Making remote measurement technology work in multiple sclerosis, epilepsy and depression: survey of healthcare professionals.

BACKGROUND: Epilepsy, multiple sclerosis (MS) and depression are long term, central nervous system disorders which have a significant impact on everyday life. Evaluating symptoms of these conditions is problematic and typically involves repeated visits to a clinic. Remote measurement technology (RMT), consisting of smartphone apps and wearables, may offer a way to improve upon existing methods of managing these conditions. The present study aimed to establish the practical requirements that would enable clinical integration of data from patients' RMT, according to healthcare professionals. METHODS: This paper reports findings from an online survey of 1006 healthcare professionals currently working in the care of people with epilepsy, MS or depression. The survey included questions on types of data considered useful, how often data should be collected, the value of RMT data, preferred methods of accessing the data, benefits and challenges to RMT implementation, impact of RMT data on clinical practice, and requirement for technical support. The survey was presented on the JISC online surveys platform. RESULTS: Among this sample of 1006 healthcare professionals, respondents were positive about the benefits of RMT, with 73.2% indicating their service would be likely or highly likely to benefit from the implementation of RMT in patient care plans. The data from patients' RMT devices should be made available to all nursing and medical team members and could be reviewed between consultations where flagged by the system. However, results suggest it is also likely that RMT data would be reviewed in preparation for and during a consultation with a patient. Time to review information is likely to be one of the greatest barriers to successful implementation of RMT in clinical practice. CONCLUSIONS: While further work would be required to quantify the benefits of RMT in clinical practice, the findings from this survey suggest that a wide array of clinical team members treating epilepsy, MS and depression would find benefit from RMT data in the care of their patients. Findings presented could inform the implementation of RMT and other digital interventions in the clinical management of a range of neurological and mental health conditions.

Resting-state functional connectivity correlates of anxiety co-morbidity in major depressive disorder.

Major depressive disorder (MDD) is frequently co-morbid with anxiety disorders. The co-morbid state has poorer functional outcomes and greater resistance to first line treatments, highlighting the need for novel treatment targets. This systematic review examined differences in resting-state brain connectivity associated with anxiety comorbidity in young- and middle-aged adults with MDD, with the aim of identifying novel targets for neuromodulation treatments, as these treatments are thought to work partly by altering dysfunctional connectivity pathways. Twenty-one studies met inclusion criteria, including a total of 1292 people with MDD. Only two studies included people with MDD and formally diagnosed co-morbid anxiety disorders; the remainder included people with MDD with dimensional anxiety measurement. The quality of most studies was judged as fair. Results were heterogeneous, partly due to a focus on a small set of connectivity relationships within individual studies. There was evidence for dysconnectivity between the amygdala and other brain networks in co-morbid anxiety, and an indication that abnormalities of default mode network connectivity may play an underappreciated role in this condition.

The impact of data from remote measurement technology on the clinical practice of healthcare professionals in depression, epilepsy and multiple sclerosis: survey.

BACKGROUND: A variety of smartphone apps and wearables are available both to help patients monitor their health and to support health care professionals (HCPs) in providing clinical care. As part of the RADAR-CNS consortium, we have conducted research into the application of wearables and smartphone apps in the care of people with multiple sclerosis, epilepsy, or depression. METHODS: We conducted a large online survey study to explore the experiences of HCPs working with patients who have one or more of these conditions. The survey covered smartphone apps and wearables used by clinicians and their patients, and how data from these technologies impacted on the respondents' clinical practice. The survey was conducted between February 2019 and March 2020 via a web-based platform. Detailed statistical analysis was performed on the answers. RESULTS: Of 1009 survey responses from HCPs, 1006 were included in the analysis after data cleaning. Smartphone apps are used by more than half of responding HCPs and more than three quarters of their patients use smartphone apps or wearable devices for health-related purposes. HCPs widely believe the data that patients collect using these devices impacts their clinical practice. Subgroup analyses show that views on the impact of this data on different aspects of clinical work varies according to whether respondents use apps themselves, and, to a lesser extent, according to their clinical setting and job role. CONCLUSIONS: Use of smartphone apps is widespread among HCPs participating in this large European survey and caring for people with epilepsy, multiple sclerosis and depression. The majority of respondents indicate that they treat patients who use wearables and other devices for health-related purposes and that data from these devices has an impact on clinical practice.

Comorbid depression and risk of cardiac events and cardiac mortality in people with diabetes: A systematic review and meta-analysis.

OBJECTIVE: To examine the association of comorbid occurrence of diabetes and depression with risk of cardiovascular endpoints including cardiovascular mortality, coronary heart disease and stroke. RESEARCH DESIGN AND METHODS: A systematic review and metaanalysis. We searched PUBMED/MEDLINE, Medscape, Cochrane Library, CINAHL, EMBASE and Scopus databases assessing cardiac events and mortality associated with depression in diabetes up until 1 December 2018. Pooled hazard ratios were calculated using random- effects models. RESULTS: Nine studies met the inclusion criteria. The combined pooled hazard ratios showed a significant association of cardiac events in people with depression and type 2 diabetes, compared to those with type 2 diabetes alone. For cardiovascular mortality the pooled hazard ratio was 1.48 (95% CI: 1.185, 1.845), p = 0.001, for coronary heart disease 1.37 (1.165, 1.605), p < 0.001 and for stroke 1.33 (1.291, 1.369), p < 0.001. Heterogeneity was high in the meta-analysis for stroke events (I-squared = 84.7%) but was lower for coronary heart disease and cardiovascular mortality (15% and 43.4% respectively). Meta-regression analyses showed that depression was not significantly associated with the study level covariates mean age, duration of diabetes, length of follow-up, BMI, sex and ethnicity (p < 0.05 for all models). Only three studies were found that examined the association of depression in type 1 diabetes, there was a high degree of heterogeneity and data synthesis was not conducted for these studies. CONCLUSIONS: We have demonstrated a 47.9% increase in cardiovascular mortality, 36.8% increase in coronary heart disease and 32.9% increase in stroke in people with diabetes and comorbid depression. The presence of depression in a person with diabetes should trigger the consideration of evidence-based therapies for cardiovascular disease prevention irrespective of the baseline risk of cardiovascular disease or duration of diabetes.

Multiple-therapy-resistant major depressive disorder: a clinically important concept.

Many novel therapeutic options for depression exist that are either not mentioned in clinical guidelines or recommended only for use in highly specialist services. The challenge faced by clinicians is when it might be appropriate to consider such 'non-standard' interventions. This analysis proposes a framework to aid this decision.Declaration of interestIn the past 3 years R.H.M.W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, LivaNova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion. D.M.B.C. has received fees from LivaNova for attending an advisory board. In the past 3 years A.J.C. has received fees for lecturing from Astra Zeneca and Lundbeck; fees for consulting from LivaNova, Janssen and Allergan; and research grant support from Lundbeck.In the past 3 years A.C. has received fees for lecturing from pharmaceutical companies namely Lundbeck and Sunovion. In the past 3 years A.L.M. has received support for attending seminars and fees for consultancy work (including advisory board) from Medtronic Inc and LivaNova. R.M. holds joint research grants with a number of digital companies that investigate devices for depression including Alpha-stim, Big White Wall, P1vital, Intel, Johnson and Johnson and Lundbeck through his mindTech and CLAHRC EM roles. M.S. is an associate at Blueriver Consulting providing intelligence to NHS organisations, pharmaceutical and devices companies. He has received honoraria for presentations and advisory boards with Lundbeck, Eli Lilly, URGO, AstraZeneca, Phillips and Sanofi and holds shares in Johnson and Johnson. In the past 3 years P.R.A.S. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending an advisory board) from life sciences companies including Corcept Therapeutics, Indivior and LivaNova. In the past 3 years P.S.T. has received consultancy fees as an advisory board member from the following companies: Galen Limited, Sunovion Pharmaceuticals Europe Ltd, myTomorrows and LivaNova. A.H.Y. has undertaken paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders and LivaNova. He has received funding for investigator initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth.

Early risk factors for depression, anxiety and post-traumatic distress after hospital admission for unintentional injury: Multicentre cohort study.

OBJECTIVE: To quantify psychological morbidity and identify baseline factors associated with depression, anxiety and post-traumatic distress symptoms up to 12 months post-injury. METHODS: Multicentre cohort study of 668 adults, aged 16 to 70, admitted to 4 UK NHS hospital trusts. Data on injury, socio-demographic characteristics and health status was collected at recruitment. Depression, anxiety and post-traumatic distress were measured at 1, 2, 4 and 12 months post-injury. Multilevel linear regression assessed associations between patient and injury characteristics and psychological outcomes over 12 months follow-up. RESULTS: Depression, anxiety and post-traumatic distress scores were highest 1 month post-injury, and remained above baseline at 2, 4 and 12 months post-injury. Moderate or severe injuries, previous psychiatric diagnoses, higher pre-injury depression and anxiety scores, middle age (45-64 years), greater deprivation and lower pre-injury quality of life (QoL) were associated with higher depression scores post-injury. Previous psychiatric diagnoses, higher pre-injury depression and anxiety scores, middle age, greater deprivation and lower pre-injury QoL were associated with higher anxiety scores post-injury. Traffic injuries or injuries from being struck by objects, multiple injures (≥3), being female, previous psychiatric diagnoses, higher pre-injury anxiety scores and greater deprivation were associated with higher post-traumatic distress scores post-injury. CONCLUSION: A range of risk factors, identifiable shortly after injury, are associated with psychological morbidity occurring up to 12 months post-injury in a general trauma population. Further research is required to explore the utility of these, and other risk factors in predicting psychological morbidity on an individual patient basis.

Cost-effectiveness of structured group psychoeducation versus unstructured group support for bipolar disorder: Results from a multi-centre pragmatic randomised controlled trial.

BACKGROUND: Bipolar disorder (BD) costs the English economy an estimated £5.2billion/year, largely through incomplete recovery. This analysis estimated the cost-effectiveness of group psychoeducation (PEd), versus group peer support (PS), for treating BD. METHODS: A 96-week pragmatic randomised controlled trial (RCT), conducted in NHS primary care. The primary analysis compared PEd with PS, using multiple imputed datasets for missing values. An economic model was used to compare PEd with treatment as usual (TAU). The perspective was Health and Personal Social Services. RESULTS: Participants receiving PEd (n=153) used more (costly) health-related resources than PS (n=151) (net cost per person £1098 (95% CI, £252-£1943)), with a quality-adjusted life year (QALY) gain of 0.023 (95% CI, 0.001-0.056). The cost per QALY gained was £47,739. PEd may be cost-effective (versus PS) if decision makers are willing to pay at least £37,500 per QALY gained. PEd costs £10,765 more than PS to avoid one relapse. The economic model indicates that PEd may be cost-effective versus TAU if it reduces the probability of relapse (by 15%) or reduces the probability of and increases time to relapse (by 10%). LIMITATIONS: Participants were generally inconsistent in attending treatment sessions and low numbers had complete cost/QALY data. Factors contributing to pervasive uncertainty of the results are discussed. CONCLUSIONS: This is the first economic evaluation of PEd versus PS in a pragmatic trial. PEd is associated with a modest improvement in health status and higher costs than PS. There is a high level of uncertainty in the data and results.

Psychological morbidity and health-related quality of life after injury: multicentre cohort study.

PURPOSE: To demonstrate the impact of psychological morbidity 1 month post-injury on subsequent post-injury quality of life (HRQoL) in a general injury population in the UK to inform development of trauma care and rehabilitation services. METHODS: Multicentre cohort study of 16-70-year-olds admitted to 4 UK hospitals following injury. Psychological morbidity and HRQoL (EQ-5D-3L) were measured at recruitment and 1, 2, 4 and 12 months post-injury. A reduction in EQ-5D compared to retrospectively assessed pre-injury levels of at least 0.074 was taken as the minimal important difference (MID). Multilevel logistic regression explored relationships between psychological morbidity 1 month post-injury and MID in HRQoL over the 12 months after injury. RESULTS: A total of 668 adults participated. Follow-up rates were 77% (1 month) and 63% (12 months). Substantial reductions in HRQoL were seen; 93% reported a MID at 1 month and 58% at 12 months. Problems with pain, mobility and usual activities were commonly reported at each time point. Depression and anxiety scores 1 month post-injury were independently associated with subsequent MID in HRQoL. The relationship between depression and HRQoL was partly explained by anxiety and to a lesser extent by pain and social functioning. The relationship between anxiety and HRQoL was not explained by factors measured in our study. CONCLUSIONS: Hospitalised injuries result in substantial reductions in HRQoL up to 12 months later. Depression and anxiety early in the recovery period are independently associated with lower HRQoL. Identifying and managing these problems, ensuring adequate pain control and facilitating social functioning are key elements in improving HRQoL post-injury.

The impact of psychological factors on recovery from injury: a multicentre cohort study.

PURPOSE: Unintentional injuries have a significant long-term health impact in working age adults. Depression, anxiety and post-traumatic stress disorder are common post-injury, but their impact on self-reported recovery has not been investigated in general injury populations. This study investigated the role of psychological predictors 1 month post-injury in subsequent self-reported recovery from injury in working-aged adults. METHODS: A multicentre cohort study was conducted of 668 unintentionally injured adults admitted to five UK hospitals followed up at 1, 2, 4 and 12 months post-injury. Logistic regression explored relationships between psychological morbidity 1 month post-injury and self-reported recovery 12 months post-injury, adjusting for health, demographic, injury and socio-legal factors. Multiple imputations were used to impute missing values. RESULTS: A total of 668 adults participated at baseline, 77% followed up at 1 month and 63% at 12 months, of whom 383 (57%) were included in the main analysis. Multiple imputation analysis included all 668 participants. Increasing levels of depression scores and increasing levels of pain at 1 month and an increasing number of nights in hospital were associated with significantly reduced odds of recovery at 12 months, adjusting for age, sex, centre, employment and deprivation. The findings were similar in the multiple imputation analysis, except that pain had borderline statistical significance. CONCLUSIONS: Depression 1 month post-injury is an important predictor of recovery, but other factors, especially pain and nights spent in hospital, also predict recovery. Identifying and managing depression and providing adequate pain control are essential in clinical care post-injury.

Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology.

The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.

Feasibility and acceptability of web-based enhanced relapse prevention for bipolar disorder (ERPonline): trial protocol.

BACKGROUND: Relapse prevention interventions for Bipolar Disorder are effective but implementation in routine clinical services is poor. Web-based approaches offer a way to offer easily accessible access to evidence based interventions at low cost, and have been shown to be effective for other mood disorders. METHODS/DESIGN: This protocol describes the development and feasibility testing of the ERPonline web-based intervention using a single blind randomised controlled trial. Data will include the extent to which the site was used, detailed feedback from users about their experiences of the site, reported benefits and costs to mental health and wellbeing of users, and costs and savings to health services. We will gain an estimate of the likely effect size of ERPonline on a range of important outcomes including mood, functioning, quality of life and recovery. We will explore potential mechanisms of change, giving us a greater understanding of the underlying processes of change, and consequently how the site could be made more effective. We will be able to determine rates of recruitment and retention, and identify what factors could improve these rates. DISCUSSION: The findings will be used to improve the site in accordance with user needs, and inform the design of a large scale evaluation of the clinical and cost effectiveness of ERPonline. They will further contribute to the growing evidence base for web-based interventions designed to support people with mental health problems.

Randomized controlled trial of computerized cognitive behavioural therapy for depressive symptoms: effectiveness and costs of a workplace intervention.

BACKGROUND: Depression and anxiety are major causes of absence from work and underperformance in the workplace. Cognitive behavioural therapy (CBT) can be effective in treating such problems and online versions offer many practical advantages. The aim of the study was to investigate the effectiveness of a computerized CBT intervention (MoodGYM) in a workplace context. METHOD: The study was a phase III two-arm, parallel randomized controlled trial whose main outcome was total score on the Work and Social Adjustment Scale (WSAS). Depression, anxiety, psychological functioning, costs and acceptability of the online process were also measured. Most data were collected online for 637 participants at baseline, 359 at 6 weeks marking the end of the intervention and 251 participants at 12 weeks post-baseline. RESULTS: In both experimental and control groups depression scores improved over 6 weeks but attrition was high. There was no evidence for a difference in the average treatment effect of MoodGYM on the WSAS, nor for a difference in any of the secondary outcomes. CONCLUSIONS: This study found no evidence that MoodGYM was superior to informational websites in terms of psychological outcomes or service use, although improvement to subthreshold levels of depression was seen in nearly half the patients in both groups.

Suicide in bipolar disorder in a national English sample, 1996-2009: frequency, trends and characteristics.

BACKGROUND: Bipolar disorder (BD) has been reported to be associated with high risk of suicide. We aimed to investigate the frequency and characteristics of suicide in people with BD in a national sample. METHOD: Suicide in BD in England from 1996 to 2009 was explored using descriptive statistics on data collected by the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness (NCI). Suicide cases with a primary diagnosis of BD were compared to suicide cases with any other primary diagnosis. RESULTS: During the study period 1489 individuals with BD died by suicide, an average of 116 cases/year. Compared to other primary diagnosis suicides, those with BD were more likely to be female, more than 5 years post-diagnosis, current/recent in-patients, to have more than five in-patient admissions, and to have depressive symptoms. In BD suicides the most common co-morbid diagnoses were personality disorder and alcohol dependence. Approximately 40% were not prescribed mood stabilizers at the time of death. More than 60% of BD suicides were in contact with services the week prior to suicide but were assessed as low risk. CONCLUSIONS: Given the high rate of suicide in BD and the low estimates of risk, it is important that health professionals can accurately identify patients most likely to experience poor outcomes. Factors such as alcohol dependence/misuse, personality disorder, depressive illness and current/recent in-patient admission could characterize a high-risk group. Future studies need to operationalize clinically useful indicators of suicide risk in BD.

Symptom-specific self-referential cognitive processes in bipolar disorder: a longitudinal analysis.

BACKGROUND: Although depression and mania are often assumed to be polar opposites, studies have shown that, in patients with bipolar disorder, they are weakly positively correlated and vary somewhat independently over time. Thus, when investigating relationships between specific psychological processes and specific symptoms (mania and depression), co-morbidity between the symptoms and changes over time must be taken into account. Method A total of 253 bipolar disorder patients were assessed every 24 weeks for 18 months using the Hamilton Rating Scale for Depression (HAMD), the Bech-Rafaelsen Mania Assessment Scale (MAS), the Rosenberg Self-Esteem Questionnaire (RSEQ), the Dysfunctional Attitudes Scale (DAS), the Internal, Personal and Situational Attributions Questionnaire (IPSAQ) and the Personal Qualities Questionnaire (PQQ). We calculated multilevel models using the xtreg module of Stata 9.1, with psychological and clinical measures nested within each participant. RESULTS: Mania and depression were weakly, yet significantly, associated; each was related to distinct psychological processes. Cross-sectionally, self-esteem showed the most robust associations with depression and mania: depression was associated with low positive and high negative self-esteem, and mania with high positive self-esteem. Depression was significantly associated with most of the other self-referential measures, whereas mania was weakly associated only with the externalizing bias of the IPSAQ and the achievement scale of the DAS. Prospectively, low self-esteem predicted future depression. CONCLUSIONS: The associations between different self-referential thinking processes and different phases of bipolar disorder, and the presence of the negative self-concept in both depression and mania, have implications for therapeutic management, and also for future directions of research.

Estimating the prevalence of medically unexplained symptoms from primary care records.

OBJECTIVES: To develop models to estimate the likely prevalence of medically unexplained symptoms (MUS) and severe MUS in a primary care practice from existing patient electronic records collected in the previous 2 years for secondary prevention and commissioning of psychological treatment. STUDY DESIGN: Cross-sectional survey comparing general practitioners' (GPs) assessment of the presence or absence of MUS and severe MUS with clinical, demographic and service use variables associated with MUS or functional somatic syndromes from previous research in the patient's routine electronic record over the previous 2 years. METHODS: Seventeen GPs from eight practices identified cases of MUS and severe MUS in 828 consecutive consulters in primary care. Models of variables associated with MUS and severe MUS were constructed using multivariate multilevel logistic regression. The predictive validity of the final models was tested, comparing predicted with observed data and expected prevalence rates from the literature. RESULTS: Models to predict MUS and severe MUS had areas under the receiver operating characteristic curve of 0.70 [95% confidence interval (CI) 0.65-0.74] and 0.76 (95% CI 0.70-0.82), respectively. Both models showed adequate goodness of fit with observed data, and had good predictive validity compared with the expected prevalence of MUS, severe MUS, and anxiety or depression. CONCLUSION: Models to predict the prevalence of MUS and severe MUS from routine practice records for commissioning purposes were successfully developed, but they require independent validation before general use. The sensitivity of these models was too low for use in clinical screening.

Depressive symptoms and pragmatic rehabilitation for chronic fatigue syndrome.

BACKGROUND: Previous research has suggested that depressed mood may predict outcome and moderate response to treatment in chronic fatigue syndrome, although findings have differed between studies. AIMS: To examine potential moderators of response to pragmatic rehabilitation v. general practitioner treatment as usual in a recent randomised trial for patients with chronic fatigue syndrome in primary care (IRCTN74156610). METHOD: Simple regressions, with weighting adjustments to allow for missing data, were calculated. Demographic, medical and psychological variables, and treatment arm, were entered separately and as an interaction term. The outcome variable in each case was change in Chalder Fatigue Scale scores, from baseline to 1-year follow-up, our primary outcome point. RESULTS: Longer illness durations predicted poorer outcome across the two treatment arms. For patients allocated to pragmatic rehabilitation compared with those allocated to treatment as usual, higher levels of depressive symptoms at baseline were associated with smaller improvements in fatigue (P = 0.022). CONCLUSIONS: For patients in primary care with higher levels of depressive symptoms, either more intensive or longer pragmatic rehabilitation, or cognitive-behavioural therapy, may be required in order to show a significant improvement in fatigue.

A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database.

OBJECTIVES: The aim of this study was to establish the relative safety and balance of risks for antidepressant treatment in older people. The study objectives were to (1) determine relative and absolute risks of predefined adverse events in older people with depression, comparing classes of antidepressant drugs [tricyclic and related antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and other antidepressants] and commonly prescribed individual drugs with non-use of antidepressant drugs; (2) directly compare the risk of adverse events for SSRIs with TCAs; (3) determine associations with dose and duration of antidepressant medication; (4) describe patterns of antidepressant use in older people with depression; and (5) estimate costs of antidepressant medication and primary care visits. DESIGN: A cohort study of patients aged 65 years and over diagnosed with depression. SETTING: The study was based in 570 general practices in the UK supplying data to the QResearch database. PARTICIPANTS: Patients diagnosed with a new episode of depression between the ages of 65 and 100 years, from 1 January 1996 to 31 December 2007. Participants were followed up until 31 December 2008. INTERVENTIONS: The exposure of interest was treatment with antidepressant medication. Antidepressant drugs were grouped into the major classes and commonly prescribed individual drugs were identified. MAIN OUTCOME MEASURES: There were 13 predefined outcome measures: all-cause mortality, sudden cardiac death, suicide, attempted suicide/self-harm, myocardial infarction, stroke/transient ischaemic attack (TIA), falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions and hyponatraemia. RESULTS: In total, 60,746 patients were included in the study cohort. Of these, 54,038 (89.0%) received at least one prescription for an antidepressant during follow-up. The associations with the adverse outcomes were significantly different between the classes of antidepressant drugs for seven outcomes. SSRIs were associated with the highest adjusted hazard ratios (HRs) for falls [1.66, 95% confidence interval (CI) 1.58 to 1.73] and hyponatraemia (1.52, 95% CI 1.33 to 1.75), and the group of other antidepressants was associated with the highest HRs for all-cause mortality (1.66, 95% CI 1.56 to 1.77), attempted suicide/self-harm (5.16, 95% CI 3.90 to 6.83), stroke/TIA (1.37, 95% CI 1.22 to 1.55), fracture (1.63, 95% CI 1.45 to 1.83) and epilepsy/seizures (2.24, 95% CI 1.60 to 3.15) compared with when antidepressants were not being used. TCAs did not have the highest HR for any of the outcomes. There were also significantly different associations between the individual drugs for seven outcomes, with trazodone, mirtazapine and venlafaxine associated with the highest rates for several of these outcomes. The mean incremental cost (for all antidepressant prescriptions) ranged between £51.58 (amitriptyline) and £641.18 (venlafaxine) over the 5-year post-diagnosis period. CONCLUSIONS: This study found associations between use of antidepressant drugs and a number of adverse events in older people. There was no evidence that SSRIs or drugs in the group of other antidepressants were associated with a reduced risk of any of the adverse outcomes compared with TCAs; however, they may be associated with an increased risk for certain outcomes. Among individual drugs trazodone, mirtazapine and venlafaxine were associated with the highest rates for some outcomes. Indication bias and residual confounding may explain some of the study findings. The risks of prescribing antidepressants need to be weighed against the potential benefits of these drugs. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Depressive and manic symptoms are not opposite poles in bipolar disorder.

OBJECTIVE: This study of 236 individuals with bipolar disorders employed longitudinal analyses to determine whether the symptoms of mania and depression can be understood as one dimension (with depression and mania as opposites) or two relatively independent dimensions. METHOD: Weekly severity ratings of manic and depression were assessed using the Longitudinal Interval Follow-up Evaluation-II for 72 weeks. The within-subjects correlation of manic and depressive severity was examined using random effects regression. RESULTS: Contrary to the one-dimension model, mania and depression symptoms were not negatively related. Indeed, the correlations of mania with depressive symptoms were quite small. CONCLUSION: The data suggest that depressive and manic symptoms are not opposite poles. Rather depressive and manic symptoms appear to fluctuate relatively independently within bipolar disorder.

Estimating probability of sustained recovery from mild to moderate depression in primary care: evidence from the THREAD study.

BACKGROUND: It is important for doctors and patients to know what factors help recovery from depression. Our objectives were to predict the probability of sustained recovery for patients presenting with mild to moderate depression in primary care and to devise a means of estimating this probability on an individual basis. METHOD: Participants in a randomized controlled trial were identified through general practitioners (GPs) around three academic centres in England. Participants were aged >18 years, with Hamilton Depression Rating Scale (HAMD) scores 12-19 inclusive, and at least one physical symptom on the Bradford Somatic Inventory (BSI). Baseline assessments included demographics, treatment preference, life events and difficulties and health and social care use. The outcome was sustained recovery, defined as HAMD score <8 at both 12 and 26 week follow-up. We produced a predictive model of outcome using logistic regression clustered by GP and created a probability tree to demonstrate estimated probability of recovery at the individual level. RESULTS: Of 220 participants, 74% provided HAMD scores at 12 and 26 weeks. A total of 39 (24%) achieved sustained recovery, associated with being female, married/cohabiting, having a low BSI score and receiving preferred treatment. A linear predictor gives individual probabilities for sustained recovery given specific characteristics and probability trees illustrate the range of probabilities and their uncertainties for some important combinations of factors. CONCLUSIONS: Sustained recovery from mild to moderate depression in primary care appears more likely for women, people who are married or cohabiting, have few somatic symptoms and receive their preferred treatment.