Second-generation Antipsychotics In Patients Research Articles

Multiple Adverse Reactions Associated With the Use of Second-Generation Antipsychotics in People With Alzheimer's Disease: A Pharmacovigilance Analysis Based on the FDA Adverse Event Reporting System.

Alzheimer's disease (AD) is a neurodegenerative condition leading to memory loss, cognitive impairment, and neuropsychiatric symptoms. Second-generation antipsychotics (SGAs) are commonly used to manage these neuropsychiatric symptoms, but their safety profile in patients with AD requires further investigation. The objective was to evaluate the safety of SGAs in patients with AD by analyzing adverse drug reactions (ADRs) using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. This study conducted a comprehensive analysis of FAERS data from 2014 to 2023, focusing on ADRs in patients with AD treated with SGAs such as risperidone, quetiapine, olanzapine, clozapine, and aripiprazole. Descriptive, disproportionality, time, and dose analysis were performed using the Bayesian confidence propagation neural network, Weibull, and physiologically based pharmacokinetic model. Out of 1289 patients with AD treated with SGAs, the most common ADRs involved the nervous system, gastrointestinal system, and cardiac disorders. Disproportionality analysis identified significant positive signals in cardiac, renal, and vascular systems. Quetiapine, risperidone, and olanzapine showed more positive signals compared with clozapine and aripiprazole. Time analysis indicated that cardiovascular ADRs occurred randomly, whereas renal ADRs increased with prolonged use. Dose analysis suggested that small doses of SGAs did not elevate the risk of multiple cardiac, renal, or vascular ADRs. The study underscores the importance of monitoring for ADRs, particularly in the cardiac and renal systems, when using SGAs in patients with AD. Future research incorporating more comprehensive clinical data is warranted to support safe and rational drug utilization.

EPH116 Factors Influencing the Use of Second-Generation Antipsychotics in Patients With Autism Spectrum Disorders

EPH116 Factors Influencing the Use of Second-Generation Antipsychotics in Patients With Autism Spectrum Disorders

Analysis of the Serie of Cases of Neuroleptic Malignant Syndrome (Cross-Sectional Observational Study)

Background: neuroleptic malignant syndrome (NMS) is the most dangerous complication of therapy with neuroleptics with high mortality. The publications on MNS are the reviews articles or case reports.The aim of study: an identification of the frequency of occurrence of NMS harm in patients of the city psychiatric hospital over a 4-year period, a clarification of the clinical manifestations of this complication, an analysis of the effectiveness of the treatment and rate of deaths.Patients and methods: 19 cases with a confirmed diagnosis of NMS who were treated for 4 years in one of the clinical psychiatric hospitals in Moscow with 1158 beds. All patients met the criteria for the diagnosis of NMS according to DSM-5 (333.92). The severity of extrapyramidal disorders was assessed on the Simpson–Angus Rating Scale (SAS). The Bush–Francis Catatonia Rating Scale (BFCRS) was used to assess the features and severity of catatonic symptoms. All patients underwent a study of the general clinical analysis and biochemical analysis of blood with the determination of the number of leukocytes and the activity of the enzyme creatine phosphokinase (CPK).Results: the incidence of NMS was 0.035% of all treated patients, mortality— 10.5%. Most often, NMS develops during treatment with haloperidol and much less frequently with the appointment of atypical antipsychotics risperidone and clozapine in patients with schizophrenia, acute polymorphic mental disorder, organic mental disorders, including dementia. The influence of such factors as gender, age, type of disease on the development of NMS has not been established. The age of patients with a fatal outcome was higher than the average for the group. The clinical picture of NMS was characterized by a combination of catatonic, extrapyramidal and somato-vegetative disorders with hyperthermia, leukocytosis and increased activity of CPK.Conclusion: today NMS remains a relatively rare, but extremely dangerous complication of antipsychotic therapy, with a high risk of death and can develop both in the treatment with first and second generation antipsychotics in patients with schizophrenia and acute polymorphic mental disorder and in organic mental disorders, including dementia.

Neutrocytopenia associated with a lurasidon therapy in a patient with paranoid schizophrenia

IntroductionLurasidon is a relatively new, second-generation antypsychotic drug with an interesting receptor profile. It is considered safe and has a low risk of side effects. This drug is effecitve in reducing the productive symptoms of schizophrenia, but also has a positive effect on negative symptoms and cognitive functions. It is a medicine with a multi-receptor mechanism of action: it mainly blocks dopaminergic D2 and serotonergic 5-HT2A receptors. According to the Summary of Product Characteristics, adverse reactions such as leucopenia, neutropenia and anaemia were too rare to estimate their frequency.ObjectivesThis study describes case of neutrocytopenia and leukocytopenia that are likely to be related to lurasidone and have resolved after discontinuation of this medicinal product. The aim of the article is to highlight the risk of using second-generation antipsychotics in patients and the occurence of blood cells disorders in particular neutrocytopenia.MethodsAn analysis of the medical history records were done to describe the case report.Results39-years-old patient treated psychiatrically for 18 years, initially for mood disorders, irritability, behavioural disorders. In 2014 she was diagnosed with paranoid schizophrenia, herlast psychiatric hospitalization took place in 2021. The patient had a history of neutrocytopenia and leukocytopenia. In December 2020, the patient was admitted to the psychiatric ward on account of active aggression against her mother. She was discharged in January 2021 with the recommendation to take paliperidone intramusculary. Due to incomplete remission of psychotic symptoms, the patient received 37 mg of lurasidone since August 2021. The blood count, which was ordered upon admission to the Department of Psychiatric Rehabilitation, showed moderate neutrocytopenia. After discontinuation of lurasidone and the recommended supplementation, the results gradually improved and finally reached the normal range. Blood cells type 23.09.2021 r. 04.10.2021 r. 14.10.2021 r. 28.10.2021 r. 10.11.2021 r. 24.11.2021 r. 08.12.2021 r.Leukocytes2,45 x 10^3/μl2,73 x 10^3/μl2,39 x 10^3/μl2,66 x 10^3/μl2,79 x 10^3/μl4,09 x 10^3/μl4,03 x 10^3/μlErythrocytes4,26 x 10^3/μl4,31 x 10^3/μl4,48 x 10^3/μl4,06 x 10^3/μl4,08 x 10^3/μl4,39 x 10^3/μl4,22 x 10^3/μlbNeutrocytes1,04 x 10^3/μl1,60 x 10^3/μl1,24 x 10^3/μl1,53 x 10^3/μl1,78 x 10^3/μl2,72 x 10^3/μl2,62 x 10^3/μlLymphocytes1,05 x 10^3/μl0,70 x 10^3/μl0,72 x 10^3/μl0,73 x 10^3/μl0,64 x 10^3/μl0,83 x 10^3/μl0,92 x 10^3/μlConclusionsThis case report shows the need for regular monitoring of blood cells parameters in patients treated with second generation antipsychotics, as there is a risk of neutrocytopenia or even agranulocitosis. If there is an obvious correlation, the dose should be reduced or switched to another medicinal product if possible and blood counts should monitored further.Disclosure of InterestNone Declared

The Use of Second-Generation Antipsychotics in Patients with Severe Schizophrenia in the Real World: The Role of the Route of Administration and Dosage-A 5-Year Follow-Up.

To assess the impact of the route of administration and doses of second-generation antipsychotics (SGAs) on treatment adherence, hospital admissions, and suicidal behaviour in patients with severe schizophrenia (Clinical Global Impression-Severity-CGI-S ≥ 5), we implemented an observational 5-year follow-up study. A total of 37.5% of the patients on oral antipsychotics (Aps) and 11.5% of those on long-acting injectables (LAIs) abandoned the treatment (p < 0.001). There were no differences in treatment discontinuation between the LAI-AP standard and high-dose groups. A total of 28.1% of the patients on oral Aps had at least one hospitalisation, as well as 13.1% of patients on LAIs (p < 0.001). There were fewer hospitalisations of patients on LAIs in the high-dose group (p < 0.05). Suicide attempts were recorded for 18% of patients on oral Aps but only for 4.6% of patients on LAIs (p < 0.001). No differences were found between the dosage groups on LAIs. Tolerability was good for all Aps and somewhat better for LAIs than oral Aps in terms of side effects (p < 0.05). There were no differences between the standard and high-dose groups. More patients discontinued treatment due to side effects in the oral AP group (p < 0.01). LAI SGA treatment was more effective than oral AP in terms of adherence and treatment outcomes for managing people with severe schizophrenia. Moreover, significant improvements were found that favour high-dose LAI SGA treatment for some of these patients. This study highlights the need to consider LAI antipsychotics and high-dose strategies for patients with severe schizophrenia.

Switching Between Second-Generation Antipsychotics in Patients with Schizophrenia and Schizoaffective Disorder: 10-Year Cohort Study in Brazil.

Objective: Switching between second-generation antipsychotics (SGAs) is a common clinical practice in the treatment of schizophrenia and schizoaffective disorders due to differences in the drugs’ tolerability and safety profiles as well as the challenge of obtaining an ideal response. However, the factors associated with SGA switching remain uncertain and related real-world data are scarce. The main objective was to identify the factors associated with the switching of SGAs in patients with schizophrenia or schizoaffective disorder. Methods: We conducted a retrospective cohort study of outpatients with schizophrenia or schizoaffective disorder, who were aged ≥18 years and received a SGA (clozapine, olanzapine, risperidone, quetiapine or ziprasidone) from a Brazilian pharmaceutical assistance program for at least 3 months. We identified SGA users from 2008 to 2017 by using a national administrative database (Ambulatory Information System-SIA/SUS). The factors associated with the switches were evaluated by Cox proportional hazards regression and adjusted for sex and age; the confidence interval was set at 95% (95% CI). Results: In total, 563,765 patients were included. Female sex, advanced age of ≥70 years, residence in the Brazilian northeast region, and the type of antipsychotic used were associated with an increased risk of switching (p < 0.001). The incidence of switching ranged from 37.6/100 person-years for clozapine users to 58.2/100 person-years for risperidone users. Compared to the adjusted hazard ratio, for clozapine users, the corresponding ratios for risperidone, ziprasidone, quetiapine and olanzapine were 1.59 (95% CI, 1.57–1.61), 1.41 (95% CI, 1.39–1.44), 1.25 (95% CI, 1.23–1.26) and 1.11 (95% CI, 1.10–1.12) respectively. Conclusion: The groups most susceptible to SGA switching in real-life setting were older individuals, women, and those living in the Brazilian northeast region. Risperidone was associated with the highest risk of switching and as expected, clozapine was associated with the lowest risk of switching than that associated with the other SGAs.

Treatment Response of Add-On Esketamine Nasal Spray in Resistant Major Depression in Relation to Add-On Second-Generation Antipsychotic Treatment.

In this meta-analysis, we aimed to estimate and compare the efficacy of add-on treatment of antidepressants with esketamine nasal spray and second-generation antipsychotics in patients with nonpsychotic major depressive disorder and inadequate response to antidepressants. Searching for acute-phase, double-blind, placebo-controlled, randomized trials, we found 22 second-generation antipsychotic (n = 8363) and 3 intranasal esketamine (n = 641) studies. Mean change in the Montgomery Åsberg Depression Rating Scale total score served as outcome. We determined a higher mean difference (vs placebo) for the pooled esketamine nasal spray trials (mean difference = 4.09, 95% confidence interval: 2.01 to 6.17) than for the pooled second-generation antipsychotic augmentation trials (mean difference = 2.05, 95% confidence interval: 1.51 to 2.59). Thus, the effect size for intranasal esketamine was nearly twice as high as those for the second-generation antipsychotics. This indicates high efficacy of add-on esketamine nasal spray in treatment-resistant major depressive disorder compared with other well-established, evidence-based pharmacological options such as augmentation with second-generation antipsychotics.

Akathisia and Newer Second-Generation Antipsychotic Drugs: A Review of Current Evidence.

Akathisia continues to present a significant challenge in clinical practice. As a class, so-called atypical, or second-generation, antipsychotics (SGAs) are the mainstay of treatment for schizophrenia and are commonly used to treat mood disorders. These medications have traditionally been distinguished from first-generation antipsychotics by their lowered risk of extrapyramidal side effects (EPS) such as dystonia, dyskinesia, akathisia, and pseudoparkinsonism. However, the occurrence of EPS, particularly akathisia, has been demonstrated to some degree in all commercially available SGAs. This review examines the incidence of akathisia in nine newer SGAs in patients with schizophrenia, bipolar disorder, and major depressive disorder (MDD). We performed a search of PubMed, ClinicalTrials.gov, Cochrane Central Register, and Google Scholar, as well as manufacturer websites and product labeling for published and unpublished clinical trials, meta-analyses, and systematic reviews. Studies evaluating adult patients with schizophrenia, bipolar disorder, or MDD were eligible for inclusion. Data on treatment-emergent akathisia rates were gathered from each study, and potential dose-response relationships were explored. A total of 177 studies were included in this review, comprising 58,069 patients across 414 treatment arms. Compared with placebo with a composite 3.7% incidence of akathisia, individual SGAs produced akathisia at total composite rates ranging from 2.9-13.0% across the included studies. High doses of an SGA were generally associated with an increased risk of akathisia. Clinicians should consider the risk of akathisia when choosing a treatment option and monitor for akathisia in patients beginning therapy with an SGA or following a dose increase of the SGA.

Considerations and Current Trends in the Management of the Geriatric Patient on a Consultation-Liaison Service.

To provide consultation-liaison psychiatrists with an updated resource that can assist in the treatment and management of geriatric patients. The current available literature has not shown any differences in efficacy between haloperidol and second-generation antipsychotics in patients with delirium. When considering relative advantages of forms of antipsychotic administration, there is no support for a superior safety profile of oral compared to intramuscular or intravenous administration. A recent meta-analysis of four randomized controlled trials concluded that when melatonin was administered to older age patients on medical wards, it significantly prevented the incidence of delirium when compared with the control group. While suvorexant administered nightly to elderly patients in acute care settings may lower the incidence of delirium, larger studies are needed to confirm this finding. Despite the black box warning of increased mortality risk in older patients with dementia, antipsychotics may be used with caution by the consultation-liaison (CL) psychiatrist to treat the neuropsychologic symptoms of dementia including hallucinations and psychosis in the hospital setting. While antidepressant studies have focused primarily on citalopram and escitalopram in the treatment of agitation in the setting of dementia, these two medications have not been adequately compared directly to other SSRIs for this condition. It is therefore not clear whether citalopram and escitalopram are more efficacious in treating agitation in the setting of dementia when compared to other SSRIs. While the evidence supporting trazodone's use is limited, it is generally well tolerated and is an option as a PRN for irritability and agitation in patients with Alzheimer's and mixed dementia. While there is some evidence to support the use of acetylcholinesterase inhibitors for treating cognitive impairments and hallucinations in Lewy body dementia, the usefulness of these agents in other forms of dementia is not well studied, and those studies did not show any benefit in the management of acute agitation. It is important to note that memantine can cause or exacerbate agitation and may be the cause of behavioral dysregulation. There is no evidence to support the routine use of benzodiazepines for behavioral improvement in patients with dementia. Escitalopram and citalopram do have a unique pharmacokinetic properties in the sense that they have been found to have 50-56% plasma protein binding, compared to sertraline, fluoxetine, and paroxetine (95% or more). Pooled analyses suggest that antidepressants are more effective than placebo in reducing the symptoms of post-stroke depression. SSRIs are considered first-line antidepressants in stroke patients, who are often elderly with underlying cardiovascular problems. Although treatment with SSRIs is recommended for post-stroke depression, there are no studies providing conclusive data on the superiority of a specific drug. Older age is associated with a better outcome from ECT, with remission rates of approximately 73% to 90% in patients over 65years. ECT is the treatment of choice for patients with psychotic depression, and elderly patients with psychotic depression have been shown to have a higher remission rate and faster time to response than depressed patients without psychotic symptoms. With the average life expectancy increase, it is projected that 19 million people will reach the age of 85 or higher, an increase from 5.5 million in 2010. With an increasing older population, psychiatric consultation in the management of geriatric patients is becoming more necessary. Psychiatrists must be aware of the unique considerations in elderly patients. In this article, we provide evidence-based guidance to the CL psychiatrist on major issues relating to the older age patient, highlighting recent trends in treatment. First, we provide background on the evaluation of the medically hospitalized geriatric patient. As rates of medical and psychiatric illnesses increase with advancing age, elderly patients are more likely to be taking a higher number of medications as compared to younger patients, and physicians must pay special attention to polypharmacy, including side effects and drug interactions in this group. Next, we focus on the diagnosis, management, and unique needs of the geriatric patient presenting with common clinical syndromes of delirium, dementia, and depression. Delirium and dementia are among the most common causes of cognitive impairment in clinical settings yet are often either unrecognized or misdiagnosed as they may have similar signs and symptoms. In addition, depression is prevalent in older adults, especially in those with comorbid medical illness. Depression can be fatal as the rates of suicide are higher in later life than in any other age group. Consultation can improve the management of elderly patients and prevent unnecessary nursing home placement.

The influence of substance use on the effectiveness of antipsychotic medication: a prospective, pragmatic study

Background: Psychosis is associated with a high prevalence of substance use, leading to worsened prognosis. Less is known about how comorbid substance abuse may influence the effectiveness of antipsychotic medications. The aim of this study was to compare the effectiveness of second generation antipsychotics in patients with psychosis with and without substance use.Methods: All patients (n = 226) were aged >18 years old had symptom level scores of ≥4 on selected psychosis items on the Positive and Negative Syndrome Scale and met ICD-10 diagnostic criteria for psychosis. Information on substance use was collected based on the Clinician Drug Use Scale. Patients were grouped at baseline according to the presence of substance use, medication history and diagnosis group. Clinical symptoms at baseline and changes at follow-up were assessed with the PANSS.Results: At baseline about 30% of the patients used substances, most frequently cannabis followed by methamphetamine. About half (47%) of the patients had no prior exposure to antipsychotic medication at inclusion. Patients who had consumed substances showed no substantial differences in the PANSS score reduction as a result of antipsychotic medication compared to patients without substance. There were, however, some group differences in relation to pattern of change that were influenced by medication history. Substance use was found to be related to stronger reduction of positive symptoms from week 4 to week 27.Conclusion: Substance use alone did not influence antipsychotic effectiveness in this sample of patients with psychosis.

Effect of second-generation antipsychotics on brain network topology in first-episode schizophrenia: A longitudinal rs-fMRI study

ObjectiveWe aimed to evaluate the functional network properties in first-episode schizophrenia (SZ) patients at baseline and after 4-months treatment with second-generation antipsychotic drugs. MethodsResting-state functional magnetic resonance imaging and graph theory approaches were utilized to evaluate the functional integration and segregation of brain networks in 36 first-episode patients (20 male/16 female) with SZ and 36 age and sex matched healthy controls (20 male/16 female). ResultsCompared with healthy controls, SZ at baseline showed lower clustering coefficient (Cp) and local network efficiency (Eloc), and this abnormal pattern was modulated with treatment of antipsychotic drugs at follow-up. Longitudinally, the increase of Cp was associated with the improvement of negative symptom. We found that the strength of functional connectivity between brain regions were significantly increased in three connections after treatment, mainly involving the frontal, parietal and occipital lobes. ConclusionThe current study suggested that antipsychotic drugs could modulate the faulty local clustering of the functional connectome in SZ. Furthermore, Cp, the parameter that reflects local clustering of topological organization, demonstrated the potential to be a connectome-based biomarker of treatment response to second-generation antipsychotics in patients with SZ.

Long-acting injectable second-generation antipsychotics in first-episode psychosis: a narrative review.

Long-acting injectable (LAI) antipsychotics could be a favorable option of treatment and have some advantages over oral medications. The aim of this study was to review the published data on the use of LAI formulation of second-generation antipsychotics (SGA) in first-episode psychosis (FEP). Using PubMed and Scopus databases, we performed a systematic literature search of articles published between 1 January 2000 and 30 April 2018, that reported clinical trials on the use of LAI SGAs in patients with FEP. Seventy-seven articles were considered eligible and full-text revised. Five studies fulfilled the inclusion criteria and evaluated the effect of LAI risperidone in FEP patients. Treatment with LAI SGAs was well accepted, and the majority of FEP patients agreed to change from an oral to an injectable formulation. At the 12-month follow-up, between 68 and 95% of FEP patients treated with LAI risperidone showed a good clinical response and 64% achieved remission of symptoms for at least 24 months of follow-up. Treatment with LAI SGAs can offer significant advantages over oral antipsychotics to FEP patients, especially to improve the adherence to medication and prevent the worsening of symptoms, the relapse, and rehospitalization associated with the discontinuation of treatment.

Mortality in patients with Parkinson disease psychosis receiving pimavanserin and quetiapine.

Parkinson disease (PD) is a complex neurodegenerative disorder. Cognitive dysfunction and psychosis are leading contributors to nursing home placement.1 Psychosis onset is associated with cognitive decline, levodopa supplementation, and visual dysfunction.2 Treatment of PD psychosis (PDP) centers on levodopa dose adjustment, use of second-generation antipsychotics (SGAs), and cholinesterase inhibitors. SGAs function via serotonergic modulation and dopamine receptors blockade. Quetiapine, a structural analogue to clozapine, is often used to treat PDP, although evidence of its efficacy is mixed in randomized controlled trials.3 Furthermore, there is a concern for increased morbidity and mortality with use of quetiapine and other SGAs in patients with dementia or those with PD, prompting a black box warning by the Food and Drug Administration (FDA).4

Hyponatremia in Association With Second-Generation Antipsychotics: A Systematic Review of Case Reports.

Hyponatremia is generally defined as a serum sodium level <135 mmol/L and is considered severe if serum sodium is <125 mmol/L. Hyponatremia is a potentially life-threatening medical comorbidity for patients with schizophrenia. The incidence of hyponatremia in patients with schizophrenia who are taking second-generation antipsychotics (SGAs) has not been well established. We conducted a systematic review of case reports of hyponatremia associated with the use of SGAs in patients with schizophrenia. We searched MEDLINE (from 1946 through September 2016) using the medical subject headings antipsychotic agents, hyponatremia, and water intoxication to identify reported diagnoses of hyponatremia following treatment with SGAs in patients with schizophrenia. We abstracted 12 potentially relevant case reports from 157 records. Nine case reports met the selection criteria. Three cases involved the use of aripiprazole (Abilify), 3 involved the use of risperidone (Risperdal), and the other 3 cases involved ziprasidone, olanzapine, and clozapine. Approximately equal numbers of males and females were represented, and 2 of the 9 patients were aged ≥60 years. The average patient age was 47 years, and the average time to the hyponatremia event was 17 days. The average serum sodium was 138 mmol/L at baseline, 112 mmol/L at treatment nadir, and 138 mmol/L after treatment discontinuation. Hyponatremia can result from the use of SGAs in patients with schizophrenia and can be avoided with proper management of treatment. Physicians, psychiatrists, and other healthcare workers should be aware of the potential for severe hyponatremia with the use of commonly prescribed SGAs. SGA-induced hyponatremia is generally reversible after discontinuing treatment.

Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is Associated with Working Memory Processing and Response to Treatment with Antipsychotics.

Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with second-generation antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment in two independent samples of patients with schizophrenia (n=63 and n=54, respectively), consistent with the previously reported separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that further exploration is needed to better understand the clinical consequences of these genotype-phenotype relationships.

Use of second generation antipsychotics for treatment-resistant major depressive disorder

Many of the second generation antipsychotics (SGAs) have been studied as adjunctive agents in the management of treatment-resistant major depressive disorder. Two have also been examined for use as monotherapy for depression. Currently, aripiprazole, olanzapine (in combination with fluoxetine), and quetiapine XR are approved by the FDA for use as adjunctive agents in the treatment of major depressive disorder, and no SGAs are FDA-approved as monotherapy for the disorder. This article reviews the available evidence regarding the use of SGAs in patients with treatment-resistant major depressive disorder and the subsequent role for these agents based on this evidence. There is evidence that aripiprazole, quetiapine, olanzapine, and risperidone can be effective in improving depressive symptoms when added to antidepressant therapy, but the benefits have to be weighed against their risk of producing serious adverse effects.

Recommandations Formalisées d’Experts de l’AFPBN : prescription des neuroleptiques et antipsychotiques d’action prolongée

Compliance is often partial with oral antipsychotics and underestimated for patients with serious mental illness. Despite their demonstrated advantages in terms of relapse prevention, depot formulations are still poorly used in routine. As part of a process to improve the quality of care, French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) Task Force elaborated a Formal Consensus for the prescription of depot antipsychotics in clinical practice. The Task Force recommends as first-line choice, the use of long-acting injectable (LAI) second-generation antipsychotics in patients with schizophrenia, schizoaffective disorder and delusional disorder. They can be considered as a second-line option as a monotherapy to prevent manic recurrence or in combination with mood stabilizer to prevent depressive recurrence in the maintenance treatment of bipolar disorder. LAI second-generation antipsychotics can also be used after a first episode of schizophrenia. Depot neuroleptics are not recommended during the early course of schizophrenia and are not appropriate in bipolar disorder. They are considered as a second-line option for maintenance treatment in schizophrenia. LAI formulations should be systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. LAI antipsychotics can be used preferentially for non-compliant patients with frequent relapses or aggressive behaviors. A specific information concerning the advantages and inconveniences of the LAI formulations, in the framework of shared-decision making must be delivered to each patient. Recommendations for switching from one oral/LAI form to another LAI and for using LAI antipsychotics in specific populations (pregnant women, elderly patients, subjects in a precarious situation, and subjects having to be treated in a prison establishment) are also proposed.

Efficacy of second-generation antipsychotics in patients at ultra-high risk and those with first- episode or multi-episode schizophrenia

AimThe aim of this study was to examine the speed of response, doses, and safety of treatment with second-generation antipsychotics (SGAs) in patients at ultra-high risk (UHR) compared to those with schizophrenia.MethodsA 12-week open-label, prospective study of SGAs was performed in UHR patients and those with first-episode schizophrenia (FES) and multi-episode schizophrenia (MES). The subjects were 14–30 years old and were recruited at Zikei Hospital, Okayama, Japan from December 1, 2006 to December 1, 2011. Treatment was carried out in a natural setting in an open-label format, but clinical evaluation was performed blind. The clinical rating scales include the Global Assessment of Functioning (GAF), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression-Severity scale (CGI-S).ResultsUHR (n = 17), FES (n = 23), and MES (n = 21) patients all showed significant improvements on the GAF, PANSS, and CGI-S. However, the UHR patients showed significantly greater improvement on the GAF at weeks 4, 8, and 12 compared to the other groups, and a significantly lower modal dose of SGAs (chlorpromazine equivalent: 183 [201.1] mg/day, mean [SD]) was needed for improvement in the UHR group. Each group was also prescribed anticholinergic agents during the study period and the UHR group had significantly fewer extrapyramidal symptoms (only 6%) compared with the FES group.ConclusionOur findings suggest that UHR patients have a better response to SGAs compared to patients with schizophrenia, and that these drugs can be given safely by minimizing the dosage of SGAs and using anticholinergic agents.

Efficacy to the second-generation antipsychotics in patients with ultra-high risk, first-episode schizophrenia and multi-episode schizophrenia

Efficacy to the second-generation antipsychotics in patients with ultra-high risk, first-episode schizophrenia and multi-episode schizophrenia

Comparative study of treatment continuation using second-generation antipsychotics in patients with schizophrenia or schizoaffective disorder

BackgroundEffectiveness of a drug is a key concept dependent on efficacy, safety, and tolerability. Time to discontinuation of treatment is also representative of effectiveness. We investigated differences in treatment discontinuation among newly started second-generation antipsychotics in the clinical setting.MethodsUsing a retrospective cohort study design, we screened all outpatients (n = 7936) who visited the Shioiri Mental Clinic between July 1, 2008 and June 30, 2010. We identified a cohort of patients (n = 703) diagnosed with schizophrenia or schizoaffective disorder and calculated the time to discontinuation of each second-generation antipsychotic.ResultsOf the 703 patients, 149 were newly treated with aripiprazole, 67 with blonanserin, 95 with olanzapine, 36 with quetiapine, 74 with perospirone, and 120 with risperidone. The time to discontinuation for all causes was significantly longer for aripiprazole than for blonanserin, olanzapine, and risperidone. In addition, aripiprazole tended to be continued for longer than quetiapine and perospirone, but these differences were not significant.ConclusionAripiprazole may be considered the best available option for long-term treatment of patients with schizophrenia or schizoaffective disorder.