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Exploring Biologic Predictors Response Disparities to Atypical Antipsychotics among Blacks: A Quasi-Systematic Review.

ABSTRACT: Purpose:Management of schizophrenia among Blacks in the United States is affected by persistent disparities. This review explored response to atypical antipsychotics among Blacks compared with other groups to assess systematic variation that may contribute to disparities. Methods:We conducted a quasi-systematic review of studies reporting response to atypical antipsychotics among Blacks compared with other groups, including effects of genetic variation. Results:Of 48 identified research articles, 29 assessed differences in outcomes without inclusion of genetic variation and 20 explored effects of genetic variation; of note: one article included both types of data. Analysis of the 29 papers with clinical outcomes only suggests that while data on efficacy and risk of movement disorders were heterogeneous, findings indicate increased risk of metabolic effects and neutropenia among Blacks. Of the 20 articles exploring effects of genetic variation, allelic or genotypic variations involving several genes were associated with altered efficacy or safety among Blacks but not Whites, including risk of decreased response involving variation in DRD4 and DRD1, and improved efficacy associated with variants in DRD2, COMT, and RGS4. Others showed significant improvement in treatment response only among Whites, including variation in DTNBP1, DRD4, and GNB3. Conclusions:The current analysis can help tailor management among Blacks using an atypical antipsychotic. Heterogeneity in genetic variation effects and response allele frequency suggests that pharmacogenetics approaches for atypical antipsychotics will need to explicitly incorporate race and ethnicity.

SUBMITTER: Jerome RN

PROVIDER: S-EPMC7138445 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Exploring Biologic Predictors Response Disparities to Atypical Antipsychotics among Blacks: A Quasi-Systematic Review.

Jerome Rebecca N RN Pulley Jill M JM Sathe Nila A NA Krishnaswami Shanthi S Dickerson Alyssa B AB Worley Katherine J KJ Wilkins Consuelo H CH

Ethnicity & disease 20200402 Suppl 1

<h4>Purpose</h4>Management of schizophrenia among Blacks in the United States is affected by persistent disparities. This review explored response to atypical antipsychotics among Blacks compared with other groups to assess systematic variation that may contribute to disparities.<h4>Methods</h4>We conducted a quasi-systematic review of studies reporting response to atypical antipsychotics among Blacks compared with other groups, including effects of genetic variation.<h4>Results</h4>Of 48 identi ...[more]

PMID: 32269465

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Project description:BackgroundAtypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics.MethodsWe examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library), and data combined for analysis where there was clinical homogeneity, with a special reference to trial duration.ResultsIn five trials (2,206 patients) participants presented with a depressive episode, and in 25 trials (6,174 patients) the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5-6, but more adverse event withdrawals (NNH 12). With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6-12 weeks, but more adverse event withdrawals (NNH of about 22) in studies of 6-12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10). In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of >or=7% (mainly olanzapine trials), somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence.ConclusionAtypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine). There is insufficient data confidently to distinguish between different atypical antipsychotics.

Project description:BackgroundIn many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics.ObjectivesTo evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses.Search strategyWe searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO.Selection criteriaWe included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses.Data collection and analysisWe extracted data independently. For continuous data we calculated weighted mean differences (MD), for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate.Main resultsThe review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50). Amisulpride induced less weight gain than risperidone (n=585, 3 RCTs, MD -0.99 CI -1.61 to -0.37) or olanzapine (n=671, 3 RCTs, MD -2.11 CI -2.94 to -1.29). Olanzapine was also associated with a higher increase of glucose (n=406, 2 RCTs, MD -7.30 CI -7.62 to -6.99). There was no difference in terms of cardiac effects and extra pyramidal symptoms (EPS) compared with olanzapine (akathisia: n= 587, 2 RCTs, RR 0.66 CI 0.36 to 1.21), compared with risperidone (akathisia: n=586, 3 RCTs, RR 0.80 CI 0.58 to 1.11) and compared with ziprasidone (akathisia: n=123, 1 RCT, RR 0.63, CI 0.11 to 3.67).Authors' conclusionsThere is little randomised evidence comparing amisulpride with other second generation antipsychotic drugs. We could only find trials comparing amisulpride with olanzapine, risperidone and ziprasidone. We found amisulpride may be somewhat more effective than ziprasidone, and more tolerable in terms of weight gain and other associated problems than olanzapine and risperidone. These data, however, are based on only ten short to medium term studies and therefore too limited to allow for firm conclusions.

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Exploring Biologic Predictors Response Disparities to Atypical Antipsychotics among Blacks: A Quasi-Systematic Review.

Publications

Exploring Biologic Predictors Response Disparities to Atypical Antipsychotics among Blacks: A Quasi-Systematic Review.

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