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Background: This paper investigates whether age of onset of depression, duration of the last episode, number of episodes, and residual symptoms of depression and anxiety are associated with depression relapse in primary care patients who have been on long–term maintenance antidepressant treatment and no longer meet ICD10 criteria for depression. Methods: An observational cohort using data from ANTLER (N = 478), a double-blind placebo-controlled trial. The primary outcome was time to relapse using the retrospective CIS-R. Participants were followed for 12 months. Results: Primary outcome was available for 468 participants. Time to relapse in those with more than five previous episodes of depression was shorter, hazard ratio (HR) 1.84 (95% confidence interval [CI] 1.23–2.75) compared to people with two episodes; HR 1.57 (95% CI 1.01–2.43) after adjustment. The residual symptoms of depression at baseline were also associated with increased relapse: HR 1.05 (95% CI 1.01–1.09) and HR 1.06 (95% CI 1.01–1.12) in the adjusted model. There was evidence of reduced rate of relapse in older age of onset group: HR 0.86 (95% CI 0.78–0.95); HR attenuated after adjustment HR 0.91 (95% CI 0.81–1.02). There was no evidence of an association between duration of the current episode and residual anxiety symptoms with relapse. Conclusions: The number of previous episodes and residual symptoms of depression were associated with increased likelihood of relapse. These factors could inform joint decision making when patients are considering tapering off maintenance antidepressant treatment or considering other treatments to prevent relapse. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence to support the use of the psychedelic drug psilocybin for difficult-to-treat depression. This paper compares the cost-effectiveness of psilocybin-assisted psychotherapy (PAP) with conventional medication, cognitive behavioural therapy (CBT), and the combination of conventional medication and CBT. Methods: A decision model simulated patient events (response, remission, and relapse) following treatment. Data on probabilities, costs and quality-adjusted life years (QALYs) were derived from previous studies or from best estimates. Expected healthcare and societal costs and QALYs over a 6-month time period were calculated. Sensitivity analyses were used to address uncertainty in parameter estimates. Results: The expected healthcare cost of PAP varied from £6132 to £7652 depending on the price of psilocybin. This compares to £3528 for conventional medication alone, £4250 for CBT alone, and £4197 for their combination. QALYs were highest for psilocybin (0.310), followed by CBT alone (0.283), conventional medication alone (0.278), and their combination (0.287). Psilocybin was shown to be cost-effective compared to the other therapies when the cost of therapist support was reduced by 50% and the psilocybin price was reduced from its initial value to £400 to £800 per person. From a societal perspective, psilocybin had improved cost-effectiveness compared to a healthcare perspective. Conclusions: Psilocybin has the potential to be a cost-effective therapy for severe depression. This depends on the level of psychological support that is given to patients receiving psilocybin and the price of the drug itself. Further data on long-term outcomes are required to improve the evidence base. [ABSTRACT FROM AUTHOR]

Background. Few data are available regarding the impact of improved depression treatment on daily functioning and disability. Methods. In two studies of more intensive depression treatment in primary care, patients initiating antidepressant treatment were randomly assigned to either usual care or to a collaborative management programme including patient education, on-site mental health treatment, adjustment of antidepressant medication, behavioural activation and monitoring of medication adherence. Assessments at baseline as well as 4 and 7 months included several measures of impairment, daily functioning and disability∶self-rated overall health, number of bodily pains, number of somatization symptoms, changes in work due to health, reduction in leisure activities due to health, number of disability days and number of restricted activity days. Results. Average data from the 4- and 7-month assessments in both studies, intervention patients reported fewer somatic symptoms (OR 0·68, 95% CI 0·46, 0·99) and more favourable overall health (OR 0·50, 95% CI 0·28, 0·91). While intervention patients fared better on other measures of functional impairment and disability, none of these differences reached statistical significance. Conclusions. More effective acute-phase depression treatment reduced somatic distress and improved self-rated overall health. The absence of a significant intervention effect on other disability measures may reflect the brief treatment and follow-up period and the influence of other individual and environmental factors on disability. [ABSTRACT FROM AUTHOR]

Background. A relationship between the anticonvulsant and antidepressant properties of electroconvulsive therapy (ECT) has been hypothesized. The goal of this study was to see whether the anticonvulsant effects of ECT could be measured in a clinical setting and whether there was any relationship between the anticonvulsant effects of ECT and the antidepressant response to it. Methods. We examined the temporal relationship between change in seizure duration (as an index of anticonvulsant activity) and improvement in Hamilton Rating Scale for Depression scores in a retrospective sample of 114 depressed patients who received 145 courses of ECT. A linear mixed effects model was utilized for analysis so that the repeated measures nature of the data could be taken into account. Results. Both seizure duration and depression scores decreased significantly through the course of ECT. However, no evidence was found for a relationship between decrease in seizure duration and clinical improvement as measured by Hamilton ratings. Conclusions. The process underlying the reduction in seizure duration through a course of ECT may not be related to antidepressant efficacy. [ABSTRACT FROM AUTHOR]

Pragmatic studies indicate that a substantial number of depressed patients do not remit with current first-line antidepressant treatments and after two failed treatment steps the chance of remission with subsequent therapies is around 15%. This paper focuses on current evidence for pharmacological treatments in resistant depression as well as possible future developments. For patients who have failed to respond to two antidepressant trials, augmentation with atypical antipsychotic drugs, specifically quetiapine and aripiprazole, has the best evidence for efficacy, though older treatments such as lithium and triiodothyronine still have utility. The striking antidepressant effect of ketamine in resistant depression has stimulated research into glutamatergic compounds; however, capturing the efficacy of ketamine with drugs suitable for continuous use has proved challenging. Growing knowledge of the pathophysiological role of inflammation in depression offers great opportunities for future treatment in terms of repurposing anti-inflammatory agents from general medicine and pre-treatment stratification of those depressed patients in whom such interventions are likely to be beneficial. Finally an older drug, the dopamine receptor agonist pramipexole, if used carefully may well improve the prospects of depressed patients who are refractory to current approaches. [ABSTRACT FROM AUTHOR]

Background: Despite their documented efficacy, substantial proportions of patients discontinue antidepressant medication (ADM) without a doctor's recommendation. The current report integrates data on patient-reported reasons into an investigation of patterns and predictors of ADM discontinuation. Methods: Face-to-face interviews with community samples from 13 countries (n = 30 697) in the World Mental Health (WMH) Surveys included n = 1890 respondents who used ADMs within the past 12 months. Results: 10.9% of 12-month ADM users reported discontinuation-based on recommendation of the prescriber while 15.7% discontinued in the absence of prescriber recommendation. The main patient-reported reason for discontinuation was feeling better (46.6%), which was reported by a higher proportion of patients who discontinued within the first 2 weeks of treatment than later. Perceived ineffectiveness (18.5%), predisposing factors (e.g. fear of dependence) (20.0%), and enabling factors (e.g. inability to afford treatment cost) (5.0%) were much less commonly reported reasons. Discontinuation in the absence of prescriber recommendation was associated with low country income level, being employed, and having above average personal income. Age, prior history of psychotropic medication use, and being prescribed treatment from a psychiatrist rather than from a general medical practitioner, in comparison, were associated with a lower probability of this type of discontinuation. However, these predictors varied substantially depending on patient-reported reasons for discontinuation. Conclusion: Dropping out early is not necessarily negative with almost half of individuals noting they felt better. The study underscores the diverse reasons given for dropping out and the need to evaluate how and whether dropping out influences short- or long-term functioning. [ABSTRACT FROM AUTHOR]

Background: Previous studies have confirmed that miR-146a-5p overexpression suppresses neurogenesis, thereby enhancing depression-like behaviors. However, it remains unclear how miR-146a-5p dysregulation produces in vivo brain structural abnormalities in patients with major depressive disorder (MDD). Methods: In this case–control study, we combined cortical morphology analysis of magnetic resonance imaging (MRI) and miR-146a-5p quantification to investigate the neuropathological effect of miR-146a-5p on cortical thickness in MDD patients. Serum-derived exosomes that were considered to readily cross the blood-brain barrier and contain miR-146a-5p were isolated for miRNA quantification. Moreover, follow-up MRI scans were performed in the MDD patients after 6 weeks of antidepressant treatment to further validate the clinical relevance of the relationship between miR-146a-5p and brain structural abnormalities. Results: In total, 113 medication-free MDD patients and 107 matched healthy controls were included. Vertex-vise general linear model revealed miR-146a-5p-dependent cortical thinning in MDD patients compared with healthy individuals, i.e., overexpression of miR-146a-5p was associated with reduced cortical thickness in the left orbitofrontal cortex (OFC), anterior cingulate cortex, bilateral lateral occipital cortices (LOCs), etc. Moreover, this relationship between baseline miR-146a-5p and cortical thinning was nonsignificant for all regions in the patients who had received antidepressant treatment, and higher baseline miR-146a-5p expression was found to be related to greater longitudinal cortical thickening in the left OFC and right LOC. Conclusions: The findings of this study reveal a relationship between miR-146a-5p overexpression and cortical atrophy and thus may help specify the in vivo mediating effect of miR-146a-5p dysregulation on brain structural abnormalities in patients with MDD. [ABSTRACT FROM AUTHOR]

Background: It remains unclear how SSRIs and other antidepressants are associated with the risk of repeated suicide attempts. We aimed to analyse the association between redeemed antidepressant prescriptions and the risk of repeated suicide attempts, hypothesising that antidepressant treatment is associated with increased risk of repeated suicide attempts. Methods: The study was based on Danish register data and a validated cohort of 1842 suicide attempts. We used three Cox regression models (crude, adjusted and propensity score matched) to analyse the data; these models included both static and dynamic time-dependent factors. Results: 1842 individuals attempted suicide in the study period, with a total of 210 repeated attempts. Individuals redeeming antidepressant prescriptions were more likely to repeat a suicide attempt. All crude models showed all antidepressants to be significant risk factors (HR around 1.39), whereas all adjusted models showed all antidepressants to be insignificant risk factors. Conclusion: We found no significant increased risk of repeated suicide attempts in individuals redeeming a prescription for any antidepressant (or only SSRIs) when considering the individuals' baseline risk of repetition. This study is based on validated suicide attempts, register data, and strong epidemiology designs, but it still has some limitations, and the results should be replicated and confirmed in other studies. [ABSTRACT FROM AUTHOR]

Background: Relatively few studies have explored the differential contributions of the accumulative dosage of psychotropic medications on mortality in patients with schizophrenia. Methods: We aimed to explore the effects of the exposure dosage of psychotropic medications on mortality during a follow-up period of 5 years with a national cohort of individuals with schizophrenia in 2010. Causes of death were linked through Taiwan's National Mortality Registry. The mean defined daily dose of antipsychotics, antidepressants, mood stabilizers, and sedative-hypnotics, were calculated and survival analyses were conducted. Results: A total of 102 964 individuals (54 151 men, 52.59%) with schizophrenia were included. Compared to patients with no exposure to antipsychotics, those with antipsychotic exposure had better survival outcomes, regardless of antipsychotic dosage. Antidepressant exposure, in low and moderate dosage, was associated with decreased all-cause mortality; exposure to mood stabilizers appeared to be associated with an increase in all-cause mortality. Although 89.7% of the patients had been prescribed sedative-hypnotics, exposure to sedative-hypnotics was associated with dose-related increased mortality risk [hazard ratio (HR) in low dose group: 1.16, 95% confidence interval (CI) 1.07–1.27; HR in moderate dose: 1.32, 95% CI 1.21–1.44; HR in high dose: 1.83, 95% CI 1.67–2.01)]. Conclusions: The results indicate that in the treatment of schizophrenia, antipsychotics and antidepressants are associated with lower mortality when using adequate dosages and mood stabilizers and sedative-hypnotics with higher mortality compared with no use. Furthermore, exposure to sedative-hypnotics is associated with a dose-related increased mortality risk which warrants clinical attention and further study. [ABSTRACT FROM AUTHOR]

Background: Prediction of treatment outcomes is a key step in improving the treatment of major depressive disorder (MDD). The Canadian Biomarker Integration Network in Depression (CAN-BIND) aims to predict antidepressant treatment outcomes through analyses of clinical assessment, neuroimaging, and blood biomarkers. Methods: In the CAN-BIND-1 dataset of 192 adults with MDD and outcomes of treatment with escitalopram, we applied machine learning models in a nested cross-validation framework. Across 210 analyses, we examined combinations of predictive variables from three modalities, measured at baseline and after 2 weeks of treatment, and five machine learning methods with and without feature selection. To optimize the predictors-to-observations ratio, we followed a tiered approach with 134 and 1152 variables in tier 1 and tier 2 respectively. Results: A combination of baseline tier 1 clinical, neuroimaging, and molecular variables predicted response with a mean balanced accuracy of 0.57 (best model mean 0.62) compared to 0.54 (best model mean 0.61) in single modality models. Adding week 2 predictors improved the prediction of response to a mean balanced accuracy of 0.59 (best model mean 0.66). Adding tier 2 features did not improve prediction. Conclusions: A combination of clinical, neuroimaging, and molecular data improves the prediction of treatment outcomes over single modality measurement. The addition of measurements from the early stages of treatment adds precision. Present results are limited by lack of external validation. To achieve clinically meaningful prediction, the multimodal measurement should be scaled up to larger samples and the robustness of prediction tested in an external validation dataset. [ABSTRACT FROM AUTHOR]

Background: Adolescent major depressive disorder (MDD) is associated with disrupted processing of emotional stimuli and difficulties in cognitive reappraisal. Little is known however about how current pharmacotherapies act to modulate the neural mechanisms underlying these key processes. The current study therefore investigated the neural effects of fluoxetine on emotional reactivity and cognitive reappraisal in adolescent depression. Methods: Thirty-one adolescents with MDD were randomised to acute fluoxetine (10 mg) or placebo. Seventeen healthy adolescents were also recruited but did not receive any treatment for ethical reasons. During functional magnetic resonance imaging (fMRI), participants viewed aversive images and were asked to either experience naturally the emotional state elicited ('Maintain') or to reinterpret the content of the pictures to reduce negative affect ('Reappraise'). Significant activations were identified using whole-brain analysis. Results: No significant group differences were seen when comparing Reappraise and Maintain conditions. However, when compared to healthy controls, depressed adolescents on placebo showed reduced visual activation to aversive pictures irrespective of the condition. The depressed adolescent group on fluoxetine showed the opposite pattern, i.e. increased visuo-cerebellar activity in response to aversive pictures, when compared to depressed adolescents on placebo. Conclusions: These data suggest that depression in adolescence may be associated with reduced visual processing of aversive imagery and that fluoxetine may act to reduce avoidance of such cues. This could reflect a key mechanism whereby depressed adolescents engage with negative cues previously avoided. Future research combining fMRI with eye-tracking is nonetheless needed to further clarify these effects. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety, obsessive-compulsive, and stress-related disorders. Hence, comparisons of adverse event rates across medications are an essential component of clinical decision-making. We aimed to compare patterns of adverse events associated with SSRIs and SNRIs in the treatment of children and adults diagnosed with these disorders through a network meta-analysis. We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies, and international registers from inception to 09 September 2022, for randomized controlled trials assessing the efficacy of SSRIs or SNRIs. We analyzed the proportion of participants experiencing at least one adverse event and incidence rates of 17 specific adverse events. We estimated incidence rates and odds ratios through network meta-analysis with random effects and three-level models. We analyzed 799 outcome measures from 80 studies (n = 21 338). Participants in medication groups presented higher rates of adverse events (80.22%, 95% CI 76.13–83.76) when compared to placebo groups (71.21%, 67.00–75.09). Nausea was the most common adverse event (25.71%, CI 23.96–27.54), while weight change was the least common (3.56%, 1.68–7.37). We found higher rates of adverse events of medications over placebo for most medications, except sertraline and fluoxetine. We found significant differences between medications for overall tolerability and for autonomic, gastrointestinal, and sleep-related symptoms. Adverse events are a common reason that patients discontinue SSRIs and SNRIs. Results presented here guide clinical decision-making when clinicians weigh one medication over another. This might improve treatment acceptability and compliance. [ABSTRACT FROM AUTHOR]

Background: Although a large variety of antidepressants agents (AD) with different mechanisms of action are available, no significant differences in efficacy and safety have been shown. However, there have been few attempts to incorporate data on subjective experiences under different AD. Method: We conducted a qualitative and quantitative analysis of the posts from the website www.askapatient.com from different AD. We reviewed a random sample of 1000 posts. Result: After applying the inclusion and exclusion criteria, we included a final sample of 450 posts, 50 on each of the most used AD: sertraline, citalopram, paroxetine, escitalopram, fluoxetine, venlafaxine, duloxetine, mirtazapine, and bupropion. Bupropion, citalopram, and venlafaxine had the higher overall satisfaction ratings. Sertraline, paroxetine, and fluoxetine had high reports of emotional blunting, while bupropion very few. Overall satisfaction with AD treatment was inversely associated with the presence of the following side-effects: suicidality, irritability, emotional blunting, cognitive disturbances, and withdrawal symptoms. After adjusting for confounders, only emotional blunting was shown to be more frequently reported by users of serotonergic agents, as compared to non-serotoninergic agents. Conclusion: This research points out that the subjective experience of patients under treatment should be taken into consideration when selecting an AD as differences between agents were evident. In contrast to the more frequent treatment decisions, users might prefer receiving a non-serotoninergic agent over a serotonergic one due to their lower propensity to produce emotional blunting. [ABSTRACT FROM AUTHOR]

Background: The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries. Methods: Face-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents. Results: 3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness. Conclusion: ADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them. [ABSTRACT FROM AUTHOR]

A new Swedish study by Reis & Källén describes approximately 15 000 women (and their babies) that, between 1995 and 2007, reported the use of antidepressants, or were prescribed such drugs, during pregnancy. In this study, pregnancy and teratogenic outcomes after exposure to tricyclic antidepressants are, for most measures, equal or worse than after exposure to selective serotonin reuptake inhibitors or other antidepressants. Based on this and on a review of the few other studies available (admittedly, a relatively small number of women on which conclusions can be based), the authors of this Editorial challenge the ‘perinatal myth’ that tricyclics are the safest choice in pregnancy. [ABSTRACT FROM PUBLISHER]

Background: There is growing interest in using composite individualized treatment rules (ITRs) to guide depression treatment selection, but best approaches for doing this are not widely known. We develop an ITR for depression remission based on secondary analysis of a recently published trial for second-line antidepression medication selection using a cutting-edge ensemble machine learning method. Methods: Data come from the SUN(^_^)D trial, an open-label, assessor blinded pragmatic trial of previously-untreated patients with major depressive disorder from 48 clinics in Japan. Initial clinic-level randomization assigned patients to 50 or 100 mg/day sertraline. We focus on the 1549 patients who failed to remit within 3 weeks and were then rerandomized at the individual-level to continuation with sertraline, switching to mirtazapine, or combining mirtazapine with sertraline. The outcome was remission 9 weeks post-baseline. Predictors included socio-demographics, clinical characteristics, baseline symptoms, changes in symptoms between baseline and week 3, and week 3 side effects. Results: Optimized treatment was associated with significantly increased cross-validated week 9 remission rates in both samples [5.3% (2.4%), p = 0.016 50 mg/day sample; 5.1% (2.7%), p = 0.031 100 mg/day sample] compared to randomization (30.1–30.8%). Optimization was also associated with significantly increased remission in both samples compared to continuation [24.7% in both: 11.2% (3.8%), p = 0.002 50 mg/day sample; 11.7% (3.9%), p = 0.001 100 mg/day sample]. Non-significant gains were found for optimization compared to switching or combining. Conclusions: An ITR can be developed to improve second-line antidepressant selection, but replication in a larger study with more comprehensive baseline predictors might produce stronger and more stable results. [ABSTRACT FROM AUTHOR]

Background: Whether smoking should be regarded as a risk factor for mental disorders remains unresolved. Prescribed psychotropic drugs can be used as indications for mental disorders. We investigated how smoking was prospectively related to prescription of antipsychotics, mood stabilizers, antidepressants, and anxiolytics. Methods: Information about smoking, including the Fagerström Test for Nicotine Dependence, and relevant confounders, were obtained from the population-based Young in Norway Study (N = 2602), with four data collection waves between 1992 and 2006. These survey data were linked with information on prescriptions for psychotropic drugs from the comprehensive, nationwide Norwegian Prescription Database from 2007 to 2015. Results: Daily smoking with high dependence in 2006 at age 28.5 (s.d. = 2.0) was associated with filling prescriptions of antipsychotics (OR, 6.57, 95% CI 2.19–19.70, p = 0.001), mood stabilizers (OR, 7.11, 95% CI 2.51–20.15, p < 0.001) and antidepressants (OR, 1.91, 95% CI 1.13–3.23, p = 0.016) 1–9 years later. Associations remained significant after adjustment for a variety of potential confounders measured before the assessment of smoking, including sociodemographic background, conduct problems, cannabis use, mental distress, and previous prescriptions for psychotropic medications. The association between smoking and prescription of anxiolytics was weaker and more unstable. Conclusions: In this study of young adults, daily smoking with high dependence was associated with later prescriptions of antipsychotics, mood stabilizers and antidepressants, indicating smoking as a risk factor for mental disorders treated with these drugs. [ABSTRACT FROM AUTHOR]

The dominant view within mental health services and research suggests that feeling depressed is a kind of medical illness, partially caused by various biological deficits which are somehow corrected by physical interventions. This article critically appraises evidence for the effectiveness and value of antidepressant drugs and electroconvulsive therapy (ECT), the two principle physical treatments recommended for depression. It also describes the negative effects of these interventions and raises concerns about how they impact the brain. We propose an alternative understanding that recognises depression as an emotional and meaningful response to unwanted life events and circumstances. This perspective demands that we address the social conditions that make depression likely and suggests that a combination of politics and common sense needs to guide us in providing help for one another when we are suffering in this way. This alternative view is increasingly endorsed around the world, including by the United Nations, the World Health Organization and service users who have suffered negative consequences of physical treatments that modify brain functions in ways that are not well-understood. [ABSTRACT FROM AUTHOR]

Background. Depression is a leading cause of disease burden worldwide and is especially problematic in people with chronic diseases, including cancer. Although depression can be effectively treated in the general population using antidepressant medication and psychological treatments, these treatments may have different benefits and harms in cancer patients. Previous reviews have not adequately addressed this topic. We therefore aimed to determine which, if any, treatments are effective for patients with diagnoses of both cancer and depression. Method. We conducted a systematic review of relevant randomized controlled trials identified through searches of Medline, EMBASE, PsycINFO and The Cochrane Central Register of Controlled Trials (CENTRAL). Results. Seven relatively small trials met the selection criteria. These provided some evidence that antidepressant medication, given alone or in combination with a psychological treatment, may be effective. We found no good evidence for psychological treatments given alone or for any other forms of treatment. Conclusions. There is very limited evidence from clinical trials to guide the treatment of cancer patients with a diagnosis of depression, especially for psychological treatments. High quality trials of treatments for depression in patients with cancer are urgently needed. [ABSTRACT FROM AUTHOR]

Background. The effects of antidepressants for treating depressive disorders have been overestimated because of selective publication of positive trials. Reanalyses that include unpublished trials have yielded reduced effect sizes. This in turn has led to claims that antidepressants have clinically insignificant advantages over placebo and that psychotherapy is therefore a better alternative. To test this, we conducted a meta-analysis of studies comparing psychotherapy with pill placebo. Method. Ten 10 studies comparing psychotherapies with pill placebo were identified. In total, 1240 patients were included in these studies. For each study, Hedges' g was calculated. Characteristics of the studies were extracted for subgroup and meta-regression analyses. Results. The effect of psychotherapy compared to pill placebo at post-test was g=0.25 [95% confidence interval (CI) 0.14-0.36, I2=0%, 95% CI 0-58]. This effect size corresponds to a number needed to treat (NNT) of 7.14 (95% CI 5.00-12.82). The psychotherapy conditions scored 2.66 points lower on the Hamilton Depression Rating Scale (HAMD) than the placebo conditions, and 3.20 points lower on the Beck Depression Inventory (BDI). Some indications for publication bias were found (two missing studies). We found no significant differences between subgroups of the studies and in meta-regression analyses we found no significant association between baseline severity and effect size. Conclusions. Although there are differences between the role of placebo in psychotherapy and pharmacotherapy research, psychotherapy has an effect size that is comparable to that of antidepressant medications. Whether these effects should be deemed clinically relevant remains open to debate. [ABSTRACT FROM AUTHOR]

Background. Deliberate self-harm (DSH) is a significant public health problem, representing a major burden in terms of morbidity to the individual and health-service utilization. While clinical guidelines suggest good practice for the short-term hospital management of DSH, there remains considerable variability in the way that services are provided.Method. A systematic review of the literature was undertaken to examine the current evidence on hospital resource use and costs involved in the short-term hospital management of adults following DSH and to elucidate the factors that influence these differences, in terms of clinical characteristics and service provision.Results. Twenty-one papers reporting on 17 studies met the inclusion criteria for review. Clinical characteristics associated with an increase in resource use included overdose with tricyclic antidepressants (TCAs) compared with selective serotonin re-uptake inhibitors (SSRIs) (weighted ratio 2·6∶1) and co-ingestion of alcohol with SSRIs. Variations in service provision, including medical admissions policy and provision of a specialist liaison service, affected resource utilization independently of the clinical needs of patients.Conclusions. Overdoses of TCAs incur substantially greater hospital costs than overdoses of SSRIs. Variations in the medical seriousness of DSH, and in the structure of service provision, affect the resources used in its short-term hospital management, with little evidence about the impact these differences have on clinical outcome. Research is needed to evaluate the impact of different styles of service provision on outcome, and to incorporate these factors into the trial design of future cost-effectiveness studies of interventions following DSH. [ABSTRACT FROM AUTHOR]

Approval and prescription of psychotropic drugs should be informed by the strength of evidence for efficacy. Using a Bayesian framework, we examined (1) whether psychotropic drugs are supported by substantial evidence (at the time of approval by the Food and Drug Administration), and (2) whether there are systematic differences across drug groups. Data from short-term, placebo-controlled phase II/III clinical trials for 15 antipsychotics, 16 antidepressants for depression, nine antidepressants for anxiety, and 20 drugs for attention deficit hyperactivity disorder (ADHD) were extracted from FDA reviews. Bayesian model-averaged meta-analysis was performed and strength of evidence was quantified (i.e. BFBMA). Strength of evidence and trialling varied between drugs. Median evidential strength was extreme for ADHD medication (BFBMA = 1820.4), moderate for antipsychotics (BFBMA = 365.4), and considerably lower and more frequently classified as weak or moderate for antidepressants for depression (BFBMA = 94.2) and anxiety (BFBMA = 49.8). Varying median effect sizes (ESschizophrenia = 0.45, ESdepression = 0.30, ESanxiety = 0.37, ESADHD = 0.72), sample sizes (Nschizophrenia = 324, Ndepression = 218, Nanxiety = 254, NADHD = 189.5), and numbers of trials (kschizophrenia = 3, kdepression = 5.5, kanxiety = 3, kADHD = 2) might account for differences. Although most drugs were supported by strong evidence at the time of approval, some only had moderate or ambiguous evidence. These results show the need for more systematic quantification and classification of statistical evidence for psychotropic drugs. Evidential strength should be communicated transparently and clearly towards clinical decision makers. [ABSTRACT FROM AUTHOR]

Background: It is well-established that media influences public perceptions, and that media coverage of psychiatry is negative compared to the rest of medicine. No studies that we know of, have compared media reporting on antidepressants and talking therapies as treatments for depression. We hypothesised that coverage of antidepressants would be more negative than that of psychotherapies in both headlines and articles. Methods: We identified online articles in The Sun, Daily Mirror, Daily Mail, Daily Express, and The Guardian between 11 June 2013 and 11 June 2018. Two raters independently evaluated their titles/content with regard to their portrayal of antidepressants and psychotherapies (positive/negative/neutral), with good inter-rater reliability. Results: We identified 221 articles. Antidepressants featured in 184 articles, of which 27 (15%) portrayed them positively, 68 (37%) negatively, and 89 (48%) neutrally; and 173 headlines, of which 24 (14%) portrayed them positively, 64 (37%) negatively, and 85 (49%) neutrally. Antidepressants received more coverage than psychotherapy, which featured in 132 articles, of which 48 (36%) portrayed them positively, 3 (2%) negatively, and 81 (61%) neutrally; and 53 headlines, of which 16 (30%) portrayed them positively, 2 (4%) negatively, and 35 (66%) neutrally. A Fisher's exact test revealed a statistically significant difference between the portrayal of antidepressants and psychotherapies in both articles (p = 2.86 × 10−15) and headlines (p = 2.79 × 10−6). Conclusion: Despite the two treatments being similarly effective, the portrayal of antidepressants in the UK online media is more negative than that of psychotherapy. This could potentially discourage patients from considering taking antidepressants, and provoke patients currently taking antidepressants to stop abruptly. [ABSTRACT FROM AUTHOR]

Background: Network analysis (NA) conceptualizes psychiatric disorders as complex dynamic systems of mutually interacting symptoms. Major depressive disorder (MDD) is a heterogeneous clinical condition, and very few studies to date have assessed putative changes in its psychopathological network structure in response to antidepressant (AD) treatment. Methods: In this randomized trial with adult depressed outpatients (n = 151), we estimated Gaussian graphical models among nine core MDD symptom-domains before and after 8 weeks of treatment with either escitalopram or desvenlafaxine. Networks were examined with the measures of cross-sectional and longitudinal structure and connectivity, centrality and predictability as well as stability and accuracy. Results: At baseline, the most connected MDD symptom-domains were fatigue–cognitive disturbance, whereas at week 8 they were depressed mood–suicidality. Overall, the most central MDD symptom-domains at baseline and week 8 were, respectively, fatigue and depressed mood; in contrast, the most peripheral symptom-domain across both timepoints was appetite/weight disturbance. Furthermore, the psychopathological network at week 8 was significantly more interconnected than at baseline, and they were also structurally dissimilar. Conclusion: Our findings highlight the utility of focusing on the dynamic interaction between depressive symptoms to better understand how the treatment with ADs unfolds over time. In addition, depressed mood, fatigue, and cognitive/psychomotor disturbance seem to be central MDD symptoms that may be viable targets for novel, focused therapeutic interventions. [ABSTRACT FROM AUTHOR]

Classifications of depression based on secondary care samples may have little relevance in primary care settings, where many patients do not fulfil criteria for major depression; for example, through having depressive symptoms that are either too mild or too brief. And yet many such patients receive antidepressant treatments (antidepressants and various psychotherapies). At a time when the appropriate recognition and treatment of people with depressive symptoms is the subject of much discussion, and there is concern about the burgeoning number of new psychiatric diagnoses, the burden and hazards of depressive disorders need to be emphasized. The paper by Pezawas et al. (2003) (in this issue) reports the findings of an epidemiological study in adolescents and young adults, and provides a detailed description of the prevalence and features of one such disruptive disorder, namely recurrent brief depression. [ABSTRACT FROM AUTHOR]

Background. The number of antidepressant drugs available in the market has grown rapidly in the last few years. The present paper underlines some of the pre-clinical and clinical problems that call close attention from the regulatory authorities when approving new drugs. Methods. We present here a review of the literature. Results. A wide heterogeneity in the action of the various antidepressants precludes any single theory about the pathogenesis and therapy of depression. Antidepressant activity, in fact, may be achieved by acting on a number of different monoaminergic mechanisms. The variety in the neurochemical effects of antidepressants is not reflected in clinical trials, which tend to stereotypy. In many cases clinical trials aim at demonstrating equivalence rather than differences in efficacy. Regulatory authorities should, therefore, pay attention in accepting the equivalence of effects of a new drug in relation to a reference one: most clinical trials of new antidepressant drugs do not have the power to detect clinically relevant differences. Conclusions. Unconventional new pre-clinical tests are needed to generate antidepressants with a different mechanism of action. Clinical studies are needed to promote objective comparative evaluation of the cost, benefits and toxic effects of new antidepressants. [ABSTRACT FROM AUTHOR]

The article reports that Perpetuating a ‘culture war' within mental health sciences that is damaging our community, and the community of patients. Topics include psychiatrists are both caring human beings and doctors who prescribe medications; and Depression is both psychosocial and biological and antidepressants are both effective and in need of improvement.

The clinical interview is the psychiatrist's data gathering procedure. However, the clinical interview is not a defined entity in the way that 'vitals' are defined as measurements of blood pressure, heart rate, respiration rate, temperature, and oxygen saturation. There are as many ways to approach a clinical interview as there are psychiatrists; and trainees can learn as many ways of performing and formulating the clinical interview as there are instructors (Nestler, 1990). Even in the same clinical setting, two clinicians might interview the same patient and conduct very different examinations and reach different treatment recommendations. From the perspective of data science, this mismatch is not one of personal style or idiosyncrasy but rather one of uncertain salience: neither the clinical interview nor the data thereby generated is operationalized and, therefore, neither can be rigorously evaluated, tested, or optimized. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is highly heterogeneous and can be classified as treatment-resistant depression (TRD) or antidepressant-responsive depression (non-TRD) based on patients' responses to antidepressant treatment. Methods for distinguishing between TRD and non-TRD are critical clinical concerns. Deficits of cortical inhibition (CI) have been reported to play an influential role in the pathophysiology of MDD. Whether TRD patients' CI is more impaired than that of non-TRD patients remains unclear. Methods: Paired-pulse transcranial magnetic stimulation (ppTMS) was used to measure cortical inhibitory function including GABAA- and GABAB-receptor-related CI and cortical excitatory function including glutamate-receptor-related intracortical facilitation (ICF). We recruited 36 healthy controls (HC) and 36 patients with MDD (non-TRD, n = 16; TRD, n = 20). All participants received evaluations for depression severity and ppTMS examinations. Non-TRD patients received an additional ppTMS examination after 3 months of treatment with the SSRI escitalopram. Results: Patients with TRD exhibited reduced short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI), as shown by abnormally higher estimates, than those with non-TRD or HC (F = 11.030, p < 0.001; F = 10.309, p < 0.001, respectively). After an adequate trial of escitalopram treatment, the LICI of non-TRD reduced significantly (t = − 3.628, p < 0.001), whereas the ICF remained lower than that of HC and showed no difference from pretreatment non-TRD. Conclusions: TRD was characterized by relatively reduced CI, including both GABAA- and GABAB-receptor-mediated neurons while non-TRD preserved partial CI. In non-TRD, SSRIs may mainly modulate GABAB-receptor-related LICI. Our findings revealed distinguishable features of CI in antidepressant-resistant and responsive major depression. [ABSTRACT FROM AUTHOR]

Background: Few studies focused on the relationship between psychological measures, major depressive disorder (MDD) and repetitive transcranial magnetic stimulation (rTMS) response. This study investigated several psychological measures as potential predictors for rTMS treatment response. Additionally, this study employed two approaches to evaluate the robustness of our findings by implementing immediate replication and full-sample exploration with strict p -thresholding. Methods: This study is an open-label, multi-site study with a total of 196 MDD patients. The sample was subdivided in a Discovery (60% of total sample, n = 119) and Replication sample (40% of total sample, n = 77). Patients were treated with right low frequency (1 Hz) or left high frequency (10 Hz) rTMS at the dorsolateral prefrontal cortex. Clinical variables [Beck Depression Inventory (BDI), Neuroticism, Extraversion, Openness Five-Factor Inventory, and Depression, Anxiety, and Stress Scale, and BDI subscales] were obtained at baseline, post-treatment, and at follow-up. Predictors were analyzed in terms of statistical association, robustness (independent replication), as well as for their clinical relevance [positive predictive value (PPV) and negative predictive value (NPV)]. Results: Univariate analyses revealed that non-responders had higher baseline anhedonia scores. Anhedonia scores at baseline correlated negatively with total BDI percentage change over time. This finding was replicated. However, anhedonia scores showed to be marginally predictive of rTMS response, and neither PPV nor NPV reached the levels of clinical relevance. Conclusions: This study suggests that non-responders to rTMS treatment have higher baseline anhedonia scores. However, anhedonia was only marginally predictive of rTMS response. Since all other psychological measures did not show predictive value, it is concluded that psychological measures cannot be used as clinically relevant predictors to rTMS response in MDD. [ABSTRACT FROM AUTHOR]

Background: Consistent evidence suggests that face-to-face cognitive-behavioural therapy (CBT) and interpersonal psychotherapy (IPT) may be equally effective depression treatments. Current clinical research focuses on detecting the best predictors-moderators of efficacy to guide treatment personalisation. However, individual moderator studies show inconsistent findings. This systematic review and meta-analysis aimed to compare the efficacy of CBT and IPT, including combined treatment with antidepressants for depression, and evaluate the predictive power of demographic, clinical presentation and treatment characteristics moderators for both therapies. Methods: PsycArticles, PsycINFO, PubMed and Cochrane Library were systematically searched through December 2017 for studies that have assessed individuals with major depression receiving either CBT or IPT in a face-to-face format both at pre- and post-treatment. Random-effects moderator meta-analyses were conducted. Results: In total 168 samples from 137 studies including 11 374 participants qualified for the meta-analytic review. CBT and IPT were equally effective across all but one prespecified moderators. For psychotherapy delivered without concomitant antidepressant treatment [antidepressant medications (ADMs)], CBT was superior to IPT (g = 1.68, Q between p = 0.037). Within-CBT moderator analyses showed that increased CBT efficacy was associated with lower age, high initial depression severity, individual format of administration and no adjunctive ADMs. Within-IPT analyses showed comparable efficacy across all moderators. Conclusions: Clinical guidance around combined treatment (psychotherapy plus ADMs) should be reconsidered. CBT alone is superior to IPT alone and to combined treatment, while IPT alone is non-inferior to combined treatment. More research is needed to assess the moderating effect of older age and number of previous episodes on IPT efficacy. [ABSTRACT FROM AUTHOR]

Background: Depression and anxiety disorders (AD) are the first and sixth leading causes of disability worldwide. Despite their high prevalence and significant disability resulted, there are limited advances in new drug development. Recently, genome-wide association studies (GWAS) have greatly advanced our understanding of the genetic basis underlying psychiatric disorders. Methods: Here we employed gene-set analyses of GWAS summary statistics for drug repositioning. We explored five related GWAS datasets, including two on major depressive disorder (MDD2018 and MDD-CONVERGE, with the latter focusing on severe melancholic depression), one on AD, and two on depressive symptoms and neuroticism in the population. We extracted gene-sets associated with each drug from DSigDB and examined their association with each GWAS phenotype. We also performed repositioning analyses on meta-analyzed GWAS data, integrating evidence from all related phenotypes. Results: Importantly, we showed that the repositioning hits are generally enriched for known psychiatric medications or those considered in clinical trials. Enrichment was seen for antidepressants and anxiolytics but also for antipsychotics. We also revealed new candidates or drug classes for repositioning, some of which were supported by experimental or clinical studies. For example, the top repositioning hit using meta-analyzed p values was fendiline, which was shown to produce antidepressant-like effects in mouse models by inhibition of acid sphingomyelinase. Conclusion: Taken together, our findings suggest that human genomic data such as GWAS are useful in guiding drug discoveries for depression and AD. [ABSTRACT FROM AUTHOR]

Background: Although cognitive-behavioural therapy (CBT) is a well-established treatment for adult depression, its efficacy and efficiency may be enhanced by better understanding its mechanism(s) of action. According to the theoretical model of CBT, symptom improvement occurs via reductions in maladaptive cognition. However, previous research has not established clear evidence for this cognitive mediation model. Methods: The present study investigated the cognitive mediation model of CBT in the context of a randomized controlled trial of CBT v. antidepressant medication (ADM) for adult depression. Participants with major depressive disorder were randomized to receive 16 weeks of CBT (n = 54) or ADM (n = 50). Depression symptoms and three candidate cognitive mediators (dysfunctional attitudes, cognitive distortions and negative automatic thoughts) were assessed at week 0 (pre-treatment), week 4, week 8 and week 16 (post-treatment). Longitudinal associations between cognition and depression symptoms, and mediation of treatment outcome, were evaluated in structural equation models. Results: Both CBT and ADM produced significant reductions in maladaptive cognition and depression symptoms. Cognitive content and depression symptoms were moderately correlated within measurement waves, but cross-lagged associations between the variables and indirect (i.e. mediated) treatment effects were non-significant. Conclusions: The results provide support for concurrent relationships between cognitive and symptom change, but not the longitudinal relationships hypothesized by the cognitive mediation model. Results may be indicative of an incongruence between the timing of measurement and the dynamics of cognitive and symptom change. [ABSTRACT FROM AUTHOR]

Background: Patient expectancy is an important source of placebo effects in antidepressant clinical trials, but all prior studies measured expectancy prior to the initiation of medication treatment. Little is known about how expectancy changes during the course of treatment and how such changes influence clinical outcome. Consequently, we undertook the first analysis to date of in-treatment expectancy during antidepressant treatment to identify its clinical and demographic correlates, typical trajectories, and associations with treatment outcome. Methods: Data were combined from two randomized controlled trials of antidepressant medication for major depressive disorder in which baseline and in-treatment expectancy assessments were available. Machine learning methods were used to identify pre-treatment clinical and demographic predictors of expectancy. Multilevel models were implemented to test the effects of expectancy on subsequent treatment outcome, disentangling within- and between-patient effects. Results: Random forest analyses demonstrated that whereas more severe depressive symptoms predicted lower pre-treatment expectancy, in-treatment expectancy was unrelated to symptom severity. At each measurement point, increased in-treatment patient expectancy significantly predicted decreased depressive symptoms at the following measurement (B = −0.45, t = −3.04, p = 0.003). The greater the gap between expected treatment outcomes and actual depressive severity, the greater the subsequent symptom reductions were (B = 0.49, t = 2.33, p = 0.02). Conclusions: Greater in-treatment patient expectancy is associated with greater subsequent depressive symptom reduction. These findings suggest that clinicians may benefit from monitoring and optimizing patient expectancy during antidepressant treatment. Expectancy may represent another treatment parameter, similar to medication compliance and side effects, to be regularly monitored during antidepressant clinical management. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop and test the feasibility of a primary care worker-led psychological intervention as the main feature of a collaborative stepped care for depression that is effective, affordable, culturally acceptable, tailored to patients' clinical condition and easily integrate-able into the primary care schedule in Nigeria. Methods: Using the Medical Research Council framework, in the first stage (modelling/theoretical development), experts reviewed and distilled evidence from literature to form the intervention components. In the second (formative) stage, local stakeholders were consulted on the practical application and feasibility of the proposed intervention. The third (piloting) stage involved testing for the clinical efficacy and acceptability of the components of the draft intervention Results: The final intervention components included a 2-stage screening (red-flagging and further evaluation), psychoeducation, low-intensity psychological therapy (problem-solving therapy for primary care), antidepressant prescription, proactive mobile telephony adherence support and referral to the mental health specialist if needed. At 3 months, 71.6% of depressed patients on the intervention improved. The intervention was perceived to be acceptable and useful by over 70% of health workers and clients and had high ratings (>70% score) by expert panels on intervention simplicity, facilitation strategies, and quality of delivery. Conclusions: The development and feasibility testing of our integrated intervention encompassed review of current literature, expert opinions and consultation with local stakeholders and end users. Our intervention package was largely deemed acceptable, relevant, useful, and feasible. Important lessons learnt with this process will help in future intervention developments. [ABSTRACT FROM AUTHOR]

Background: Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with high rates of psychiatric disorders, including schizophrenia in up to 30% of individuals with the syndrome. Despite this, we know relatively little about trajectories and predictors of persistence of psychiatric disorders from middle childhood to early adulthood. Accordingly, we followed youth over four timepoints, every 3 years, to assess long-term trajectories of attention-deficit hyperactivity disorder (ADHD), anxiety, mood, and psychosis-spectrum disorders (PSDs), as well as medication usage. Methods: Eighty-seven youth with 22q11DS and 65 controls between the ages of 9 and 15 years at the first timepoint (T1; mean age 11.88 ± 2.1) were followed for 9 years (mean age of 21.22 ± 2.01 years at T4). Baseline cognitive, clinical, and familial predictors of persistence were identified for each class of psychiatric disorders. Results: Baseline age and parent-rated hyperactivity scores predicted ADHD persistence [area under curve (AUC) = 0.81]. The presence of family conflict predicted persistence of anxiety disorders (ADs) whereas parent ratings of child internalizing symptoms predicted persistence of both anxiety and mood disorders (MDs) (AUC = 0.84 and 0.83, respectively). Baseline prodromal symptoms predicted persistent and emergent PSDs (AUC = 0.83). Parent-reported use of anti-depressants/anxiolytics increased significantly from T1 to T4. Conclusions: Psychiatric, behavioral, and cognitive functioning during late childhood and early adolescence successfully predicted children with 22q11DS who were at highest risk for persistent psychiatric illness in young adulthood. These findings emphasize the critical importance of early assessments and interventions in youth with 22q11DS. [ABSTRACT FROM AUTHOR]

Background: Bulimia nervosa (BN), a mental disorder that causes significant impairment, can be treated with psychological, pharmacological, nutrition-based and self-help interventions. We conducted a pre-registered meta-analysis of randomized-controlled trials (RCTs) to assess the efficacy of these interventions in up to 19 different interventions. Methods: Database search terms were combined for BN and RCTs from database inception to March 2017. Abstinence from binge eating episodes, compensatory behaviors, the absence of a BN diagnosis and reduction of symptom severity were considered as primary outcome variables, reduction of self-reported eating pathology and depression served as secondary outcome variables. Retrieved RCTs were meta-analyzed using fixed and random effects models. Results: RCT (79 trials; 5775 participants) effects post-treatment revealed moderate to large intervention effects for psychotherapy [mostly cognitive-behavioral therapy (CBT)] for primary outcome variables. Slightly reduced effects were obtained for self-help and moderate effects for pharmacotherapy. Similarly, psychotherapy yielded large to very large effects in regard to secondary outcome variables, while moderate to large effects were observed for self-help, Pharmacotherapy and combined therapies. Meta-analyses for the pre to post changes within group confirmed these findings. Additionally, follow-up analyses revealed the sustainability of psychotherapies in terms of large effects in primary outcome criteria, while these effects were moderate for self-help, pharmacotherapy, and combined therapies. Conclusions: Most psychological and pharmacological interventions revealed to be effective in BN treatment. Taking effect size, sustainability of the intervention, as well as the consistency of findings and available evidence into consideration, CBT can be recommended as the best intervention for the initial treatment of BN. [ABSTRACT FROM AUTHOR]

Background: We do not know how primary care treatment of depression varies by age across both psychotropic medication and psychological therapies. Methods: Cohort study including 19 710 people aged 55+ with GP recorded depression diagnoses and 26 276 people with recorded depression symptoms during the period 2009–2013, from 373 General Practices in The Health Improvement Network (THIN) database in England. Main outcomes were initiation of treatment with anti-depressants, anxiolytics, hypnotics, anti-psychotic drugs, referrals to psychological therapies within 6 months of onset. Results: Treatment rates with antidepressants are high for those recorded with new depression diagnoses (87.1%) or symptoms of depression (58.7%). Treatment in those with depression diagnoses varies little by age. In those with depressive symptoms there was a J-shaped pattern with reduced antidepressant treatment in those in their 60s and 70s followed by increased treatment in the oldest age groups (85+ years), compared with those aged 55–59 years. Other psychotropic drug prescribing (hypnotics/anxiolytics, antipsychotics) all increase with increasing age. Recorded referrals for psychological therapies were low, and decreased steadily with increasing age, such that women aged 75–79 years with depression diagnoses had around six times lower odds of referral (OR 0.17, 95% CI 0.1–0.29) than those aged 55–59 years, and men aged 80–84 years had around seven times lower (OR 0.14, 95% CI 0.05–0.36). Conclusions: The oldest age groups with new depression diagnoses and symptoms have fewer recorded referrals to psychological therapies, and higher psychotropic drug treatment rates in primary care. This suggests potential inequalities in access to psychological therapies. [ABSTRACT FROM AUTHOR]

BackgroundPrevious studies have examined if maternal antidepressant medication during pregnancy increase the risk of autism spectrum disorder (ASD) in the offspring, but the results have been conflicting.MethodsIn a population-based cohort of 179 007 children born in 2006 and 2007 and followed through 2014 when aged 7 and 8, we estimated relative risks (RRs) of ASD and 95% confidence intervals (CIs) from Cox regression in children exposed to any antidepressant medication during pregnancy, and nine specific antidepressant drugs. Analyses were adjusted for potential confounders and were conducted in the full population sample, and in a clinically relevant sub-sample of mothers with at least one diagnosis of depression or anxiety during life.ResultsThe adjusted RR of ASD in children of mothers who used antidepressant medication during pregnancy was estimated at 1.23 (95% CI 0.96–1.57), and at 1.07 (95% CI 0.80–1.43) in women with a history of depression or anxiety. Analyses of specific antidepressants initially revealed increased RRs of offspring ASD confined to citalopram and escitalopram (RR: 1.47; 95% CI 0.92–2.35) and clomipramine (RR: 2.86; 95% CI 1.04–7.82).ConclusionMedication with antidepressants during pregnancy does not appear to be causally associated with an increased risk of ASD in the offspring. Instead, the results suggest that the association is explained by factors related to the underlying susceptibility to psychiatric disorders. Based on these findings, the risk of ASD in the offspring should not be a consideration to withhold treatment with commonly used antidepressant drugs from pregnant women. [ABSTRACT FROM PUBLISHER]

The article reports that why drugs and electricity have created a public health disaster. Topics include define diabetes as blood sugar levels that are too high and can evaluate treatment by measuring its effects on blood sugar; and scientific ontology and epistemology are appropriate for developing technical knowledge on diabetes with experiences of suffering have been known for many cultures potential value for deepening our experiential knowledge of the human condition.

A substantial proportion of the burden of depression arises from its recurrent nature. The risk of relapse after antidepressant medication (ADM) discontinuation is high but not uniform. Predictors of individual relapse risk after antidepressant discontinuation could help to guide treatment and mitigate the long-term course of depression. We conducted a systematic literature search in PubMed to identify relapse predictors using the search terms ‘(depress* OR MDD*) AND (relapse* OR recurren*) AND (predict* OR risk) AND (discontinu* OR withdraw* OR maintenance OR maintain or continu*) AND (antidepress* OR medication OR drug)’ for published studies until November 2014. Studies investigating predictors of relapse in patients aged between 18 and 65 years with a main diagnosis of major depressive disorder (MDD), who remitted from a depressive episode while treated with ADM and were followed up for at least 6 months to assess relapse after part of the sample discontinued their ADM, were included in the review. Although relevant information is present in many studies, only 13 studies based on nine separate samples investigated predictors for relapse after ADM discontinuation. There are multiple promising predictors, including markers of true treatment response and the number of prior episodes. However, the existing evidence is weak and there are no established, validated markers of individual relapse risk after antidepressant cessation. There is little evidence to guide discontinuation decisions in an individualized manner beyond overall recurrence risk. Thus, there is a pressing need to investigate neurobiological markers of individual relapse risk, focusing on treatment discontinuation. [ABSTRACT FROM PUBLISHER]

BackgroundCognitive dysfunction in depression and bipolar disorder (BD) is insufficiently targeted by available treatments. Erythropoietin (EPO) increases neuroplasticity and may improve cognition in mood disorders, but the neuronal mechanisms of these effects are unknown. This functional magnetic resonance imaging (fMRI) study investigated the effects of EPO on neural circuitry activity during working memory (WM) performance.MethodPatients with treatment-resistant major depression, who were moderately depressed, or with BD in partial remission, were randomized to eight weekly infusions of EPO (40 000 IU) (N = 30) or saline (N = 26) in a double-blind, parallel-group design. Patients underwent fMRI, mood ratings and blood tests at baseline and week 14. During fMRI patients performed an n-back WM task.ResultsEPO improved WM accuracy compared with saline (p = 0.045). Whole-brain analyses revealed that EPO increased WM load-related activity in the right superior frontal gyrus (SFG) compared with saline (p = 0.01). There was also enhanced WM load-related deactivation of the left hippocampus in EPO-treated compared to saline-treated patients (p = 0.03). Across the entire sample, baseline to follow-up changes in WM performance correlated positively with changes in WM-related SFG activity and negatively with hippocampal response (r = 0.28–0.30, p < 0.05). The effects of EPO were not associated with changes in mood or red blood cells (p ⩾0.08).ConclusionsThe present findings associate changes in WM-load related activity in the right SFG and left hippocampus with improved executive function in EPO-treated patients. Clinical trial registration: clinicaltrials.gov: NCT00916552. [ABSTRACT FROM AUTHOR]

BackgroundKetamine and non-ketamine N-methyl-d-aspartate receptor antagonists (NMDAR antagonists) recently demonstrated antidepressant efficacy for the treatment of refractory depression, but effect sizes, trajectories and possible class effects are unclear.MethodWe searched PubMed/PsycINFO/Web of Science/clinicaltrials.gov until 25 August 2015. Parallel-group or cross-over randomized controlled trials (RCTs) comparing single intravenous infusion of ketamine or a non-ketamine NMDAR antagonist v. placebo/pseudo-placebo in patients with major depressive disorder (MDD) and/or bipolar depression (BD) were included in the analyses. Hedges’ g and risk ratios and their 95% confidence intervals (CIs) were calculated using a random-effects model. The primary outcome was depressive symptom change. Secondary outcomes included response, remission, all-cause discontinuation and adverse effects.ResultsA total of 14 RCTs (nine ketamine studies: n = 234; five non-ketamine NMDAR antagonist studies: n = 354; MDD = 554, BD = 34), lasting 10.0 ± 8.8 days, were meta-analysed. Ketamine reduced depression significantly more than placebo/pseudo-placebo beginning at 40 min, peaking at day 1 (Hedges' g = −1.00, 95% CI −1.28 to −0.73, p < 0.001), and loosing superiority by days 10–12. Non-ketamine NMDAR antagonists were superior to placebo only on days 5–8 (Hedges' g = −0.37, 95% CI −0.66 to −0.09, p = 0.01). Compared with placebo/pseudo-placebo, ketamine led to significantly greater response (40 min to day 7) and remission (80 min to days 3–5). Non-ketamine NMDAR antagonists achieved greater response at day 2 and days 3–5. All-cause discontinuation was similar between ketamine (p = 0.34) or non-ketamine NMDAR antagonists (p = 0.94) and placebo. Although some adverse effects were more common with ketamine/NMDAR antagonists than placebo, these were transient and clinically insignificant.ConclusionsA single infusion of ketamine, but less so of non-ketamine NMDAR antagonists, has ultra-rapid efficacy for MDD and BD, lasting for up to 1 week. Development of easy-to-administer, repeatedly given NMDAR antagonists without risk of brain toxicity is of critical importance. [ABSTRACT FROM PUBLISHER]

BackgroundAdverse effects of antidepressants are most common at the beginning of the treatment, but possible also later. We examined the association between antidepressant use and work-related injuries taking into account the duration of antidepressant use.MethodAntidepressant use and work-related injuries between 2000 and 2011 were measured among 66 238 employees (mean age 43.8 years, 80% female) using linkage to national records (the Finnish Public Sector study). We analysed data using time-dependent modelling with individuals as their own controls (self-controlled case-series design).ResultsIn 2238 individuals who had used antidepressants and had a work-related injury during a mean follow-up of 7.8 years, no increase in the risk of injury was observed in the beginning of antidepressant treatment. However, an increased injury risk was seen after 3 months of treatment (rate ratio, compared with no recent antidepressant use, 1.27, 95% confidence interval 1.10–1.48). This was also the case among those who had used only selective serotonin reuptake inhibitors (n = 714; rate ratio 1.41, 95% confidence interval 1.08–1.83).ConclusionsAntidepressant use was not associated with an increased risk of work-related injury at the beginning of treatment. Post-hoc analyses of antidepressant trials are needed to determine whether long-term use of antidepressants increases the risk of work-related injury. [ABSTRACT FROM PUBLISHER]

BackgroundStudies have linked ethnic differences in depression rates with neighbourhood ethnic density although results have not been conclusive. We looked at this using a novel approach analysing whole population data covering just over one million GP patients in four London boroughs.MethodUsing a dataset of GP records for all patients registered in Lambeth, Hackney, Tower Hamlets and Newham in 2013 we investigated new diagnoses of depression and antidepressant use for: Indian, Pakistani, Bangladeshi, black Caribbean and black African patients. Neighbourhood effects were assessed independently of GP practice using a cross-classified multilevel model.ResultsBlack and minority ethnic groups are up to four times less likely to be newly diagnosed with depression or prescribed antidepressants compared to white British patients. We found an inverse relationship between neighbourhood ethnic density and new depression diagnosis for some groups, where an increase of 10% own-ethnic density was associated with a statistically significant (p < 0.05) reduced odds of depression for Pakistani [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.70–0.93], Indian (OR 0.88, CI 0.81–0.95), African (OR 0.88, CI 0.78–0.99) and Bangladeshi (OR 0.94, CI 0.90–0.99) patients. Black Caribbean patients, however, showed the opposite effect (OR 1.26, CI 1.09–1.46). The results for antidepressant use were very similar although the corresponding effect for black Caribbeans was no longer statistically significant (p = 0.07).ConclusionNew depression diagnosis and antidepressant use was shown to be less likely in areas of higher own-ethnic density for some, but not all, ethnic groups. [ABSTRACT FROM PUBLISHER]

BackgroundTricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) may be associated with lower heart rate variability (HRV), a condition associated with increased mortality risk. We aimed to investigate the association between TCAs, SSRIs and HRV in a population-based study.MethodIn the prospective Rotterdam Study cohort, up to five electrocardiograms (ECGs) per participant were recorded (1991–2012). Two HRV variables were studied based on 10-s ECG recordings: standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD). We compared the HRV on ECGs recorded during use of antidepressants with the HRV on ECGs recorded during non-use of any antidepressant. Additionally, we analysed the change in HRV on consecutive ECGs. Those who started or stopped using antidepressants before the second ECG were compared with non-users on two ECGs.ResultsWe included 23 647 ECGs from 11 729 participants (59% women, mean age 64.6 years at baseline). Compared to ECGs recorded during non-use of antidepressants (n = 22 971), SDNN and RMSSD were lower in ECGs recorded during use of TCAs (n = 296) and SSRIs (n = 380). Participants who started using TCAs before the second ECG had a decrease in HRV and those who stopped had an increase in HRV compared to consistent non-users (p < 0.001). Starting or stopping SSRIs was not associated with HRV changes.ConclusionTCAs were associated with a lower HRV in all analyses, indicating a real drug effect. For SSRIs the results are mixed, indicating a weaker association, possibly due to other factors. [ABSTRACT FROM PUBLISHER]

BackgroundMinimal efficacy differences have been found between cognitive behavioral therapy (CBT) and psychodynamic therapies for depression, but little is known about patient characteristics that might moderate differential treatment effects. We aimed to generate hypotheses regarding such potential prescriptive factors.MethodWe conducted post-hoc model-based recursive partitioning analyses alongside a randomized clinical trial comparing the efficacy of CBT and short-term psychodynamic supportive psychotherapy (SPSP). Severely depressed patients received additional antidepressant medication. We included 233 adults seeking treatment for a major depressive episode in psychiatric outpatient clinics, who completed post-treatment assessment. Post-treatment mean Hamilton Depression Rating Scale scores constituted the main outcome measure.ResultsWhile treatment differences (CBT v. SPSP) were minimal in the total sample of patients (d = 0.04), model-based recursive partitioning indicated differential treatment efficacy in certain subgroups of patients. SPSP was found more efficacious among moderately depressed patients receiving psychotherapy only who showed low baseline co-morbid anxiety levels (d = −0.40) and among severely depressed patients receiving psychotherapy and antidepressant medication who reported a duration of the depressive episode of ⩾1 year (d = −0.31), while CBT was found more efficacious for such patients reporting a duration <1 year (d = 0.83).ConclusionsOur findings are observational and need validation before they can be used to guide treatment selection, but suggest that knowledge of prescriptive factors can help improve the efficacy of psychotherapy for depression. Depressive episode duration and co-morbid anxiety level should be included as stratification variables in future randomized clinical trials comparing CBT and psychodynamic therapy. [ABSTRACT FROM PUBLISHER]

BackgroundWhile oral antidepressants reach efficacy after weeks, single-dose intravenous (i.v.) ketamine has rapid, yet time-limited antidepressant effects. We aimed to determine the efficacy and safety of single-dose i.v. ketamine augmentation of escitalopram in major depressive disorder (MDD).MethodThirty outpatients with severe MDD (17-item Hamilton Rating Scale for Depression total score ⩾24) were randomized to 4 weeks double-blind treatment with escitalopram 10 mg/day+single-dose i.v. ketamine (0.5 mg/kg over 40 min) or escitalopram 10 mg/day + placebo (0.9% i.v. saline). Depressive symptoms were measured using the Montgomery–Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology – Self-Report (QIDS-SR). Suicidal ideation was evaluated with the QIDS-SR item 12. Adverse psychopathological effects were measured with the Brief Psychiatric Rating Scale (BPRS)-positive symptoms, Young Mania Rating Scale (YMRS) and Clinician Administered Dissociative States Scale (CADSS). Patients were assessed at baseline, 1, 2, 4, 24 and 72 h and 7, 14, 21 and 28 days. Time to response (⩾50% MADRS score reduction) was the primary outcome.ResultsBy 4 weeks, more escitalopram + ketamine-treated than escitalopram + placebo-treated patients responded (92.3% v. 57.1%, p = 0.04) and remitted (76.9% v. 14.3%, p = 0.001), with significantly shorter time to response [hazard ratio (HR) 0.04, 95% confidence interval (CI) 0.01–0.22, p < 0.001] and remission (HR 0.11, 95% CI 0.02–0.63, p = 0.01). Compared to escitalopram + placebo, escitalopram + ketamine was associated with significantly lower MADRS scores from 2 h to 2 weeks [(peak = 3 days–2 weeks; effect size (ES) = 1.08–1.18)], QIDS-SR scores from 2 h to 2 weeks (maximum ES = 1.27), and QIDS-SR suicidality from 2 to 72 h (maximum ES = 2.24). Only YMRS scores increased significantly with ketamine augmentation (1 and 2 h), without significant BPRS or CADSS elevation.ConclusionsSingle-dose i.v. ketamine augmentation of escitalopram was safe and effective in severe MDD, holding promise for speeding up early oral antidepressant efficacy. [ABSTRACT FROM PUBLISHER]

BackgroundThe Beck Depression Inventory, 2nd edition (BDI-II) is widely used in research on depression. However, the minimal clinically important difference (MCID) is unknown. MCID can be estimated in several ways. Here we take a patient-centred approach, anchoring the change on the BDI-II to the patient's global report of improvement.MethodWe used data collected (n = 1039) from three randomized controlled trials for the management of depression. Improvement on a ‘global rating of change’ question was compared with changes in BDI-II scores using general linear modelling to explore baseline dependency, assessing whether MCID is best measured in absolute terms (i.e. difference) or as percent reduction in scores from baseline (i.e. ratio), and receiver operator characteristics (ROC) to estimate MCID according to the optimal threshold above which individuals report feeling ‘better’.ResultsImprovement in BDI-II scores associated with reporting feeling ‘better’ depended on initial depression severity, and statistical modelling indicated that MCID is best measured on a ratio scale as a percentage reduction of score. We estimated a MCID of a 17.5% reduction in scores from baseline from ROC analyses. The corresponding estimate for individuals with longer duration depression who had not responded to antidepressants was higher at 32%.ConclusionsMCID on the BDI-II is dependent on baseline severity, is best measured on a ratio scale, and the MCID for treatment-resistant depression is larger than that for more typical depression. This has important implications for clinical trials and practice. [ABSTRACT FROM PUBLISHER]

Background. The National Institute of Health and Care Excellence (NICE) in England and Wales recommends the combination of pharmacotherapy and psychotherapy for the treatment of moderate to severe depression. However, the costeffectiveness analysis on which these recommendations are based has not included psychotherapy as monotherapy as a potential option. For this reason, we aimed to update, augment and refine the existing economic evaluation. Method. We constructed a decision analytic model with a 27-month time horizon.We compared pharmacotherapy with cognitive-behavioural therapy (CBT) and combination treatment for moderate to severe depression in secondary care from a healthcare service perspective. We reviewed the literature to identify relevant evidence and, where possible, synthesized evidence from clinical trials in a meta-analysis to inform model parameters. Results. The model suggested that CBT as monotherapy was most likely to be the most cost-effective treatment option above a threshold of £22 000 per quality-adjusted life year (QALY). It dominated combination treatment and had an incremental cost-effectiveness ratio of £20 039 per QALY compared with pharmacotherapy. There was significant decision uncertainty in the probabilistic and deterministic sensitivity analyses. Conclusions. Contrary to previous NICE guidance, the results indicated that even for those patients for whom pharmacotherapy is acceptable, CBT as monotherapy may be a cost-effective treatment option. However, this conclusion was based on a limited evidence base, particularly for combination treatment. In addition, this evidence cannot easily be transferred to a primary care setting. [ABSTRACT FROM AUTHOR]