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Despite well-established guidelines for managing major depressive disorder, its extensive disability burden persists. This Value of Treatment mission from the European Brain Council aimed to elucidate the nature and extent of “gaps” between best-practice and current-practice care, specifically to:
1. Identify current treatment gaps along the care pathway and determine the extent of these gaps in comparison with the stepped-care model and
After agreement upon a set of relevant treatment gaps, data pertaining to each gap were gathered and synthesized from several sources across six European countries. Subsequently, a modified Delphi approach was undertaken to attain consensus among an expert panel on proposed recommendations for minimizing treatment gaps.
Four recommendations were made to increase the depression diagnosis rate (from ~50% episodes), aiming to both increase the number of patients seeking help, and the likelihood of a practitioner to correctly detect depression. These should reduce time to treatment (from ~1 to ~8 years after illness onset) and increase rates of treatment; nine further recommendations aimed to increase rates of treatment (from ~25 to ~50% of patients currently treated), mainly focused on targeting the best treatment to each patient. To improve follow-up after treatment initiation (from ~30 to ~65% followed up within 3 months), seven recommendations focused on increasing continuity of care. For those not responding, 10 recommendations focused on ensuring access to more specialist care (currently at rates of ~5–25% of patients).
The treatment gaps in depression care are substantial and concerning, from the proportion of people not entering care pathways to those stagnating in primary care with impairing and persistent illness. A wide range of recommendations can be made to enhance care throughout the pathway.
Dietary interventions did not prevent depression onset nor reduced depressive symptoms in a large multi-center randomized controlled depression prevention study (MooDFOOD) involving overweight adults with subsyndromal depressive symptoms. We conducted follow-up analyses to investigate whether dietary interventions differ in their effects on depressive symptom profiles (mood/cognition; somatic; atypical, energy-related).
Baseline, 3-, 6-, and 12-month follow-up data from MooDFOOD were used (n = 933). Participants received (1) placebo supplements, (2) food-related behavioral activation (F-BA) therapy with placebo supplements, (3) multi-nutrient supplements (omega-3 fatty acids and a multi-vitamin), or (4) F-BA therapy with multi-nutrient supplements. Depressive symptom profiles were based on the Inventory of Depressive Symptomatology.
F-BA therapy was significantly associated with decreased severity of the somatic (B = −0.03, p = 0.014, d = −0.10) and energy-related (B = −0.08, p = 0.001, d = −0.13), but not with the mood/cognition symptom profile, whereas multi-nutrient supplementation was significantly associated with increased severity of the mood/cognition (B = 0.05, p = 0.022, d = 0.09) and the energy-related (B = 0.07, p = 0.002, d = 0.12) but not with the somatic symptom profile.
Differentiating depressive symptom profiles indicated that food-related behavioral interventions are most beneficial to alleviate somatic symptoms and symptoms of the atypical, energy-related profile linked to an immuno-metabolic form of depression, although effect sizes were small. Multi-nutrient supplements are not indicated to reduce depressive symptom profiles. These findings show that attention to clinical heterogeneity in depression is of importance when studying dietary interventions.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
The Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) are the most frequently used observer-rated and self-report scales of depression, respectively. It is important to know what a given total score or a change score from baseline on one scale means in relation to the other scale.
We obtained individual participant data from the randomised controlled trials of psychological and pharmacological treatments for major depressive disorders. We then identified corresponding scores of the HAMD and the BDI (369 patients from seven trials) or the BDI-II (683 patients from another seven trials) using the equipercentile linking method.
The HAMD total scores of 10, 20 and 30 corresponded approximately with the BDI scores of 10, 27 and 42 or with the BDI-II scores of 13, 32 and 50. The HAMD change scores of −20 and −10 with the BDI of −29 and −15 and with the BDI-II of −35 and −16.
The results can help clinicians interpret the HAMD or BDI scores of their patients in a more versatile manner and also help clinicians and researchers evaluate such scores reported in the literature or the database, when scores on only one of these scales are provided. We present a conversion table for future research.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
The influence of baseline severity has been examined for antidepressant
medications but has not been studied properly for cognitive–behavioural
therapy (CBT) in comparison with pill placebo.
To synthesise evidence regarding the influence of initial severity on
efficacy of CBT from all randomised controlled trials (RCTs) in which
CBT, in face-to-face individual or group format, was compared with
pill-placebo control in adults with major depression.
A systematic review and an individual-participant data meta-analysis
using mixed models that included trial effects as random effects. We used
multiple imputation to handle missing data.
We identified five RCTs, and we were given access to individual-level
data (n = 509) for all five. The analyses revealed that
the difference in changes in Hamilton Rating Scale for Depression between
CBT and pill placebo was not influenced by baseline severity (interaction
P = 0.43). Removing the non-significant interaction
term from the model, the difference between CBT and pill placebo was a
standardised mean difference of –0.22 (95% CI –0.42 to –0.02,
P = 0.03, I2 = 0%).
Patients suffering from major depression can expect as much benefit from
CBT across the wide range of baseline severity. This finding can help
inform individualised treatment decisions by patients and their
Sandra Dietrich, research fellow at the Department of Psychiatry, Leipzig University, Germany,
Lisa Wittenburg, project manager for the European Alliance Against Depression at the Department of Psychiatry, University of Leipzig, Germany,
Ella Arensman, Director of Research at the National Suicide Research Foundation, and Honorary Senior Lecturer,
Airi Värnik, Professor of Mental Health at Tallinn University, Estonia,
Ulrich Hegerl, Head and Medical Director of the Clinic of Psychiatry at Leipzig University, Germany
There has been much discussion about the most suitable terminology for suicidal acts and researchers have tried to find a common terminology and classification as well as operational definitions for the range of suicidal behaviours (O'Carroll et al, 1996; Maris, 2002; De Leo et al, 2004). In this chapter, we use the outcome-based term ‘fatal suicidal acts’ for suicidal behaviour that results in death and ‘non-fatal suicidal acts’ for suicidal actions that do not result in death.
There is no consensus on the definition of fatal suicidal acts, making it difficult, for instance, to collect accurate, comparable total rates of suicide. Numerous definitions are used, the most widely accepted being the definition produced by the World Health Organization (WHO, 2007a): ‘the act of deliberately killing oneself’. Apart from fatal suicidal acts, it is also of great importance to consider non-fatal suicidal acts, because they are one of the strongest predictors of suicide and have significant economic, medical and social costs. Non-fatal suicidal acts are also often called ‘attempted suicide’ (especially in the USA), ‘parasuicide’ and ‘deliberate self-harm’ (especially in Europe), but also ‘non-fatal suicidal behaviour’, ‘non-fatal self-inflicted harm’, ‘self-injury’ and ‘self-directed violence’. The usage of these terms varies considerably between countries.
Approximately one million people died from fatal suicidal acts in the year 2000, reflecting a ‘global’ mortality rate of 16 per 100 000, or one death every 30 seconds. Suicide is now among the three leading causes of death among those aged 15–45 years (both sexes) and in a growing number of countries the first cause of mortality among men aged 15–34. These figures do not include non-fatal suicidal acts, which are up to 20 times more frequent than fatal suicidal acts (WHO, 2007b). According to WHO estimates, approximately 1.53 million people will die from fatal suicidal acts in 2020, and 10–20 times more people will attempt suicide worldwide. This represents on average one death every 20 seconds and one attempt every 1–2 seconds (WHO, 1999).
Background. The global burden and large diagnostic and therapeutic deficits associated with depressive disorders call for intervention programs. The aim of the Nuremberg Alliance against Depression (NAD) is to establish and to assess the effectiveness of a four-level intervention program for improving the care of patients with depression.
Method. A 2-year intervention program was performed in Nuremberg (480000 inhabitants) at four levels: training of family doctors and support through different methods; a public relations campaign informing about depression; cooperation with community facilitators (teachers, priests, local media, etc.); and support for self-help activities as well as for high-risk groups. The effects of the 2-year intervention on the number of suicidal acts (completed suicides plus suicide attempts, main outcome criterion) were evaluated with respect to a 1-year baseline and a control region (Wuerzburg, 270000 inhabitants).
Results. Compared to the control region, a reduction in frequency of suicidal acts was observed in Nuremberg during the 2-year intervention (2001 v. 2000: −19·4%; p[les ]0·082; 2002 v. 2000: −24%, p[les ]0·004). Considering suicide attempts only (secondary outcome criterion), the same effect was found (2001 v. 2000: −18·3%, p[les ]0·023; 2002 v. 2000: −26·5%, p<0·001). The reduction was most noticeable for high-risk methods (e.g. hanging, jumping, shooting). Concerning completed suicides, there were no significant differences compared to the control region.
Conclusions. The NAD appeared to be effective in reducing suicidality. It provides a concept as well as many methods that are currently being implemented in several other intervention regions in Germany and in other countries.
Electroencephalography is the only diagnostic instrument directly reflecting cortical neuronal functioning, and it remains an important clinical tool in the diagnosis and differential diagnosis of Alzheimer's disease (AD). Although a normal EEG is found in many patients with mild AD, a pathological EEG is an important finding, because such a result is not in line with differential diagnoses such as depression or pseudodementia within a dissociative disorder. The vast majority of patients with moderate to servere AD have a pathological EEG. A normal EEG in this patient group is more in line with subcortical dementia or frontal lobe degeneration than with AD. Compared to SPECT or routine structural brain imaging (cCT, MRT), EEG has a comparable diagnosis sensitivity and a higher specificity. For monitoring changes of brain function by serial recordings (e.g., during therapy with antidementia drugs), EEG is the best available method.
Accurate and early diagnosis of Alzheimer's Disease (AD)
with reliable and noninvasive methods is of great importance
for clinical practice as effective and specific antidementive
therapies become available. The aim of the study was to evaluate
the clinical relevance of event-related P300 in the early diagnosis
of AD. Thirty patients with AD, 26 patients with mild cognitive
impairment (MCI) from our Memory Clinic and 26 age-matched healthy
controls (HC) were studied with event-related P300 potentials.
Amplitudes of temporo-basal dipoles (TB-P300) were significantly
diminished in AD compared to HC and MCI. Furthermore, latencies
of temporo-superior dipoles (TS-P300) were significantly prolonged
in AD compared with HC. Sensitivity was 90.0% for the
differentiation of patients with AD from HC (specificity 79.1%)
using reduced TB-P300 amplitudes and prolonged TS-P300 latencies.
Similar results were found using Pz amplitudes as well as Fz
latencies. Our data suggest that TB-P300 amplitudes and TS-P300
latencies may be an accurate clinically available, nonexpensive,
noninvasive, and reliable marker for AD.
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