The recent questioning of the antidepressant effect selective serotonin reuptake inhibitors (SSRIs) is partly based on observation that approximately half company-sponsored trials have failed to reveal a significant difference between active drug and placebo. Most these applied Hamilton depression rating scale assess symptom severity, sum score for its 17 items (HDRS-17-sum) serving as parameter. In this study, we examined whether negative outcomes many SSRI may be caused by use frequently...

Abstract The possible dose-dependency for the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) remains controversial. We believe we have conducted first comprehensive patient-level mega-analysis exploring this issue, one incentive being to address possibility that inclusion low-dose arms in previous meta-analyses may caused an underestimation efficacy these drugs. All company-sponsored, acute-phase, placebo-controlled, fixed-dose trials using Hamilton Depression...

Abstract The clinical response to selective serotonin reuptake inhibitors (SSRIs) in depression takes weeks be fully developed and is still not entirely understood. This study aimed determine the direct indirect effects of SSRIs relative a placebo control condition on symptoms depression. We included data 8262 adult patients with major participating 28 industry-sponsored US Food Drug Administration (FDA) registered trials efficacy SSRIs. Clinical were assessed by 17 separate items Hamilton...

Long sea level records with high temporal resolution are of paramount importance for future coastal protection and adaptation plans. Here we discuss the application machine learning techniques to some regression problems commonly encountered when analyzing such time series. The performance artificial neural networks is compared that multiple linear models on data from Swedish coast. found be superior local forcing used together remote meteorological forcing, whereas show similar excluded....

It has been suggested that the superiority of antidepressants over placebo in controlled trials is merely a consequence side effects enhancing expectation improvement by making patient realize he/she not on placebo. We explored this hypothesis patient-level post hoc-analysis including all industry-sponsored, Food and Drug Administration-registered placebo-controlled citalopram or paroxetine adult major depression used Hamilton Depression Rating Scale (HDRS) included week 6 symptom assessment...

Abstract Objectives The aim was to describe the pre‐diagnostic and post‐diagnostic psychopharmacological treatment of bipolar disorder over past two decades. Methods We identified all 16 288 individuals aged ≥ 18 years, who received their first diagnosis at a psychiatric hospital in Denmark between 1997 2014. For each calendar year, we calculated proportion patients (with index date respective years) were prescribed 2 years preceding following disorder. diagnosed with from 2007 2010 (n =...

Abstract The Hamilton Depression Rating Scale (HDRS-17) measures symptoms that may overlap with common antidepressant side effects (e.g., sexual dysfunction), thus making it possible of treatment are erroneously rated as depression, and vice versa. This study uses patient-level data from previously conducted trials to assess whether effect ratings co-vary HDRS-17 ratings. Data all HDRS-17-rated, industry-sponsored pre- post-marketing ( n = 4647) comparing the serotonin noradrenaline reuptake...

The efficacy of antidepressants in major depressive disorder has been continually questioned, mainly on the basis studies using sum-score Hamilton Depression Rating Scale as a primary outcome parameter. On this measure show standardised mean difference around 0.3, which some authors suggested is below cut-off for clinical significance. Prompted by recent review that, argument, concluded should not be used adults with disorder, we (a) evidence support significance espoused that article (a...

Selective serotonin reuptake inhibitors (SSRIs) have been claimed to elicit or aggravate suicidal ideation. Aims To explore the effect of SSRIs on suicidality item Hamilton Rating Scale for Depression (HRSD).We undertook a patient-level mega-analysis adults with depression participating in industry-sponsored studies sertraline, paroxetine citalopram, comparing patients an SSRI (n = 5681) those placebo 2581) respect HRSD-rated suicidality. Separate analyses were conducted young (age 18-24; n...

Abstract Objectives In analysis of randomized controlled trials (RCTs) with patient-reported outcome measures (PROMs), Item Response Theory (IRT) models that allow for heterogeneity in the treatment effect at item level merit consideration. These “item-level heterogeneous effects” (IL-HTE) can provide more accurate statistical inference, researchers to better generalize their results, and resolve critical identification problems estimation interaction effects. this study, we extend IL-HTE...

Greater initial severity on the 30-item Positive and Negative Syndrome Scale (PANSS-30) correlates positively with antipsychotic-placebo separation trial dropout, but it is unknown whether these associations are present also PANSS-derived subscales. We assessed relationship between as measured by PANSS-30 four PANSS symptom subscales: positive (PANSS-POS), negative (PANSS-NEG), general (PANSS-GEN) 6-item (PANSS-6) subscales, using patient-level data from 18 placebo-controlled risperidone...

Since several recent meta-analyses report a dose-response relationship for the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs), we investigated how these drugs are dosed in clinical practice.Through linkage nation- or region-wide registers, describe SSRI doses 50,365 individuals residing Region Västra Götaland, Sweden, with an incident diagnosis depression and initiating treatment between 2007 2016. The primary question was to elucidate what extent had been...

A new machine learning based bias correction method is presented and applied to sea level in a regional climate model. The corrections derived using this depend on the state of model it corrects. This contrasts with conventional methods that operate distributions output variables. dependence states allows for better performance classical skill scores, but also limits applicability models can perform hindcasts. very large dataset corrected hourly levels from many different emission scenarios...

Abstract In order for measurement-based care to be implemented, there is a need brief rating instruments that can administered in short amount of time, but are still sufficiently informative. Here, we assessed the drug–placebo sensitivity six-item subscale (PANSS-6) 30-item Positive and Negative Syndrome Scale (PANSS-30) using large collection patient-level data ( n = 6685) from randomized controlled trials risperidone paliperidone. When analyzing by study, found no material difference mean...

Potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) are used in research to reflect the quality of drug treatment older people have been suggested for inclusion core outcome sets evaluation interventions improved prescribing. Their validation so far, however, is primarily restricted expert opinion-based processes.To evaluate performance 3 explicit PIM/PPO criteria as diagnostic tools identify inadequate patients.This study analyzed patients aged 65 years...