Tolerability Of Second-generation Antipsychotics Research Articles

Second-Generation Antipsychotics in Management of Acute Pediatric Bipolar Depression: A Systematic Review and Meta-analysis.

Objectives: To evaluate the efficacy in reduction of depressive symptoms, and safety and tolerability of second-generation antipsychotics (SGAs) to manage pediatric bipolar depression (PBD). Methods: We conducted a systematic review for randomized clinical trials (RCTs) for PBD in MEDLINE, Scopus, and EMBASE. Four (quetiapine: 2, lurasidone: 1, olanzapine-fluoxetine combination [OFC]: 1) out of 569 studies met the criteria for inclusion in meta-analysis. RevMan was used for statistical analysis, and the mean difference (MD) between mean children's depression rating scale-revised (CDRS-R) score was used to measure treatment difference between SGA and placebo. Results: Lurasidone displayed a significant reduction in depressive symptoms (MD -5.70, 95% confidence interval [CI] -8.67 to -2.73) in PBD, followed by OFC (MD -5.00, 95% CI -8.64 to -1.36) and quetiapine (MD -2.30, 95% CI -6.80 to 2.20; MD 1.00, 95% CI -9.88 to 11.88). The response was significantly higher for lurasidone (59.5% vs. 36.5%; p < 0.001) and OFC (78.2% vs. 59.2%, p = 0.003) compared with placebo. There was no statistically significant MD in treatment and response rates between quetiapine and placebo in all RCTs. The weighted mean CDRS-R total score difference was -4.58 (95% CI -6.59 to -2.56) and overall effect was significant (p < 0.00001). Importantly, the p value for heterogeneity was 0.46, which indicated that there was no heterogeneity between outcomes of the studies. The number needed to treat (NNT) for lurasidone was 4.3, followed by OFC (NNT = 5.3) and quetiapine (NNT = 12.5; NNT = 25). Conclusion: Our findings showed lurasidone and OFC were more efficacious than placebo for acute depressive episodes in PBD. RCTs of treatments for PBD remain scarce pressing the need for more research.

32.1 Second-Generation Antipsychotics (SGA) in the Management of Acute Pediatric Bipolar Depression: A Systematic Review and Meta-Analysis

This session aims to evaluate the efficacy in the reduction of depressive symptoms, and the safety and tolerability of second-generation antipsychotics (SGAs) to manage pediatric bipolar disorder (PBD). CorrectionJournal of the American Academy of Child & Adolescent PsychiatryVol. 61Issue 1PreviewIn the 2021 Scientific Proceedings supplement to JAACAP, New Research Poster 32.1 “Second-Generation Antipsychotics (SGA) in the Management of Acute Pediatric Bipolar Depression: A Systematic Review and Meta-Analysis”, (2021;60:S214), the academic degree of Riddhi Patel, MBBS, MPH, was incorrectly listed, and the name of coauthor Tanya Machado, MBBS, was spelled incorrectly. Full-Text PDF

Adjunctive second-generation antipsychotics for specific symptom domains of schizophrenia resistant to clozapine: A meta-analysis

A fair amount of subjects with schizophrenia do not respond to clozapine and are defined ‘ultra-resistant’. In this systematic review and meta-analysis, we tested the efficacy of adjunctive second-generation antipsychotics (SGAs) for main symptom domains (positive, negative, and depressive symptoms) in individuals with clozapine-resistant schizophrenia. We searched main electronic databases till December 2017. We included twelve double-blind, randomized, placebo-controlled trials (RCTs), evaluating the efficacy of SGAs for clozapine non/partial responders. We did not find any difference between SGAs and placebo (standardized mean difference, SMD = −0.21; p = 0.170; I2 = 68.0%) in improving positive symptoms. The effect size varied according to RCT duration (p = 0.025) and assessment methods (p = 0.016). Low-moderate effects of SGAs on both negative (SMD = −0.38; p = 0.005; I2 = 62.7%) and depressive symptoms (SMD = −0.35; p = 0.003; I2 = 4.9%), were estimated. In sum, our meta-analysis highlights the lack of efficacy of SGAs as add-on treatment for positive symptoms in clozapine-resistant schizophrenia. A small benefit of SGAs was estimated for both negative and depressive symptoms. Further RCTs are needed to establish efficacy and tolerability of SGAs or other augmentation strategies for different symptoms of clozapine-resistant schizophrenia.

Is There Room for Second-Generation Antipsychotics in the Pharmacotherapy of Panic Disorder? A Systematic Review Based on PRISMA Guidelines.

A role for second-generation antipsychotics (SGAs) in the treatment of panic disorders (PD) has been proposed, but the actual usefulness of SGAs in this disorder is unclear. According to the PRISMA guidelines, we undertook an updated systematic review of all of the studies that have examined, in randomized controlled trials, the efficacy and tolerability of SGAs (as either monotherapy or augmentation) in the treatment of PD, with or without other comorbid psychiatric disorders. Studies until 31 December 2015 were identified through PubMed, PsycINFO, Embase, Cochrane Library and Clinical trials.gov. Among 210 studies, five were included (two involving patients with a principal diagnosis of PD and three involving patients with bipolar disorder with comorbid PD or generalized anxiety disorder). All were eight-week trials and involved treatments with quetiapine extended release, risperidone and ziprasidone. Overall, a general lack of efficacy of SGAs on panic symptoms was observed. Some preliminary indications of the antipanic effectiveness of risperidone are insufficient to support its use in PD, primarily due to major limitations of the study. However, several methodological limitations may have negatively affected all of these studies, decreasing the validity of the results and making it difficult to draw reliable conclusions. Except for ziprasidone, SGAs were well tolerated in these short-term trials.

Simultaneous Comparison of Efficacy and Tolerability of Second-Generation Antipsychotics in Schizophrenia: Mixed-Treatment Comparison Analysis Based on Head-to-Head Trial Data.

ObjectiveSecond-generation antipsychotics have been repeatedly shown to be superior to placebo. However, the comparative efficacy among these drugs has not been systematically evaluated. In this study, we used Mixed Treatment Comparison (MTC) procedures to elucidate the comparative efficacy and tolerability of second-generation antipsychotics.MethodsSeven antipsychotics were selected based on the availability of the relevant data. Data were gathered from a series of review article published by the Cochrane Collaboration. Six outcome measures were analyzed: 1) percentage of no clinically important response as defined by the original authors, 2) PANSS total score change from baseline to endpoint, 3) percentage of akathisia, 4) percentage of antiparkinson medication use, 5) percentage of total body weight increase more than 7%, and 6) percentage of drop-out due to any reasons.ResultsAll the second-generation antipsychotics included in this study showed fairly similar efficacy but widely different tolerability. In terms of efficacy, amisulpride, clozapine and olanzapine were ranked higher than aripiprazole, quetiapine and ziprasidone. Clozapine and olanzapine were superior in terms of akathisia and extrapyramidal symptom risk, but, far more prone to induce clinically important weight gain.ConclusionUsing MTC methodology, we could line up the second generation antipsychotics according to their hierarchical superiority in terms of efficacy and tolerability. Though the wide overlap among the confidence intervals and the inconsistency between the direct and indirect comparison results may limit the validity of these results, it may still allow the important insights into the relative merits of the available drugs.

P.3.d.008 Simultaneous comparison of efficacy and tolerability of second-generation antipsychotics in schizophrenia: a Mixed Treatment Comparison analysis

P.3.d.008 Simultaneous comparison of efficacy and tolerability of second-generation antipsychotics in schizophrenia: a Mixed Treatment Comparison analysis

Treating Generalized Anxiety Disorder With Second Generation Antipsychotics

Most individuals with generalized anxiety disorder (GAD) fail to achieve remission despite standard treatments. As a result, we examined the efficacy and tolerability of second-generation antipsychotics (SGAs) as (a) augmentation or (b) monotherapy for GAD. We searched MEDLINE, EMBASE, PsycINFO, the Cochrane Library, controlled trials databases, and the abstracts of scientific meetings for all trials of GAD treatment with SGAs in adults. Randomized, double-blind, parallel-group trials examining SGA augmentation and monotherapy were meta-analyzed. Five augmentation studies containing 912 adults with refractory GAD indicated that SGA augmentation was not more likely to produce clinical response or remission than placebo and was associated with an increased risk of all-cause discontinuation (relative risk [RR] = 1.43; 95% confidence interval [CI], 1.04-1.96). There was no difference in the Hamilton Anxiety Rating Scale on change from baseline or weight gain between groups. Four SGA monotherapy studies containing 1383 patients with GAD indicated that treatment with 150 mg of quetiapine was more likely to lead to a clinical response (RR = 1.31; 95% CI, 1.20-1.44), remission (RR = 1.44; 95% CI, 1.23-1.68), and a greater decrease in the Hamilton Anxiety Rating Scale score (-3.66; 95% CI, -5.13 to -2.19) than placebo. However, an increased risk of all-cause discontinuation (RR = 1.30; 95% CI, 1.09-1.54) and weight gain (2.2 lb; 95% CI, 1.16-3.24) was observed. Existing data suggest that SGAs are not superior to placebo as augmentation for refractory GAD. Quetiapine monotherapy is more efficacious than placebo for uncomplicated GAD, but issues with adverse effects and tolerability may limit its use.

P01-366-New treatment option in resistant schizophrenia in adolescence - case study

Early-onset schizophrenia has not only more severe course than in adults, it is also associated with poor response to antipsychotic treatment. There are only limited data about effectiveness, safety and tolerability of second generation antipsychotics (SGA) in children, but current recommendations suggest using atypical antipsychotics as the first line treatment.Case study15-year-old schoolboy admitted to psychiatric hospital after acute psychotic episode. His symptoms started 2 years ago. After a few months he was diagnosed schizophrenia paranoid type. During 2 years he has been hospitalized many times because of persistent psychotic symptoms. He was treated using: risperidon, olanzapine, amisulpride, quetiapine, ziprasidone, perfenazin. All the drugs were ineffective, all were used in full doses, given no shorter than 8 weeks. Patient did not cooperate in treatment - he spits out or has hide the tablets, has to be controlled during drug supplies. He did not responded to long-acting injections of risperidon. Finally the treatment has been changed to new form of olanzapine in extended release injections started 210 mg i.m. every 14 days increased to 300 mg after 2 weeks. After 2 months of treatment (5 injections) reduction of positive and negative symptoms of schizophrenia was observed. Patients starts to socialize, attend school. He is on the drug now, the drug is well tolerated.

Second-generation antipsychotics for anxiety disorders

Anxiety disorders are common and disabling conditions, with a lifetime prevalence of 17% in the general population. Due to high rates of treatment resistance, there is interest in new pharmacological treatment options such as second-generation antipsychotics. To evaluate the efficacy and tolerability of second-generation antipsychotics as monotherapy or adjunctive treatment for people with anxiety disorders. The Cochrane Depression, Anxiety and Neurosis Group's controlled trial registers (CCDANCTR-Studies and CCDANCTR-References) were searched up to 21 July 2010. The author team ran complementary searches on ClinicalTrials.gov. We included all randomised trials (RCTs) comparing second-generation antipsychotic drugs with placebo, benzodiazepines, pregabalin or antidepressants. Participants were people with generalised anxiety disorder, panic disorder and specific phobias including social phobia. Two authors extracted data independently. For dichotomous data we calculated odds ratios (OR) and their 95% confidence intervals (CI). For continuous data we calculated mean differences (MD) based on a random-effects model. The review currently includes eleven RCTs with 4144 participants on three second-generation antipsychotics (olanzapine, quetiapine, risperidone). Nine studies investigated the effects of second-generation antipsychotics in generalised anxiety disorder, only two studies investigated the effects in social phobia. There were no studies on panic disorder or any other primary anxiety disorder.Seven studies investigated the effects of quetiapine. Participants with generalised anxiety disorder responded significantly better to quetiapine than to placebo (4 RCTs, N = 2265, OR = 2.21, 95% CI 1.10 to 4.45). However, they were more likely to drop out due to adverse events, to gain weight, to suffer from sedation or to suffer from extrapyramidal side effects. When quetiapine was compared with antidepressants, there was no significant difference in efficacy-related outcomes, but more participants in the quetiapine groups dropped out due to adverse events, gained weight and feeling sedated. Only two very small studies with a total of 36 participants examined olanzapine and found no difference in response to treatment. Two trials compared adjunctive treatment with risperidone with placebo and found no difference in response to treatment. We identified eligible trials on quetiapine, risperidone and olanzapine. The available data on olanzapine and risperidone are too limited to draw any conclusions. Monotherapy with quetiapine seems to be efficacious in reducing symptoms of generalised anxiety disorder and this effect may be similar to that of antidepressants. However, quetiapine's efficacy must be weighed against its lower tolerability.

Características diferenciales de eficacia y tolerabilidad de los antipsicóticos de segunda generación en el tratamiento de trastornos psicóticos en niños y adolescentes

Over the last few years, there has been a marked increase in the prescription of second-generation antipsychotics (SGA) for the treatment of psychotic disorders and other psychiatric conditions in children and adolescents. However, few reports compare the tolerability and efficacy of the different SGAs in this population. We review the literature on the differential characteristics of efficacy and tolerability of SGA in the pediatric population. Our results show that SGAs are not a homogeneous group, but that each drug has a distinct profile, particularly with respect to side effects, especially metabolic complications. Comparisons between SGAs have shown that treatment with olanzapine was associated with greater weight gain and increased cholesterol levels, and that treatment with risperidone was associated with a greater increase in prolactin levels. Therefore, the specific profile of an SGA should be taken into consideration when prescribing these drugs.

Efficacy and tolerability of second-generation antipsychotics in children and adolescents with schizophrenia.

Early-onset schizophrenia-spectrum (EOSS) disorders (onset of psychotic symptoms before 18 years of age) represent a severe variant associated with significant chronic functional impairment and poor response to antipsychotic treatment. All drugs with proven antipsychotic effects block dopamine D2 receptors to some degree. The ongoing development of the dopamine and other neurotransmitter receptor systems during childhood and adolescence may affect clinical response and susceptibility to side effects in youth. A literature search was conducted of clinical trials of antipsychotics in children and adolescents with EOSS disorders between 1980 and 2007 from the Medline database, reference lists, and conference proceedings. Trials were limited to double-blind studies of duration of 4 or more weeks that included 15 or more patients. Ten clinical trials were identified. Antipsychotic medications were consistently found to reduce the severity of psychotic symptoms in children and adolescents when compared with placebo. The superiority of clozapine has been now demonstrated relative to haloperidol, standard-dose olanzapine, and “high-dose” olanzapine for EOSS disorders. However, limited comparative data are available regarding whether there are differences among the remaining second-generation antipsychotics (SGAs) in clinical effectiveness. The available data from short-term studies suggest that youth might be more sensitive than adults to developing antipsychotic-related adverse side effects (eg, extrapyramidal side effects, sedation, prolactin elevation, weight gain). In addition, preliminary data suggest that SGA use can lead to the development of diabetes in some youth, a disease which itself carries with it significant morbidity and mortality. Such a substantial risk points to the urgent need to develop therapeutic strategies to prevent and/or mitigate weight gain and diabetes early in the course of treatment in this population.

Efficacy and Tolerability of Second-Generation Antipsychotics in Children and Adolescents With Schizophrenia

Efficacy and Tolerability of Second-Generation Antipsychotics in Children and Adolescents With Schizophrenia