scholarly journals Early Nonresponse Determined by the Clinical Global Impressions Scale Predicts Poorer Outcomes in Youth with Schizophrenia Spectrum Disorders Naturalistically Treated with Second-Generation Antipsychotics

2013 ◽  
Vol 23 (10) ◽  
pp. 665-675 ◽  
Author(s):  
Marie Stentebjerg-Olesen ◽  
Pia Jeppesen ◽  
Anne K. Pagsberg ◽  
Anders Fink-Jensen ◽  
Sandeep Kapoor ◽  
...  
2021 ◽  
Vol 12 ◽  
Author(s):  
Marius H. Sneller ◽  
Nini de Boer ◽  
Sophie Everaars ◽  
Max Schuurmans ◽  
Sinan Guloksuz ◽  
...  

Background: Individuals with severe mental illness experience increased morbidity and mortality compared to the general population. Adverse effects of antipsychotics, including weight gain, may contribute to the development of metabolic syndrome (MetS), which is associated with increased risks of all-cause and cardiovascular disease mortality. We aim to provide a comprehensive overview of clinical, biochemical and genetic factors associated with MetS among patients with schizophrenia spectrum disorders using second-generation antipsychotics (SGA).Methods: A literature search was performed in Pubmed and Embase to identify all cohort studies, cross-sectional studies and clinical trials investigating associations with MetS in patients with schizophrenia spectrum disorders using SGAs. We extracted and enumerated clinical, biochemical and genetic factors reported to be associated with MetS. We defined factors associated with MetS as factors being reported as associated with MetS in two or more studies.Results: 58 studies were included in this review (n = 12,123). In total, 62 factors were found to be associated with increased risk of MetS. Thirty one out of 58 studies investigated factors that were reported as associated with MetS in two or more studies. With regard to clinical factors, we found gender, higher age, concomitant use of mood stabilizers, higher baseline and current BMI, earlier SGA exposure, higher dose, longer duration of treatment, psychosis and tobacco smoking to be significantly associated with MetS. Furthermore, the biochemical factors hypo-adiponectinemia, elevated levels of C-reactive protein (CRP) and higher white blood cell (WBC) count were identified as factors associated with MetS. Among pharmacogenetic factors, the rs1414334 C-allele of the HTR2C-gene was associated with MetS in patients using SGA.Conclusion: In this systematic review investigating clinical, biochemical and genetic factors associated with MetS in patients using SGAs we found that higher age, higher baseline BMI, higher current BMI and male as well as female gender were positively associated with MetS across all antipsychotics. This study may set the stage for the application of clinical, biochemical and genetic factors to predict the risk of developing MetS in patients using SGAs. Future research is needed to determine which patients using SGAs are at risk to develop MetS in clinical practice.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Chakrapani Balijepalli ◽  
Eric Druyts ◽  
Michael J. Zoratti ◽  
Ping Wu ◽  
Salmaan Kanji ◽  
...  

Background. Treatment of schizophrenia with first- and second-generation antipsychotics has been associated with elevated prolactin levels, which may increase the risk for prolactin-related adverse events. Methods. Randomized controlled trials (RCTs) included in a recent systematic review were considered for this analysis. A Bayesian network meta-analysis was used to compare changes in prolactin levels in pediatric patients diagnosed with schizophrenia or schizophrenia spectrum disorders treated with second-generation antipsychotics (SGAs). Results. Five RCTs, including 989 patients combined, have evaluated the changes in prolactin for pediatric patients after 6 weeks of treatment with risperidone, quetiapine, aripiprazole, olanzapine, and paliperidone. In the overall study population, treatment with risperidone was associated with the highest increase in mean prolactin levels compared to other SGAs. Patients treated with risperidone 4–6 mg/day were found to experience the greatest increases (55.06 ng/ml [95% CrI: 40.53–69.58]) in prolactin levels, followed by risperidone 1–3 mg/day, paliperidone 3–6 mg/day, and paliperidone 6–12 mg/day. Conclusions. This study shows that there are differences in SGAs ability to cause hyperprolactinemia. Further, there is clear evidence of safety concerns with risperidone and paliperidone treatment in adolescent schizophrenia patients. Registration. PROSPERO CRD42014009506.


2020 ◽  
Author(s):  
Maria S. Neumeier ◽  
Stephanie Homan ◽  
Stefan Vetter ◽  
Erich Seifritz ◽  
John M. Kane ◽  
...  

Background: Side effects of antipsychotic drugs play a key role in non-adherence and discontinuation of treatment in schizophrenia spectrum disorders (SSD). Precision medicine aims to minimize such side effects by selecting the right treatment for the right patient. However, to determine the extent of precision medicine that is required, we need to (1) show that there is indeed variation in side effects and (2) estimate the amount of variation in those side effects between patients. While clinical observations suggest that such variation may be considerable, a statistical comparison of side effect variation between active and control treatments is required to confirm this. Here, we hypothesized to find larger side effect variation in treatment compared with control in patients treated with first and second generation antipsychotics. Methods: We included double-blind, placebo-controlled, randomized controlled trials (RCTs) of adults with a diagnosis of SSD and prescription for licensed antipsychotic drugs. Standard deviations of the pre-post treatment differences of weight gain, prolactin levels,and corrected QT (QTc) times were extracted. Data quality and validity were ensured by following the PRISMA guidelines. The outcome measure was the overall variability ratio of treatment to control across RCTs. Individual variability ratios were weighted by the inverse-variance method and entered into a random-effects model. Results: We included N = 16578 patients for weight gain, N = 16633 patients for prolactin levels, and N = 10384 patients for QTc time. Variability ratios (VR) were significantly increased for weight gain (VR = 1.08; 95% CI: 1.02 - 1.14; P = 0.004) and prolactin levels (VR = 1.38; 95% CI: 1.17 - 1.62; P < 0.001) but did not reach significance for QTc time (VR = 1.05; 95% CI: 0.98 - 1.12; P = 0.135). Conclusion: We found increased variability in major side effects in patients with SSD under treatment with second generation antipsychotics, suggesting that subgroups of patients or even individual patients may benefit from improved treatment allocation through stratified or personalized medicine, respectively.


2013 ◽  
Vol 16 (6) ◽  
pp. 1205-1218 ◽  
Author(s):  
Jian-Ping Zhang ◽  
Juan A. Gallego ◽  
Delbert G. Robinson ◽  
Anil K. Malhotra ◽  
John M. Kane ◽  
...  

Abstract Because early treatment choice is critical in first-episode schizophrenia-spectrum disorders (FES), this meta-analysis compared efficacy and tolerability of individual second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs) in FES. We conducted systematic literature search (until 12 December 2010) and meta-analysis of acute, randomized trials with ⩾1 FGA vs. SGA comparison; patients in their first episode of psychosis and diagnosed with schizophrenia-spectrum disorders; available data for psychopathology change, treatment response, treatment discontinuation, adverse effects, or cognition. Across 13 trials (n = 2509), olanzapine (seven trials) and amisulpride (one trial) outperformed FGAs (haloperidol: 9/13 trials) in 9/13 and 8/13 efficacy outcomes, respectively, risperidone (eight trials) in 4/13, quetiapine (one trial) in 3/13 and clozapine (two trials) and ziprasidone (one trial) in 1/13, each. Compared to FGAs, extrapyramidal symptom (EPS)-related outcomes were less frequent with olanzapine, risperidone and clozapine, but weight gain was greater with clozapine, olanzapine and risperidone. Pooled SGAs were similar to FGAs regarding total psychopathology change, depression, treatment response and metabolic changes. SGAs significantly outperformed FGAs regarding lower treatment discontinuation, irrespective of cause, negative symptoms, global cognition and less EPS and akathisia, while SGAs increased weight more (p < 0.05–0.01). Results were not affected by FGA dose or publication bias, but industry-sponsored studies favoured SGAs more than federally funded studies. To summarize, in FES, olanzapine, amisulpride and, less so, risperidone and quetiapine showed superior efficacy, greater treatment persistence and less EPS than FGAs. However, weight increase with olanzapine, risperidone and clozapine and metabolic changes with olanzapine were greater. Additional FES studies including broader-based SGAs and FGAs are needed.


2009 ◽  
Vol 194 (5) ◽  
pp. 439-445 ◽  
Author(s):  
Manuel J. Cuesta ◽  
Elena García de Jalón ◽  
M. Soledad Campos ◽  
Victor Peralta

BackgroundCognitive impairment in schizophrenia-spectrum disorders is highly prevalent and notably influences functional outcomes.AimsTo characterise the cognitive effectiveness of second-generation antipsychotic drugs.MethodOne hundred consecutive and previously unmedicated patients with first-episode schizophrenia-spectrum disorders were admitted. Seventy-seven completed baseline, 1-month and 6-month psychopathological and neuropsychological assessments. Patients were randomised to risperidone or olanzapine treatment. Four final treatment allocation groups were defined since patients continued treatment in their normal setting: risperidone, olanzapine, mixed and no-antipsychotic groups.ResultsThere were no differences in cognitive effectiveness between the four treatment groups. Reliable change index methods demonstrated that nearly a half of patients showed an improvement in Global Cognitive Score at the 6-month assessment. Improvement on the neuropsychological tests ranged from 17 to 54%.A strong predictor of cognitive response was poor performance on baseline neuropsychological tests; response was moderately influenced by a low premorbid scholastic performance and IQ.ConclusionsCognitive improvement related to second-generation antipsychotic drugs appeared within the first 4 weeks of treatment and persisted at 6 months irrespective of treatment group. Greater cognitive dysfunction at baseline and lower premorbid cognitive background predicted cognitive improvement in our sample.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S314-S315
Author(s):  
Maria Susanne Neumeier ◽  
Stephanie Winkelbeiner ◽  
John Kane ◽  
Erich Seifritz ◽  
Maximilian Huhn ◽  
...  

Abstract Background Adverse effects of antipsychotic drugs play a key role in non-compliance and discontinuation of treatment in Schizophrenia Spectrum Disorders (SSD). Precision medicine aims to minimize such adverse effects by selecting the right treatment for the right patients. To determine the need for precision medicine we need to estimate the amount of variation in adverse effects between patients. While clinical experience suggests that such variation is considerable, analyzing how variation differs between treated and untreated patients can answer this question. Here, we hypothesized to find larger variation in treatment compared to control groups of patients treated with second generation antipsychotics. Methods We included double-blind, placebo-controlled, randomized trials of adults with a diagnosis of schizophrenia spectrum disorders and prescription for licensed antipsychotic drugs. Means and variances of the pretreatment and posttreatment outcome differences of weight gain, prolactine levels, and corrected QTC times were extracted. Data quality and validity were ensured by following the PRISMA guidelines. The outcome measure was the overall variability ratio of treatment to control across RCTs. Individual variability ratios were weighted by the inverse-variance method and entered into a random-effects model. Results We included N = 13 282 patients for weight gain, N = 11 767 for prolactine levels, and N = 7 203 for QTC time. For all the measured adverse effects, variances were greater in treatment compared to control. Specifically, variance ratios were increased for weight gain (VR = 1.13, 95% CI: 1.06, 1.20), prolactine levels (VR = 1.38, 95% CI: 1.13, 1.68) and QTc time (VR = 1.06, 95% CI: 1.01, 1.12). Discussion We found increased variability in the major side effects that patients with SSD had under treatment with second generation antipsychotics. Indeed, some patients were more susceptible than others to weight gain, prolactine level increase, and QTC time increase, suggesting that precision medicine in antipsychotic treatment should be informed by individual differences in side effects rather than treatment effects. Future studies should aim at finding biological predictors of such individual differences in side effects.


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