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- Hieronymus, Fredrik, 1986, et al.
(author)
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Influence of baseline severity on the effects of SSRIs in depression: an item-based, patient-level post-hoc analysis
- 2019
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In: Lancet Psychiatry. - : Elsevier BV. - 2215-0374 .- 2215-0366. ; 6:9, s. 745-752
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Journal article (peer-reviewed)abstract
- Background Reports claiming that antidepressants are effective only in patients with severe depression have affected treatment guidelines but these reports usually use a disputed measure of improvement, a decrease in the sum-score of the 17-item Hamilton Depression Rating Scale (HDRS-17), and are based on group-level rather than patient-level data. Method In this item-based, patient-level, post-hoc analysis, we pooled data from all completed, acute-phase, placebo-controlled, industry-sponsored, H DRS-based trials of the SSRIs citalopram, paroxetine, or sertraline in adult major depression. Patient-level data were pooled and subjected to item-based post-hoc analyses to assess the effect of baseline severity of depression on the response to treatment as assessed with HDRS-17 sum score, the depressed mood item of the HDRS, a six-item HDRS subscale (HDRS-6), and the remaining 11 HDRS items not included in this subscale (non-HDRS-6). Patients were defined as having non-severe depression if they had a baseline HDRS-17 sum score of 18 points or less and as having severe depression if they had a score of 27 points or more. Findings Our study population consisted of 8262 patients from 28 placebo-controlled SSRI trials. Participants were treated with either citalopram (n=744), paroxetine (n=2981), sertraline (n=1202), fluoxetine (active-control group; n=754), or placebo (n=2581). 654 patients were defined as having non-severe depression and 1377 as having severe depression. Patients with non-severe and severe depression did not differ with respect to SSRI-induced decrease in depressed mood and other HDRS symptoms belonging to the HDRS-6 subscale. However, after exclusion of patients with rare extreme baseline values, a positive association was seen between severity and efficacy when using HDRS-17 sum score as the effect parameter. This result was largely due to a more pronounced response to treatment with respect to non-HDRS-6 items in patients with severe depression than in those with non-severe depression. This outcome could be explained by non-HDRS-6 items, more so than HDRS-6 items, being more severe and prevalent at baseline in severe than in non-severe cases; hence, less room was left for improvement in these areas in patients with non-severe depression. Interpretation The use of an outcome measure that includes symptoms that rate low at baseline in patients with non-severe depression might result in the interpretation that SSRIs are ineffective in these patients. With respect to alleviation of HDRS-6 items, SSRIs appear to be as effective in patients with non-severe depression as in those with severe depression. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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| 3. |
- Hieronymus, Fredrik, et al.
(author)
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Influence of baseline severity on the effects of SSRIs in depression: an item-based, patient-level post-hoc analysis
- 2019
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In: The Lancet Psychiatry. - 2215-0366 .- 2215-0374. ; 6:9, s. 745-752
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Journal article (peer-reviewed)abstract
- Background: Reports claiming that antidepressants are effective only in patients with severe depression have affected treatment guidelines but these reports usually use a disputed measure of improvement, a decrease in the sum-score of the 17-item Hamilton Depression Rating Scale (HDRS-17), and are based on group-level rather than patient-level data. Method: In this item-based, patient-level, post-hoc analysis, we pooled data from all completed, acute-phase, placebo-controlled, industry-sponsored, H DRS-based trials of the SSRIs citalopram, paroxetine, or sertraline in adult major depression. Patient-level data were pooled and subjected to item-based post-hoc analyses to assess the effect of baseline severity of depression on the response to treatment as assessed with HDRS-17 sum score, the depressed mood item of the HDRS, a six-item HDRS subscale (HDRS-6), and the remaining 11 HDRS items not included in this subscale (non-HDRS-6). Patients were defined as having non-severe depression if they had a baseline HDRS-17 sum score of 18 points or less and as having severe depression if they had a score of 27 points or more. Findings: Our study population consisted of 8262 patients from 28 placebo-controlled SSRI trials. Participants were treated with either citalopram (n=744), paroxetine (n=2981), sertraline (n=1202), fluoxetine (active-control group; n=754), or placebo (n=2581). 654 patients were defined as having non-severe depression and 1377 as having severe depression. Patients with non-severe and severe depression did not differ with respect to SSRI-induced decrease in depressed mood and other HDRS symptoms belonging to the HDRS-6 subscale. However, after exclusion of patients with rare extreme baseline values, a positive association was seen between severity and efficacy when using HDRS-17 sum score as the effect parameter. This result was largely due to a more pronounced response to treatment with respect to non-HDRS-6 items in patients with severe depression than in those with non-severe depression. This outcome could be explained by non-HDRS-6 items, more so than HDRS-6 items, being more severe and prevalent at baseline in severe than in non-severe cases; hence, less room was left for improvement in these areas in patients with non-severe depression. Interpretation: The use of an outcome measure that includes symptoms that rate low at baseline in patients with non-severe depression might result in the interpretation that SSRIs are ineffective in these patients. With respect to alleviation of HDRS-6 items, SSRIs appear to be as effective in patients with non-severe depression as in those with severe depression.
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| 4. |
- Hollis, Chris, et al.
(author)
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Methylphenidate and the risk of psychosis in adolescents and young adults : a population-based cohort study
- 2019
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In: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 6:8, s. 651-658
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Journal article (peer-reviewed)abstract
- Background: There is a clinical concern that prescribing methylphenidate, the most common pharmacological treatment for attention-deficit hyperactivity disorder (ADHD), might increase the risk of psychotic events, particularly in young people with a history of psychosis. We aimed to determine whether the risk of psychotic events increases immediately after initiation of methylphenidate treatment or, in the longer term, 1 year after treatment initiation in adolescents and young adults with and without a previously diagnosed psychotic disorder.Methods: In this cohort study, we used population-based observational data from the Swedish Prescribed Drug Register, the National Patient Register, and the Total Population Register, three population-based registers containing data on all individuals in Sweden, to attain data on sex, birth, death, migration, medication use, and psychotic events for all eligible participants. We screened individuals on these registers to identify those receiving methylphenidate treatment, and who were aged 12-30 years at the start of treatment, for their inclusion in the study. We used a within-individual design to compare the incidence of psychotic events in these individuals during the 12-week periods immediately before and after methylphenidate initiation. Longer term risk was assessed by comparing the incidence of psychotic events 12 weeks before methylphenidate initiation and during a 12-week period one calendar year before the initiation of methylphenidate with the incidence of these events during the 12-week period one calendar year after methylphenidate initiation. We estimated the incidence rate ratios (IRR) and 95% CIs of psychotic events after the initation of methylphenidate treatment, relative to the events before treatment, which were defined as any hospital visit (inpatient admission or outpatient attendance, based on data from the National Patient Register) because of psychosis, using the International Classification of Diseases version 10 definition. Analyses were stratified by whether the individual had a history of psychosis.Findings: We searched the Swedish Prescribed Drug Register to find eligible individuals who had received methylphenidate between Jan 1, 2007 and June 30, 2012. 61 814 individuals were screened, of whom 23 898 (38.7%) individuals were assessed and 37 916 (61.3%) were excluded from the study because they were outside of the age criteria at the start of treatment, they had immigrated, emigrated, or died during the study period, or because they were administered other ADHD medications. The median age at methylphenidate initiation was 17 years, and a history of psychosis was reported in 479 (2.0%) participants. The IRR of psychotic events in the 12-week period after initiation of methylphenidate treatment relative to that in the 12-week period before treatment start was 1.04 (95% CI 0.80-1.34) in adolescents and young adults without a history of psychosis and 0.95 (0.69-1.30) among those with a history of psychosis.Interpretation: Contrary to clinical concerns, we found no evidence that initiation of methylphenidate treatment increases the risk of psychotic events in adolescents and young adults, including in those individuals with a history of psychosis. Our study should reassure clinicians considering initiating methylphenidate treatment for ADHD in adolescents and young adults, and it challenges the widely held view in clinical practice that methylphenidate should be avoided, or its use restricted, in individuals with a history of psychosis.
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- Kim, Jong Yeob, et al.
(author)
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Environmental risk factors and biomarkers for autism spectrum disorder: an umbrella review of the evidence
- 2019
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In: Lancet psychiatry. - : ELSEVIER SCI LTD. - 2215-0374 .- 2215-0366. ; 6:7, s. 590-600
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Research review (peer-reviewed)abstract
- Background Numerous studies have identified potential risk factors and biomarkers for autism spectrum disorder. We aimed to study the strength and validity of the suggested environmental risk factors or biomarkers of autism spectrum disorder. Methods We did an umbrella review and systematically appraised the relevant meta-analyses of observational studies. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for papers published between database inception and Oct 17, 2018, and screened the reference list of relevant articles. We obtained the summary effect, 95% CI, heterogeneity, and 95% prediction intervals. We examined small study effects and excess significance. We did analyses under credibility ceilings. This review is registered with PROSPERO, number CRD42018091704. Findings 46 eligible articles yielded data on 67 environmental risk factors (544 212 cases, 81 708 787 individuals) and 52 biomarkers (15 614 cases, 15 433 controls). Evidence of association was convincing for maternal age of 35 years or over (relative risk [RR] 1.31, 95% CI 1.18-1.45), maternal chronic hypertension (odds ratio [OR] 1.48, 1.29-1.70), maternal gestational hypertension (OR 1.37, 1.21-1.54), maternal overweight before or during pregnancy (RR 1.28, 1.19-1.36), pre-eclampsia (RR 1.32, 1.20-1.45), prepregnancy maternal antidepressant use (RR 1.48, 1.29-1.71), and maternal selective serotonin reuptake inhibitor (SSRI) use during pregnancy (OR 1.84, 1.60-2.11). Only two associations, maternal overweight before or during pregnancy and SSRI use during pregnancy, retained their high level of evidence under subset sensitivity analyses. Evidence from biomarkers was scarce, being supported by p values close to the significance threshold and too few cases. Interpretation Convincing evidence suggests that maternal factors, such as age and features of metabolic syndrome, are associated with risk of autism spectrum disorder. Although SSRI use during pregnancy was also associated with such risk when exposed and non-exposed groups were compared, this association could be affected by other confounding factors, considering that prepregnancy maternal antidepressant use was also convincingly associated with higher risk of autism spectrum disorder. Findings from previous studies suggest that one possible confounding factor is underlying maternal psychiatric disorders. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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| 7. |
- Gardner, Frances, et al.
(author)
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Equity effects of parenting interventions for child conduct problems: a pan-European individual participant data meta-analysis.
- 2019
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In: The Lancet Psychiatry. - 2215-0374. ; 6:6, s. 518-527
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Journal article (peer-reviewed)abstract
- Childhood conduct problems are a costly public health problem and are five times more common in socially disadvantaged groups than they are in advantaged groups. Untreated, conduct problems have a poor prognosis, with increasing gaps between socioeconomic groups, and high rates of subsequent criminality. Incredible Years is a high quality parenting programme for reducing conduct problems and is widely disseminated in Europe. Many trials have shown Incredible Years to be effective but the potential effects of parenting interventions on social inequality are unknown. Some behavioural interventions (eg, smoking cessation programmes), although beneficial overall, can widen inequality gaps. Because single trials and aggregate-level meta-analyses are ill equipped for examining differential intervention (moderator) effects, we pooled individual-level trial data to assess the effects of Incredible Years on social equity.We did a systematic review and individual participant data meta-analysis by searching CINAHL, Embase, Global Health, Medline, and PsycINFO, for studies published from inception to March 15, 2019. We also searched the Incredible Years website library and consulted with experts, including the European Incredible Years mentors' network. We included data from all completed randomised trials of the Incredible Years parenting intervention in Europe that included children aged 1-12 years, including unpublished trials, without restriction on publication year or outcome measures. We included prevention (selective or universal) and treatment or indicated prevention trials (for children diagnosed or above the clinical cutoff for conduct problems). We excluded trials or conditions within trials that were not randomised, included additional non-parenting material (eg, child-focused interventions), or were abbreviated, non-standard versions of the usual Incredible Years intervention of 12-14 weekly sessions. We requested individual participant data from the study authors. The primary outcome was child conduct problems, assessed using the Eyberg Child Behavior Inventory Intensity (ECBI-I) scale. Moderators were analysed using multilevel modelling with multiple imputation.Of 15 European trials of Incredible Years parenting programmes (n=1696 children), individual participant data were unavailable for one trial and one trial did not assess the primary outcome. Children were aged 2-10 years (median 5·1), 492 (30%) of 1651 children were from an ethnic minority and 931 (58%) of 1614 were from low-income families. Families who received the Incredible Years intervention reported an overall reduction in child conduct problems (13·5 points on the ECBI-I scale, 95% CI 10·9-16·1). There were no differential effects by family disadvantage (indicated by poverty, lone parenthood, teenage parenthood, household joblessness, or low education), or ethnic minority status.We found no evidence for differential effects by social disadvantage, suggesting that Incredible Years is unlikely to widen socioeconomic inequalities in conduct problems. Furthermore, the programme might be an important tool for reducing social disparities and improving poor long-term outcomes in disadvantaged families because follow-up studies indicate that benefits persist. Clinicians and commissioners can be reassured that the programme is similarly effective for families from different backgrounds.UK National Institute for Health Research.
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