’ quality of life and contribute to non-adherence. The aim of this study was to assess the prevalence and management practice of first generation antipsychotics induced side effects among schizophrenic patients. Methods The study was conducted at Amanuel Mental Specialized Hospital from March to June, 2017. Data from patients were collected using a pretested structured questionnaire. Demographics and side effects of antipsychotics were collected by face to face interview. Clinical characteristics, medications and previous history of adverse drug events were extracted from medical records using data abstraction format. The data were analyzed using statistical software for social sciences (SPSS) version 20. Descriptive statistics and chi-square tests were done. Statistical significance was considered at p  < 0.05. Results Out of 356 participants, 300 of them had complete data and were included in the study. The mean age of participants was 33.71 ± 10.2 years. The majority, 195(65.0%), of participants were males. Most of the participants, 293(97.7%), developed FGA medication induced side effects. One hundred sixty three (54.3%) participants were treated with Trihexyphenidyl for FGAs induced side effects. Dose reduction of antipsychotics was done for 51(17.0%) participants. Most of the participants’ side effects were not managed according to American Psychiatric Association guideline; 178 (82.4%). The most common types of FGAs induced side effects were cardiovascular side effects 169(56.3%); sedation and CNS side effects 149(49.6%); and extrapyramidal side effects 114(38.0%). There is a significant association between occurrence of side effects of FGAs and duration of illness ( P  = 0.04). Conclusions The prevalence of first generation antipsychotics induced side effects was high. However, management practice of the side effects was minimal.

Fluphenazine decanoate licenced as a long-acting injectable (LAI) first-generation antipsychotic (FGA) was withdrawn from sale in 2018. This study evaluates if its withdrawal resulted in increased relapse rates of psychosis in an Irish patient cohort and examines which prescribed alternative antipsychotic medications were associated with more optimal outcomes. Fifteen participants diagnosed with a psychotic disorder were included. A mirror-image study over 24-months' pre-and post-withdrawal of fluphenazine was conducted. Kaplan-Meier survival and proportional hazards analyses were conducted. The impact of alternate antipsychotic agents (LAI flupenthixol compared to other antipsychotic medications) was evaluated. Semi-structured interviews with participants examined subjective opinions regarding the change in their treatment. Seven participants (46.7%) relapsed in the 24-month period subsequent to fluphenazine discontinuation compared to one individual (6.7%) in the previous identical time-period ( = 0.035). Flupenthixol treatment was associated with reduced relapse rates compared to other antipsychotics ( = 5.402, = 0.02). Thematic analysis revealed that participants believed that the discontinuation of fluphenazine deleteriously impacted the stability of their mental disorder. The withdrawal of fluphenazine was associated with increased relapse rate in individuals previously demonstrating stability of their psychotic disorder. While acknowledging the limitation of small sample size, preliminary evidence from this study suggests that treatment with the first-generation antipsychotic (FGA) flupenthixol was associated with a lower risk of relapse compared to SGAs. Reasons for this lower risk of relapse are not fully clear but could be related to dopamine hypersensitivity with this treatment change.

ADRs to antipsychotics are amongst the major challenges in the treatment of patients with psychotic disorders. The extent of patient-reported ADRs assessed in many studies using standardized scales is found to be inconsistent. However, there is a paucity of such research in Eritrea. The aim of the study is therefore to determine the magnitude, nature, and the possible risk factors associated with ADRs of the first generation antipsychotics in outpatients with schizophrenia at Saint Mary Neuro-Psychiatric National Referral Hospital in Asmara, Eritrea, using the LUNSERS self-rating scale. A cross-sectional, descriptive and analytical study design utilizing a quantitative approach was employed. Data were collected from patients' self-administered questionnaires, interviews, and medical records. The collected variables were analyzed using SPSS 22.0 with descriptive statistics, correlation, t-tests, ANOVA, and multiple regression. Statistical significance was tested at -value<0.05. In this study, 93.8% of the research participants experienced at least one ADR. LUNSERS total mean score of the relevant items was 28.01 (SD=18.46) with 24.7% of the study participants scoring medium-to-high. The prevalence of the categories of ADRs was psychic (91.3%), autonomic (78.1%), extra-pyramidal (76.9%), miscellaneous (66.5%), hormonal (58.3%), anti-cholinergic (44.2%), and allergic reactions (44.2%). At multivariate level, factors significantly and positively associated with total ADR score were smoking ( =0.028) and being at secondary educational level ( =0.015). There was high prevalence of ADRs with moderate-to-high overall ADR scores in a significant number of patients. The most frequently reported ADRs were psychic, autonomic, extra-pyramidal, hormonal, and miscellaneous. Smoking and secondary level of education were found to be the main determinants of ADRs.