Correction: Do side effects of antidepressants impact efficacy estimates based on the Hamilton Depression Rating Scale? A pooled patient-level analysis.
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SUBMITTER: Hieronymus F
PROVIDER: S-EPMC8105385 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
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Correction: Do side effects of antidepressants impact efficacy estimates based on the Hamilton Depression Rating Scale? A pooled patient-level analysis.
Hieronymus Fredrik F Lisinski Alexander A Eriksson Elias E Østergaard Søren Dinesen SD
Translational psychiatry 20210507 1
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Project description: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 that side effects of antidepressant treatment are erroneously rated as symptoms of depression, and vice versa. This study uses patient-level data from previously conducted antidepressant treatment trials to assess whether side effect ratings co-vary with HDRS-17 ratings. Data from all HDRS-17-rated, industry-sponsored pre- and post-marketing trials (n = 4647) comparing the serotonin and noradrenaline reuptake inhibitor, duloxetine, to placebo and/or to a selective serotonin reuptake inhibitor were pooled; three studies, which utilised sub-therapeutic doses, did not have symptom-level ratings available and could not be included. Severity was assessed for side effects related to sleep, somatic anxiety, gastrointestinal function, and sexual dysfunction. Analysis of covariance was used to assess the relation between these side effects and ratings of relevant HDRS-17-derived outcome parameters. Side effects related to sleep, somatic anxiety and sexual dysfunction significantly and exclusively associated with higher scores on HDRS-17 items measuring the corresponding domains. Side effects related to gastrointestinal function associated with higher HDRS-17 item scores on all assessed domains. Treatment outcome was significantly related to side effect severity when assessed using HDRS-17-sum (beta 0.32 (0.074), p < 0.001), but not when the HDRS-6-sum-score (beta 0.035 (0.043), p = 0.415) or the depressed mood item (beta 0.007 (0.012), p = .527) were used as effect parameters. That some HDRS-17 items co-vary with common antidepressant side effects suggests some of these adverse events are counted twice, potentially leading to an underestimation of antidepressant efficacy.
| S-EPMC8079707 | biostudies-literature
Project description:ObjectivesWe investigated the predictive value of subset scales and full versions of the Hamilton Rating Scale for Depression (HAMD) for therapeutic outcomes in ECT.MethodsThis secondary analysis of patients with major depression (N = 136; 63% female; age = 56.7 [SD = 14.8]) from the EFFECT-Dep trial (NCT01907217) examined the predictive value of Evans-6, Toronto-7, Gibbons-8 and Maier-Philip 6 HAMD subset scales and three 'full' versions (HAMD-17, HAMD-21 and HAMD-24) on therapeutic outcomes. We also examined early improvement on subset scales and full versions as predictors of response and remission and explored predictive abilities of individual HAMD-24 items.ResultsThe subset scales and full scales lacked sufficient predictive ability for response and remission. Receiver operating characteristic curves identified a lack of discriminative capacity of HAMD subset scales and full versions at baseline to predict response and remission. Only the Maier-Philip-6 was significantly associated with percentage reduction in HAMD-24 scores from baseline to end of ECT course. Early improvement on most of the subset scales and full versions was a sensitive and specific predictor of response and remission. Four of the HAMD-24 items were significantly associated with response and one with remission.ConclusionsLimited utility of the HAMD subset scales and full versions in this context highlight a need for more tailored depression rating scales for ECT.
| S-EPMC8577745 | biostudies-literature
Project description:The objective of this study is to explore the associations between the patient-reported Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire (PHQ)-9 and clinician-reported 17-item Hamilton Depression Rating Scale (HAMD-17) in order to facilitate clinical decision-making. An integrated efficacy dataset of three randomized placebo-controlled trials (NCT02614547, NCT02942004, and NCT02942017) evaluating brexanolone injection, a neuroactive steroid chemically identical to allopregnanolone, in women with postpartum depression was used for this post hoc analysis. Data were pooled across treatment arms. Associations were assessed at day 30 (end-of-trial follow-up). Pearson correlation assessed the relationship between EPDS and PHQ-9 item and total scores and HAMD-17 total score. Cohen's kappa assessed agreement of EPDS remission (score < 10) and PHQ-9 remission (score < 5) with HAMD-17 remission (score ≤ 7). Ordinary least squares (OLS) regression models were used to develop equations estimating HAMD-17 total scores from EPDS and PHQ-9 scores, respectively. The total scores showed large correlations (HAMD-17/EPDS: r = 0.71, p < 0.001; HAMD-17/PHQ-9: r = 0.75, p < 0.001). Individual EPDS and PHQ-9 items significantly correlated (r= 0.35 to 0.67, all p < 0.001) with HAMD-17 total score. EPDS had 79% sensitivity and 67% specificity to detect HAMD-17 remission; corresponding estimates for PHQ-9 were 76% and 78%. OLS models yielded the following equations: HAMD-17 total = 2.66 + (EPDS total × 0.87) and HAMD-17 total = 3.99 + (PHQ-9 total × 0.97). There were large and statistically significant associations between patient-reported outcomes (EPDS, PHQ-9) and clinician-reported outcomes (HAMD-17) as clinical improvements were associated with patient-reported symptom improvement. These results provide tools to help translate clinical trial data to clinical practice, thus aiding shared decision-making for this critical population.
| S-EPMC7497318 | biostudies-literature
Project description:BackgroundThe 17-item Hamilton Depression Rating Scale (HDRS17) is used world-wide as an observer-rated measure of depression in randomised controlled trials (RCTs) despite continued uncertainty regarding its factor structure. This study investigated the dimensionality of HDRS17 for patients undergoing treatment in UK mental health settings with moderate to severe persistent major depressive disorder (PMDD).MethodsExploratory Structural Equational Modelling (ESEM) was performed to examine the HDRS17 factor structure for adult PMDD patients with HDRS17 score ≥16. Participants (n = 187) were drawn from a multicentre RCT conducted in UK community mental health settings evaluating the outcomes of a depression service comprising CBT and psychopharmacology within a collaborative care model, against treatment as usual (TAU). The construct stability across a 12-month follow-up was examined through a measurement equivalence/invariance (ME/I) procedure via ESEM.ResultsESEM showed HDRS17 had a bi-factor structure for PMDD patients (baseline mean (sd) HDRS17 22.6 (5.2); 87% PMDD >1 year) with an overall depression factor and two group factors: vegetative-worry and retardation-agitation, further complicated by negative item loading. This bi-factor structure was stable over 12 months follow up. Analysis of the HDRS6 showed it had a unidimensional structure, with positive item loading also stable over 12 months.ConclusionsIn this cohort of moderate-severe PMDD the HDRS17 had a bi-factor structure stable across 12 months with negative item loading on domain specific factors, indicating that it may be more appropriate to multidimensional assessment of settled clinical states, with shorter unidimensional subscales such as the HDRS6 used as measures of change.
| S-EPMC7588071 | biostudies-literature
Project description:Background: The Hamilton Rating Scale for Depression (HAMD-17) has been used for several decades to assess the severity of depression. Multiple studies have documented defects in this scale and deemed it unsuitable for clinical evaluation. The HAMD-6, which is the abbreviated version of HAMD-17, has been shown to be effective in assessing the core symptoms of depression with greater sensitivity than HAMD-17. And the Patient Health Questionnaire-9 (PHQ-9) is suggested as an effective alternative to the HAMD-17 because of its simplicity and ease-of-use. Methods: Research was completed involving 1,741 participants having major depressive disorder. Cronbach's alpha, intraclass correlation coefficient (ICC) and weighted Kappa analysis was used to determine the reliability of the scales. Pearson correlation analysis and factor analysis were used to analyze validity. Item response theory (IRT) was used to analyze psychological characteristics of items in both the HAMD-17 and PHQ-9. Results: Reliability analysis showed that the Cronbach's alpha of the HAMD-17, HAMD-6 and PHQ-9 were 0.829, 0.764, and 0.893 respectively, and the ICC of the three scales ranged from 0.606 to 0.744. The Kappa score of the consistency of depression severity assessment was 0.248. Validity analysis showed that the PHQ-9 was a single factor structure, and the total score of the scale was strongly correlated with the HAMD-17 (r = 0.724, P < 0.001). The IRT analysis showed that the discrimination parameters of the PHQ-9 were higher than that of the HAMD-17 in all dimensions. The HAMD-6 had the lowest measurement accuracy in distinguishing the severity of depression, while the PHQ-9 had the highest measurement accuracy. Conclusion: Results showed that the PHQ-9 was satisfactory in terms of reliability, validity and distinguishing the severity of depression. It is a simple, rapid, effective and reliable tool which can be used as an alternative to the HAMD-17 to assess the severity of depression.
| S-EPMC8599822 | biostudies-literature
Project description:AimPresynaptic and post-synaptic glutamatergic modulation is associated with antidepressant activity that takes several weeks to reach a maximal full effect. Limiting mood elevating effects after single drug administration may be the result of compensatory synaptic processes. Therefore, using augmentation treatment with agents having presynaptic and post-synaptic effects on the glutamatergic system, this study aims to evaluate the effect of augmentation therapy on the rate of change in mood elevation in patients with bipolar depression.MethodsIn a pilot study, 29 outpatients with bipolar depression on a stable lamotrigine dose regimen received placebo or memantine pills daily (titrated up by 5 mg week⁻¹ to 20 mg) in a randomized, double-blind, parallel group, 8 week study. Patients were evaluated weekly using the 17-item Hamilton Depression Rating Score (HDRS) and all data were analyzed simultaneously. Linear, exponential, maximal effect, Gompertz and inverse Bateman functions were evaluated using a Bayesian approach population pharmacodynamic model framework. In these models, differences in parameters were examined across the memantine and placebo augmentation groups.ResultsA Gompertz function with a treatment switch on the parameter describing the speed of HDRS decline (γ, 95% confidence interval [CI]) best described the data (γ(memantine) = 1.8, 95% CI 0.9, 3.6), γ(placebo) = 1.2, 95% CI 0.5, 3.5)). Between subject variability was identified on baseline HDRS (2.9, 95% CI 1.5, 4.4) and amplitude of score improvement (4.3, 95% CI 2.7, 6.5).ConclusionsThis pharmacodynamic approach identified an increased speed of response after memantine augmentation, compared with placebo augmentation in bipolar depression patients.
| S-EPMC3575945 | biostudies-literature
Project description:The Hamilton rating scale for depression (HRSD) is considered the gold standard for the assessment of major depressive disorder. Nevertheless, it has drawbacks such as reliance on retrospective reports and a relatively long administration time. Using a combination of an experience sampling method with mobile health technology, the present study aimed at developing and conducting initial validation of HRSD-D, the first digital image-based assessment of the HRSD. Fifty-three well-trained HRSD interviewers selected the most representative image for each item from an initial sample of images. Based on their responses, we developed the prototype of HRSD-D in two versions: trait-like (HRSD-DT) and state-like (HRSD-DS). HRSD-DT collects one-time reports on general tendencies to experience depressive symptoms; HRSD-DS collects daily reports on the experience of symptoms. Using a total of 1933 responses collected in a preclinical sample (N = 86), we evaluated the validity and feasibility of HRSD-D, based on participant reports of HRSD-DT at baseline, and 28 consecutive daily reports of HRSD-DS, using smartphone devices. HRSD-D showed good convergent validity with respect to the original HRSD, as evident in high correlations between HRSD-DS and HRSD (up to Bstd = 0.80). Our combined qualitative and quantitative analyses indicate that HRSD-D captured both dynamic and stable features of symptomatology, in a user-friendly monitoring process. HRSD-D is a promising tool for the assessment of trait and state depression and contributes to the use of mobile technologies in mental health research and practice.
| S-EPMC9395406 | biostudies-literature
Project description:BACKGROUND:It has been claimed that efficacy estimates based on the Hamilton Depression Rating-Scale (HDRS) underestimate antidepressants true treatment effects due to the instrument's poor psychometric properties. The aim of this study is to compare efficacy estimates based on the HDRS with the gold standard procedure, the Montgomery-Asberg Depression Rating-Scale (MADRS). METHODS AND FINDINGS:We conducted a meta-analysis based on the comprehensive dataset of acute antidepressant trials provided by Cipriani et al. We included all placebo-controlled trials that reported continuous outcomes based on either the HDRS 17-item version or the MADRS. We computed standardised mean difference effect size estimates and raw score drug-placebo differences to evaluate thresholds for clinician-rated minimal improvements (clinical significance). We selected 109 trials (n = 32,399) that assessed the HDRS-17 and 28 trials (n = 11,705) that assessed the MADRS. The summary estimate (effect size) for the HDRS-17 was 0.27 (0.23 to 0.30) compared to 0.30 (0.22 to 0.38) for the MADRS. The effect size difference between HDRS-17 and MADRS was thus only 0.03 and not statistically significant according to both subgroup analysis (p = 0.47) and meta-regression (p = 0.44). Drug-placebo raw score difference was 2.07 (1.76 to 2.37) points on the HDRS-17 (threshold for minimal improvement: 7 points according to clinician-rating and 4 points according to patient-rating) and 2.99 (2.24 to 3.74) points on the MADRS (threshold for minimal improvement: 8 points according to clinician-rating and 5 points according to patient-rating). CONCLUSIONS:Overall there was no meaningful difference between the HDRS-17 and the MADRS. These findings suggest that previous meta-analyses that were mostly based on the HDRS did not underestimate the drugs' true treatment effect as assessed with MADRS, the preferred outcome rating scale. Moreover, the drug-placebo differences in raw scores suggest that treatment effects are indeed marginally small and with questionable importance for the average patient.
| S-EPMC7043778 | biostudies-literature
Project description:BACKGROUND:Previous research suggests that the 17-item Hamilton Depression Rating Scale (HAM-D17) is less sensitive in detecting differences between active treatment and placebo for major depressive disorder (MDD) than is the HAM-D6 scale, which focuses on six core depression symptoms. Whether HAM-D6 shows greater sensitivity when comparing two active MDD treatment arms is unknown. METHODS:This post hoc analysis used data from the intent-to-treat (ITT) cohort (N = 1541) of the Genomics Used to Improve DEpression Decisions (GUIDED) trial, a rater- and patient-blinded randomized controlled trial. GUIDED compared combinatorial pharmacogenomics-guided care with treatment as usual (TAU) in patients with MDD. Percent of symptom improvement, response rate and remission rate from baseline to week 8 were evaluated using both scales. Analyses were performed for the full cohort and for the subset of patients who at baseline were taking medications predicted by the test to have moderate or significant gene-drug interactions. A Mokken scale analysis was conducted to compare the homogeneity of HAM-D17 with that of HAM-D6. RESULTS:At week 8, the guided-care arm demonstrated statistically significant benefit over TAU when the HAM-D6 (∆ = 4.4%, p = 0.023) was used as the continuous measure of symptom improvement, but not when using the HAM-D17 (∆ = 3.2%, p = 0.069). Response rates increased significantly for guided-care compared with TAU when evaluated using both HAM-D6 (∆ = 7.0%, p = 0.004) and HAM-D17 (∆ = 6.3%, p = 0.007). Remission rates also were significantly greater for guided-care versus TAU using both measures (HAM-D6 ∆ = 4.6%, p = 0.031; HAM-D17 ∆ = 5.5%, p = 0.005). Patients in the guided-care arm who at baseline were taking medications predicted to have gene-drug interactions showed further increased benefit over TAU at week 8 for symptom improvement (∆ = 7.3%, p = 0.004) response (∆ = 10.0%, p = 0.001) and remission (∆ = 7.9%, p = 0.005) using HAM-D6. All outcomes showed continued improvement through week 24. Mokken scale analysis demonstrated the homogeneity and unidimensionality of HAM-D6, but not of HAM-D17, across treatment arms. CONCLUSIONS:The HAM-D6 scale identified a statistically significant difference in symptom improvement between combinatorial pharmacogenomics-guided care and TAU, whereas the HAM-D17 did not. The demonstrated utility of pharmacogenomics-guided treatment over TAU as detected by the HAM-D6 highlights its value for future biomarker-guided trials comparing active treatment arms. TRIAL REGISTRATION:Clinicaltrials.gov: NCT02109939. Registered 10 April 2014.
| S-EPMC6935147 | biostudies-literature
Project description:IntroductionThe Integrated Alzheimer's Disease Rating Scale (iADRS) has been used to detect differences in disease progression in early Alzheimer's disease (AD). The objectives of this study were to enhance understanding of iADRS point changes within the context of clinical trials, and to establish a minimal clinically important difference (MCID) on the iADRS.MethodsData from AMARANTH and EXPEDITION3 were analyzed using various approaches, including anchor-based, distribution-based, regression analyses, and cumulative distribution function (CDF) plots. Three potential anchors were examined, including the Clinical Dementia Rating-Sum of Boxes, Mini-Mental State Examination, and Functional Activities Questionnaire. Triangulation of all results was used to determine the MCID for participants with mild cognitive impairment (MCI) due to AD and AD with mild dementia.ResultsAll three anchors met criteria for "sufficiently associated" (|r| = 0.4-0.7). Cumulatively, results from anchor-based and distribution-based results converged to suggest an iADRS MCID of 5 points for MCI due to AD and 9 points for AD with mild dementia. Regression analyses and CDF plots supported these values.DiscussionThese findings suggest the iADRS can be used in clinical trials to detect a clinically meaningful outcome of AD progression.
| S-EPMC9169866 | biostudies-literature