scholarly journals Lamotrigine Therapy for Bipolar Depression: Analysis of Self-Reported Patient Data

2018 ◽  
Vol 5 (4) ◽  
pp. e63 ◽  
Author(s):  
Antoine Nzeyimana ◽  
Kate EA Saunders ◽  
John R Geddes ◽  
Patrick E McSharry
Keyword(s):  
Bipolar Disorder ◽  
Time Series ◽  
Depressive Symptoms ◽  
Sample Size ◽  
Coefficient Of Variation ◽  
Classification Accuracy ◽  
Bipolar Depression ◽  
Explanatory Power ◽  
Mean Difference ◽  
The Mean

Background Depression in people with bipolar disorder is a major cause of long-term disability, possibly leading to early mortality and currently, limited safe and effective therapies exist. Although existing monotherapies such as quetiapine have limited proven efficacy and practical tolerability, treatment combinations may lead to improved outcomes. Lamotrigine is an anticonvulsant currently licensed for the prevention of depressive relapses in individuals with bipolar disorder. A double-blinded randomized placebo-controlled trial (comparative evaluation of Quetiapine-Lamotrigine [CEQUEL] study) was conducted to evaluate the efficacy of lamotrigine plus quetiapine versus quetiapine monotherapy in patients with bipolar type I or type II disorders. Objective Because the original CEQUEL study found significant depressive symptom improvements, the objective of this study was to reanalyze CEQUEL data and determine an unbiased classification accuracy for active lamotrigine versus placebo. We also wanted to establish the time it took for the drug to provide statistically significant outcomes. Methods Between October 21, 2008 and April 27, 2012, 202 participants from 27 sites in United Kingdom were randomly assigned to two treatments; 101: lamotrigine, 101: placebo. The primary variable used for estimating depressive symptoms was based on the Quick Inventory of Depressive Symptomatology—self report version 16 (QIDS-SR16). The original CEQUEL study findings were confirmed by performing t test and linear regression. Multiple features were computed from the QIDS-SR16 time series; different linear and nonlinear binary classifiers were trained to distinguish between the two groups. Various feature-selection techniques were used to select a feature set with the greatest explanatory power; a 10-fold cross-validation was used. Results From weeks 10 to 14, the mean difference in QIDS-SR16 ratings between the groups was −1.6317 (P=.09; sample size=81, 77; 95% CI −0.2403 to 3.5036). From weeks 48 to 52, the mean difference was −2.0032 (P=.09; sample size=54, 48; 95% CI −0.3433 to 4.3497). The coefficient of variation (σ/μ) and detrended fluctuation analysis (DFA) exponent alpha had the greatest explanatory power. The out-of-sample classification accuracy for the 138 participants who reported more than 10 times after week 12 was 62%. A consistent classification accuracy higher than the no-information benchmark was obtained in week 44. Conclusions Adding lamotrigine to quetiapine treatment decreased depressive symptoms in patients with bipolar disorder. Our classification model suggested that lamotrigine increased the coefficient of variation in the QIDS-SR16 scores. The lamotrigine group also tended to have a lower DFA exponent, implying a substantial temporal instability in the time series. The performance of the model over time suggested that a trial of at least 44 weeks was required to achieve consistent results. The selected model confirmed the original CEQUEL study findings and helped in understanding the temporal dynamics of bipolar depression during treatment. Trial Registration EudraCT Number 2007-004513-33; https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-004513-33/GB (Archived by WebCite at http://www.webcitation.org/73sNaI29O).

scholarly journals Lamotrigine Therapy for Bipolar Depression: Analysis of Self-Reported Patient Data (Preprint)

2017 ◽  
Author(s):  
Antoine Nzeyimana ◽  
Kate EA Saunders ◽  
John R Geddes ◽  
Patrick E McSharry
Keyword(s):  
Bipolar Disorder ◽  
Time Series ◽  
Depressive Symptoms ◽  
Sample Size ◽  
Coefficient Of Variation ◽  
Classification Accuracy ◽  
Bipolar Depression ◽  
Explanatory Power ◽  
Mean Difference ◽  
The Mean

BACKGROUND Depression in people with bipolar disorder is a major cause of long-term disability, possibly leading to early mortality and currently, limited safe and effective therapies exist. Although existing monotherapies such as quetiapine have limited proven efficacy and practical tolerability, treatment combinations may lead to improved outcomes. Lamotrigine is an anticonvulsant currently licensed for the prevention of depressive relapses in individuals with bipolar disorder. A double-blinded randomized placebo-controlled trial (comparative evaluation of Quetiapine-Lamotrigine [CEQUEL] study) was conducted to evaluate the efficacy of lamotrigine plus quetiapine versus quetiapine monotherapy in patients with bipolar type I or type II disorders. OBJECTIVE Because the original CEQUEL study found significant depressive symptom improvements, the objective of this study was to reanalyze CEQUEL data and determine an unbiased classification accuracy for active lamotrigine versus placebo. We also wanted to establish the time it took for the drug to provide statistically significant outcomes. METHODS Between October 21, 2008 and April 27, 2012, 202 participants from 27 sites in United Kingdom were randomly assigned to two treatments; 101: lamotrigine, 101: placebo. The primary variable used for estimating depressive symptoms was based on the Quick Inventory of Depressive Symptomatology—self report version 16 (QIDS-SR16). The original CEQUEL study findings were confirmed by performing t test and linear regression. Multiple features were computed from the QIDS-SR16 time series; different linear and nonlinear binary classifiers were trained to distinguish between the two groups. Various feature-selection techniques were used to select a feature set with the greatest explanatory power; a 10-fold cross-validation was used. RESULTS From weeks 10 to 14, the mean difference in QIDS-SR16 ratings between the groups was −1.6317 (P=.09; sample size=81, 77; 95% CI −0.2403 to 3.5036). From weeks 48 to 52, the mean difference was −2.0032 (P=.09; sample size=54, 48; 95% CI −0.3433 to 4.3497). The coefficient of variation (σ/μ) and detrended fluctuation analysis (DFA) exponent alpha had the greatest explanatory power. The out-of-sample classification accuracy for the 138 participants who reported more than 10 times after week 12 was 62%. A consistent classification accuracy higher than the no-information benchmark was obtained in week 44. CONCLUSIONS Adding lamotrigine to quetiapine treatment decreased depressive symptoms in patients with bipolar disorder. Our classification model suggested that lamotrigine increased the coefficient of variation in the QIDS-SR16 scores. The lamotrigine group also tended to have a lower DFA exponent, implying a substantial temporal instability in the time series. The performance of the model over time suggested that a trial of at least 44 weeks was required to achieve consistent results. The selected model confirmed the original CEQUEL study findings and helped in understanding the temporal dynamics of bipolar depression during treatment. CLINICALTRIAL EudraCT Number 2007-004513-33; https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-004513-33/GB (Archived by WebCite at http://www.webcitation.org/73sNaI29O).

scholarly journals Technical note: Inherent benchmark or not? Comparing Nash–Sutcliffe and Kling–Gupta efficiency scores

2019 ◽  
Vol 23 (10) ◽  
pp. 4323-4331 ◽  
Author(s):  
Wouter J. M. Knoben ◽  
Jim E. Freer ◽  
Ross A. Woods
Keyword(s):  
Time Series ◽  
Coefficient Of Variation ◽  
Ad Hoc ◽  
Model Performance ◽  
Technical Note ◽  
Mean Flow ◽  
Model Adequacy ◽  
Robust Model ◽  
The Mean ◽  
Adequacy Assessment

Abstract. A traditional metric used in hydrology to summarize model performance is the Nash–Sutcliffe efficiency (NSE). Increasingly an alternative metric, the Kling–Gupta efficiency (KGE), is used instead. When NSE is used, NSE = 0 corresponds to using the mean flow as a benchmark predictor. The same reasoning is applied in various studies that use KGE as a metric: negative KGE values are viewed as bad model performance, and only positive values are seen as good model performance. Here we show that using the mean flow as a predictor does not result in KGE = 0, but instead KGE =1-√2≈-0.41. Thus, KGE values greater than −0.41 indicate that a model improves upon the mean flow benchmark – even if the model's KGE value is negative. NSE and KGE values cannot be directly compared, because their relationship is non-unique and depends in part on the coefficient of variation of the observed time series. Therefore, modellers who use the KGE metric should not let their understanding of NSE values guide them in interpreting KGE values and instead develop new understanding based on the constitutive parts of the KGE metric and the explicit use of benchmark values to compare KGE scores against. More generally, a strong case can be made for moving away from ad hoc use of aggregated efficiency metrics and towards a framework based on purpose-dependent evaluation metrics and benchmarks that allows for more robust model adequacy assessment.

Measuring Ethanol in Blood and Breath for Legal Purposes: Variability between Laboratories and between Breath-Test Instruments

1992 ◽  
Vol 38 (5) ◽  
pp. 743-747 ◽  
Author(s):  
A W Jones ◽  
K M Beylich ◽  
A Bjørneboe ◽  
J Ingum ◽  
J Mørland
Keyword(s):  
Healthy Volunteers ◽  
Coefficient Of Variation ◽  
Breath Test ◽  
Venous Blood ◽  
Mean Difference ◽  
The Mean ◽  
Highly Correlated

Abstract We determined the concentrations of ethanol in nearly simultaneous specimens of venous blood (BAC) and end-expired breath (BrAC) after healthy volunteers drank moderate amounts of alcohol. BAC was measured at two laboratories and BrAC was analyzed with two instruments (Intoxilyzer 5000) from the same manufacturer. The mean difference in BAC between laboratories was 0.0105 mg/g (SD 0.0219); 95% of the differences ranged from -0.0333 to 0.0543 mg/g. The mean difference in BrAC between instruments was 0.0153 mg/L (SD 0.0136), and 95% of the differences ranged from -0.0119 to 0.0425 mg/L. The coefficient of variation (CV) between laboratories was 2.9% compared with 4.5% between breath-test instruments. Venous BAC (y) and BrAC (x) were highly correlated (r = 0.978). However, when the Intoxilyzer instruments indicated that BrAC had reached zero, the actual BAC was 0.135 mg/g, according to the average forensic laboratory reports. The Intoxilyzer 5000 breath analyzers used in this study seem to have a constant analytical bias.

scholarly journals Homicide attempt due to medication induced mania

2021 ◽  
Author(s):  
Jordan Berry ◽  
Naghmeh Mokhber ◽  
Arun Prakash ◽  
Ajay Prakash ◽  
Julie Zamprogna
Keyword(s):  
Bipolar Disorder ◽  
Major Depressive Disorder ◽  
Depressive Symptoms ◽  
Mental Disorders ◽  
Bipolar Depression ◽  
Bipolar Disorders ◽  
Depressive State ◽  
Major Depressive ◽  
Difficult Situation ◽  
Serotonergic Antidepressant

Bipolar disorders are a group of mental disorders characterized by fluctuations in mood, with depressive symptoms generally dominating the course of disorder. Research on the efficacy of serotonergic antidepressants in bipolar depression is controversial and as a result, treatment of depressive symptoms in bipolar disorder is difficult. A particularly difficult situation arises when bipolar disorder is unrecognized and the depressive state is treated as major depressive disorder with the use of serotonergic antidepressants, which can result in the phenomenon of antidepressant induced mania (AIM). In this report, we present a case of antidepressant induced mania (AIM) with homicidal ideation after initiation of serotonergic antidepressants. Here, we discuss the importance of monitoring for bipolar disorder after prescribing serotonergic antidepressant therapy as well as medico-legal considerations.

scholarly journals Une méthode asymptotique pour tester la validité du modèle d’équilibre d’actifs financiers (MEDAF) avec pour exemple la bourse de Paris

2009 ◽  
Vol 57 (2) ◽  
pp. 225-243
Author(s):  
Emmanuel Apel
Keyword(s):  
Time Series ◽  
Sample Size ◽  
Stock Exchange ◽  
Rate Of Return ◽  
Residual Variance ◽  
Cross Sectional ◽  
Market Portfolio ◽  
The Mean ◽  
Squared Residuals ◽  
Mean Variance

ABSTRACT One of the problems in testing the validity of the two-parameter CAPM is the determination of an efficient proxy market portfolio to represent the true market portfolio. We test the mean-variance efficiency of a pre-specified market portfolio by using a method proposed by Roll (1976) for testing the linear relation between the rate of return of an asset and its beta, and hence the mean-variance efficiency of a proxy market portfolio. This procedure exploits the asymptotic exact linearity condition of the rate of return and beta by measuring the rate of decrease of cross-sectional residual variance with respect to increasing time-series sample size. The technique is applied to samples of companies on the Paris Stock Exchange for the period 1969-1978: 144 companies and twenty-nine different time series. The results indicate that although the sum of the squared residuals of a CAPM-type regression declines as the number of time observations increases, the sum of the squared residuals does not approach zero as the temporal sample size increases, as would be required for the market proxy of our pre-specified sample to be efficient.

scholarly journals Repeatability and comparability of simulated K values between a grid projection-based device and a Placido/dual Scheimpflug device

2020 ◽  
Vol 2 (4) ◽  
pp. 270-280
Author(s):  
Julian Matius Tagal
Keyword(s):  
Coefficient Of Variation ◽  
Ocular Trauma ◽  
Mean Difference ◽  
Absolute Difference ◽  
Limits Of Agreement ◽  
The Mean ◽  
Mean Differences ◽  
The Right

Purpose: To evaluate the repeatability and comparability of simulated K values obtained by the Galilei G4 Corneal Tomographer and the iDesign Wavefront Abberometer. Methods: The right eyes of 100 consecutive pre-laser-assisted in situ keratomileusis (LASIK) patients were included in this study. Patients with a history or signs of previous corneal or ocular trauma and infection were excluded. Paired corneal measurements for flat (K1) and steep (K2) meridians were obtained with both the Galilei and the iDesign. Repeatability was evaluated by calculating the coefficient of variation (CV) of the paired measurements. The comparability between platforms was evaluated by calculation of the mean differences followed by the construction of Bland-Altman plots and calculation of limits of agreement (LOA). Results: While the mean CV for both devices was low (0.17% versus 0.57% for the Galilei and iDesign, respectively), a large proportion of eyes measured by the iDesign (22%) showed an absolute difference of > 0.5 D between paired readings, compared to 1% as measured by the Galilei. The Galilei consistently measured higher than the iDesign. Although the mean difference did not exceed 0.17 D, the LOAs were unacceptablywide at -0.52 D to 0.85 D and -0.69 D to 0.89 D for K1 and K2, respectively. Conclusion: As regards keratometry, the iDesign demonstrated clinically unacceptable repeatability. Both platforms demonstrated sufficiently wide LOA that we could not recommend that they are used interchangeably.

scholarly journals Technical note: Inherent benchmark or not? Comparing Nash-Sutcliffe and Kling-Gupta efficiency scores

2019 ◽  
Author(s):  
Wouter J. M. Knoben ◽  
Jim E. Freer ◽  
Ross A. Woods
Keyword(s):  
Time Series ◽  
Coefficient Of Variation ◽  
Model Performance ◽  
Technical Note ◽  
Mean Flow ◽  
The Mean

Abstract. A traditional metric used in hydrology to summarize model performance is the Nash-Sutcliffe Efficiency (NSE). Increasingly an alternative metric, the Kling-Gupta Efficiency (KGE), is used instead. When NSE is used, NSE = 0 corresponds to using the mean flow as a benchmark predictor. The same reasoning is applied in various studies that use KGE as a metric: negative KGE values are often viewed in the literature as bad model performance and positive values are seen as good model performance. Here we show that using the mean flow as a predictor does not result in KGE = 0, but instead KGE = 1−√2 ≈ −0.41. Thus, KGE values greater than −0.41 indicate that a model improves upon the mean flow benchmark – even if the model's KGE value is negative. NSE and KGE values cannot be directly compared, because their relationship is non-unique and depends in part on the coefficient of variation of the observed time series. Therefore, we argue that modellers should not let their understanding of NSE values guide them in interpreting KGE values and instead develop new understanding based on the constitutive parts of the KGE metric and the explicit use of benchmark values to compare KGE scores against.

Improved Fluorometric Method for Determining Selenium

1978 ◽  
Vol 61 (4) ◽  
pp. 927-930 ◽  
Author(s):  
Phyllis A Whetter ◽  
Duane E Ullrey
Keyword(s):  
Skeletal Muscle ◽  
Standard Deviation ◽  
Standard Error ◽  
Coefficient Of Variation ◽  
Biological Materials ◽  
Mean Difference ◽  
Fluorometric Method ◽  
Aoac Method ◽  
The Mean ◽  
Selenium Analysis

Abstract A previously reported method for selenium analysis of biological materials has been modified to reduce equipment requirements and labor, resulting in 40—80 determinations in an 8-hr period. Digestions are performed on hot plates in Erlenmeyer flasks, and neutralization, chelation with EDTA, complexing with 2,3- diaminonaphthalene, and extraction of the piazoselenol into cyclohexane are completed in the same vessel. Flotation of the cyclohexane layer into the neck of the flask with water allows convenient transfer to fluorometer tubes. Representative analytical values for serum, skeletal muscle, liver, kidney, corn, and alfalfa hay are presented. The mean recovery (± standard deviation) of added selenite selenium in 84 determinations was 98.1±7.1%. The mean coefficient of variation (± standard error) of repeated analyses of the same samples was 6.98±0.78%. The mean difference (± standard error) between values determined by the proposed method and the AOAC method was -0.03±0.60%.

scholarly journals 156 The Broad Efficacy of Cariprazine Across Symptoms in Patients with Bipolar I Disorder: Post Hoc Analysis of Randomized, Placebo-Controlled Trials

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 300-300
Author(s):  
Lakshmi N. Yatham ◽  
Eduard Vieta ◽  
Roger S. McIntyre ◽  
Rakesh Jain ◽  
Willie R. Earley ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Depressive Symptoms ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Partial Agonist ◽  
Controlled Trials ◽  
Bipolar I Disorder ◽  
Manic Symptoms ◽  
Bipolar Mania ◽  
Post Hoc

Abstract:Study Objective:Patients with bipolar disorder experience a wide range of depressive and manic symptoms. Only 2 drugs are FDA-approved to treat episodes of both mania and depression in patients with bipolar disorder, highlighting the need for treatments with proven efficacy at opposite poles of the bipolar spectrum. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, is approved in the US for the treatment of both bipolar depression and manic and mixed episodes associated with bipolar I disorder. Cariprazine has previously demonstrated broad efficacy in patients with bipolar mania, with significantly greater improvement in favor of cariprazine vs placebo (PBO) across all individual symptom domains (P<.001) measured by the Young Mania Rating Scale (YMRS). Additionally, cariprazine has demonstrated efficacy vs PBO in 3 phase II/III clinical studies in patients with depressive episodes associated with bipolar I disorder (NCT01396447, NCT02670538, NCT02670551). To further assess the broad efficacy of cariprazine in patients with bipolar I disorder, we performed post hoc analyses to evaluate the range of depressive symptoms comprising the individual items of the Montgomery-Åsberg Depression Rating Scale (MADRS) in patients from the bipolar depression studies.Methods:Data from the 3 randomized, double-blind, PBO-controlled trials in patients with bipolar depression were pooled. Least squares (LS) mean change from baseline to week 6 in MADRS individual items was assessed in the pooled cariprazine 1.5 and 3 mg/d groups vs PBO using a mixed-effects model for repeated measures in the intent-to-treat (ITT) population.Results:There were 1383 patients in the ITT population (placebo=460; cariprazine 1.5-3 mg/d=923). At week 6, LS mean change from baseline was significantly greater for cariprazine 1.5-3 mg/d vs PBO on 9 of 10 individual MADRS items: Apparent Sadness (-2.0 vs -1.6, P<.0001); Reported Sadness (-2.0 vs -1.6, P<.0001); Reduced Sleep (-1.6 vs -1.4, P=.0357); Reduced Appetite (-1.2 vs -1.0, P=.0001); Concentration Difficulties (-1.5 vs -1.2, P=.0002); Lassitude (-1.7 vs -1.4, P=.0003); Inability To Feel (-1.7 vs -1.5, P=.0009); Pessimistic Thoughts (-1.4 vs -1.2, P=.0054) and Suicidal Thoughts (-0.3 vs -0.2, P=.0383); differences between cariprazine and PBO on the Inner Tension item were not significant.Conclusions:Significant improvement in most MADRS single items suggests broad efficacy in depressive symptoms for cariprazine 1.5-3 mg/d vs PBO in patients with bipolar depression. Coupled with broad efficacy in manic symptoms as demonstrated by significant improvement in all YMRS individual items in patients with bipolar mania or mixed episodes, cariprazine appears be effective across the range of symptoms that affect patients with bipolar disorder.Funding Acknowledgements:Supported by Allergan plc.

Adaptation and validation of the Korean Version of the Bipolar Depression Rating Scale (K-BDRS)

2016 ◽  
Vol 33 (S1) ◽  
pp. s236-s237
Author(s):  
W.M. Bahk ◽  
M.D. Kim ◽  
Y.E. Jung ◽  
Y.S. Woo ◽  
J. Lee ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Depressive Symptoms ◽  
Psychometric Properties ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Depression Scale ◽  
Reliability And Validity ◽  
Hamilton Depression Scale ◽  
Young Mania ◽  
Korean Version

ObjectivesThe Bipolar Depression Rating Scale (BDRS) is a scale for assessment of the clinical characteristics of bipolar depression. The primary aims of this study were to describe the development of the Korean version of the BDRS (K-BDRS) and to establish more firmly its psychometric properties in terms of reliability and validity.MethodsThe study included 141 patients (62 male and 79 female) who had been diagnosed with bipolar disorder, were currently experiencing symptoms of depression, and were interviewed using the K-BDRS. Other measures included the Montgomery and Asberg Depression Scale (MADRS), the 17-item Hamilton Depression Scale (HAMD), and the Young Mania Rating Scale (YMRS). Additionally, the internal consistency, concurrent validity, inter-rater reliability, and test-retest reliability of the K-BDRS were evaluated.ResultsThe Cronbach's α-coefficient for the K-BDRS was 0.866, the K-BDRS exhibited strong correlations with the HAMD (r = 0.788) and MADRS (r = 0.877), and the mixed symptoms score of the K-BDRS was significantly correlated with the YMRS (r = 0.611). An exploratory factor analysis revealed three factors that corresponded to psychological depressive symptoms, somatic depressive symptoms, and mixed symptoms.ConclusionsThe present findings suggest that the K-BDRS has good psychometric properties and is a valid and reliable tool for assessing depressive symptoms in patients with bipolar disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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