Use Of First-generation Antipsychotics Research Articles

Reduction of benztropine use duration in acute psychiatry: A quality improvement initiative.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Secondary to the risk of antipsychotic-induced acute dystonia, prophylactic use of benztropine is occasionally warranted but is recommended for no longer than 7 days after initiating an antipsychotic, correlating to the period of highest dystonia risk. Despite the associated increased anticholinergic burden, many clinicians continue to order benztropine for periods exceeding the recommended prophylactic duration. We investigated the reduction of benztropine use duration subsequent to implementation of truncated electronic entry orders to improve benztropine prescribing within an acute psychiatric facility. Data were collected for psychiatric inpatients admitted between January and June 2020 who were prescribed scheduled benztropine. In a quality improvement initiative implemented in April 2022, electronic orders for benztropine were modified from a 180-day to a 7-day duration, with subsequent postintervention data collection. The primary outcomes included a change in the duration of benztropine use for any indication in the hospital, and a change in the percentage of patients meeting predetermined "unnecessary use" criteria. Secondary analyses included the percentage of patients with discharge prescriptions for scheduled benztropine (either for prophylaxis or for other indications) in the pre- and postintervention periods. 73 pre- and 77 postintervention individual patients/encounters were included. Following the intervention, in-hospital duration of benztropine use for any indication decreased from a median of 14 days to a median of 7.5 days (P < 0.05), and appropriate use increased by 92.9%. The percentage of patients with prescriptions for scheduled benztropine decreased from 67.1% in the preintervention group to 29.9% in the postintervention group. Decreased benztropine use duration, by means of truncated order entry sentences, during inpatient psychiatric admissions, appears feasible regardless of dual antipsychotic or first-generation antipsychotic use, and may reduce the rates of benztropine prescriptions written for discharge.

Sex-specific differences in the clinical profile among psychiatric patients with pulmonary Embolism: a hospital-based retrospective study

BackgroundPulmonary embolism (PE) is a severe and life-threatening complication of venous thromboembolism. However, there is a lack of systematic studies on differences between female and male PE patients. This paper aimed to compare the sex-specific differences in clinical characteristics and laboratory indicators in psychotic patients with PE.MethodsThis retrospective study enrolled psychiatric patients with PE from June 2018 to June 2022 at Shenzhen Kangning Hospital (Shenzhen Mental Health Center). Demographic characteristics, factors associated with PE, and laboratory indices were collected to assess sex-specific differences.ResultsOf the 168 patients, 87 (51.8%) were female and 81 (48.2%) were male, with a mean age of 58 years for females and 46 years for male patients. The male group had higher ratio of hyperprolactinemia, more patients using antipsychotic medications, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation than the female group (p < 0.05). Female patients were significantly older, exhibited a higher prevalence of diabetes, and had a greater number of patients taking antidepressants and hypnotics/sedatives than male patients (p < 0.05). Schizophrenia spectrum disorders were more prevalent in male patients, while female patients had a higher incidence of mood disorders (p < 0.05). Among patients aged < 45 years, the male group had higher D-dimer levels at PE onset and greater D-dimer difference (p < 0.05). Among all 112 patients aged ≥ 45 years, male patients were more likely than female patients to have respiratory tract infections, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation (p < 0.05). The multiple linear regression analysis indicated that hyperprolactinemia and the use of first-generation antipsychotics (FGAs) were associated with D-dimer levels at PE onset in male patients, while the time of PE onset and protective restraints were associated with D-dimer levels at PE onset in female patients (p < 0.05).ConclusionPE-associated clinical features differ between male and female patients. These differences may imply that the processes and mechanisms of PE onset are sex specific. Male patients are more likely to have respiratory tract infections and higher D-dimer levels at PE onset than female patients. The use of FGAs may be associated with increased D-dimer in male psychiatric patients, while protective restraints may be associated with increased D-dimer in female psychiatric patients.

Antipsychotic agents in anxiety disorders: An umbrella review.

Although not approved for the treatment of anxiety disorders (except trifluoperazine) there is ongoing off-label, unapproved use of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) for anxiety disorders. There have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of which focused on SGAs. The specific aims of this umbrella review are to: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to traditional antidepressant treatments and other nonantipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects. The review protocol is registered on PROSPERO (CRD42021237436). An initial search was undertaken to identify systematic reviews and meta-analyses from inception until 2020, with an updated search completed August 2021 and January 2023. The searches were conducted in PubMed, MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), and the Cochrane Library through hand searches of references of included articles. Review quality was measured using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) scale. The original and updated searches yielded 1796 and 3744 articles respectively, of which 45 were eligible. After final review, 25 systematic reviews and meta-analyses were included in the analysis. Most of the systematic reviews and meta-analyses were deemed low-quality through AMSTAR-2 with only one review being deemed high-quality. In evaluating the monotherapies with antipsychotics compared with first-line treatments for anxiety disorder there was insufficient evidence due to flawed study designs (such as problems with randomization) and small sample sizes within studies. There was limited evidence suggesting efficacy of antipsychotic agents in anxiety disorders other than quetiapine in generalized anxiety disorder (GAD). This umbrella review indicates a lack of high-quality studies of antipsychotics in anxiety disorders outside of the use of quetiapine in GAD. Although potentially effective for anxiety disorders, FGAs and SGAs may have risks and side effects that outweigh their efficacy, although there were limited data. Further long-term and larger-scale studies of antipsychotics in anxiety disorders are needed.

Use of First-Generation Antipsychotics in an Adolescent Male with Catatonic Schizophrenia.

Use of First-Generation Antipsychotics in an Adolescent Male with Catatonic Schizophrenia.

EVALUATION OF THE QUALITY OF LIFE OF SCHIZOPHRENIC PATIENTS TREATED WITH FIRST AND SECOND GENERATION ANTIPSYCHOTICS

Introduction- The quality of life of patients with schizophrenia has been extensively studied, however the benefit of using second-generation antipsychotics (SGA) on the subjective quality of life of patients needs to be clarified. Objective- To compare the quality of life in patients with schizophrenia treated with first generation antipsychotics (FGA) to those treated with SGA. Method - This is a cross-sectional study that included patients with schizophrenia according to the criteria of Diagnostic and Statistical Manual of Mental Disorders (DSM-5), treated with FGA or SGA, stabilized under the same treatment for at least 2 months, and having no psychiatric or somatic comorbidity. The evaluation of the clinical profile of the patients was performed by PANSS (Positive And Negative Syndrome Scale). The quality of life assessment was made using the Medical Outcomes Study 36-item Short Form (MOS-SF36). Results - from a total of 67 patients, 37 were under FGA and 30 under SGA. The two groups are clinically comparable based on the PANSS scale. No significant differences were found in overall scores in terms of physical and mental health, and in their sub-scales scores, between both groups. Conclusion - In our study, we found no significant difference in subjective quality of life in patients with schizophrenia based on the use of FGA and SGA. This study, as well as the contradictory results encountered in the literature, prove that the concept of quality of life is complex, and cannot be reduced to the biologic dimension alone.

Comparative Effects of 30 Antipsychotics on Risk of Catatonia

Objective: Catatonia is a life-threatening psychomotor syndrome that occurs in approximately 10% of patients with acute psychiatric illnesses. Although some case reports have argued that first generation antipsychotics (FGAs) are more likely to induce catatonia than second generation antipsychotics (SGAs), no large observational study has confirmed this hypothesis. We investigated whether FGAs were associated with an increased risk of reporting catatonia when compared with SGAs. Methods: A pharmacovigilance study was performed within VigiBase to compare the cases of catatonia syndromes reported in patients exposed to FGAs with those reported in patients exposed to SGAs. This approach is similar in concept to case-control study, but adapted to a pharmacovigilance database, and allows the estimation of reporting odds ratios (RORs) with 95% confidence intervals. Results: We identified 60,443 adverse effects reported in patients who received FGAs and 253,067 adverse effects reported in patients treated with SGAs. Compared with SGAs, the use of FGAs was associated with an increased risk of reporting catatonia syndromes (ROR = 2.2; 95% CI, 2.0–2.3). Consistent results were observed when the analysis was restricted to reports generated from physicians, reports from the US, and reports with the highest completeness score. The highest RORs were found for molindone (6.0; 95% CI, 3.1–10.4) and haloperidol (3.8; 95% CI, 3.5–4.0). Conclusions: In this large pharmacovigilance study of patients exposed to antipsychotics, the use of FGAs was associated with an increased risk of reporting catatonia syndromes compared to the use of SGAs. This increased risk is consistent with the pharmacodynamic hypothesis of antipsychotic-induced catatonia. Our results warrant replication in population-based studies.

Prescription of Anticholinergic Drugs in Patients With Schizophrenia: Analysis of Antipsychotic Prescription Patterns and Hospital Characteristics.

In several clinical guidelines for schizophrenia, long-term use of anticholinergic drugs is not recommended. We investigated the characteristics of the use of anticholinergics in patients with schizophrenia by considering psychotropic prescription patterns and differences among hospitals. A cross-sectional, retrospective prescription survey at the time of discharge was conducted on 2027 patients with schizophrenia from 69 Japanese hospitals. We examined the relations among psychotropic drug prescriptions regarding anticholinergic prescription. We divided the hospitals into three groups—low rate group (LG), medium rate group (MG), and high rate group (HG)—according to their anticholinergic prescription rates, and analyzed the relationship between anticholinergic prescription rates and antipsychotic prescription. Anticholinergic drugs were prescribed to 618 patients (30.5%), and the prescription rates were significantly higher for high antipsychotic doses, antipsychotic polypharmacy, and first-generation antipsychotics (FGAs) use. The anticholinergic prescription rate varied considerably among hospitals, ranging from 0 to 66.7%, and it was significantly higher in patients with antipsychotic monotherapy, antipsychotic polypharmacy, and normal and high doses of antipsychotics in HG than in those LG and MG. The anticholinergics prescription rate in patients with second-generation antipsychotic monotherapy in HG was also significantly higher than in those LG and MG; however, the difference was no longer significant in patients with FGA monotherapy. Conclusively, in addition to high antipsychotic doses, antipsychotic polypharmacy, and FGA use, hospital characteristics influence the prescribing of anticholinergic drugs.

Antipsychotic prescription patterns and associated factors among the elderly with psychiatric illnesses.

Prescribing rate of antipsychotics in elderly patients with psychiatric illnesses has been increasing all over the world. However, there is a lack of research examining the use of antipsychotics at psychiatric hospitals. We aim to find out long-term trends in antipsychotic prescriptions and factors associated with the use of antipsychotics in the elderly population. All outpatient visits with patients aged over 65 years between 2006 and 2015 in a psychiatric hospital were included in the analysis. Demographic and clinical data, including patient age, sex, National Health Insurance status, psychiatric diagnosis and antipsychotic prescription, were retrieved through the electronic medical information system. In this study, we found that prescribing rate of antipsychotics has increased around 5.07% through the study period (from 57.25% in 2006 to 60.15% in 2015, P < 0.001). Among all antipsychotics, there was an increase in the use of second-generation antipsychotics with a simultaneous decline in the use of first-generation antipsychotics. Logistic regression analysis showed advanced age, female gender and certification for catastrophic illnesses were positively associated with the use of antipsychotics. Furthermore, patients most likely to be prescribed an antipsychotic were those with psychotic disorders, followed by dementia, and then affective or neurotic disorders. The results of this study were consistent with the worldwide trend of increasing prescriptions of second-generation antipsychotics among elderly patients with psychiatric illnesses. Despite the potential benefits of these medications on certain psychiatric symptoms, clinicians need to exercise due caution as they may also cause potentially serious side effects among the elderly population.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

First-generation antipsychotics use and reduced risk of pneumonia—Clinical implications in SARS-CoV2 treatment: A systematic review and meta-analysis of observational studies

Penfluridol Induced Extrapyramidal symptoms (EPS): A Case ReportSereen Rose Thomson, Balaji Ommurugan, Shalini Adiga, Navin Patil, Saurish Reddy

Healthcare resource use and costs for people with type 2 diabetes mellitus with and without severe mental illness in England: longitudinal matched-cohort study using the Clinical Practice Research Datalink.

Approximately 60 000 people in England have coexisting type 2 diabetes mellitus (T2DM) and severe mental illness (SMI). They are more likely to have poorer health outcomes and require more complex care pathways compared with those with T2DM alone. Despite increasing prevalence, little is known about the healthcare resource use and costs for people with both conditions. To assess the impact of SMI on healthcare resource use and service costs for adults with T2DM, and explore the predictors of healthcare costs and lifetime costs for people with both conditions. This was a matched-cohort study using data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics for 1620 people with comorbid SMI and T2DM and 4763 people with T2DM alone. Generalised linear models and the Bang and Tsiatis method were used to explore cost predictors and mean lifetime costs respectively. There were higher average annual costs for people with T2DM and SMI (£1930 higher) than people with T2DM alone, driven primarily by mental health and non-mental health-related hospital admissions. Key predictors of higher total costs were older age, comorbid hypertension, use of antidepressants, use of first-generation antipsychotics, and increased duration of living with both conditions. Expected lifetime costs were approximately £35 000 per person with both SMI and T2DM. Extrapolating nationally, this would generate total annual costs to the National Health Service of around £250 m per year. Our estimates of resource use and costs for people with both T2DM and SMI will aid policymakers and commissioners in service planning and resource allocation.

The 12-year trend report of antipsychotic usage in a nationwide claims database derived from four million people in Japan

The current study aimed to describe the use of antipsychotics to clarify the gap between clinical guidelines and health care practice in Japan. We used data from the JMDC Claims Database (JMDC Inc., Tokyo, Japan), a nationwide claims database, from 2005 to 2016. Antipsychotics were defined as drugs coded as N05A with the Anatomical Therapeutic and Chemical (ATC) codes. We described the annual changes in proportions based on the number of patients prescribed any antipsychotics. From the database of 4,081,102 people, the data of 12,382 patients was extracted by applying the following exclusion criteria: no use of antipsychotics, missing the prescription date or dose, inpatients, prescribed antipsychotics only for use as needed, prescribed only injectable antipsychotics except for long-acting injections (LAIs), without schizophrenia as the primary disease, not exceeding 75 mg/day chlorpromazine equivalent, and less than 18 years old. The use of second-generation antipsychotics (SGA) has been expanding, while the use of first-generation antipsychotics has been decreasing. Aripiprazole accounted for the highest proportion of prescribed antipsychotics (31.9%) in 2016. Even though clozapine is categorized as a SGA, it accounted for a paltry 0.2%. The proportion of prescribed antipsychotics accounted for by LAIs was less than 5%. Although the use of antipsychotics for schizophrenia in Japan mostly corresponds to various clinical guidelines, limited use of clozapine and LAIs was identified. Further research focusing on the factors affecting the prescription of these underused antipsychotics may help advance the pharmacological therapy of schizophrenia.

Frequency and Correlates of Acute Dystonic Reactions After Antipsychotic Initiation in 441 Children and Adolescents.

Objective: To determine the incidence of acute dystonic reactions (ADRs) and risk factors for ADRs in children and adolescents treated with antipsychotics. Methods: This was a retrospective chart review-based cohort study of consecutive patients who attended a university hospital's child and adolescent psychiatry department between 2015 and 2017 and who were treated with antipsychotics and had at least two follow-up visits. Results: Thirty of 441 patients (6.8%) 4-19 years of age who were treated with antipsychotics for conduct disorders (21.5%), attention-deficit/hyperactivity disorder (13.2%) and, irritability and aggression that accompanied intellectual disability (12.9%) and followed for 99.5 ± 223.3 (median: 34) days developed ADRs. ADRs developed in 11/391 patients (2.8%) treated with one antipsychotic and 19/50 patients (38.0%) treated with two antipsychotics (p < 0.001). In patients treated with one antipsychotic that developed ADRs, the time to ADRs was 4.0 ± 4.0 days after antipsychotic initiation and 2.7 ± 2.4 days after an increase in the antipsychotic dose. The time to ADRs in those treated with two antipsychotics was 3.0 ± 2.3 days after the addition of the second antipsychotic and 1.6 ± 0.8 days after a dose increase in the second antipsychotic. The incidence of ADRs during antipsychotic monotherapy was 10.5% with first-generation antipsychotics (FGAs) and 2.2% with second-generation antipsychotics (SGAs; p = 0.037). The antipsychotic was changed due to ADRs in 12/30 (40.0%) of ADR cases. Independent factors associated with ADRs were antipsychotic polypharmacy (p < 0.0001), inpatient treatment (p = 0.013), FGA use (p = 0.015), and diagnoses of schizophrenia (p = 0.039) or bipolar disorder (p < 0.0001). Conclusion: SGAs and low-potency FGA monotherapy in children and adolescents were associated with a relatively low ADR risk, whereas high- and mid-potency FGAs were associated with a high risk. Independent predictors of ADRs were antipsychotic polypharmacy, inpatient treatment, FGAs, and schizophrenia or bipolar disorder diagnoses, which may be related to more aggressive antipsychotic dosing.

Antipsychotic use in Northern Italian inter-episode bipolar disorder patients: considering both second- and first-generation agents.

Evidence supports increasing antipsychotic use in bipolar disorder, especially second-generation antipsychotics. However, data regarding first-generation antipsychotic contemporary use are limited. We studied 380 Northern Italian bipolar disorder inter-episode patients, grouped according to current antipsychotic use, stratified by bipolar subtype (BDI vs. BDII). Furthermore, we compared first-generation antipsychotic users vs. non-users. In our sample (n = 357), 81.8% were taking antipsychotics (74% second-generation antipsychotics, 24.1% first-generation antipsychotics), with antipsychotic use in BDI significantly more prevalent than in BDII (85.2% vs. 72.0%). Overall, antipsychotic users vs. non-users had higher rates of hypo/manic last episode, lifetime psychiatric hospitalization, psychosis, and current psychotropic use, but lower rates of anxiety disorder main comorbidity and current antidepressant use. First-generation antipsychotic use rates (30.3% in BDI vs. 6.5% in BDII) were associated with more frequently being unpartnered, having elevated first/last episodes, higher lifetime hospitalization, involuntary commitment, psychosis, and psychosocial rehabilitation rates, and more current psychotropic use, but lower Global Assessment Functioning scores and less current antidepressant use. Bipolar disorder patients had robust antipsychotic (second-generation antipsychotic > first-generation antipsychotic) use, consistently with previous reports. FGAs were still prescribed for a substantial group of patients, likely suffering from severe bipolar disorder. Prescriptions need to be monitored to assess their appropriateness and adherence to evidence-based recommendations.

Periodontal disease and effects of antipsychotic medications in patients newly diagnosed with schizophrenia: a population-based retrospective cohort.

Compared with the general population, individuals with schizophrenia have a higher risk of periodontal disease, which can potentially reduce their life expectancy. However, evidence for the early development of periodontal disease in schizophrenia is scant. The current study investigated risk factors for periodontal disease in patients newly diagnosed with schizophrenia. We identified a population-based cohort of patients in Taiwan with newly diagnosed schizophrenia who developed periodontal disease within 1 year of their schizophrenia diagnosis. Treatment with antipsychotics and other medications was categorised according to medication type and duration, and the association between medication use and the treated periodontal disease was assessed through logistic regression. Among 3610 patients with newly diagnosed schizophrenia, 2373 (65.7%) had an incidence of treated periodontal disease during the 1-year follow-up. Female sex (adjusted odds ratios [OR] 1.40; 95% confidence interval [CI] 1.20-1.63); young age (adjusted OR 0.99; 95% CI 0.98-0.99); a 2-year history of periodontal disease (adjusted OR 2.45; 95% CI 1.84-3.26); high income level (adjusted OR 2.24; 95% CI 1.64-3.06) and exposure to first-generation (adjusted OR 1.89; 95% CI 1.54-2.32) and secondary-generation (adjusted OR 1.33; 95% CI 1.11-1.58) antipsychotics, anticholinergics (adjusted OR 1.24; 95% CI 1.03-1.50) and antihypertensives (adjusted OR 1.91; 95% CI 1.64-2.23) were independent risk factors for periodontal disease. Hyposalivation - an adverse effect of first-generation antipsychotics (FGAs) (adjusted OR 2.00; 95% CI 1.63-2.45), anticholinergics (adjusted OR 1.27; 95% CI 1.05-1.53) and antihypertensives (adjusted OR 1.90; 95% CI 1.63-2.22) - was associated with increased risk of periodontal disease. Therefore, hypersalivation due to FGA use (adjusted OR 0.72; 95% CI 0.59-0.88) was considered a protective factor. The current study highlights that early prevention of periodontal disease in individuals with schizophrenia is crucial. Along with paying more attention to the development of periodontal disease, assessing oral health regularly, helping with oral hygiene, and lowering consumption of sugary drinks and tobacco, emphasis should also be given by physicians to reduce the prescription of antipsychotics to the extent possible under efficacious pharmacotherapy for schizophrenia.

Medication-Induced Akathisia with Newly Approved Antipsychotics in Patients with a Severe Mental Illness: A Systematic Review and Meta-Analysis.

Akathisia is a common and distressing movement disorder that can be associated with the use of antipsychotics. It is characterized by a subjective (inner restlessness) and an objective (excessive movements) component. Akathisia can have a negative impact on clinical outcome and even lead to treatment discontinuation. Although medication-induced akathisia is more commonly associated with the use of first-generation antipsychotics (FGAs), it also occurs with second-generation antipsychotics (SGAs), including the newly approved antipsychotics (NAPs) asenapine, lurasidone, iloperidone, cariprazine, and brexpiprazole. Until now, no meta-analysis has been published on the risk of akathisia for all NAPs, as monotherapy or adjunctive treatment, in patients with a severe mental illness. The primary objectives of this systematic review and meta-analysis were to (i) compare akathisia incidence rates of the NAPs, as monotherapy or adjunctive treatment, in adult patients with a severe mental illness (i.e., schizophrenia, bipolar disorder, or major depressive disorder), using data from published and unpublished randomized controlled trials; and (ii) examine the role of several study characteristics explaining differences in akathisia incidence rates between studies. A systematic literature search, using the PubMed, EMBASE, and Cochrane Library databases (until October 2018), was conducted for English-language placebo- as well as active-controlled clinical trials, including subjective (percentage of patients reporting akathisia) and/or scale-defined medication-induced akathisia incidence rates with NAPs (as monotherapy or as adjunctive treatment) in adult patients with schizophrenia, bipolar disorder, or major depressive disorder. Additional unpublished clinical trials were identified through the ClinicalTrials.gov electronic database. Two meta-analyses (incidence rates and odds ratio [OR] [placebo vs. active] of medication-induced akathisia with NAPs) were performed to obtain an optimal estimation of akathisia risks of adult patients with a severe mental illness under these treatment conditions and to assess the role of study characteristics. Two hundred and thirteen reports were selected as potentially eligible for our meta-analysis. Of these, 48 met the inclusion criteria. Eight records, identified through the ClinicalTrials.gov database and cross-referencing, and which fulfilled the inclusion criteria, were added, resulting in a total of 56 records (iloperidone = 5, asenapine = 11, lurasidone = 15, brexpiprazole = 13, cariprazine = 12). The estimated weighted mean incidence rate of akathisia was 7.7% (95% confidence interval [CI] 6.5-9.1), with estimates being 3.9% (95% CI 2.4-6.3) for iloperidone, 6.8% (95% CI 5.1-9.0) for asenapine, 10.0% (95% CI 7.4-13.5) for brexpiprazole, 12.7% (95% CI 10.1-16.1) for lurasidone, and 17.2% (95% CI 13.4-22.1) for cariprazine. After Tukey-adjustment for multiple testing, the incidence rate of akathisia was significantly (p < 0.05) lower for iloperidone than for brexpiprazole, lurasidone, and cariprazine. In addition, the incidence rate of akathisia was significantly (p < 0.05) lower for asenapine than for lurasidone and cariprazine. Finally, the incidence rate of akathisia was significantly (p < 0.05) lower for brexpiprazole than for cariprazine. Type of medication (p < 0.0001), diagnosis (p = 0.02), and race (p = 0.0003) significantly explained part of the heterogeneity of the incidence estimates of akathisia between studies. The estimated weighted OR of akathisia under medication, compared with placebo, was 2.43 (95% CI 1.91-3.10). The OR was smallest for iloperidone (OR 1.20; 95% CI 0.42-3.45) and increased for brexpiprazole (OR 2.04; 95% CI 1.09-3.83), asenapine (OR 2.37; 95% CI 1.32-4.27), lurasidone (OR 3.74; 95% CI 2.32-6.02), and cariprazine (OR 4.35; 95% CI 2.80-6.75). Only type of medication (p = 0.03) explained systematic differences in the OR for akathisia between placebo versus active treatment across studies. After Tukey-adjustment for multiple testing, no significant differences between these ORs were found. The severity of akathisia with NAPs generally is mild to moderate, only leading to treatment discontinuation in a minority of cases (< 5%). The use of a NAP raises the akathisia risk more than two-fold when compared with patients receiving placebo. Although distinctions between the different NAPs were not clear in placebo-controlled trials, the results of our meta-analyses and systematic review generally indicate that these differences more than likely reflect real differences, with iloperidone showing the most and cariprazine showing the least benign akathisia profile. Moreover, due to patient characteristics and methodological issues, incidence rates of akathisia with NAPs found in this meta-analysis may even be an underestimation of true incidence rates.

Increased risk of chronic liver disease in patients with major depressive disorder: A population-based study

ObjectiveThis study investigated the prevalence and incidence of chronic liver disease in patients with major depressive disorder (MDD), and aimed to identify associated factors. MethodsData of 766,427 adult subjects aged ≥18 years were randomly selected from the National Health Research Institute database from the year 2005. The study first searched for subjects with at least one primary diagnosis of MDD in 2005, and then for those with a primary or secondary diagnosis of chronic liver disease were also identified. The differences in the prevalence of chronic liver disease and its associated factors between patients with MDD and the general population in 2005 were then analyzed. We also compared the incidence of chronic liver disease in patients with MDD and in the general population from 2006 to 2010. ResultsThe prevalence of chronic liver disease in patients with MDD was 2.27 times as high as that of the general population in 2005 (12.4% vs. 5.8%; odds ratio (OR) = 2.27; 95% confidence interval (CI) = 2.07–2.48). The average annual incidence of chronic liver disease in patients with MDD during 2006–2010 was also higher than that of the general population (2.6% vs. 1.7%; risk ratio (RR) = 1.52; 95% CI = 1.37–1.7). ConclusionsPatients with MDD had a significantly higher prevalence and incidence of chronic liver disease than the general population. Among patients with MDD, an older age, the male sex, diabetes, hyperlipidemia and first-generation antipsychotic use were factors associated with chronic liver disease.

Tardive Dyskinesia and Akathasia: A Dopamine System Theory Clinical Review

Long term use of first generation anti-psychotics (FGAs) have been theorized in the formation of motion disorders Tardive Dyskinesia and Akathasia and due to the breakdown in the extra pyramidal system (EPS) located in the Basal Ganglia [1]. The second generation anti-psychotics (SGAs) were sourced to be the “treatment” of TD by blocking dopamine receptors with dopamine agonists of the D2-D5 receptors while also being seen as the genesis of AK. However, the blocking of the receptors in both motion disorders is a theory known as the dopamine blockage theory, despite the intermingle of other neurotransmitters such as Serotonin and Norepinephrine [2]

Attitudes to antipsychotics: a multi-site survey of Canadian psychiatry residents

PurposeThe purpose of this paper is to identify the training needs of the next generation of psychiatrists, and barriers in prescribing first-generation antipsychotics (FGAs), long-acting injectable (LAIs) antipsychotics and clozapine.Design/methodology/approachAn electronic survey was sent to psychiatry residents (N= 75/288, 26 percent) at four Canadian residency programs in late December 2017. The survey was based on an instrument originally developed at the University of Cambridge and consisted of 31 questions in 10 content domains.FindingsNearly 80 percent of residents were aware that FGAs and second-generation antipsychotics (SGAs) have similar efficacy. However, extra-pyramidal symptoms and lack of training experience were the leading concerns associated with the prescribing of FGAs. Although over 90 percent of residents felt confident about initiating an oral SGA as a regular medication, only 40 percent did so with FGAs. Confidence with initiating LAIs and clozapine was 60 and 61 percent, respectively.Practical implicationsThe survey highlights the need for better training in the use of FGAs, clozapine and LAIs. These medications can be effectively used in providing patients with the most appropriate evidence-based treatment options to improve treatment outcomes, while ensuring that these resources are not lost to the future generations of psychiatrists.Originality/valueThe survey may be the first of its kind to assess antipsychotic prescribing attitudes in Canadian psychiatry residents in multiple sites.

Tobacco smoking is associated with antipsychotic medication, physical aggressiveness, and alcohol use disorder in schizophrenia: results from the FACE-SZ national cohort.

Tobacco smoking is common in schizophrenia and is one of the main causes of premature mortality in this disorder. Little is known about clinical correlates and treatments associated with tobacco smoking in patients with schizophrenia. Still, a better characterization of these patients is necessary, in a personalized care approach. Aggressiveness and childhood trauma have been associated with tobacco smoking in general population, but this association has never been explored in schizophrenia. Our study examines the clinical and therapeutic characteristics of tobacco smoking in schizophrenia. 474 stabilized patients (mean age = 32.2; 75.7% male gender; smokers n = 207, 54.6%) were consecutively included in the network of the FondaMental Expert centers for Schizophrenia and assessed with valid scales. Current tobacco status was self-declared. Aggressiveness was self-reported with Buss-Perry Aggressiveness Questionnaire and Childhood Trauma with Childhood Trauma Questionnaire. Ongoing treatment was reported. In univariate analysis, tobacco smoking was associated with lower education level (p < 0.01), positive syndrome (p < 0.01), higher physical aggressiveness (p < 0.001), alcohol dependence (p < 0.001), and First Generation Antipsychotics (FGAs) use (p = 0.018). In a multivariate model, tobacco smoking remained associated with physical aggressiveness (p < 0.05), current alcohol dependence (p < 0.01) and FGA use (p < 0.05). No association was observed with childhood trauma history, mood disorder, suicidal behavior, psychotic symptom, global functioning or medication adherence. Patients with tobacco use present clinical and therapeutic specificities, questioning the neurobiological links between tobacco and schizophrenia. They could represent a specific phenotype, with specific clinical and therapeutic specificities that may involve interactions between cholinergic-nicotinic system and dopaminergic system. Further longitudinal studies are needed to confirm the potential efficacy of second generation antipsychotics (SGAs) on tobacco use in schizophrenia and to develop effective strategies for tobacco cessation in this population.