Early improvement as a resilience signal predicting later remission to antidepressant treatment in patients with Major Depressive Disorder: Systematic review and meta-analysis.

Early improvement of depressive symptoms during the first two weeks of antidepressant treatment has been discussed to be a resilience signal predicting a later positive treatment outcome in patients with Major Depressive Disorder (MDD). However, the predictive value of early improvement varies between studies, and the use of different antidepressants may explain heterogeneous results. The objective of this review was to assess the predictive value of early improvement on later response and remission and to identify antidepressants with the highest chance of early improvement. We included 17 randomized controlled trials investigating early improvement in 14,779 adult patients with MDD compar…

P-515 - CGI Rating to predict antidepressant treatment under naturalistic conditions

Introduction Recent studies have shown that psychopathological rating by the Hamilton Depression Rating scale (HAMD) is well established and highly predictive for later response. In this study we aimed to find out if Clinical Global Impression (CGI) scale is suitable to guide antidepressive treatment under naturalistic conditions. Methods Inpatients with a major depressive disorder and treatment with citalopram were included and rated using in parallel the HAMD scale and the CGI scale weekly at baseline to day 35. According to CGI the sample has been divided in “CGI improver” (CGI = 2–4) and “CGI non-improver” (CGI = 5–6). Response was defined as HAMD sum score reduction by at least 50%. Re…

Early onset of depression and treatment outcome in patients with major depressive disorder

Major depressive disorder (MDD) is a highly heterogeneous disorder, which may partly explain why treatment outcome using antidepressants is unsatisfactory. We investigated the onset of depression as a possible clinical marker for therapy response prediction in the context of somatic biomarkers blood pressure and plasma electrolyte concentration. 889 MDD patients were divided into early (EO, n = 226), intermediate (IO, n = 493), and late onset (LO, n = 169) patients and were analyzed for differences in socio-demographic and clinical parameters, comorbidities and treatment outcome as well as systolic blood pressure and electrolytes. EO patients more often suffered from a recurrent depression,…

A monoamine oxidase B gene variant and short-term antidepressant treatment response.

Genetic differences among patients suffering from Major Depression are likely to contribute to interindividual differences in medication treatment response. Thus, the identification of gene variants affecting drug response is needed in order to be able to predict response to psychopharmacological drugs. This study analyzed a possible association of the common A644G single nucleotide polymorphism (SNP) within intron 13 of the monoamine oxidase B (MAOB) gene with antidepressant treatment response. The study population consisted of n = 102 patients with major depression (criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; DSM-IV) participating in a randomized do…

Association analysis between variants of the interleukin-1beta and the interleukin-1 receptor antagonist gene and antidepressant treatment response in major depression

André Tadic1, Dan Rujescu2, Matthias J Müller3, Ralf Kohnen4, Hans H. Stassen5, Armin Szegedi6, Norbert Dahmen11Department of Psychiatry, University of Mainz, Germany; 2Department of Psychiatry, University of Munich, Germany; 3Clinic for Psychiatry and Psychotherapy, Marburg-Sued, Germany, and Clinic for Psychiatry and Psychotherapy, Giessen, Germany; 4IMEREM, Nuernberg, Germany; 5Department of Psychiatry, University of Zurich, Switzerland; 6Organon, Roseland, NJ, USAAbstract: This study investigated the possible association of the interleukin-1 beta (IL-1β) C-511T promoter polymorphism and the interleukin-1 receptor antagonist (IL-1Ra) (86bp)n variable number o…

Confirmation of association of the GABRA2 gene with alcohol dependence by subtype-specific analysis

Objectives: Three recent studies revealed a haplotypic association of alcohol dependence with the gene encoding the {alpha}2 subunit of the {gamma}-aminobutyric acid type A (GABAA) receptor (GABRA2). The present study examined whether variation of the GABRA2 gene confers susceptibility to different subtypes of alcohol dependence in the German population. Methods: A total of 257 German alcohol-dependent patients and 88 healthy population controls were genotyped for six single-nucleotide polymorphisms covering the middle part and the 3′ end of GABRA2. Allelic, genotypic and haplotypic comparisons were done for subgroups of alcohol-dependent patients with a presumed high genetic load. Results:…

Effects of age on depressive symptomatology and response to antidepressant treatment in patients with major depressive disorder aged 18 to 65 years

Background: There is evidence that symptomatology in patients with major depressive disorder (MDD) changes with age. However, studies comparing depressive symptomatology between different age groups during antidepressant therapy are rare. We compared demographic and clinical characteristics in depressed patients of different age groups at baseline and during treatment. Methods: 889 MDD inpatients were divided into four age groups (18–29, 30–39, 40–49, 50–65 yrs.). Demographic and clinical characteristics including depressive symptomatology (assessed by the Inventory of Depressive Symptoms) were assessed at baseline and weekly during treatment. Results: At baseline, young patients (18–29 yea…

TheMAOA T941G polymorphism and short-term treatment response to mirtazapine and paroxetine in major depression

This study investigated the possible association of the MAOA T941G gene variant with differential antidepressant response to mirtazapine and/or paroxetine in 102 patients with major depression (DSM-IV criteria) participating in a randomized double-blind controlled clinical trial. Female mirtazapine-treated patients homozygous for the T-allele had a significantly faster and better treatment response than TG/GG-patients. In males, we failed to show an association between MAOA T941G gene variant and mirtazapine response. In the paroxetine-treated group, there were no significant differences in treatment response between MAOA T941G genotype groups. Time course of response and antidepressant eff…

Value of genetic and epigenetic testing as biomarkers of response to antidepressant treatment

Major depressive disorder (MDD) is one of the most prevalent and disabling psychiatric disorders worldwide and therefore an important public health priority. The selection process of antidepressant treatment is primarily guided by trial and error, and the outcomes with current antidepressant strategies are disappointing. The biological background of the disease is heterogeneous with presumably multiple biological systems involved. With the aim to individualize antidepressant treatment, multiple candidate gene and a few genome-wide association studies have been performed, but so far with very limited success. To address the dynamic changes of depressive symptoms and their response to treatme…

WITHDRAWN: Association analysis between the early change of serum brain-derived neurotrophic factor (sBDNF) and final change of depression severity during antidepressant treatment: A pilot study.

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Randomized controlled study of early medication change for non-improvers to antidepressant therapy in major depression – The EMC trial

Patients with Major Depressive Disorder (MDD) and no improvement after two weeks of antidepressant pharmacotherapy have a high risk of treatment failure. The aim of the study was to determine whether an early medication change (EMC) strategy is superior to a guideline-based treatment in MDD patients without improvement after two weeks of antidepressant pharmacotherapy. Eight-hundred-and-eighty-nine patients with MDD were enrolled, 879 patients received the SSRI escitalopram. Of those, 192 patients had no improvement, defined as a reduction of < 20% on the Hamilton Depression Rating Scale (HAMD-17) after 14 days of treatment, and were randomly assigned to open treatment with the EMC strategy…

W05-01 - Rationale and Design of an RCT Comparing “EMC-Strategy” with TAU in Patients with Major Depression - the EMC Trial

IntroductionFor Major Depression, current guidelines recommend treatment durations of 3-8 weeks until optimisation in case of insufficient outcome. Many retrospective studies indicate that improvement (HAMD-17 decrease ≥20%) occurs usually within 10-14 days and that non-improvement after 14 days of treatment is highly predictive for poor clinical outcome.MethodsIn level 1 of the EMC trial, non-improvers after 14 days of antidepressant treatment will be randomised to “early medication change” (EMC) strategy or treatment according to current guidelines (TAU). EMC schedules treatment optimisations on day 15 and day 29 in case of non-improvement. TAU schedules a medication change after 28 days …

Modulatory role of the brain-derived neurotrophic factor Val66Met polymorphism on the effects of serious life events on impulsive aggression in borderline personality disorder.

Impulsive aggression belongs to the key features of borderline personality disorder (BPD). In the development of BPD, serious life events are known to play a major role. Acute and chronic stress has been suggested to inhibit hippocampal brain-derived neurotrophic factor (BDNF) synthesis and to mediate neural plasticity in response to adverse social experiences. Recently it has been reported that the frequency of violent suicide attempts is higher in adult suicide attempters reporting severe childhood sexual abuse and carrying the Val(66)Val genotype of the BDNF Val(66)Met polymorphism. In this study we analysed modulating effects of BDNF Val(66)Met polymorphism on the effects of physical ma…

P01-92 - Early Changes are Associated with late Changes of BDNF Serum Levels in Inpatients with Major Depression During Short-term Antidepressant Treatment

ObjectivesMean BDNF serum concentration is lower in patients with major depression (MD) as compared to healthy controls. BDNF increases during the course of antidepressant treatment. This increase has been associated with symptom amelioration. The aim of this study was to analyse the relation between early and late BDNF changes during antidepressant treatment.MethodsForty-six patients with MD according to DSM-IV were included for this study. Patients were treated as clinically indicated. Depression severity was assessed by HAMD-17 by trained raters from baseline to week 6 in weekly intervals. Serum at each visit (baseline, V1-V6) was obtained from whole blood after centrifugation with 1.000…

EPA-0703 – Performance of the hamilton depression rating subscales to predict antidepressant treatment response in the early course of treatment

Early improvement ( EI ), i.e. a symptom reduction from baseline of at least 20% after 2 weeks, has been proven to be a clinically useful predictor for later treatment outcome. In most studies EI is identified by using the sum score of the Hamilton Depression Rating Scale (HAMD). Several unidimensional subscales of the HAMD exist, which have proven to be an economic measure of treatment change. Their ability to detect onset of improvement in comparison to the full HAMD has not been researched yet. The present study investigated in patients with major depression (MD) (1) whether the HAMD subscales are a valid and economic option to predict antidepressant treatment response in the early cours…

Lack of modulating effects of the COMT Val158Met polymorphism on the association of serious life events (SLE) and impulsivity in patients with Borderline Personality Disorder

A combined marker of early non-improvement and the occurrence of melancholic features improve the treatment prediction in patients with Major Depressive Disorders

Abstract Background Early Improvement of depressive symptoms within two weeks of antidepressant treatment is a highly sensitive but less specific predictor of later treatment outcome. The aim of this study was to identify clinical features at treatment initiation which are associated with early improvement and non-improvement as well as to identify variables predicting non-remission in patients showing an early improvement. Methods 889 patients with a major depressive episode according to DSM-IV who had participated in an antidepressant treatment trial served as study sample. Clinical predictors (demographic variables, psychopathology, comorbid disorders) were analysed in 698 (79%) early im…

Association Between Citalopram Serum Levels and Clinical Improvement of Patients With Major Depression

Imaging studies have shown that serum concentrations of the selective serotonin reuptake inhibitor citalopram correlate with serotonin transporter (5-HTT) occupancy in vivo. In patients with major depressive disorders treated with citalopram, 80% 5-HTT occupancy was considered to be necessary for maximal therapeutic effects, which requires citalopram serum concentrations of at least 50 ng/mL. The aim of this study was to compare treatment outcome in patients with citalopram serum concentrations greater than and less than 50 ng/mL after 7 days of treatment. This study included inpatients with acute major depressive disorder according to International Classification of Disease, 10th Revision …

Association analysis between gene variants of the tyrosine hydroxylase and the serotonin transporter in borderline personality disorder.

For patients with borderline personality disorder (BPD), we previously reported an independent effect of the catechol-o-methyl-transferase (COMT) low-activity (Met(158)) allele and an interaction with the low-expression allele of the deletion/insertion (short/long or S/L, resp.) polymorphism in the serotonin transporter-linked promoter region (5-HTTLPR). The purpose of the present study was to extend these findings to the tyrosine hydroxylase (TH) Val(81)Met single nucleotide polymorphism (SNP), the 5-HTTLPR S/L polymorphism incorporating the recently described functional A/G SNP within the long allele of the 5-HTTLPR (rs25531) as well as the variable number of tandem repeat (VNTR) polymorp…

Association analysis of SCN9A gene variants with borderline personality disorder

Borderline personality disorder (BPD) is a serious psychiatric disorder affecting about 1-2% of the general population. Key features of BPD are emotional instability, strong impulsivity, repeated self-injurious behavior (SIB) and dissociation. In the etiology of BPD and its predominant symptoms, genetic factors have been suggested. The voltage-gated sodium channel Nav1.7 is expressed in sensory neurons and in the hippocampus, a key region of the limbic system probably dysfunctional in BPD and dissociative disorders. The alpha-subunit of Nav1.7 is encoded by the SCN9A gene on chromosome 2 and variations of SCN9A can lead to complete inability to sense pain. The aim of the present study was t…

Severe Tremor After Cotrimoxazole-Induced Elevation of Venlafaxine Serum Concentrations in a Patient With Major Depressive Disorder

: We describe a female patient who was an extensive metabolizer of cytochrome P450 isoenzyme (CYP) 2D6 and an intermediate metabolizer of CYP2C19 (genotype: CYP2C19 *1/*2). She exhibited high serum concentrations of venlafaxine and O-desmethylvenlafaxine and developed severe tremor after comedication with cotrimoxazole (sulfamethazole/trimethoprim). Venlafaxine is mainly metabolized by O- and N-demethylation. O-demethylation is catalyzed by the highly polymorphic CYP2D6 and N-demethylation by several enzymes, CYP2C19, CYP2C9, and CYP3A4. The observed overall pharmacokinetic effect was most probably the result of decreased N-demethylation of venlafaxine by (1) reduced expression of CYP2C19 d…

Early reactions of brain-derived neurotrophic factor in plasma (pBDNF) and outcome to acute antidepressant treatment in patients with Major Depression.

Abstract In Major Depressive Disorder, a growing data base suggests that the onset of antidepressants’ action can be detected by improvement of depressive symptoms in the first 10–14 days of treatment. Previous studies showed that the mean concentration of the brain-derived neurotrophic factor (BDNF) in blood increases during antidepressant treatment and positively correlates with amelioration of MDD symptoms. We previously showed an association between very early changes of the serum BDNF concentration and treatment outcome ( Tadic et al., 2011 . Prog Neuropsychopharmacol Biol Psychiatry 35, 415–420). However, no study has yet investigated whether BDNF concentration in plasma increases in …

Early improvement of executive test performance during antidepressant treatment predicts treatment outcome in patients with Major Depressive Disorder

Executive dysfunctions frequently occur in patients with Major Depressive Disorder and have been shown to improve during effective antidepressant treatment. However, the time course of improvement and its relationship to treatment outcome is unknown. The aim of the study was to assess the test performance and clinical outcome by repetitive assessments of executive test procedures during antidepressant treatment. Executive test performance was assessed in 209 –patients with Major Depressive Disorder (mean age 39.3 ± 11.4 years) and 84 healthy controls five times in biweekly intervals from baseline to week 8. Patients were treated by a defined treatment algorithm within the early medication c…

Association of aMAOAgene variant with generalized anxiety disorder, but not with panic disorder or major depression

This study was conducted to detect a possible association of a T941G single nucleotide polymorphism (SNP) in the monoamine oxidase A (MAOA) gene with generalized anxiety disorder (GAD), panic disorder (PD), or major depression (MD). Fifty GAD patients (34 females and 16 males), 38 PD patients (21 females and 17 males), and 108 MD patients (80 females and 28 males) were included. The comparison group consisted of 276 (132 females and 144 males) unrelated healthy individuals. The 941T allele was over-represented in patients suffering from GAD (chi(2) = 6.757; df = 1; P < 0.01, not corrected for multiple testing) when compared to healthy volunteers. No association was observed in MD or PD. Thi…

Interaction between gene variants of the serotonin transporter promoter region (5-HTTLPR) and catecholO-methyltransferase (COMT) in borderline personality disorder

Borderline personality disorder (BPD) is characterized by a heterogeneous symptomatology with instability in impulse control, interpersonal relationships and self-image. BPD patients display repeated self-injury, chronic suicidal tendencies and emotional dysregulation, mainly dysregulation of negative affect. In its etiology, genetic and environmental factors have been suggested. Recently, an investigation in male healthy volunteers found gene–gene effects of the catechol-O-methyl-transferase (COMT) low-activity (Met158) and the low-expression allele of the deletion/insertion (short/long or S/L, respectively) polymorphism in the serotonin transporter-linked promoter region (5-HTTLPR) on the…

Gender differences in axis I and axis II comorbidity in patients with borderline personality disorder.

&lt;i&gt;Background/Aims:&lt;/i&gt; Differences in the clinical presentation of men and women with borderline personality disorder (BPD) are of potential interest for investigations into the neurobiology, genetics, natural history, and treatment response of BPD. The purpose of this study was to investigate gender differences in axis I and axis II comorbidity and in diagnostic criteria in BPD patients. &lt;i&gt;Methods:&lt;/i&gt; 110 women and 49 men with BPD were assessed with the computer-based version of the Munich-Composite International Diagnostic Interview and the Structured Clinical Interview for DSM-IV Personality Disorders. Gender differences were investigated for the following outc…

Early Improvement and Serum Concentrations of Citalopram to Predict Antidepressant Drug Response of Patients with Major Depression

Post hoc analyses of clinical trials have shown that early improvement around day 14 is highly predictive for later response. More- over, evidence has been given that suffi ciently high concentrations of antidepressant drugs in blood are required to attain response. In this study, we determined cut-off levels for citalo- pram serum concentrations and clinical improve- ment during the early phase of treatment to predict later response and the predictive power of these measures either alone or in combination. Methods: Inpatients with depressive disorder according to ICD-10 who received citalopram were included. Psychopathology was assessed by the 17-item Hamilton Depression (HAMD-17) rating s…

The catechol o-methyltransferase (COMT) val158met polymorphism modulates the association of serious life events (SLE) and impulsive aggression in female patients with borderline personality disorder (BPD)

Wagner S, Baskaya O, Anicker NJ, Dahmen N, Lieb K, Tadic A. The catechol o‐methyltransferase (COMT) val158met polymorphism modulates the association of serious life events (SLE) and impulsive aggression in female patients with borderline personality disorder (BPD). Objective: We analyzed i) the effects of serious life events (SLE) on impulsive aggression, and ii) modulating effects of the COMT Val158Met polymorphism on the association between SLEs and impulsive aggression in borderline personality disorder (BPD). Method: One hundred and twelve female BPD patients from Germany were included in this study. Impulsive aggression was assessed by the Buss‐Durkee‐Hostility Inventory (BDHI). Result…

Early improvement is a predictor of treatment outcome in patients with mild major, minor or subsyndromal depression

Abstract Background There is substantial evidence that early improvement (EI) under antidepressant treatment is a clinically useful predictor of later treatment outcome in patients with major depressive disorders. The aim of this study was to test whether EI can also be used as a predictor for treatment outcome in patients with mild major, minor or subsyndromal depression, i.e. patients, who are typically treated by general practitioners. Methods Analyses were carried out using data from 223 patients of a 10-weeks randomized, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural therapy (CBT) in patients with mild major, minor or subsyndromal depressio…

Body mass index (BMI) in major depressive disorder and its effects on depressive symptomatology and antidepressant response

Obesity is one of the most prevalent somatic comorbidities of Major Depressive Disorder (MDD). We aimed to investigate the relationship between body mass index (BMI) and MDD, the symptomatology of the disorder as well as the outcome of antidepressant treatment.Early medication change (EMC) trial participants with BMI measurement (n = 811) were categorized according to WHO-criteria in normal or low weight (BMI  25), overweight (25- 30), and obese (≥30). Depression severity and BMI was assessed in weekly intervals up to 8 weeks. BMI at baseline and course of BMI during the study were investigated in linear regression models as possible moderators of therapy response. Possible moderators such …

The catechol-O-methyltransferase Val108/158Met polymorphism affects short-term treatment response to mirtazapine, but not to paroxetine in major depression.

The catechol-O-methyltransferase (COMT) is a major degrading enzyme in the metabolic pathways of catecholaminergic neurotransmitters such as dopamine and norepinephrine. This study investigated whether the functionally relevant Val(108/158)Met gene variant is associated with differential antidepressant response to mirtazapine and/or paroxetine in 102 patients with major depression (DSM-IV criteria) participating in a randomized clinical trial with both drugs. In patients treated with mirtazapine, but not paroxetine, allelic variations in the COMT gene were associated with differential response. COMT(VAL/VAL) and COMT(VAL/MET) genotype carriers showed a better response than COMT(MET/MET)-bea…

The Amount of Mitochondrial DNA in Blood Reflects the Course of a Depressive Episode

P-491 - Sensitivity to changes during antidepressant treatment: a comparison of unidimensional depression rating scales in patients with minor depression

In the efficacy evaluation of antidepressant treatments the total score of the Hamilton Depression Rating Scale (HAMD) is still regarded as the’gold standard’. Studies suggest that unidimensional subscales of the HAMD, which capture the core depressive symptoms, outperform the full HAMD regarding the detection of antidepressant treatment effects. The present study compared several unidimensional subscales of the HAMD and the Inventory of Depressive Symptomatology (IDS) regarding their sensitivity to changes in depression symptoms in a sample of patients with minor depression (MIND). Biweekly IDS-C28 and HAMD17 data from 287 patients of a 10-week randomised, placebo-controlled trial comparin…