The purpose of this study was to examine whether prior evidence of an inverse relationship between initial body weight and subsequent antipsychotic-induced weight change represents true effect modification or a statistical artifact, regression to the mean (RTM). We conducted a post-hoc analysis after pooling seven randomized, placebo- or active-controlled trials of ziprasidone and other antipsychotic agents. ANCOVA was applied to evaluate treatment-by-baseline body mass index (BMI) range interaction effect on weight change. Regression analysis was applied to estimate the potential bias due to RTM. Statistical interaction tests between baseline BMI ranges and treatment assignments (haloperidol, olanzapine, risperidone, or ziprasidone, versus placebo) were not significant within studies or across studies. Correlation between baseline and follow-up measurements of body weight in placebo-treated subjects was less than perfect (r=0.87, 6-month cohort), leading to RTM. Consistent with predictions based on RTM, the greatest weight change, on average, was observed in subgroups with baseline weights differing the most from the population mean. Our findings suggest that the previously observed correlation between baseline BMI and weight change subsequent to antipsychotic treatment reflects in part RTM, and not effect modification. This class of drugs appears to cause similar weight gain in both high and low baseline BMI groups.
"aimed to assess the effects of pharmacological interventions on improving cognitive performance in schizophrenia. Enhancements included the use of placebo in the acute phase and an active control to examine practice effects and bias due to regression-to-the-mean (Allison et al., 2009), adherence to the consensus research design (Buchanan et al., 2005), and a performance-based, co-primary measure of functional capacity (Mausbach et al, 2007). It also addressed the pseudospecificity issues by adjustment for concurrent symptomatic improvement in PANSS total and subscales (Harvey et al., 2013). "
"Although, the atypical antipsychotics offered, since their discovery, new perspectives and many advantages over conventional neuroleptics (greater impact on negative and neuro-cognitive symptoms and better safety profile) this does not mean that they do not display considerable side effects, which can result in discontinuation of treatment . Atypical antipsychotic drugs, in particular some of them, influence cellular lipogenesis and are associated with metabolic side effects including weight gain, body mass index (BMI)/blood Insulin level increase    . "
[Show abstract][Hide abstract] ABSTRACT: Atypical antipsychotics, especially some of them, influence cellular lipogenesis, being associated with metabolic side effects including weight gain. Due to the increasing use of atypical antipsychotics in children and adolescents, their metabolic and endocrine adverse effects are of particular concern especially within this pediatric population that appears to be at greater risk. Genetic factors with a possible influence on atypical antipsychotics adverse effects include CYP2D6 polymorphisms. Our study, performed in 2009-2014, with a two-year enrolment period during which we recruited children and adolescents with a diagnosis of schizophrenia or bipolar disorder on treatment with the antipsychotics (Risperidone, Aripiprazole or Olanzapine), included 81 patients, aged between 9 and 20 years, median age being 15.74 years. The gender percentage was 54% girls÷46% boys. The CYP2D6 genotyping was performed after enrolment of the last patient. Based on the CYP2D6 genotype, three activity groups were identified and compared and we found that the patients with wt÷*4 genotype, intermediary metabolizer (carrier of one functional and one non-functional allele) have significantly higher weight gain values than the patients who did not exhibit allele *4. The CYP2D6 genotype in children and adolescents with schizophrenia and bipolar disorder, proved to be a good predictor for the response to atypical antipsychotics and the side effects registered. The significant correlations between the CYP2D6 polymorphisms and the weight gain÷BMI (body mass index) increase, as major side effects induced by antipsychotics proved the fact that the pharmacogenetic screening is needed in the future clinical practice, allowing for individualized, tailored treatment, especially for at-risk individuals.
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 10/2014; 55(3):877-884. · 0.66 Impact Factor
"Thus patients with a lower BMI at T0 had a higher increase in BMI at T6. This effect is likely to have been infl uenced by " regression to the mean " , resulting in patients with extreme BMIs at T0 more likely to have less extreme BMIs at T6 (Bland and Altman 1994; Allison et al. 2009). Similarly, 55 patients (71%) showed an increased Ins:Glc ratio with mean of 0.35 U/mol per patient (see Table II). "
[Show abstract][Hide abstract] ABSTRACT: Objectives. Metabolic disturbances are major adverse side effects in the treatment of schizophrenia patients with antipsychotics. A substantial proportion of patients discontinue treatment with second-generation antipsychotics due to weight gain. The objective of this study was to investigate molecular factors predisposing patients to the development of such metabolic disturbances. Methods. We investigated whether serum molecules measured before treatment initiation were associated with subsequent weight gain following a 6-week treatment with antipsychotics. The concentrations of 191 molecules were measured longitudinally in serum from 77 schizophrenia patients using multiplex immunoassays. Results. This showed that the levels of 10 serum molecules at T0 were significantly associated with ΔBMI, which included interleukin-6 receptor, epidermal growth factor and thyroid stimulating hormone. Conclusions. Our results suggest that patients who experience antipsychotic-induced weight gain have specific molecular alterations already prior to treatment. Further studies are required to validate and evaluate current findings in the context of response and side-effect development. This may ultimately lead to molecular tests that can aid in the selection of antipsychotic treatments.
The World Journal of Biological Psychiatry 09/2013; 16(1). DOI:10.3109/15622975.2013.817685 · 4.18 Impact Factor
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