Isabella Helmreich

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

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 depression. EI was defined as a reduction of > or =20% on the 17-item Hamilton Rating Scale for Depression (HAMD-17) compared with baseline within the first 2 weeks of treatment. The predictive value of EI for stable response at week 8 and 10 (> or =50% HAMD-17 sum score reduction at weeks 8 and 10) and stable remission (HAMD-17 sum score < or =7 at weeks 8 and 10) was evaluated. RESULTS In both the sertraline- and CBT-treatment group, EI was a highly sensitive predictor for later stable response (76% and 82%, respectively) and stable remission (70% and 75%, respectively). In patients without EI, only a small proportion of sertraline or CBT-treated patients achieved stable response (20.9% and 5.9%, respectively) or stable remission (18.6% and 8.8%, respectively). Patients with EI were by far more likely to achieve stable response or stable remission than patients without as indicated by high odds ratios (95% confidence interval) of 8.1 (3.0-21.8) and 3.8 (1.4-10.1) for sertraline, and 11.1 (2.1-58.4) and 7.2 (1.7-30.8) for CBT-treated patients, respectively. LIMITATIONS Sample sizes were relatively low in different treatment groups. CONCLUSION The identification of early improvement might be useful in clinical decision making in the early course of treatment of patients with mild major, minor and subthreshold depression.

Reliability of three alternate forms of the trail making tests a and B.

The majority of patients with Major Depressive Disorder (MDD) suffer from significant executive dysfunctions. To investigate the time course of executive functions during antidepressant treatment, repeated measures of executive functions are necessary. In order to avoid practice effects, the assessment of alternate forms is suggested. The aim of this study was to compare the processing times of four alternate versions of the Trail Making Test (TMT) A and B in patients with MDD. Fifty-five subjects with DSM-IV MDD were included in the study. We analyzed mean processing times and retest reliability of the four versions of TMT A and B. Mean processing times did not differ between the four tested versions of TMT A and B. Retest reliability of TMT A and B was between 0.76 and 0.89 and between 0.86 and 0.94, respectively. Because of their identical difficulty and high reliability, the herein described versions of the TMT A and B are suitable for sequential testing of executive functioning.

The resilience framework as a strategy to combat stress-related disorders

Consistent failure over the past few decades to reduce the high prevalence of stress-related disorders has motivated a search for alternative research strategies. Resilience refers to the phenomenon of many people maintaining mental health despite exposure to psychological or physical adversity. Instead of aiming to understand the pathophysiology of stress-related disorders, resilience research focuses on protective mechanisms that shield people against the development of such disorders and tries to exploit its insights to improve treatment and, in particular, disease prevention. To fully harness the potential of resilience research, a critical appraisal of the current state of the art — in terms of basic concepts and key methods — is needed. We highlight challenges to resilience research and make concrete conceptual and methodological proposals to improve resilience research. Most importantly, we propose to focus research on the dynamic processes of successful adaptation to stressors in prospective longitudinal studies.

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 (n = 97; venlafaxine XR for study days 15-56; in case of sustained non-improvement on day 28, lithium augmentation for days 29-56) or TAU (n = 95; escitalopram continuation; non-responders on day 28 were switched to venlafaxine XR for four weeks, i.e. days 29-56). The primary outcome was remission (HAMD-17 ≤ 7) after 8 weeks of treatment as assessed by blinded raters. Remission rates were 24% for EMC and 16% for TAU, which was not significantly different (p = 0.2056). Sensitivity analyses for the primary and secondary effectiveness endpoints consistently showed favorable results for patients randomized to EMC. The results confirm data from post-hoc analyses of clinical trials showing that early non-improvement identifies patients who likely need alternate interventions. However, the herein used two-step switch/augmentation strategy for this risk group was not more effective than the control intervention. Alternate strategies and other design aspects are discussed in order to support researchers addressing the same research question.

Standardized Rater Training for the Hamilton Depression Rating Scale (HAMD17) and the Inventory of Depressive Symptoms (IDSC30)

out in preparation of a randomized clinical trial comparing an early medication change strategy with treatment as usual in patients with major depressive disorders (ClinicalTrials.gov, identifier No. NCT00974155). Twenty-one participants were included in the study (19 women and 2 men). Mean age ( 8 SD) of the raters was 34 8 6.1 years (range: 28–50). Seventeen were psychologists and 4 were psychiatric residents. Mean clinical experience ( 8 SD) of the raters was 1.6 8 1.6 years (range: 0–5 years). All raters were familiar with HAMD 17 but had no standardized training before and were unfamiliar with IDS C30 . HAMD 17 and IDS C30 interviews were conducted according to the literature [5] . All patients had given informed, written, video-taped consent prior to the interview. Five video tapes of patients (4 women and 1 man) with major depression according to the DSM-IV criteria [6] were presented during a 1-day course. Three patients were rated with HAMD and IDS, and 2 with HAMD 17 only. Prior to the training, the video tapes were rated by two experienced raters (S.W. and A.T.). The experts had 7 and 9 years of experience with the use of different depression rating scales including HAMD and IDS. According to the expert ratings, the patients had HAMD 17 total scores (average of both experts) of 15, 6, 13, 15 and 15 and IDS C30 One approach to increase objectivity and reliability in the application of rating instruments in clinical practice as well as in clinical trials is the implementation of standardized trainings for the participating raters. Inter-rater reliability scores are established parameters to assess the quality of standardized rater trainings. Establishing the inter-rater reliability in clinical practice as well as in studies of depression treatment is of high importance because the absence of rater trainings has been shown to weaken the quality of severity ratings in clinical routine as well as the results in clinical trials [1] . In a previous study, Müller and Dragecivic [2] reported on a standardized rater training for the Hamilton Depression Rating Scale (HAMD 17 ) [3] in psychiatric novices. This rater training was carried out using three video-taped interviews of depressed patients in 21 psychiatric novices. Results showed sufficiently high inter-rater reliability for most of the individual HAMD 17 items as well as for the HAMD 17 total score, suggesting that three training sessions are adequate to establish satisfactory inter-rater reliability. The aim of the present study was to analyze the inter-rater reliability of the HAMD 17 and the Inventory of Depressive Symptoms (IDS C30 ) [4] in a standardized training. The rater training was carried Received: May 25, 2010 Accepted: June 22, 2010 Published online: November 11, 2010

Sensitivity to changes during antidepressant treatment : a comparison of unidimensional subscales of the Inventory of Depressive Symptomatology (IDS-C) and the Hamilton Depression Rating Scale (HAMD) in patients with mild major, minor or subsyndromal 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’. We previously had shown that the Inventory of Depressive Symptomatology (IDS) was more sensitive to detect depressive symptom changes than the HAMD17 (Helmreich et al. 2011). Furthermore, studies suggest that the unidimensional subscales of the HAMD, which capture the core depressive symptoms, outperform the full HAMD regarding the detection of antidepressant treatment effects. The aim of the present study was to compare several unidimensional subscales of the HAMD and the IDS regarding their sensitivity to changes in depression symptoms in a sample of patients with mild major, minor or subsyndromal depression (MIND). Biweekly IDS-C28 and HAMD17 data from 287 patients of a 10-week randomised, placebo-controlled trial comparing the effectiveness of sertraline and cognitive–behavioural group therapy in patients with MIND were converted to subscale scores and analysed during the antidepressant treatment course. We investigated sensitivity to depressive change for all scales from assessment-to-assessment, in relation to depression severity level and placebo–verum differences. The subscales performed similarly during the treatment course, with slight advantages for some subscales in detecting treatment effects depending on the treatment modality and on the items included. Most changes in depressive symptomatology were detected by the IDS short scale, but regarding the effect sizes, it performed worse than most subscales. Unidimensional subscales are a time- and cost-saving option in judging drug therapy outcomes, especially in antidepressant treatment efficacy studies. However, subscales do not cover all facets of depression (e.g. atypical symptoms, sleep disturbances), which might be important for comprehensively understanding the nature of the disease depression. Therefore, the cost-to-benefit ratio must be carefully assessed in the decision for using unidimensional subscales.

The Inventory of Depressive Symptomatology (IDS-C28) is more sensitive to changes in depressive symptomatology than the Hamilton Depression Rating Scale (HAMD17) in patients with mild major, minor or subsyndromal depression

Depression rating scales play a decisive role in the assessment of the severity of depression and the evaluation of the efficacy of antidepressant treatments. The Hamilton Depression Rating Scale (HAMD) is regarded as the ‘gold standard’; nevertheless, studies suggest that the Inventory of Depressive Symptomatology (IDS) is more sensitive to detect symptom changes. The aim of the present study was to investigate whether the IDS is more sensitive in detecting changes in depression symptoms in patients with mild major, minor or subsyndromal depression (MIND). Biweekly IDS-C28 and HAMD17 data from 340 patients of a 10-week randomized, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural therapy in patients with MIND were analysed. We investigated sensitivity to change for both scales (1) from assessment-to-assessment, (2) in relation to depression severity level, and (3) in relation to DSM-IV depression criterion symptoms. The IDS-C28 was more sensitive in detecting changes in depression symptomatology over the treatment course as well as for different severity levels, especially in patients with a low depression severity. It assesses the DSM-IV criteria more thoroughly, is better able to track the change of cognitive symptoms and to identify residual symptoms. Both scales are well able to assess depressive symptomatology. However, the IDS-C28 surpasses the HAMD17 in detecting small changes especially in the core symptoms of depression. This is important for an optimal treatment by capturing early improvements, enabling prompt reactions and detecting residual symptoms.

Intervention studies to foster resilience – A systematic review and proposal for a resilience framework in future intervention studies

Psychological resilience refers to the phenomenon that many people are able to adapt to the challenges of life and maintain mental health despite exposure to adversity. This has stimulated research on training programs to foster psychological resilience. We evaluated concepts, methods and designs of 43 randomized controlled trials published between 1979 and 2014 which assessed the efficacy of such training programs and propose standards for future intervention research based on recent developments in the field. We found that concepts, methods and designs in current resilience intervention studies are of limited use to properly assess efficacy of interventions to foster resilience. Major problems are the use of definitions of resilience as trait or a composite of resilience factors, the use of unsuited assessment instruments, and inappropriate study designs. To overcome these challenges, we propose 1) an outcome-oriented definition of resilience, 2) an outcome-oriented assessment of resilience as change in mental health in relation to stressor load, and 3) methodological standards for suitable study designs of future intervention studies. Our proposals may contribute to an improved quality of resilience intervention studies and may stimulate further progress in this growing research field.

Hamilton depression rating subscales to predict antidepressant treatment outcome in the early course of treatment

BACKGROUND Hamilton depression rating scale (HAMD) subscales provide an economic alternative for the full scale; however, their ability to detect onset of improvement in the early course of treatment (EI) has not yet been researched. The present study investigated in patients with major depression (MD) whether the subscales are a comparable option to predict treatment remission in the early course of treatment. METHODS Based on data from 210 MD patients of a 6-week randomised, placebo-controlled trial comparing mirtazapine (MIR) and paroxetine (PAR), the discriminative and predictive validity of EI for (stable) remission at treatment end was evaluated for seven subscales and the HAMD17 in the total and in treatment subgroups (MIR vs. PAR). Receiver operating characteristics (ROC) curves (at week 2) and the Clinical Global Impression scales (CGI) (at study endpoint) were used to validate the 20% EI criterion for the subscales. RESULTS Only the Evans6 and Toronto7 subscale had almost the same predictive value as the HAMD17 (e.g., sensitivities stable remission Evans6/Toronto7: 96/95% vs. 96% HAMD17). The optimal cut-off for EI to predict remission was just below 20% for most subscales and slightly over 20% for stable remission. LIMITATIONS Study sample representativeness, non-independence of subscales, missing external validation criterion, lack of control group. CONCLUSIONS The Evans6 and Toronto7 subscales are valuable alternatives in situations, where economic aspects play a larger role. A sum score reduction of ≥20% as definition for EI seems also appropriate for the HAMD subscales, in the total as well as in the antidepressant subgroups.

Population-based validation of a German version of the Brief Resilience Scale

Smith and colleagues developed the Brief Resilience Scale (BRS) to assess the individual ability to recover from stress despite significant adversity. This study aimed to validate the German version of the BRS. We used data from a population-based (sample 1: n = 1.481) and a representative (sample 2: n = 1.128) sample of participants from the German general population (age ≥ 18) to assess reliability and validity. Confirmatory factor analyses (CFA) were conducted to compare one- and two-factorial models from previous studies with a method-factor model which especially accounts for the wording of the items. Reliability was analyzed. Convergent validity was measured by correlating BRS scores with mental health measures, coping, social support, and optimism. Reliability was good (α = .85, ω = .85 for both samples). The method-factor model showed excellent model fit (sample 1: χ2/df = 7.544; RMSEA = .07; CFI = .99; SRMR = .02; sample 2: χ2/df = 1.166; RMSEA = .01; CFI = 1.00; SRMR = .01) which was significantly better than the one-factor model (Δχ2(4) = 172.71, p < .001) or the two-factor model (Δχ2(3) = 31.16, p < .001). The BRS was positively correlated with well-being, social support, optimism, and the coping strategies active coping, positive reframing, acceptance, and humor. It was negatively correlated with somatic symptoms, anxiety and insomnia, social dysfunction, depression, and the coping strategies religion, denial, venting, substance use, and self-blame. To conclude, our results provide evidence for the reliability and validity of the German adaptation of the BRS as well as the unidimensional structure of the scale once method effects are accounted for.