The effects of COVID-19 on European healthcare provision for working-age adults with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide, and yet delivery of care for this illness is rife with gaps. The COVID-19 pandemic has had far reaching implications for every facet of healthcare, and MDD is no exception. This scoping review aimed to ascertain the impacts of COVID-19 on the delivery of MDD care in Europe, as well as to evaluate any novel MDD care strategies trialled in this period. METHODS: We searched the PubMed and PsycINFO databases up to January 2022 with a strategy centred around COVID-19 and MDD. Full texts of eligible studies examining working-age adults and conducted in Europe were evaluated against several criteria. All outcomes were then extracted and a narrative synthesis was constructed to summarise identified themes. RESULTS: Of 1,744 records identified in our search, 11 articles were eligible for inclusion in the review. In general, these studies reported a decrease in treatment rates, access to care, and perceived access to care during the COVID-19 pandemic. In addition, digital interventions trialled during the pandemic were broadly well-received by users, though their efficacy in improving MDD care was ambiguous. CONCLUSIONS: Despite a limited number of pertinent studies, this scoping review identified a trend of exacerbated treatment gaps in MDD care during the pandemic. Several of our pre-specified gaps, including delays to detection or treatment of depression and rates of follow-up contacts, remained unexplored in the context of COVID-19. This highlights the need for further investigation to obtain a full understanding of the relationship between COVID-19 and MDD care in Europe.

Viewpoint: Assessing the value of mental health treatments in Europe.

One in eight individuals worldwide lives with a mental health disorder. For many European countries, the prevalence is even higher, with one in four people reporting mental health problems [1]. Three-quarters of all mental health disorders develop before age 25, with many presenting initially in undiagnosed forms already in the mid-teens and eventually manifesting as severe disorders and lasting into old age [2]. There is also growing evidence that mental health disorder symptoms cross diagnoses and people frequently have more than one mental health disorder [3].

Economic impact of reducing treatment gaps in depression.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent across Europe. While evidence-based treatments exist, many people with MDD have their condition undetected and/or untreated. This study aimed to assess the cost-effectiveness of reducing treatment gaps using a modeling approach. METHODS: A decision-tree model covering a 27-month time horizon was used. This followed a care pathway where MDD could be detected or not, and where different forms of treatment could be provided. Expected costs pertaining to Germany, Hungary, Italy, Portugal, Sweden, and the UK were calculated and quality-adjusted life years (QALYs) were estimated. The incremental costs per QALY of reducing detection and treatment gaps were estimated. RESULTS: The expected costs with a detection gap of 69% and treatment gap of 50% were €1236 in Germany, €476 in Hungary, €1413 in Italy, €938 in Portugal, €2093 in Sweden, and €1496 in the UK. The incremental costs per QALY of reducing the detection gap to 50% ranged from €2429 in Hungary to €10,686 in Sweden. The figures for reducing the treatment gap to 25% ranged from €3146 in Hungary to €13,843 in Sweden. CONCLUSIONS: Reducing detection and treatment gaps, and maintaining current patterns of care, is likely to increase healthcare costs in the short term. However, outcomes are improved, and reducing these gaps to 50 and 25%, respectively, appears to be a cost-effective use of resources.

The organization of psychiatric care in France: current aspects and future challenges.

In the last four decades, psychiatric care in France has led to the development of catchment area-based service provision. Within each geographical area teams are now responsible for psychiatric care both at outpatient and inpatient levels. However, financial and economic constraints have led to a reduction in beds and staffing levels. The numbers of psychiatrists in private practice has remained more or less the same over the years due to steady demand and other factors. As in many other western European countries, de-institutionalization has been a major driver in the evolution of psychiatric care delivery in France. This is linked with several developments, including the introduction of more efficient pharmaceutical drugs which have reduced the likelihood of relapse. Other factors which have influenced this include the progressive 'de-stigmatization' of psychiatric disorders and policy changes leading to significant bed reduction. All of these factors are inter-linked and have influenced psychiatric care delivery. In this paper we provide an overview of the current state of psychiatric care and its delivery in France.

Wayfinding: the effects of large displays and 3-D perception.

Large displays and stereopsis have been shown to improve performance in several virtual navigation tasks. In the present research, we sought to determine whether wayfinding could benefit from these factors. Participants were tested in a virtual town. There were three viewing conditions: a desktop, a large screen, and a large screen on which the virtual environment was viewed in three dimensions (3-D) using polarized glasses. Participants explored the town and had to remember the location of several landmarks. Their memory of the layout of the town was tested by asking them to navigate from one landmark to another, taking the shortest route possible. All groups performed equally well in terms of the distance traveled to target locations. From this result, we concluded that large displays and 3-D perception do not significantly contribute to wayfinding. Thus, experimental paradigms and training programs that utilize wayfinding are as valuable when administered on standard desktops as on more sophisticated and costly equipment and do not induce simulator sickness as large displays tend to do.

Efficacy, safety, and tolerability of fixed-dose desvenlafaxine 50 and 100 mg/day for major depressive disorder in a placebo-controlled trial.

The objective of this study was to assess the efficacy, safety, and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) 50 and 100 mg/day for major depressive disorder (MDD). A multicenter, randomized, double-blind, placebo-controlled trial was conducted in Europe and South Africa. Outpatients with MDD received fixed-dose desvenlafaxine (50 or 100 mg/day) or placebo for 8 weeks. The primary efficacy variable was the 17-item Hamilton Rating Scale for Depression total score; secondary measures included Clinical Global Impressions-Improvement scores. The intent-to-treat population included 483 patients: desvenlafaxine 50 mg (n=164), desvenlafaxine 100 mg (n=158), and placebo (n=161). At the last-observation-carried-forward analysis (final evaluation) using analysis of covariance, adjusted mean changes from baseline on the Hamilton Rating Scale for Depression were significantly greater for both desvenlafaxine 50 mg (-13.2; P=0.002) and 100 mg (-13.7; P<0.001) versus placebo (-10.7). Significant differences on the Clinical Global Impressions-Improvement scores were observed for desvenlafaxine 50 mg (P=0.002) and 100 mg (P<0.001) versus placebo. Both doses of desvenlafaxine were generally well tolerated. The most common treatment-emergent adverse events were nausea, dizziness, insomnia, constipation, fatigue, anxiety, and decreased appetite. Fixed doses of desvenlafaxine 50 and 100 mg/day are safe, generally well tolerated, and effective at a clinically relevant level for the treatment of MDD.

Hippocampal abnormalities and memory deficits: new evidence of a strong pathophysiological link in schizophrenia.

The central goals of this manuscript are (1) to better characterize what appears to be the most parsimonious account of schizophrenic long-term memory impairment in the neuropsychological literature: a contextual binding deficit rooted in the medial temporal lobes; (2) to link this deficit to concrete abnormalities at the level of the hippocampus; and (3) to suggest that this deficit could lead to the functional impairment experienced by schizophrenia patients in their daily lives. As far as long-term memory is concerned in schizophrenia, there seems to be a general agreement to conclude that explicit mechanisms are disturbed compared to relatively spared implicit mechanisms. More precisely, both subsystems of explicit memory (i.e., episodic and semantic) appear to be dysfunctional in this patient population. Errors during the encoding processes could be responsible for this dysfunction even if retrieval per se is not totally spared. Recently, a number of studies have suggested that impairments in conscious recollection and contextual binding are closely linked to episodic memory deficit. Since the hippocampal formation is considered to be the central element in the neural support for contextual binding and episodic memory, we have conducted an extensive review of the literature concerning the hippocampal formation in schizophrenia. Emerging evidence from varying disciplines confirm the coherence of the different anomalies reported concurrently at the neuroanatomical, neurodevelopmental, biochemical, and genetic levels. It seems highly probable that the synaptic disorganization in the hippocampus concerns the regions crucial for encoding and contextual binding memory processes. The consequences of these deficits could result in schizophrenia patients experiencing major difficulties when facing usual events which have not been encoded with their proper context.

Value of schizophrenia treatment II: Decision modelling for developing early detection and early intervention services in the Czech Republic.

BACKGROUND: Positive findings on early detection and early intervention services have been consistently reported from many different countries. The aim of this study, conducted within the European Brain Council project "The Value of Treatment", was to estimate costs and the potential cost- savings associated with adopting these services within the context of the Czech mental health care reform. METHODS: Czech epidemiological data, probabilities derived from meta-analyses, and data on costs of mental health services in the Czech Republic were used to populate a decision analytical model. From the health care and societal perspectives, costs associated with health care services and productivity lost were taken into account. One-way sensitivity analyses were conducted to explore the uncertainty around the key parameters. RESULTS: It was estimated that annual costs associated with care as usual for people with the first episode of psychosis were as high as 46 million Euro in the Czech Republic 2016. These annual costs could be reduced by 25% if ED services were adopted, 33% if EI services were adopted, and 40% if both, ED and EI services, were adopted in the country. Cost-savings would be generated due to decreased hospitalisations and better employment outcomes in people with psychoses. CONCLUSIONS: Adopting early detection and early intervention services in mental health systems based on psychiatric hospitals and with limited access to acute and community care could generate considerable cost- savings. Although the results of this modelling study needs to be taken with caution, early detection and early intervention services are recommended for multi-centre pilot testing accompanied by full economic evaluation in the region of Central and Eastern Europe.

Value of schizophrenia treatment I: The patient journey.

BACKGROUND: The aim of the European Brain Council project "The Value of Treatment" was to provide evidence-based, cost-effective policy recommendations for a patient-centered and sustainable coordinated care model for brain disorders. The first part of schizophrenia study examined the needs and gaps in the patients' care pathway. METHODS: Descriptive analysis was based on an inventory of needs and treatment opportunities, using focus group sessions, expert interviews, users' input, and literature review. Three patient pathways were selected: indicated prevention, duration of untreated psychosis, and relapse prevention. RESULTS: The analysis identified several critical barriers to optimal treatment. Available health care services often miss or delay detection of symptoms and diagnosis in at-risk individuals. There is a lack of illness awareness among patients, families, and the public; scarcity of information, training and education among primary care providers; stigmatizing beliefs. Early symptom recognition and timely intervention result in better outcome and prognosis; effective management leads to a functional recovery. In the current model of care, there is insufficient cooperation between health and social care providers, patients and families, inadequate utilization of pharmacological and psychosocial interventions, lacking patient monitoring, and low implementation of integrated community care. CONCLUSIONS: Early detection and early intervention programs, timely intervention, and relapse prevention are essential for effective management of schizophrenia. It requires a paradigm shift from symptom control, achieving and maintaining remission, to the emphasis on recovery. Since the current services are not able to accomplish this goal, changes in mental health policies are needed.

Antidepressant effect in older depressed patients: the lessons of two agomelatine trials.

The present paper reports in parallel the findings of the two phase III trials that evaluated the efficacy of agomelatine in older depressed patients. It describes how the particular methodological innovations (particularly in relation to patient selection, design and accuracy of diagnosis of depression) introduced in study 2 have improved the quality of recruitment of patients and the assay sensitivity. Study 1 lacked assay sensitivity, and among the many differences with study 2, the inclusion of unexpected mildly ill patients could have inflated the placebo response. The increased demands on investigators in study 2 appear to have reduced the placebo effect and showed a robust benefit of agomelatine. The two agomelatine studies offer the opportunity to discuss hypotheses that have been raised to explain the low level of response of older patients to available antidepressants.

Spontaneous appetence for wheel-running: a model of dependency on physical activity in rat.

According to human observations of a syndrome of physical activity dependence and its consequences, we tried to examine if running activity in a free activity paradigm, where rats had a free access to activity wheel, may present a valuable animal model for physical activity dependence and most generally to behavioral dependence. The pertinence of reactivity to novelty, a well-known pharmacological dependence predictor was also tested. Given the close linkage observed in human between physical activity and drugs use and abuse, the influence of free activity in activity wheels on reactivity to amphetamine injection and reactivity to novelty were also assessed. It appeared that (1) free access to wheel may be used as a valuable model for physical activity addiction, (2) two populations differing in activity amount also differed in dependence to wheel-running. (3) Reactivity to novelty did not appeared as a predictive factor for physical activity dependence (4) activity modified novelty reactivity and (5) subjects who exhibited a high appetence to wheel-running, presented a strong reactivity to amphetamine. These results propose a model of dependency on physical activity without any pharmacological intervention, and demonstrate the existence of individual differences in the development of this addiction. In addition, these data highlight the development of a likely vulnerability to pharmacological addiction after intense and sustained physical activity, as also described in man. This model could therefore prove pertinent for studying behavioral dependencies and the underlying neurobiological mechanisms. These results may influence the way psychiatrists view behavioral dependencies and phenomena such as doping in sport or addiction to sport itself.

Impulsivity but not venturesomeness is related to morningness.

The Composite Scale of Morningness (CSM) is a psychometrically sound instrument available in several languages, including French, aimed at arranging individuals along a continuum from high "eveningness" to high "morningness." On the other hand, impulsivity is involved in many personality disorders and is thought to be orthogonal to venturesomeness, which can be seen as a component of the broader construct of sensation seeking. We hypothesized that evening-type subjects would be more impulsive than morning-types. Self-administered questionnaires were distributed to students, and only complete forms were analyzed (194 males and 358 females). A four-way analysis of covariance showed significant effects of age, gender and impulsivity, but not venturesomeness, on morningness in the sense of a higher degree of eveningness in more impulsive subjects. In addition, the correlation coefficients in both genders were similar to those reported in smaller samples. Our findings deserve further interest because, regardless of gender, they suggest a possible physiopathological approach to impulsivity that may be accessible by circadian interventions such as midday bright light exposure or pharmacological treatments.

Efficacy of Desvenlafaxine 50 mg/d Versus Placebo in the Long-Term Treatment of Major Depressive Disorder: A Randomized, Double-Blind Trial.

OBJECTIVE: To examine long-term (11-month) antidepressant efficacy of desvenlafaxine 50 mg/d across a broad range of clinical and functional outcomes in patients with major depressive disorder. METHOD: Adult outpatients (≥ 18 years) with major depressive disorder (DSM-IV criteria) and a 17-item Hamilton Depression Rating Scale (HDRS-17) total score ≥ 20 at screening and baseline who responded to 8 weeks of open-label desvenlafaxine 50 mg/d and had a continuing stable response through week 20 were randomly assigned to receive placebo or desvenlafaxine 50 mg/d in a 6-month, double-blind, randomized withdrawal period. Depressive symptoms were evaluated using the HDRS-17, 6-item HDRS, and Clinical Global Impressions-Severity of Ilness and -Improvement (CGI-S, CGI-I). Health outcomes included the Work Productivity and Activity Impairment (WPAI) questionnaire and the World Health Organization 5-Item Well-Being Index (WHO-5). The trial was conducted from June 2009 to March 2011 at 87 study sites in 14 countries worldwide. RESULTS: Of 874 patients enrolled in open-label treatment, 548 patients were randomly assigned to receive double-blind placebo (n = 276) or desvenlafaxine 50 mg/d (n = 272). At the end of the 6-month double-blind treatment, improvements in depressive symptoms were better maintained among the desvenlafaxine- than placebo-treated patients on all efficacy endpoints (all P ≤ .001); in the desvenlafaxine group, 21.8% (vs 42.9% in the placebo group) had CGI-I ratings of 5, 6, and 7 (minimally worse/much worse/very much worse), and 74.4% met criteria for remission (placebo: 54.2%). WPAI and WHO-5 scores indicated significantly better productivity and well-being with continued desvenlafaxine (vs placebo, P ≤ .001). CONCLUSIONS: Long-term treatment with desvenlafaxine 50 mg/d maintained improvements in major depressive disorder among adult outpatients who exhibited a stable therapeutic response. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00887224.

A randomized, placebo-controlled trial of sertraline for prophylactic treatment of highly recurrent major depressive disorder.

OBJECTIVE: Previous antidepressant maintenance trials have used the same medication from acute through maintenance phases, confounding the interpretation of prophylactic effects. The purpose of this study was to determine whether sertraline prevents the recurrence of major depressive disorder among patients with recurrent depression who had been treated to remission with medications other than sertraline. METHOD: Patients who had experienced at least three documented episodes of major depressive disorder within the last 4 years and who were currently in full remission were eligible. The last episode must have been treated for at least 4 months with any antidepressant except sertraline. For the initial single-blind placebo lead-in phase, 371 patients were included; 288 were included in the analyses for the 18-month double-blind phase in which patients were randomly assigned to sertraline (50 or 100 mg) or placebo (two capsules per day). Recurrence was defined as a depressive episode that fulfilled DSM-IV criteria or the appearance of symptoms that required the administration of another antidepressant treatment. RESULTS: Sixty-one patients discontinued before the double-blind phase, including 33 who experienced a relapse. Out of the 288 who entered the double-blind prophylactic phase, 123 discontinued, including 65 for recurrences. Recurrences were significantly lower in the sertraline groups compared with placebo (sertraline, 50 mg: 16 [16.8%] of 95; sertraline, 100 mg: 16 [17.0%] of 94; placebo: 33 [33.3%] of 99). Patients treated with sertraline also had a significantly longer time until recurrence compared with placebo-treated patients. CONCLUSIONS: Among remitted patients with a history of multiple depressive episodes, sertraline at a dose of either 50 or 100 mg/day prevented recurrences significantly more than did placebo.

Neuroplasticity: from MRI to depressive symptoms.

Morphological and functional changes have been repeatedly reported in the brain organization of depressed patients. The main modifications demonstrated by structural magnetic resonance imaging (MRI) are a reduction in the gray matter volume within the prefrontal cortex, the hippocampus, and the striatum. The reduction in gray matter volume and the morphological atrophy are probably due to an excess of neural loss (apoptosis) and an altered regulation of the neurotrophic processes. Hence, a deficit in neurotrophic factor synthesis (brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, NT-4/5, Bcl-2, etc.) may be responsible for increased apoptosis in the hippocampus and prefrontal cortex corresponding to the cognitive impairment described in depression. This hypothesis seems to be confirmed by the decreased expression of neurotrophic factors (e.g., BDNF mRNA) in animal models of depression. In parallel, the neural plasticity (functional aspects of synaptic connectivity and long-term potential activity [LTP]) is decreased. However, the most interesting data concern the possible reversibility of this dysregulation with antidepressant treatment. For example, communication between the hippocampus and the prefrontal cortex could be re-established, enabling in a way the cognitive processes to be "reset." From a clinical point of view, the consequences of such a phenomenon are manifold:

Sertraline versus fluoxetine in the treatment of major depression: a combined analysis of five double-blind comparator studies.

The aim of this study was to examine response and remission rates in outpatients treated with sertraline or fluoxetine who were suffering from two depression subtypes: anxious-depression and severe depression. Data were pooled from five double-blind studies comparing fluoxetine versus sertraline for the treatment of DSM-III-R or IV major depression. Clinical outcome was assessed using the Hamilton Depression Rating Scale (HAM-D) and the Clinical Global Impression-Improvement scale (CGI-I). One thousand and eighty-eight patients were randomized, with 654 (60%) meeting criteria for anxious depression and 212 (19%) meeting criteria for high severity depression. For the total sample, treatment response was similar for both sertraline and fluoxetine. In the high severity subgroup, the mean (+/-SD) HAM-D score at week 12 was 8.9+/-5.7 for sertraline and 10.8+/-6.9 for fluoxetine (P=0.07), and the mean (+/-SD) CGI-I score was 1.5+/-0.7 for sertraline and 2.0+/-1.1 for fluoxetine (P=0.005). CGI-I responder rates were 88% versus 71% (P=0.03) in the high severity subgroup, and 84% versus 79% (P=0.16) in the anxious-depression subgroup. Overall, sertraline and fluoxetine showed comparable antidepressant efficacy, although sertraline may offer an advantage in those patients with severe depression.

Written but not oral verbal production is preserved in young schizophrenic patients.

The aim of this study is to discover whether the language capabilities of young schizophrenic patients are more affected in speaking than in writing or whether the disorders are equivalent in the two modes. To do this, we compared spoken and written descriptions of pictures obtained from 10 schizophrenic patients with those produced by 10 control subjects. These productions were analysed on the basis of objective indices. The syntax and coherence of the productions were evaluated by judges. The comparison of the performances of the controls and schizophrenic patients supports the hypothesis that the latter suffer from a language disorder affecting the oral mode but impacting less frequently and less severely on the written mode. These results are discussed in the light of the cognitive mechanisms which may provide an explanation of these language disorders.

How does the Hospital and Anxiety and Depression Scale measure anxiety and depression in healthy subjects?

Many anxiety and depression scales are commonly used, although the assumption that they all measure the same construct may be questioned. Thus, researchers have to pay attention to the nature of the scales they use. The Hospital Anxiety and Depression Scale (HADS) was constructed in 1983 to allow a rapid and separate measure of depression and generalised anxiety. Surprisingly, since its introduction, there has been no comprehensive documentation of its psychometric properties. Therefore, as a contribution to assessing the construct validity of the HADS, we conducted a set of confirmatory factor analyses in a sample of 195 healthy students. None of the formerly proposed models fit our data. We were able to split the original Anxiety subscale into two components that we have labelled 'Anxiety' and 'Restlessness', while the original Depression subscale is slightly modified. The results are discussed from both clinical and theoretical points of view.