Sleep deprivation as a treatment for major depressive episodes: A systematic review and meta-analysis.

Sleep deprivation, alone or in combination with pharmacological treatment and as part of a chronotherapy package, is of potential use for people with major depressive episodes, however the evidence base is still conflicting. The aim of this systematic review and meta-analysis is to assess the clinical effects of sleep deprivation in comparison to any other intervention for the acute and long-term treatment of mood disorders. We searched electronic databases and trial registries (last update: 16th October 2021) for published and unpublished randomised controlled trials recruiting participants with a major depressive episode in unipolar or bipolar affective disorder. The clinical outcomes of interest were the reduction in depressive symptoms at different timepoints and the number of participants experiencing at least one side effect. Overall, 29 trials (1246 participants) were included. We did not find any difference in change in symptoms or all-cause discontinuation between interventions including SD compared to a control of the same intervention except without SD. In the included studies there were no available data for adverse events. Using the most methodologically rigorous approach, we did not find evidence that the addition of sleep deprivation to treatment packages leads to enhanced depressive outcomes.

Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study.

BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. INTERPRETATION: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. FUNDING: UK Research and Innovation and National Institute for Health Research.

Consent to discuss participation in research: a pilot study.

BACKGROUND: Equitable access to research studies needs to be increased for all patients. There is debate about which is the best approach to use to discuss participation in research in real-world clinical settings. OBJECTIVE: We aimed to determine the feasibility of asking all clinical staff within one hospital Trust (an organisation that provides secondary health services within the English and Welsh National Health Service) to use a newly created form on the Trust's electronic patient records system, as a means of asking patients to consent to discuss participation in research (the opt-in approach). We also aimed to collect feedback from patients and clinicians about their views of the opt-in approach. METHODS: Four pilot sites were selected in the Trust: two memory clinics, an adult mental health team and an acute adult ward. Data were collected in three phases: (1) for 6 months, pilot site staff were asked to complete a consent to discuss participation in research form with patients; (2) staff feedback on the form was collected through an online survey; and (3) patient feedback was collected through focus groups. FINDINGS: Of 1779 patients attending services during the pilot period, 197 (11%) had a form completed by staff and 143 (8%) opted-in to finding out about research. Staff cited limited time, low priority and poor user experience of the electronic patient records system as reasons for low uptake of the form. Patients generally approved of the approach but offered suggestions for improvement. CONCLUSIONS: There were mixed results for adopting an opt-in approach; uptake was very low, limiting its value as an effective strategy for improving access to research. CLINICAL IMPLICATIONS: Alternative strategies to the opt-in approach, such as transparent opt out approaches, warrant consideration to maximise access to research within routine clinical care.

Imagery-Focused Cognitive Therapy (ImCT) for Mood Instability and Anxiety in a Small Sample of Patients with Bipolar Disorder: a Pilot Clinical Audit.

BACKGROUND: Despite the global impact of bipolar disorder (BD), treatment success is limited. Challenges include syndromal and subsyndromal mood instability, comorbid anxiety, and uncertainty around mechanisms to target. The Oxford Mood Action Psychology Programme (OxMAPP) offered a novel approach within a cognitive behavioural framework, via mental imagery-focused cognitive therapy (ImCT). AIMS: This clinical audit evaluated referral rates, clinical outcomes and patient satisfaction with the OxMAPP service. METHOD: Eleven outpatients with BD received ImCT in addition to standard psychiatric care. Mood data were collected weekly from 6 months pre-treatment to 6 months post-treatment via routine mood monitoring. Anxiety was measured weekly from start of treatment until 1 month post-treatment. Patient feedback was provided via questionnaire. RESULTS: Referral and treatment uptake rates indicated acceptability to referrers and patients. From pre- to post-treatment, there was (i) a significant reduction in the duration of depressive episode relapses, and (ii) a non-significant trend towards a reduction in the number of episodes, with small to medium effect size. There was a large effect size for the reduction in weekly anxiety symptoms from assessment to 1 month follow-up. Patient feedback indicated high levels of satisfaction with ImCT, and underscored the importance of the mental imagery focus. CONCLUSIONS: This clinical audit provides preliminary evidence that ImCT can help improve depressive and anxiety symptoms in BD as part of integrated clinical care, with high patient satisfaction and acceptability. Formal assessment designs are needed to further test the feasibility and efficacy of the new ImCT treatment on anxiety and mood instability.

Computer Game Play Reduces Intrusive Memories of Experimental Trauma via Reconsolidation-Update Mechanisms.

Memory of a traumatic event becomes consolidated within hours. Intrusive memories can then flash back repeatedly into the mind's eye and cause distress. We investigated whether reconsolidation-the process during which memories become malleable when recalled-can be blocked using a cognitive task and whether such an approach can reduce these unbidden intrusions. We predicted that reconsolidation of a reactivated visual memory of experimental trauma could be disrupted by engaging in a visuospatial task that would compete for visual working memory resources. We showed that intrusive memories were virtually abolished by playing the computer game Tetris following a memory-reactivation task 24 hr after initial exposure to experimental trauma. Furthermore, both memory reactivation and playing Tetris were required to reduce subsequent intrusions (Experiment 2), consistent with reconsolidation-update mechanisms. A simple, noninvasive cognitive-task procedure administered after emotional memory has already consolidated (i.e., > 24 hours after exposure to experimental trauma) may prevent the recurrence of intrusive memories of those emotional events.

Positive Imagery-Based Cognitive Bias Modification as a Web-Based Treatment Tool for Depressed Adults: A Randomized Controlled Trial.

Depression is a global health problem requiring treatment innovation. Targeting neglected cognitive aspects may provide a useful route. We tested a cognitive-training paradigm using positive mental imagery (imagery cognitive bias modification, imagery CBM), developed via experimental psychopathology studies, in a randomized controlled trial. Training was delivered via the Internet to 150 individuals with current major depression. Unexpectedly, there was no significant advantage for imagery CBM compared with a closely matched control for depression symptoms as a whole in the full sample. In exploratory analyses, compared with the control, imagery CBM significantly improved anhedonia over the intervention and improved depression symptoms as a whole for those participants with fewer than five episodes of depression and those who engaged to a threshold level of imagery. Results suggest avenues for improving imagery CBM to inform low-intensity treatment tools for depression. Anhedonia may be a useful treatment target for future work.

Folic acid supplementation for prevention of mood disorders in young people at familial risk: a randomised, double blind, placebo controlled trial.

BACKGROUND: Clinical mood disorders often become clinically manifest in the later teenage years and early twenties and can be associated with a poor long-term prognosis. The primary prevention of these disorders would therefore have great public health value. Nutritional supplements are a feasible intervention for primary prevention and several epidemiological studies have indicated links between low folate status and depressive symptomatology in the general population. METHOD: A randomised, double blind, parallel group, placebo-controlled trial in which participants, aged 14-24 years, at increased familial risk of mood disorder, were randomised to folic acid (2.5 mg daily) or identical placebo liquid for a maximum of 36 months. Primary outcome data (the onset of a DSM-IV mood disorder) were collected from 112 participants; 56 per group. RESULTS: The incidence of mood disorder in the folic acid and placebo groups were 14.3% and 17.9% respectively, a non-significant difference. However, there was post-hoc evidence that folic acid delayed the time to onset of mood disorder in those participants who became unwell. LIMITATIONS: Small sample size and rate of onset of mood disorders lower than expected. CONCLUSIONS: Although long term folic acid supplementation was well tolerated, with high levels of adherence, there was no evidence that it reduced the incidence of mood disorder compared to those taking placebo.

Understanding the problems developing a healthy living programme in patients with serious mental illness: a qualitative study.

BACKGROUND: People with serious mental illness are at an increased risk of physical ill health. Mortality rates are around twice those of the general population with higher levels of cardiovascular disease, metabolic disease, diabetes, and respiratory illness. Although genetics may have a role in the physical health problems of these patients, lifestyle and environmental factors such as smoking, obesity, poor diet, and low levels of physical activity play a prominent part. METHODS: A qualitative grounded theory approach was used to understand the problems experienced by these individuals when asked to attend a healthy living programme. Three main areas were explored: the influence of potential barriers, health problems, and general attitudes towards healthy living. RESULTS: Thirteen patients were interviewed during the study. Many did not recall receiving an initial invitation letter to the programme. Several believed that there was no necessity to attend as they had already had recent routine health checks by their general practitioner. The patients' current level of mental and physical health was important with symptoms such as depression, anxiety or arthritis affecting interest in the programme. Patients described that they found smoking enjoyable or calming in its effect. Dietary intake was determined by taste or gaining pleasure in eating certain types of food. Several lessons were learnt during this research that may aid future research and practice. Participation seemed to be better if the approach was first made by the patient's own community keyworker. This contact may have provided a greater opportunity to explain the purpose and importance of the programme. Alternative appointments should be considered when certain patients are in better physical and mental health. Healthy living programmes need to be flexible and adaptive to individual patient needs. Assistance from their community worker may help engagement. Simple measures may improve participation and reduce potential barriers. CONCLUSION: These findings highlighted some of the problems encountered by patients when attempting to participate in a healthy living programme. These results may be useful when implementing future healthy living interventions for patients with serious mental disorders.

Valproic acid, valproate and divalproex in the maintenance treatment of bipolar disorder.

BACKGROUND: Bipolar disorder is a recurrent illness that is amongst the top 30 causes of disability worldwide and is associated with significant healthcare costs. In the past, emphasis was placed solely on the treatment of acute episodes of bipolar disorder; recently, the importance of episode prevention and of minimisation of iatrogenicity has been recognised. For many years, lithium was the only mood stabiliser in common use, and it remains an agent of first choice in the preventative treatment of bipolar disorder. However, an estimated 20% to 40% of patients may not respond adequately to lithium. Valproate is an anticonvulsant drug that has been shown to be effective in acute mania and is frequently used in maintenance treatment of bipolar disorder. When the acceptability of long-term treatment is considered, together with efficacy, the adverse event profile of a medication is also important. This is an update of a Cochrane review first published in 2001 and last updated in 2009. OBJECTIVES: 1. To determine the efficacy of valproate continuation and maintenance treatment:a) in preventing or attenuating manic, depressive and mixed episodes of bipolar disorder;b) in preventing or attenuating episodes of bipolar disorder in patients with rapid cycling disorder; and; c) in improving patients' general health and social functioning, as measured by global clinical impression, employment and marital stability.2. To review the acceptability to patients of long-term valproate treatment, as measured by numbers of dropouts and reasons for dropping out, by compliance and by reference to patients' expressed views regarding treatment.3. To investigate the adverse effects of valproate treatment (including general prevalence of side effects) and overall mortality rates. SEARCH METHODS: Search of the Cochrane Register of Controlled Trials and the Cochrane Depression, Anxiety and Neurosis Group Register (CCDANCTR) (to January 2013), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years), EMBASE, (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). No language restrictions were applied. Reference lists of relevant papers and previous systematic reviews were handsearched. Pharmaceutical companies marketing valproate and experts in this field were contacted for supplemental data. SELECTION CRITERIA: Randomised controlled trials allocating participants with bipolar disorder to long-term treatment with valproate or any other mood stabiliser, or antipsychotic drugs, or placebo. Maintenance treatment was defined as treatment instituted specifically or mainly to prevent further episodes of illness. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data. A double-entry procedure was employed by two review authors. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. For dichotomous data, risk ratios were calculated with 95% confidence intervals (CIs). For statistically significant results, we calculated the number needed to treat for an additional beneficial outcome (NNTB) and the number needed to treat for an additional harmful outcome (NNTH). For continuous data, mean differences (MDs) or standardised mean differences (SMDs) were calculated along with 95% CIs. MDs were used when the same scale was used to measure an outcome; SMDs were employed when different scales were used to measure the same outcome. The primary analysis used a fixed-effect model. Binary outcomes were calculated on a strict intention-to-treat (ITT) basis; dropouts were included in this analysis. When data were missing and the method of "last observation carried forward" (LOCF) had been used to do an ITT analysis, then the LOCF data were used. MAIN RESULTS: Six randomised controlled trials (overall 876 participants) lasting 6 to 24 months were included. Two studies (overall 312 participants) compared valproate with placebo, four studies (overall 618 participants) valproate with lithium, one study (overall 23 participants) valproate with olanzapine and one study (overall 220 participants) valproate with the combination of valproate plus lithium. In terms of study quality, most studies reported the methods used to generate random sequence; however, only one study reported enough details on allocation concealment. Four of six included studies described their design as "double blind", but only two trials reported full details about blinding. Valproate was more effective than placebo in preventing study withdrawal due to any mood episode (RR 0.68, 95% CI 0.49 to 0.93; NNTB 8), but no difference in efficacy was found between valproate and lithium (RR 1.02, 95% CI 0.87 to 1.20). Valproate was associated with fewer participants dropping out of treatment for any cause when compared with placebo or lithium (RR 0.82, 95% CI 0.71 to 0.95 and RR 0.87, 95% CI 0.77 to 0.98, respectively). However, combination therapy with lithium plus valproate was more likely to prevent relapse than was monotherapy with valproate (RR 0.78, 95% CI 0.63 to 0.96). Significant differences in adverse event frequencies were found, and lithium was associated with more frequent diarrhoea, polyuria, increased thirst and enuresis, whereas valproate was associated with increased sedation and infection. AUTHORS' CONCLUSIONS: Limited evidence supports the efficacy of valproate in the long-term treatment of bipolar disorder. Clinicians and patients should consider acceptability and tolerability profile when choosing between lithium and valproate-their combination or other agents-as long-term treatment for bipolar disorder.

Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder.

CONTEXT: Although differences in clinical characteristics exist between major depressive disorder (MDD) and bipolar disorder (BD), consistent structural brain abnormalities that distinguish the disorders have not been identified. OBJECTIVES: To investigate structural brain changes in MDD using meta-analysis of primary studies; assess the effects of medication, demographic, and clinical variables; and compare the findings with those of a meta-analysis of studies on BD. DATA SOURCES: The MEDLINE, EMBASE, and PsycINFO databases were searched for studies from January 1, 1980, to February 2, 2010. STUDY SELECTION: Two hundred twenty-five studies that used magnetic resonance imaging or x-ray computed tomography to compare brain structure in patients with MDD with that of controls were included in an online database, and 143 that measured common brain structures were selected for meta-analysis. DATA EXTRACTION: Twenty-five variables, including demographic and clinical data, were extracted from each study, when available. For the meta-analysis, mean structure size and standard deviation were extracted for continuous variables, and the proportion of patients and controls with an abnormality in brain structure was extracted for categorical variables. DATA SYNTHESIS: Compared with the structure of a healthy brain, MDD was associated with lateral ventricle enlargement; larger cerebrospinal fluid volume; and smaller volumes of the basal ganglia, thalamus, hippocampus, frontal lobe, orbitofrontal cortex, and gyrus rectus. Patients during depressive episodes had significantly smaller hippocampal volume than patients during remission. Compared with BD patients, those with MDD had reduced rates of deep white matter hyperintensities, increased corpus callosum cross-sectional area, and smaller hippocampus and basal ganglia. Both disorders were associated with increased lateral ventricle volume and increased rates of subcortical gray matter hyperintensities compared with healthy controls. CONCLUSIONS: The meta-analyses revealed structural brain abnormalities in MDD that are distinct from those observed in BD. These findings may aid investigators attempting to discriminate mood disorders using structural magnetic resonance imaging data.

Mood stability versus mood instability in bipolar disorder: a possible role for emotional mental imagery.

A cognitive model of bipolar disorder suggests that mental imagery acts as an emotional amplifier of mood and may be heightened in bipolar disorder. First, we tested whether patients with bipolar disorder would score higher on mental imagery measures than a matched healthy control group. Second, we examined differences in imagery between patients divided into groups according to their level of mood stability. Mood ratings over approximately 6-months, made using a mobile phone messaging system, were used to divide patients into stable or unstable groups. Clinician decisions of mood stability were corroborated with statistical analysis. Results showed (I) compared to healthy controls, patients with bipolar disorder had significantly higher scores for general mental imagery use, more vivid imagery of future events, higher levels of intrusive prospective imagery, and more extreme imagery-based interpretation bias; (II) compared to patients with stable mood, patients with unstable mood had higher levels of intrusive prospective imagery, and this correlated highly with their current levels of anxiety and depression. The findings were consistent with predictions. Further investigation of imagery in bipolar disorder appears warranted as it may highlight processes that contribute to mood instability with relevance for cognitive behaviour therapy.

Depression in adults: drug and physical treatments.

INTRODUCTION: Depression may affect up to 10% of the population, with half of affected people having recurrence of their symptoms. In mild to moderate depression, there is no reliable evidence that any one treatment is superior in improving symptoms of depression, but the strength of evidence supporting different treatments varies. In severe depression, only prescription antidepressants and electroconvulsive therapy are known to improve symptoms. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in mild to moderate and severe depression, and in treatment-resistant depression? Which interventions reduce relapse rates? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 88 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressant drugs (tricyclic antidepressants [including low-dose tricyclic antidepressants], selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, or venlafaxine), continuing prescription antidepressant drugs, electroconvulsive therapy, exercise, lithium augmentation, pindolol augmentation, and St John's wort.

Mental imagery as an emotional amplifier: application to bipolar disorder.

Cognitions in the form of mental images have a more powerful impact on emotion than their verbal counterparts. This review synthesizes the cognitive science of imagery and emotion with transdiagnostic clinical research, yielding novel predictions for the basis of emotional volatility in bipolar disorder. Anxiety is extremely common in patients with bipolar disorder and is associated with increased dysfunction and suicidality, yet it is poorly understood and rarely treated. Mental imagery is a neglected aspect of bipolar anxiety although in anxiety disorders such as posttraumatic stress disorder and social phobia focusing on imagery has been crucial for the development of cognitive behavior therapy (CBT). In this review we present a cognitive model of imagery and emotion applied to bipolar disorder. Within this model mental imagery amplifies emotion, drawing on Clark's cyclical panic model [(1986). A cognitive approach to panic. Behaviour Research and Therapy, 24, 461-470]. We (1) emphasise imagery's amplification of anxiety (cycle one); (2) suggest that imagery amplifies the defining (hypo-) mania of bipolar disorder (cycle two), whereby the overly positive misinterpretation of triggers leads to mood elevation (escalated by imagery), increasing associated beliefs, goals, and action likelihood (all strengthened by imagery). Imagery suggests a unifying explanation for key unexplained features of bipolar disorder: ubiquitous anxiety, mood instability and creativity. Introducing imagery has novel implications for bipolar treatment innovation--an area where CBT improvements are much-needed.

Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials.

The objective of this review was to determine the effectiveness, adverse effects and acceptability of folate in the treatment of depression. Electronic databases (Cochrane Controlled Trials Register and the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register) and reference lists were searched, and authors, experts and pharmaceutical companies contacted to identify randomized controlled trials that compared treatment with folic acid or 5'-methyltetrahydrofolic acid to an alternative treatment, for patients with a diagnosis of depressive disorder. Three randomized trials (247 participants) were included. Two studies assessed the use of folate in addition to other treatment, and found that adding folate reduced Hamilton Depression Rating Scale (HDRS) scores on average by a further 2.65 points [95% confidence interval (CI) 0.38-4.93]. Fewer patients treated with folate experienced a reduction in their HDRS score of less than 50% at 10 weeks (relative risk 0.47, 95% CI 0.24-0.92). The remaining study found no statistically significant difference when folate alone was compared with trazodone. The identified trials did not find evidence of any problems with the acceptability or safety of folate. The limited available evidence suggests folate may have a potential role as a supplement to other treatment for depression. It is currently unclear if this is the case both for people with normal folate levels, and for those with folate deficiency.

Generating evidence to inform policy and practice: the example of the second generation "atypical" antipsychotics.

The introduction of the second generation "atypical" antipsychotics has been heralded as a major advance in the treatment of schizophrenia and other psychotic disorders. Systematic reviews have revealed only modest advantages over conventional antipsychotics and uncertainty about long-term efficacy and safety, yet the second generation antipsychotic drugs have been widely accepted into clinical practice. Although the existing evidence of the benefits and harms of atypical antipsychotics can facilitate decision making about individual patients, the randomized evidence remains inadequate to make valid and fully evidence-based policy statements such as clinical practice guidelines that are designed to apply to groups of patients. Further large randomized trials are needed, but these require patients and clinicians to be in equipoise, or substantially uncertain, about alternative therapies. Premature clinical practice guidelines or expert opinion can lead to changes in clinical practice that make it difficult or impossible to conduct the required trials and are therefore a disservice to patients.