Trials Of Second Generation Antipsychotics Research Articles

22.1 Can Pediatric Bipolar Disorder be Successfully Treated When Comorbid With Conduct Disorder? A Secondary Analysis of Six Clinical Trials of Second Generation Antipsychotics

Pediatric bipolar disorder (BP) is highly comorbid with conduct disorder (CD) and its presence adds to the high morbidity of BP disorder. While there are no known pharmacological treatments for CD, pediatric BP is responsive to treatment. Yet, it is not known whether antimanic treatments remain efficacious in the context of comorbid CD. The main aim of this secondary analysis study was to examine whether pediatric BP responds to second-generation antipsychotics (SGAs) when comorbid with CD. This finding could have important clinical and public health significance by providing a pharmacological option for this highly morbid comorbid condition. We conducted a secondary analysis of 6 prospective 8-week open-label trials of second-generation antipsychotics (SGAs; risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) using identical methodology in youth with BP with and without comorbid CD. Of 165 youths with BP, 54% (N = 89) met criteria for comorbid CD. The antimanic effects observed were almost identical in BP youths with and without comorbid CD, as measured either by a reduction in Young Mania Rating Scale (YMRS) ≥30% or Clinical Global Impression (CGI)-Improvement scale ≤2 (p = 0.23), or by the more stringent definition of a reduction in YMRS ≥50% (p = 0.61). Pediatric BP can be effectively treated with SGAs in the context of comorbid CD. Based on previous research showing that remission of BP is associated with remission of CD, if confirmed, these findings raise the possibility that antimanic treatment of youth with BP comorbid with CD could have secondary benefits in mitigating the morbidity associated with CD.

Factors associated with discontinuation in the drug and placebo groups of trials of second generation antipsychotics for acute schizophrenia: A meta-regression analysis: Discontinuation in antipsychotic trials

This study investigated factors associated with discontinuation in double-blind, randomized, placebo-controlled trials (DBRPCTs) of second-generation antipsychotics (SGAs) for acute schizophrenia, with a view to establishing what factors were associated with all-cause discontinuation. 77 eligible studies (96 comparisons; n = 22,678) were included in this study. Thirty-one factors potentially affecting all-cause discontinuation, related to the participants, study design, and drugs, were included in a meta-regression analysis that examined the factors associated with discontinuation rates in treatment and placebo groups and/or the treatment–placebo group difference in discontinuation. Smaller improvements in Positive and Negative Syndrome Scale total scores from baseline to endpoint were associated with higher discontinuation rates in both the treatment and placebo groups, and smaller response rates in the treatment group were associated with higher discontinuation rates in the treatment group. These factors were also associated with the treatment–placebo group difference in discontinuation. Although the risk of weight gain from SGA use was not associated with discontinuation rates in either the treatment or placebo groups, SGAs with a risk of weight gain were associated with a larger treatment–placebo group difference in discontinuation, although the reason is unknown. Factors associated with discontinuation rates in both treatment and placebo groups did not influence the treatment–placebo group difference in discontinuation. The efficacy and the risk of weight gain of SGAs seemed to influence treatment–placebo group difference in discontinuation in DBRPCTs of SGAs for acute schizophrenia.

Impact of DSM-5 changes on the diagnosis and acute treatment of schizophrenia.

To examine the consequences and validity of changes in Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 diagnostic criteria for schizophrenia, eg, omission of subtypes, using a large dataset of double-blind, randomized, placebo-controlled schizophrenia trials. Data from 22 short-term efficacy registration trials of second generation antipsychotics for the treatment of acute psychotic episodes in patients with schizophrenia (N = 5233), submitted to the Dutch regulatory authority were analyzed. We examined whether patients in these pre-DSM-5 trials met the diagnostic criteria for schizophrenia according to DSM-5. Using linear regression, we examined differences in effect size between DSM-IV subtypes and between DSM-5 symptom dimensions. Over 99.5% of the patients met DSM-5 diagnostic criteria for schizophrenia and no differences in effect size were found between schizophrenia subtypes (P = .65). Symptom dimensions that respond best to treatment with second generation antipsychotics were hallucinations, delusions, disorganized speech, and mania (Hedge's g -0.23 to -0.31). Results of clinical trials in patients with pre-DSM-5 schizophrenia also apply to patients diagnosed with DSM-5 schizophrenia. Omission of the classic subtypes is justified as they are not predictive of response to treatment. The DSM-5 C-RDPSS scale adds valuable information to the categorical diagnosis of schizophrenia, which is relevant for antipsychotic response.

Autism spectrum disorders and sleep disturbances in a pediatric patient

INTRODUCTION Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that often presents before the child enters the educational system and is characterized by developmental deficits with impairments in three main areas [1] personal, [2] social, and [3] academic or occupational functioning. The neurodevelopmental disorders represent a group of conditions with an onset early in the developmental period. Sleep disorders are commonly reported by parents of children with an ASD diagnosis with between 50% to 80% of parents reporting sleep problems with their children. Problems can be categorized into dyssomnias (problems falling and/or remaining asleep) and parasomnias (abnormal and/or unnatural movements, behaviors, emotions, perceptions, and dreams).

An analysis of the effect of funding source in randomized clinical trials of second generation antipsychotics for the treatment of schizophrenia

Objective The effect of funding source on the outcome of randomized controlled trials has been investigated in several medical disciplines; however, psychiatry has been largely excluded from such analyses. In this article, randomized controlled trials of second generation antipsychotics in schizophrenia are reviewed and analyzed with respect to funding source (industry vs. non-industry funding). Method A literature search was conducted for randomized, double-blind trials in which at least one of the tested treatments was a second generation antipsychotic. In each study, design quality and study outcome were assessed quantitatively according to rating scales. Mean quality and outcome scores were compared in the industry-funded studies and non-industry-funded studies. An analysis of the primary author's affiliation with industry was similarly performed. Results Results of industry-funded studies significantly favored second generation over first generation antipsychotics when compared to non-industry-funded studies. Non-industry-funded studies showed a trend toward higher quality than industry-funded studies; however, the difference between the two was not significant. Also, within the industry-funded studies, outcomes of trials involving first authors employed by industry sponsors demonstrated a trend toward second generation over first generation antipsychotics to a greater degree than did trials involving first authors employed outside the industry ( p=0.05). Conclusions While the retrospective design of the study limits the strength of the findings, the data suggest that industry bias may occur in randomized controlled trials in schizophrenia. There appears to be several sources by which bias may enter clinical research, including trial design, control of data analysis and multiplicity/redundancy of trials.