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Background: People with mental health conditions were potentially more vulnerable than others to the neuropsychiatric effects of the COVID-19 pandemic and the global efforts taken to contain it. The aim of this multinational study was to examine the changes in psychotropic drug prescribing during the pandemic among people with depressive and anxiety disorders., Methods: This study included electronic medical records and claims data from nine databases in six countries (France, Germany, Italy, the UK, South Korea, and the USA) of patients with a diagnosis of depressive or anxiety disorders between 2016 and 2021. The outcomes were monthly prevalence rates of antidepressant, antipsychotic, and anxiolytic drug prescribing. The associations between the pandemic and psychotropic drug prescribing were examined with interrupted time series analyses for the total sample and stratified by sex and age group. People with lived experience were not involved in the research and writing process., Findings: Between Jan 1, 2016 and Dec 31, 2020, an average of 16 567 914 patients with depressive disorders (10 820 956 females [65·31%] and 5 746 958 males [34·69%]) and 15 988 451 patients with anxiety disorders (10 688 788 females [66·85%] and 5 299 663 males [33·15%]) were identified annually. Most patients with depressive disorders and anxiety disorders were aged 45-64 years. Ethnicity data were not available. Two distinct trends in prescribing rates were identified. The first pattern shows an initial surge at the start of the pandemic (eg, antipsychotics among patients with depressive disorders in MDCD_US (rate ratio [RR] 1·077, 95% CI 1·055-1·100), followed by a gradual decline towards the counterfactual level (RR 0·990, 95% CI 0·988-0·992). The second pattern, observed in four databases for anxiolytics among patients with depressive disorders and two for antipsychotics among patients with anxiety disorders, shows an immediate increase (eg, antipsychotics among patients with anxiety disorders in IQVIA_UK: RR 1·467, 95% CI 1·282-1·675) without a subsequent change in slope (RR 0·985, 95% CI 0·969-1·003). In MDCD_US and IQVIA_US, the anxiolytic prescribing rate continued to increase among patients younger than 25 years for both disorders., Interpretation: The study reveals persistently elevated rates of psychotropic drug prescriptions beyond the initial phase of the pandemic. These findings underscore the importance of enhanced mental health support and emphasise the need for regular review of psychotropic drug use among this patient group in the post-pandemic era., Funding: University Grants Committee, Research Grants Council, The Government of the Hong Kong Special Administrative Region., Competing Interests: Declaration of interests HL reports grants from Research Grants Council of Hong Kong, outside the submitted work. WCYL reports research grants from AIR@InnoHK administered by Innovation and Technology Commission, outside the submitted work. JH reports grants from UKRI, Consultancy Fees from Wellcome Trust and Juli Health, and patents pending and stock from Juli Health, outside the submitted work. COT reports stock or stock options and other financial or non-financial interests from Roche Pharmaceutical as an employee, outside the submitted work. XL reports grants from IQVIA, outside the submitted work. SF and DMK report stock or stock options and other financial or non-financial interests from Johnson and Johnson as employees, outside the submitted work. JL reports stock or stock options and other financial or non-financial interests from IQVIA as an employee, outside the submitted work. KKCM reports grants from the CW Maplethorpe Fellowship, National Institute of Health Research, UK, Hong Kong Research Grant Council, and the European Commission Horizon 2020 Framework, outside the submitted work. ICKW reports grants from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK and Novartis, the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, and National Health and Medical Research Council in Australia, consulting fees from IQVIA, payment for expert testimony and a role as an independent non-executive director of Jacobson Medical, Hong Kong, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Positive leadership behaviours at work are associated with worker well-being and performance. However there is less knowledge about whether exposure to low levels of positive leadership behaviours increase workers' risk of clinical mental disorders. We investigated whether low levels of positive leadership behaviours are prospectively associated with risk of treatment for depressive and anxiety disorders. In a cohort study, we linked survey data from 59,743 respondents from the Work Environment and Health in Denmark survey with national health register data. Leadership behaviours were measured with an eight-item scale. Treatment was defined as redeemed prescription for antidepressants or anxiolytics or hospital treatment for depression or anxiety. Using Cox proportional hazard regression, adjusting for demographic variables, job type and sector, adverse life events and childhood adversities, we estimated the association between leadership behaviours at baseline and risk of treatment during follow-up. We identified 999 cases of depression and anxiety treatment during follow-up. Compared to high levels of leadership behaviours, exposure to medium low and low levels were associated with an increased risk of treatment after adjustment for covariates. The results suggest that low levels of positive leadership behaviours are associated with an increased risk of treatment for depressive or anxiety disorders., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The article reflects the results of a number of studies that demonstrate the therapeutic effectiveness of Recognan (citicoline) in anxiety-depressive and asthenic disorders against the background of somatic and neurological diseases, in the correction of post-stroke depression. Recent experimental animal studies prove the effect of citicoline on anxiety and depression. In the complex effect, Recognan potentiates the main pharmacological effect of antidepressants and anxiolytics. In some studies, a dose-dependent change in animal behavior has been observed in response to the analgesic and antidepressant effects of citicoline. The effectiveness of citicoline in combination with transcranial direct current stimulation in the treatment of depression has been shown. The analysis of these research materials allows us to recommend Recognan in the complex therapy of asthenic and anxiety-depressive disorders in response to such pathological conditions as anxiety, asthenia, depression.

The RSCI and PubMed search databases have requested publications over the past 40 years on the search queries «fluvoxamine», «anxiety-depressive disorders», «anxiety», «depression», «comorbidity», devoted to the effectiveness of fluvoxamine in various variants of disorders of the anxiety-depressive spectrum, anxiety depressions. The data of the above studies indicate that fluvoxamine (Zovart San) in doses of 50-300 mg / day is a highly effective remedy for the treatment of not only anxiety depressions and genesis (psychogenic, organic, mixed, autochthonous-endogenous) and severity (up to psychotic), but also a wider range of anxiety-depressive disorders, including adaptation disorders, obsessive-compulsive disorder, somatized, dysmorphic, insomniac symptom complexes and eating disorders. A wide range of clinical effects of fluvoxamine is due to its main and additional mechanisms of action: blockade of serotonin reuptake, σ 1-agonist activity and the effect on the metabolism of melatonin and neurosteroids catabolism.

Ethnopharmacological Relevance: Shugan granule is derived from Xiaoyao powder, a traditional Chinese medicine that has been shown to be effective in treating emotional disorders. At present, there is no standard drug treatment for mixed anxiety-depressive disorder (MADD), and no evidence-based clinical trial has been performed for any drug, meaning MADD patients are unable to obtain standardized treatment., Aim of the Study: The purpose of this clinical trial was to test the clinical efficacy and safety of Shugan granules in the treatment of MADD, and to provide clinical trial-based support along with drug recommendations for the treatment of MADD., Materials and Methods: A multicenter, randomized, double-blind, placebo-controlled study was conducted on 400 patients with MADD recruited from January 1, 2019 to December 31, 2020, and they were randomly divided into test and placebo groups with a 1:1 ratio. Subjects in the test group (n = 200) received oral administration of Shugan granules, while subjects in the placebo group (n = 200) received oral administration of a Shugan granule simulator. The treatment lasted for 8 weeks. The Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale-17 (HAMD-17), Clinical Global Impression Scale (CGIS), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used to evaluate efficacy. In addition, the traditional Chinese medicine (TCM) syndrome scale for MADD was developed to observe improvements of related symptoms in patients after treatment based on the disease guidelines of TCM and the clinical manifestations of depression. Furthermore, the safety of Shugan granules was evaluated during and after treatment., Results: After 8 weeks of treatment, the total scores for HAMA, HAMD, SAS, and SDS in the test group were significantly lower than those in the placebo group (P < 0.01). The proportion of patients with efficacy index (EI) > 1 for the CGIS score in the test group was significantly higher than that in the placebo group (P < 0.01). The efficacy of treatment in the test group based on the TCM syndrome scale was 70.16% and 88.27% after 4 weeks and 8 weeks, respectively, which was significantly higher than that in the placebo group (44.27% and 66.67% after 4 weeks and 8 weeks, respectively; P < 0.01). The disappearance rate of single symptoms in the test group was 20-30% higher than that in the placebo group, with a significant difference between groups (P < 0.05). During the treatment period, the incidence of adverse reactions was 2.05% in the test group and 2.06% in the placebo group, with no significant differences noted (P = 1.0000)., Conclusion: Shugan granule was more effective than placebo in the treatment of MADD. Moreover, there was no significant difference between the two groups in terms of safety. This paper provides a clinical therapeutic regime using Shugan granule for the treatment of MADD., (Copyright © 2022. Published by Elsevier B.V.)

Background: Classical psychedelics are a group of drugs which act as agonists on the serotonin-2A (5-HT2A) receptor. Evidence suggests they may have a uniquely rapid and enduring positive effect on mood. However, marked heterogeneity between methodological designs in this emerging field remains a significant concern., Aims: To determine how differences in the type of psychedelic agent used and the number of dosing sessions administered affect subjects' depression and anxiety outcomes and adverse drug reactions (ADR)., Methods: This review collected and screened 1591 records from the MEDLINE and Web of Science databases for clinical trials reporting objective data on mood for subjects with a known anxiety or depression., Results: After screening, nine clinical trials met inclusion criteria. Meta-analysis of these studies showed significant, large positive effect sizes for measures of anxiety (Cohen's d  = 1.26) and depression (Cohen's d  = 1.38) overall. These positive effects were also significant at acute (⩽1 week) and extended (>1 week) time points. No significant differences were observed between trials using different psychedelic agents (psilocybin, ayahuasca or lysergic acid diethylamide (LSD)), however, a significant difference was observed in favour of trials with multiple dosing sessions. No serious ADR were reported., Conclusion: Psilocybin, ayahuasca and LSD all appear to be effective and relatively safe agents capable of producing rapid and sustained improvements in anxiety and depression. Moreover, the findings of the present analysis suggest that they may show a greater efficacy when given to patients over multiple sessions as compared to the more common single session used in many of the existing trials.

Introduction: Between one third and one half of the population that has suffered a stroke present with a neuropsychiatric disorder (NPD), which often goes underdiagnosed., Aim: To study the association between the presence of NPDs and coping strategies in stroke patients., Subjects and Methods: Prospective, longitudinal and comparative study in a sample of patients with ischaemic stroke with and without the presence of NPDs. Both sociodemographic and clinical variables were collected. Neurological impairment (National Institute of Health Stroke Scale) and coping (Brief Coping Orientation to Problems Experienced) were assessed at three and 12 months. The period studied was from 2013 to 2017., Results: A total of 82 patients were analysed, with a mean age of 67.6 ± 10.4 years, 52.4% of whom were male. Of them, 14 with NPD and 36 without NPD answered the Brief Coping Orientation to Problems Experienced coping scale, and the remaining 32 were excluded because of aphasia/dysphasia. At three months, dimensions of active coping, social support, denial and behavioural disengagement were observed in the NPD group, and at 12 months, denial and behavioural disengagement persisted, and planning, self-distraction and self-incrimination dimensions appeared., Conclusions: Results show the need to motivate patients to seek more effective strategies, to identify problems when they arise, to consider them as surmountable and to inhibit impulsive or inappropriate responses, replacing them with emotional responses and appropriate behaviours.

Background: The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication., Method: We longitudinally investigated the relationship between patients' prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions., Results: We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = -0.00254, SE = 0.000595, P < .0001; estimate = -0.02644, SE = 0.00833, P = .002, respectively)., Conclusion: Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients' types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders., (© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.)

The forced swim stress test (FST) is widely used for screening pharmacological or non-pharmacological strategies with potential antidepressant activities. Recent data have suggested that repeated FST for five consecutive days (i.e., 5d-RFSS) could be used to generate a robust depressive-like phenotype in mice. However, the face, construct, and predictive validities of 5d-RFSS have been recently challenged. This study took advantage of recent findings showing that mice vulnerability to anxiety is enhanced when animals are stressed during the dark phase, to provide new insight into the relevance of this model. Our results showed a progressive increase in time of immobility in 5d-RFSS mice relative to control non-stressed animals (sham). Three weeks later, we noticed that 5d-RFSS mice injected with the vehicle compound (Veh) still exhibited a high level of immobility in the FST whereas this behavior was reversed by the antidepressant drug amitriptyline (AMI). However, 5d-RFSS/Veh and 5d-RFSS mice/AMI mice showed normal performances in the open field, the novelty suppressed feeding and the tail suspension tests. Despite this lack of generalized behavioral deficits, an impairment of different parameters characterizing the hypothalamic-pituitary-adrenal (HPA) axis reactivity was evidenced in 5d-RFSS mice/Veh but not in 5d-RFSS mice/AMI. Despite anomalies in the HPA axis, the activity of the central serotonergic system remained unaffected in 5d-RFSS mice relative to controls. From our results, it is suggested that learned immobility does not replicate the broad spectrum of depressive symptoms observed in other chronic models of depression such as the unpredictable chronic mild stress (UCMS) model, the chronic social defeat stress (CSDS) model or chronic corticosterone (CORT) exposure but its influence on the HPA axis is remarkable. Further experiments are warranted to makes this model suitable for modelling depression and therefore refine its translational applicability.

The endocannabinoid system (ECS) has received extensive attention for its neuroprotective effect on the brain. This system comprises endocannabinoids, endocannabinoid receptors, and the corresponding ligands and proteins. The molecular players involved in their regulation and metabolism are potential therapeutic targets for neuropsychiatric diseases including anxiety, depression and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The inhibitors of two endocannabinoid hydrolases, i.e., fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), have the capacity to increase the level of endocannabinoids indirectly, causing fewer side effects than those associated with direct supplementation of cannabinoids. Their antidepressant and anxiolytic mechanisms are considered to modulate the hypothalamic-pituitary-adrenal axis and regulate synaptic and neural plasticity. In terms of AD/PD, treatment with FAAH/MAGL inhibitors leads to reduction in amyloid β-protein deposition and inhibition of the death of dopamine neurons, which are commonly accepted to underlie the pathogenesis of AD and PD, respectively. Inflammation as the cause of depression/anxiety and PD/AD is also the target of FAAH/MAGL inhibitors. In this review, we summarize the application and involvement of FAAH/MAGL inhibitors in related neurological diseases. Focus on the latest research progress using FAAH/MAGL inhibitors is expected to facilitate the development of novel approaches with therapeutic potential.

Background: Antidepressant use later in pregnancy has been associated with preeclampsia and postpartum haemorrhage (PPH) in some studies., Objectives: To evaluate the association between patterns of prenatal antidepressant dose across gestationand risk of precclampsia and PPH., Methods: We utilised OptumLabs® Data Warehouse (2012-2016) administrative health care claims, identifying 226 932 singleton liveborn deliveries for this retrospective cohort study. Antidepressant dispensing doses were converted to fluoxetine equivalents. Using k-means longitudinal, we identified women with similar patterns of antidepressant exposure, that is, trajectory groups, during the first 20 and 35 gestational weeks. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between trajectory groups and preeclampisa (20-week groups) and PPH (35-week groups), adjusting for demographics, co-morbidities, and other psychotropic medications. Linear trend tests assessing increasing risk of the outcomes across groups were performed., Results: Among 15 041 (6.6%) pregnancies exposed to an antidepressant, the following trajectory groups were identified: A-low exposure, starting pregnancy at ~10 mg/d, with 1st trimester reduction/discontinuation, B-low sustained exposure of ~20 mg/d, C-moderate exposure (~40 mg/d) with 1st trimester reduction/discontinuation, D-moderate sustained exposure of ~40 mg/d, and E-high sustained exposure of ~75 mg/d. In the low exposure with reduction/discontinuation trajectory, risks were 8.2% for preeclampsia and 2.7% for PPH. Compared with this group, low, moderate, and high sustained trajectories were associated with preeclampsia (adjusted RR 1.17, 95% CI 1.01, 1.34; RR 1.31, 95% CI 1.12, 1.54; and RR 1.41, 95% CI 1.05, 1.90, respectively) and PPH (RR 1.32, 95% CI 1.05, 1.66; RR 1.35, 95% CI 1.03, 1.78; RR 2.51, 95% CI 1.69, 3.71, respectively); P < .01 for linear trend tests for both outcomes. There was no increased risk for either outcome for moderate exposure with reduction/discontinuation (trajectory C)., Conclusions: Women with sustained antidepressant exposure, especially at higher doses, were at increased risk for preeclampsia and PPH, but underlying depression and anxiety may contribute to the increased risk., (© 2020 John Wiley & Sons Ltd.)

Background: Benzodiazepines (BZDs) have been widely used to treat anxiety; however, the risk of adverse health effects caused by their long-term use is high. This study examined the factors associated with the duration and higher daily dose of BZDs use among a population with anxiety or depressive disorders., Methods: A cross-sectional study design was used. Patients from a psychiatric outpatient department who had been prescribed BZDs were recruited. Data were collected from 250 patients., Results: Nearly 94% of patients were long-term BZDs users. The mean duration of BZDs use was 5.5 years; and mean defined daily dose (DDD) of BZDs use, converted to diazepam milligram equivalent (DDD), was 1.53 DME-DDD. Patients who knew more about alternative treatments were less prone to use BZD longer. Patients aged 65 years or older and those with difficulty falling asleep were more prone to use BZDs longer. Patients who were currently taking BZDs at higher daily dose were those who felt more depressed, prescribed second generation antipsychotics, suffered from disrupted sleep, less aware of alternative treatments, had comorbid chronic physical illness, and were current smokers., Limitations: The cross-sectional study design limited its ability to confirm causal relationships., Conclusions: Long-term and excessive daily dose of BZDs use in patients with depressive or anxiety disorders needs to be noted. Providing information or program of non-pharmacological treatment in reducing anxiety and improving specific sleep disturbance is suggested. Elderly, suffering from depressive mood, had comorbid chronic physical illness need to be targeted for further intervention., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: The prevalence of psychiatric disease in patients with eosinophilic esophagitis (EoE) is not fully characterized. We aimed to determine the prevalence of psychiatric disease and centrally acting medication use in a cohort of children and adults with EoE and evaluated whether psychiatric disease affects the EoE clinical presentation., Methods: We conducted a retrospective study of newly diagnosed cases with EoE at the University of North Carolina from 2002 to 2018. Psychiatric comorbidities and relevant treatments were extracted from the medical records. The demographic and clinical features of patients with EoE with and without psychiatric diagnoses, and those with and without psychiatric medication use, were compared., Results: Of 883 patients (mean age 26.6 years, 68% men, 79% white), 241 (28%) had a psychiatric comorbidity. The most common diagnosis was anxiety (23%) followed by depression (17%); 28% of patients were treated pharmacologically. There were 45 patients (5%) treated pharmacologically without a psychiatric diagnosis for chronic pain syndromes, insomnia, and/or epilepsy. Cases with EoE with a psychiatric diagnosis were more likely to be women, white, and 18 years or older and to have a longer symptom duration before diagnosis., Dicussion: Psychiatric comorbidities were common in EoE, seen in a third of adults and more than 1 in 7 children, and with similar proportions receiving a prescription medication. These illnesses affected the EoE presentation because psychiatric comorbidities were more likely in older, female, and white patients with a longer duration of symptoms preceding diagnosis.

Background: Post-traumatic stress disorder (PTSD) is an extreme mood disorder that occurs after experiencing extreme stress, and patients with this disorder are known to accompany with symptoms of depression, anxiety, and memory impairments. Silibinin (SIL) is a natural polyphenolic flavonoid and is the main active ingredient of silymarin, which is primarily extracted from the milk thistle. Although some studies have assessed the properties of this flavonoid, the potential of SIL as a treatment for PTSD patients and its mechanisms of action have yet to be fully elucidated., Methods: After exposure to a model of single prolonged stress (SPS), the open field test (OFT) and forced swimming test (FST), were used to investigate the effects of SIL on anxiety- and depression-like symptoms in male rats. The rats received of SIL (25, 50, and 100 mg/kg) for 14 days following exposure to SPS., Results: Administration of SIL significantly improved anxiety-like behaviors in the OFT, depression-like behaviors in the FST, and freezing behavior in fear conditioning test. SIL also increased levels of serotonin in the hippocampus (Hipp) and amygdala, and enhanced expression of tryptophan hydroxylase-1 mRNA in the Hipp. The administration of SIL also inhibited SPS-induced decreases dopamine levels and increases norepinephrine levels in the Hipp., Conclusions: Taken together, the present findings suggest that SIL can be a useful therapeutic ingredient for the treatment of trauma stress-associated symptoms, including PTSD-induced anxiety and depression caused by PTSD.

Purpose of Review: This review is to summarize most recent evidence published in the last 18 months on medical and recreational use of cannabis and cannabinoids in relation to anxiety, depression (unipolar and bipolar), and dysregulation of emotions as part of posttraumatic stress disorders (PTSD) and emotionally instable personality disorders. It also covers the investigation of endocannabinoids as potential biomarkers in these conditions. This is important with increasing medicinal use of cannabinoids and growing social tolerance towards recreational cannabis use., Recent Findings: There is some recent evidence suggesting cannabinoids, cannabidiol or cannabidiol-enriched cannabis preparations have anxiolytic properties. In addition, depression may be worsened by cannabis use, however, randomized controlled trials (RCT) are lacking. New evidence also suggests that cannabidiol or cannabidiol-enriched cannabis use for PTSD and emotion regulation can induce hyporesponse to fear and stress. Further, several lines of evidence point to the endocannabinoid system as a key player in some of the reviewed disorders, in particular anxiety and PTSD., Summary: The most recent evidence for a therapeutic use of cannabinoids in the reviewed conditions is weak and lacking well designed RCTs. However, there is some indication of the role of the endocannabinoid system in these conditions that warrant further studies.

Purpose: To examine whether depression, anxiety disorder, and their co-occurrence would increase the risk of mortality in patients with breast cancer, and whether antidepressant treatment would reduce the same., Methods: Data were retrieved from the database of the Korean National Health Insurance Service. Of 145,251 patients diagnosed with breast cancer between 2007 and 2014, 20,870 patients diagnosed with depression or anxiety disorder one year before breast cancer diagnosis were excluded. Thus, data of 124,381 patients were included in this study., Results: Depression and anxiety disorder were associated with an increased risk of mortality [Hazard Ratio (HR) 1.26, 95% CI 1.18-1.36; HR 1.14, 95% CI 1.08-1.22, respectively] and their co-occurrence further increased the risk (HR = 1.38, 95% CI 1.24-1.54). Antidepressant treatment was related to a reduced risk of mortality. Compared to patients without any psychiatric comorbidity with no antidepressant treatment, the mortality risk increased in patients with either psychiatric comorbidity or both, but the risk seemed to attenuate with antidepressant treatments., Conclusion: The current findings suggest that psychiatric comorbidities are markers of increased mortality risk in patients with breast cancer, and antidepressant treatment may attenuate the risk. This underscores the need for screening and treating depression and anxiety disorders to improve survival in patients with breast cancer.

Background: Depression and anxiety are prevalent psychiatric disorders that carry significant morbidity. Pharmacological and psychosocial interventions are used to manage these conditions, but their efficacy is limited. Recent interest into the use of psychedelic-assisted therapy using ayahuasca, psilocybin or lysergic acid diethylamide (LSD) may be a promising alternative for patients unresponsive to traditional treatments. This review aims to determine the efficacy and tolerability of psychedelics in the management of resistant depression., Methods: Clinical trials investigating psychedelics in patients with depression and/or anxiety were searched via MEDLINE, EMBASE and PsychINFO. Efficacy was assessed by measuring symptom improvement from baseline, and tolerability was evaluated by noting the incidence and type of adverse effects reported. Risk of bias was assessed., Results: Seven studies, with 130 patients, were analysed in this review. Three were conducted in patients with depression, two in patients with anxiety and two in patients with both. In a supportive setting, ayahuasca, psilocybin, and LSD consistently produced immediate and significant anti-depressant and anxiolytic effects that were endured for several months. Psychedelics were well-tolerated. The most common adverse effects were transient anxiety, short-lived headaches, nausea and mild increases in heart rate and blood pressure., Limitations: At present, the number of studies on this subject is very limited; and the number of participating patients within these is also limited as the treatment under investigations is a relatively novel concept., Conclusions: Though further evidence is required, psychedelics appear to be effective in significantly reducing symptoms of depression and anxiety and are well-tolerated., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To evaluate the impact of the Canterbury earthquakes on the mental health of older people by examining dispensing patterns of psychotropic medication., Method: Dispensing data from community pharmacies for antidepressants, antipsychotics, anxiolytics, and sedative/hypnotics are routinely recorded in a national database. Longitudinal data are available for residents of the Canterbury District Health Board (DHB) (n = 67 760 at study onset) and the rest of New Zealand (n = 469 055 at study onset). We compared older age dispensing data between 2008 and 2018 for Canterbury DHB with older age dispensing data nationally in order to assess the impact of the Canterbury earthquakes on the mental health of older persons., Results: Older age residents of Canterbury are dispensed antidepressants, antipsychotics, and anxiolytics at higher rates than national comparators, but this finding predated the onset of the earthquakes. Short-term increases in anxiolytic and sedative/hypnotic dispensing occurred for the month following the February 2011 earthquake. No other short- or longer-term increases in dispensing of psychiatric medication were present., Conclusion: The February 2011 Canterbury earthquake caused a short-term increase in dispensing of anxiolytics and sedative/hypnotics. No longer-term effects on dispensing were observed. This suggests that older persons sought assistance for insomnia and anxiety in the aftermath of the most devastating earthquake, but longer-term rates of clinically significant anxiety and depression for older persons did not increase as a consequence of the earthquakes sequence., (© 2019 John Wiley & Sons, Ltd.)

Introduction: Dietary supplements are very widely used in the general population and there is a growing market for them, which is against the recommendations of the German Society for Nutrition. There is some evidence that dietary supplements are useful additions in the treatment of psychiatric disorders. This review is an overview of available practical knowledge regarding the use of supplements in psychiatric treatment. In particular, the review focused on the diagnosis of depression and anxiety in terms of supplement treatment., Methods: This is a narrative review of the evidence regarding supplements for treating anxiety and depression. We searched PubMed to 2018. Two reviewers screened the citations and abstracted the data. Phytopharmaceutical attends and animal-based data were excluded., Results: There are strong indications regarding the impact of supplements on the selected psychiatric disorders, but at this time, there only a few randomized clinical studies available, so evidence for these findings is quite low. However, it must be noted that there are strong hints for a relationship between vitamin D level and depression. Furthermore, various supplements have got potentially an influence on the characteristics of depression., Discussion: This review summarizes the current knowledge about supplements when used for some psychiatric conditions, but the data does not provide compelling evidence in any direction. There are only indications that there is an influence of supplements on psychiatric diseases. In support of this, there is further need for high-quality studies in this field. Reviews on other diagnoses, such as schizophrenia and dementia, will be part of further work., Competing Interests: The authors all declare no conflicts of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Investigating adverse events associated with antidepressant treatments in adolescents is important given the concerns about increased risk of suicidal ideation and behavior in this age group. The aim of this study is to investigate adverse and serious adverse events associated with the treatment of anxiety (cognitive behavioral therapy (CBT)-only, CBT-plus-placebo, and CBT-plus-fluoxetine) in anxious school-refusing adolescents., Methods: A side-effect symptom checklist was completed by participants prior to commencing treatment and during treatment (weekly/fortnightly)., Results: CBT-plus-fluoxetine was well tolerated and not associated with higher levels of adverse events than the other treatments. Adverse events in all groups decreased over time, and the only adverse event distinct to fluoxetine was nausea. Baseline anxiety predicted higher levels of adverse events. There was one suicide attempt in the CBT-plus-placebo group but no statistically significant difference in suicide attempts between groups. Participants with a comorbid depressive disorder were more likely to report self-injury ideation but not suicidal ideation compared with those who did not have comorbid depressive disorder. Frequency of suicidal ideation and non-suicidal self-injury was significantly lower in the CBT-plus-fluoxetine group compared with the CBT-only group. Frequency of self-injury ideation was significantly lower in the CBT-plus-fluoxetine group compared with both other groups., Conclusions: Overall, the treatments were well tolerated and fluoxetine plus CBT appeared to be protective against suicidal ideation, non-suicidal self-injury, and self-injury ideation in this sample.

Background: Antidepressants have a low rate of response paired with a delayed onset of action. Translational studies are thus seeking for novel targets for antidepressant drug development. Preclinical evidence has demonstrated that the endocannabinoid system plays an important role in mood and stress response, even if drugs targeting this system have not yet become available for clinical use. The dietary supplement N-Palmitoylethanolamide (PEA) is a fatty acid amide belonging to the endocannabinoid system with potential antidepressant properties., Methods: We performed a bibliographic search to review current knowledge on the potential antidepressant effects of PEA and its underlying mechanism of action., Results: PEA targets not only the peroxisome proliferator-activated receptor-alpha (PPAR-α), but also the endocannabinoid system, binding the G-protein-coupled receptor 55, a non-CB 1 /CB 2 cannabinoid receptor, and also the CB 1 /CB 2 receptors, although with a weak affinity. Preclinical studies have shown antidepressant activity of PEA in animal paradigms of depression and of depression associated with neuropathic pain and traumatic brain injury. In a translational perspective, PEA is increased in stress conditions, and a randomized, double-blind study in depressed patients indicated a fast-antidepressant action of PEA when associated with citalopram., Limitations: There are still limited preclinical and clinical studies investigating the effect of PEA upon the endocannabinoid system and its potential as antidepressant., Conclusions: PEA has potential antidepressant effects alone or in combinations with other classes of antidepressants. Future studies in depressed patients are needed to confirm the mood-modulating properties of PEA and its role as a biomarker of depression., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To determine whether genetic variants in a pharmacokinetic gene (the number of CYP2C19 reduced function alleles [RFAs]), and in pharmacodynamic genes ( HTR2A , SLC6A4 , and GRIK4 ) influence sertraline tolerability and response in a cohort of pediatric patients with anxiety and depressive disorders. Methods: A retrospective analysis was performed using the electronic medical record data of 352 patients <19 years of age being treated for anxiety and/or depressive disorders with sertraline and who underwent routine clinical CYP2C19 genotyping. Additional genotyping and analysis of variants in HTR2A , SLC6A4 , and GRIK4 were conducted for 249 patients. Multivariate regression models testing for associations with CYP2C19 were adjusted for concomitant use of interacting medications. Combinatorial classification and regression tree (CART) analyses containing all pharmacokinetic and pharmacodynamic genes and clinical factors were performed. Results: The maximum sertraline dose during the initial titration period of sertraline was inversely associated with the number of CYP2C19 RFAs and sertraline dose at 60 ( p  = 0.025) and 90 days ( p  = 0.025). HTR2A rs6313 was associated with sertraline dose ( p  = 0.011) and time to the average maximum sertraline dose ( p  = 0.039). Regarding efficacy, the number of CYP2C19 RFAs was not associated with the sertraline dose at the time of response ( p  = 0.22), whereas for the pharmacodynamic genes, only HTR2A rs6313 was associated with response dose ( p  = 0.022). An association was observed between predicted expression levels of SLC6A4 and the duration on sertraline ( p  = 0.025). Combinatorial CART and multivariate regression analyses implicated that pharmacodynamic genes and clinical factors influence the maximum sertraline dose and response dose. The total number of side effects was not associated with any of the variants tested. Conclusion: Both pharmacokinetic and pharmacodynamic factors, in addition to clinical and demographic components, influence sertraline dose, response, and tolerability, thereby necessitating further research to assess for the validity of these pharmacogenetic associations in children and adolescents.

In recent years increased interest in the connection of intestinal microflora and the state of human health resulted in a great deal of research on the influence of intestinal microflora in particular on mental health, including works on affective functions of the central nervous system (CNS). Previous studies on animals have revealed the existence of a bi-directional communication system between the gastrointestinal microbiota and the central nervous system, the so-called .gut-brain axis' which modulates functioning of CNS through immunological, endocrine and neuronal mechanisms. Clinical studies have shown a connection between supplementation of probiotics containing specific species and strains of bacteria and the regulation of the body's response to stress and with the exacerbation of depressive and anxiety symptoms in humans. Studies have also demonstrated differences in the composition of the intestinal microflora of patients with a diagnosis of major depressive disorder in comparison with the healthy population. The aim of this article is to present the current state of knowledge on the relationship between composition of intestinal microflora and affective functions of CNS and on effects of supplementation of probiotics on depressive and anxiety symptoms in humans. Previous studies on the use of probiotics in the prophylaxis and treatment of depressive and anxiety disorders included too small groups of persons, especially in groups of patients diagnosed with depression, to be able to clearly determine the effectiveness of probiotics in prevention and, in particular, treatment of these disorders in humans.

Introduction: Few studies have examined pre-pregnancy depression/anxiety and antidepressant/anxiolytic medication use in relation to hypertension disorders of pregnancy, i.e. chronic hypertension (CH), pre-eclampsia (PE), and gestational hypertension (GH)., Methods: This nested case-control study uses Blue Cross Blue Shield of Michigan (BCBSM) claims data of women with singleton live birth pregnancies (2010-2014) enrolled from 2 years prior to last menstrual period to ninety days after delivery. All women with ICD-9CM codes for CH, PE, GH, or unspecified hypertension were included as cases; women without hypertension were randomly sampled as controls. Linkage to Michigan birthfiles resulted in a sample of 12,647 women. Using weighted logistic regression, cases and controls were compared for depression and/or anxiety diagnoses (ICD-9CM codes) and anti-depressant and/or anxiolytic prescriptions throughout the study period. Depression and anxiety were defined as primary diagnosis in ≥1 inpatient or ≥2 outpatient visits., Results: Among women with hypertension disorders of pregnancy, 59% had PE or GH, referred to here as pregnancy hypertension (PH). PH was associated with anti-depressant use prior to LMP only, (aOR = 1.2 95%CI 1.0, 1.5), continued use, (aOR = 1.4 95%CI 1.1, 1.7), and initiation of anxiolytic medication during pregnancy, (aOR = 2.5 95%CI 1.6, 4.2). In this latter group, 96% started medication before PH diagnosis. CH and PH were not associated with depression or anxiety in the absence of anti-depressants/anxiolytics., Conclusion: While anti-depressants/anxiolytics may be useful indicators in risk stratification for pregnancy hypertension, the same does not appear to be true for depression/anxiety without related medication use., (Copyright © 2019 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the effects of onabotulinumtoxinA treatment for chronic migraine (CM) on comorbid symptoms of depression, anxiety, fatigue and poor sleep quality., Methods: The Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open-Label (COMPEL) study is a multicentre, open-label, prospective study assessing the long-term safety and efficacy of onabotulinumtoxinA 155 U over nine treatments (108 weeks) in adults with CM. The Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Disorder (GAD-7) scales were used to assess the effects of onabotulinumtoxinA on comorbid symptoms of depression and anxiety, respectively. A clinically meaningful improvement was assessed by the percentage of patients experiencing a ≥1 severity category reduction in PHQ-9 and GAD-7. The effects of onabotulinumtoxinA on associated sleep quality and fatigue were assessed using the Pittsburgh Sleep Quality Index and Fatigue Severity Scale, respectively., Results: OnabotulinumtoxinA treatment was associated with sustained reduction in headache days and PHQ-9 and GAD-7 scores in the analysis population (n=715) over 108 weeks. PHQ-9 and GAD-7 scores were significantly reduced at all time points in patients with clinically significant symptoms of depression and/or anxiety at baseline. By week 108, 78.0% and 81.5% had clinically meaningful improvement in depression and anxiety symptoms, respectively. Sleep quality and symptoms of fatigue also improved; however, less is understood about clinically meaningful changes in these measures. No new safety concerns were identified., Conclusion: In addition to reducing headache frequency, onabotulinumtoxinA treatment for CM was associated with clinically meaningful reduction in symptoms of depression and anxiety, and improved associated symptoms of poor sleep quality and fatigue., Trial Registration Number: NCT01516892., Competing Interests: Competing interests: AMB has served on advisory boards for Allergan, Amgen, Alder, Teva, Supernus, Promius, Eaglet and Lilly, and has received funding for speaking from Allergan, Amgen, Pernix, Supernus, Depomed, Avanir and Promius. He holds patents for onabotulinumtoxinA in migraine assigned to Allergan. SJT is an employee of the Dartmouth-Hitchcock Medical Center and receives a salary from the American Headache Society (AHS). He also serves as a consultant for Acorda, Alder, Alexsa, Allergan, Amgen, ATI, BioVision, Cefaly, Charleston Laboratories, DeepBench, Dr Reddy’s, ElectroCore, Eli Lilly, eNeura, GLG, Guidepoint Global, Impax, Neurolief, Novartis, Scion Neurostim, Slingshot Insights, Supernus, Teva and Zosano, and has received royalties for books published by Springer. His employer receives research grants from Alder, Allergan, Amgen, ATI, Dr Reddy's, Scion Neurostim, Teva and Zosano. LDR has served as a speaker for Avanir, Pernix and Merck. AMA and AO are employees of Allergan, and AMA holds stock in the company. DCB has received grant support and honoraria from Allergan, Avanir, Amgen, Eli Lilly and Company, and Promius, and for work on the editorial board of Current Pain and Headache Reports. SDS has served as a consultant and/or advisory panel member and received honoraria from Alder BioPharmaceuticals, Allergan, Amgen, Avanir Pharmaceuticals, eNeura, ElectroCore Medical, Eli Lilly and Company, Medscape and Teva Pharmaceuticals, and grants from Amgen and Teva Pharmaceuticals. His employer has received research support from Allergan, Amgen, Cumberland Pharmaceuticals, ElectroCore Medical, Eli Lilly and Company, and Troy Healthcare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Serotonergic function is known to fluctuate in association with light and temperature. Serotonin-related behaviors and disorders similarly vary with climatic exposure, but the associations are complex. This complexity may reflect the importance of dose and timing of exposure, as well as acclimation. This cross-sectional study tests how average climate exposures (ambient temperature and solar insolation) vary with the prevalence of a group of SSRI-treated disorders. For comparison, we similarly studied a group of disorders not treated by SSRIs (i.e substance use disorders). Psychiatric prevalence data were obtained from the Collaborative Psychiatric Epidemiology Surveys (CPES). Average yearly solar insolation was obtained from NASA's NLDAS-2 Forcing Dataset Information. Average yearly temperature was obtained from NOAA's US Climate Normals. Logistic regression models were generated to assess the relationship between these two climatic factors and the prevalence of SSRI-treated and substance use disorders. Age, gender, race, income, and education were included in the models to control for possible confounding. Temperature and insolation were significantly associated with the SSRI-responsive group. For an average 1 GJ/m 2 /year increase, OR was 0.90 (95% CI 0.85-0.96, p = 0.001), and for an average 10 °F increase, OR was 0.93 (95% CI 0.88-0.97, p = 0.001). This relationship was not seen with substance use disorders (insolation OR: 0.97, p = 0.682; temperature OR: 0.96, p = 0.481). These results warrant further investigation, but they support the hypothesis that chronic exposure to increased temperature and light positively impact serotonin function, and are associated with reduced prevalence of some psychiatric disorders. They also support further investigation of light and hyperthermia treatments., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Studies of probiotics have suggested they have a positive effect on anxiety and depressive symptoms in humans. This study investigated the effect of consuming the probiotic Bifidobacterium breve A-1 on anxiety and depressive symptoms in patients with schizophrenia and explored its effect on immune products such as cytokines and chemokines., Methods: In this open-label single-arm study, all participants received B. breve strain A-1 (10 11 cfu/day) for 4 weeks followed by 4 weeks of observation. The primary outcome was the Hospital Anxiety and Depression Scale (HADS) score. Secondary outcomes were anxiety and depressive symptoms on the Positive and Negative Syndrome Scale (PANSS), blood test findings, and fecal microbiome composition., Results: Twenty-nine outpatients completed the study. HADS total score and PANSS anxiety/depression score were significantly improved at 4 weeks. Based on the criterion of a greater than 25% reduction in HADS total score at 4 weeks from baseline, there were 12 responders and 17 non-responders. Responders were found to have fewer negative symptoms, reduced intake of dairy products, and higher relative abundance of Parabacteroides in the gut microbiome than non-responders. Moreover, IL-22 and TRANCE expression was significantly increased at 4 weeks from baseline in responders but not in non-responders., Limitations: This open-label, single-arm study cannot exclude a placebo effect., Conclusions: The results suggest the potential effect of B. breve A-1 in improving anxiety and depressive symptoms in patients with schizophrenia. Further studies should investigate this effect in patients with other psychiatric conditions and assess dietary habits and the gut microbiome., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose of Review: This narrative review synthesized recent research related to obesity in adolescents with psychiatric disorders, with a focus on epidemiology, mechanisms, and weight management approaches. The paper reviews literature on depressive and anxiety disorders, bipolar disorder, and schizophrenia spectrum and other psychotic disorders., Recent Findings: Depression has a bidirectional relationship with obesity. Bipolar disorder and schizophrenia spectrum disorders, and their treatments, increase the risk of developing obesity. Mechanisms underlying this weight gain include lifestyle and environmental factors and psychiatric medications, though emerging evidence has also suggested the role of genetic and neuroendocrine processes. Evidence about the most effective treatments for obesity in adolescents with psychiatric disorders remains limited. Adolescents with psychiatric disorders are at high risk for obesity. Close monitoring for increases in weight and cardiometabolic risk factors with use of antipsychotic and mood-stabilizing medications is recommended. Clinical trials are needed that test the efficacy of weight management strategies for this population.

Background: Antidepressants remain controversial, partly due to allegations that disappointing results were buried and because of their modest average efficacy.
AIM: To investigate bias in the antidepressant literature and the possibilities for predicting which patients with depression or anxiety do receive significant benefits from antidepressants.
METHOD: We investigated bias by comparing information from the US Food and Drug Administration with the published literature. To predict response, we used patient data from randomized trials.
RESULTS: Of all studies on depression or anxiety, 50% and 72% were positive, compared to 95% and 96% of all published studies. Safety outcomes were poorly reported in published articles and unpublished studies were often 'bundled' into pooled-trials publications with positive conclusions. We found an association between severity and antidepressant efficacy for some, but not all, anxiety disorders; previous research has found inconsistent evidence for this association for depression. Furthermore, patients with depression that showed early improvement were more likely to attain a good response, irrespective of which symptoms improved.
CONCLUSION: These results demonstrate the severe impact of bias on the antidepressant literature. Severity and early improvement predicted a good response, but more information is needed to improve predictions. The increased accessibility of individual patient data will hopefully soon enable further progress in this area.

Background: Polypharmacy is a geriatric syndrome defined variously as the use of potentially inappropriate drugs and/or the concurrent use of multiple medications including prescription and over-the-counter drugs. An association has been shown between polypharmacy and physical health, increased morbidity and increased mortality. However, there is little information regarding the association between polypharmacy and physical disease, personality trait and mental health problems in elderly. The aim of this study was to investigate potential predictive psychosocial factors related to polypharmacy in elderly Thai people., Methods: The study analysed the secondary data from the Depressive Disorders, Anxiety Disorders, Suicide Risk and Associated Factors Among Elderly Thai People Program (DAS Study) which was funded by National Research Council of Thailand and conducted between January 2012 and April 2013. Demographic and baseline clinical characteristics including sex, age, education, living alone or with others, access to health care privilege and monthly income were described. The number of medication, physical diseases and mental health problems (i.e. depression, anxiety, and personality trait of neuroticism) were analyzed using descriptive statistics, chi-square and proportional odds logistic regression., Results: The 803 participants consumed an average of 2.13 prescribed medicines daily (SD 1.46, median = 2). The largest group used 3 medications (18.6%). Predictors found to be associated with polypharmacy in the logistic regression model included hypertension (OR = 1.985, 95% CI = 1.420-2.775), anxiety disorder (OR = 4.402, 95% CI = 2.630-7.367), number of diseases (OR = 2.140, 95% CI = 1.874-2.445), depressive disorder (OR = 1.470, 95% CI = 1.080-2.001), diabetes mellitus (OR = 1.864, 95% CI = 1.122-3.098) and dyslipidemia (OR = 0.511, 95%CI = 0.325-0.803)., Conclusions: The prevalence of polypharmacy among Thai elderly was relatively high compared to other related studies. Several aspects should be taken into consideration before starting an additional medication in elderly patients. In addition to the number of physical disease that leads to polypharmacy, general practitioners should be aware of anxiety, depression, and personality trait of neuroticism that may be related to polypharmacy. Early detection for such condition as well as non-pharmacological intervention could be one way to help reduce polypharmacy in the elderly.

Phosphodiesterase 2 (PDE2) plays an important role in treatment of stress-related depression through regulation of antioxidant defense and neuroprotective mechanisms. However, the causal relationship between PDE2 and the prevalence of depression and anxiety upon exposure to oxidative stress has not been investigated. The present study examined whether the effects of PDE2 inhibition on oxidative stress were directly involved in reduced ROS by regulating NADPH subunits gp91phox oxidase. The results suggested that the PDE2 inhibitor Bay 60-7550 reversed oxidative stress-induced behavioral signature, i.e. depression and anxiety. Pretreatment with the oxidizing agent DTNB completely blocked, while the reducing agent DTT and the NADPH oxidase inhibitor apocynin potentiated the effects of Bay 60-7550 on behavioral abnormalities, demonstrating the relationship between PDE2 and oxidative stress. Consistently, an in vitro test revealed the positive correlation between ROS and PDE2 levels. Moreover, Bay 60-7550 decreased corticosterone-induced gp91phox expression, which is the source of ROS. The subsequent study suggested that Bay 60-7550 induced decrease in ROS and increase in cAMP/cGMP, pVASP, pCREB, and the neurotrophic factor BDNF levels, which were completely blocked by CRISPR/Cas9-mediated gp91phox overexpression and potentiated by gp91phox siRNA-based antioxidant strategies. The in vivo test in stressed mice further suggested that gp91phox overexpression completely blocked the antidepressant- and anxiolytic-like effects of Bay 60-7550, while gp91phox knockdown enhanced such effects. These results provide solid evidence that the antidepressant- and anxiolytic-like effects of Bay 60-7550 against stress are causally related to down-regulation of gp91phox and activation of the cAMP/cGMP-pVASP-CREB-BDNF signaling pathway., (Copyright © 2018. Published by Elsevier Ltd.)

Bakgrunn: Det er økt interesse for psykedeliske stoffer til bruk i behandling av psykiske lidelser. Stoffene regnes som trygge når de gis innenfor en klinisk ramme. Eldre studier fra før 1970 har metodologiske svakheter, men i de senere år har det kommet lovende resultater fra bruk ved unipolar depresjon, depresjon ved livstruende sykdom, angst og avhengighet. Formålet med denne litteraturgjennomgangen er å gi en oversikt over nyere resultater og disse studienes begrensninger., Kunnskapsgrunnlag: Vi søkte i databasen PubMed etter kliniske studier fra perioden 1990-2017 med søkeordene angst, depresjon, avhengighet og psykedeliske stoffer. Kvaliteten på studiene ble så vurdert ut ifra metode og styrkeberegning., Resultater: Søket ga 424 artikler, hvorav ni ble inkludert (fire om angst og depresjon ved livstruende sykdom, to om depresjon, to om avhengighetslidelse og én om tvangslidelse). To dobbeltblinde, randomiserte, kontrollerte fase II-studier med et moderat antall pasienter fant umiddelbar, markert og vedvarende effekt av én enkeltdose psilocybin mot angst og depresjon ved livstruende sykdom. De andre studiene hadde mer usikre resultater. Det var ingen alvorlige bivirkninger eller rapportering om avhengighet., Fortolkning: Psykedeliske stoffer i behandling av flere psykiske lidelser har vist lovende resultater, men studiene er små og har metodologiske utfordringer. Det er behov for systematiske kliniske studier for å skaffe solid dokumentasjon for effekt og etablere rutiner for overvåkning av mulige bivirkninger.

Background: Naturalistic and small randomized trials have suggested that pharmacogenetic testing may improve treatment outcomes in depression, but its cost-effectiveness is not known. There is growing enthusiasm for personalized medicine, relying on genetic variation as a contributor to heterogeneity of treatment effects. We sought to examine the relationship between a commercial pharmacogenetic test for psychotropic medications and 6-month cost of care and utilization in a large commercial health plan., Methods: We performed a propensity-score matched case-control analysis of longitudinal health claims data from a large US insurer. Individuals with a mood or anxiety disorder diagnosis (N = 817) who received genetic testing for pharmacokinetic and pharmacodynamic variation were matched to 2,745 individuals who did not receive such testing. Outcomes included number of outpatient visits, inpatient hospitalizations, emergency room visits, and prescriptions, as well as associated costs over 6 months., Results: On average, individuals who underwent testing experienced 40% fewer all-cause emergency room visits (mean difference 0.13 visits; P < 0.0001) and 58% fewer inpatient all-cause hospitalizations (mean difference 0.10 visits; P < 0.0001) than individuals in the control group. The two groups did not differ significantly in number of psychotropic medications prescribed or mood-disorder related hospitalizations. Overall 6-month costs were estimated to be $1,948 (SE 611) lower in the tested group., Conclusions: Pharmacogenetic testing represents a promising strategy to reduce costs and utilization among patients with mood and anxiety disorders., (© 2018 Wiley Periodicals, Inc.)

Previous research has shown that fibroblast growth factor 2 protein (FGF2) can act as an anxiolytic and anti-depressive agent in rodents. Levels of hippocampal FGF2 and FGF2 receptors are decreased in post-mortem brains of individuals with mood disorders. No changes in FGF2 were noted in the post-mortem brains of individuals with mood disorders that were successfully treated with anti-depressant medication prior to death. Mutations in the FGF2 gene in humans have been shown to predict non-responsiveness to the therapeutic effects of selective serotonin reuptake inhibitors (SSRIs). These findings suggest that FGF2 may potentially be a target of and/or required for the therapeutic effects of antidepressant medications. To test this, we employed a rodent model of depressive behaviour, chronic variable stress (CVS) in conjunction with antidepressant treatment (fluoxetine) in wild-type (WT) and FGF2 knockout mice (FGF2KO) and examined depressive and anxiety behaviors. Results showed that fluoxetine reversed the effects of CVS on depressive and anxiety behaviours in wild-type mice only, suggesting that the FGF2 gene is indeed necessary for the therapeutic effects of fluoxetine. Interestingly, CVS decreased hippocampal FGF2 levels and fluoxetine partially reversed this effect. Because FGF2 has been previously shown to modify HPA activity through hippocampal glucocorticoid receptors (GR), we examined levels of glucocorticoid receptors and found a decrease in GR in response to CVS, with a further decrease in FGF2KO. No effect of fluoxetine on GR was observed in either WT or FGF2KO mice. This suggests that further changes in glucocorticoid receptors are not necessary for the anti-depressant effects of fluoxetine in WT mice, although decreased glucocorticoid receptors in response to FGF2 deletion may preclude the therapeutic actions of fluoxetine in FGF2KO. Whether astroglia, astroglial functions, or HPA changes are the downstream target of FGF2-mediated changes induced by fluoxetine remains to be determined, however, the current study reaffirms the potential of FGF2 as a novel therapeutic target in the treatment of depression and anxiety disorders., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Treatment with selective serotonin reuptake inhibitors (SSRIs) is common and is considered safe and effective in the treatment of anxiety and depressive disorders in pediatric populations. SSRI administration, however, is associated with adverse metabolic effects. The aim of this preliminary study was to evaluate the possible influence of a 6-month SSRI treatment on metabolic parameters in children and adolescents with depressive and/or anxiety disorders., Methods: Metabolic parameters (glucose, cholesterol, triglycerides, low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) were monitored in 22 children and adolescents (16 boys and 6 girls, aged 8-18 years) at baseline and after 6 months of SSRI treatment for depression and/or anxiety., Results: Six months of SSRI treatment did not affect serum glucose, cholesterol, or triglycerides significantly, but a tendency (p = 0.06) toward elevation in serum LDL accompanied by a parallel reduction in HDL levels was detected., Conclusion: It appears that the 6-month SSRI treatment is metabolically safe in children and adolescents and does not affect the glucose or lipid profile. Long-term large-scale studies in pediatric populations focusing on the possible impact of long-term SSRI treatment (>6 months) on metabolic parameters are warranted.

Depression is one of the foremost psychological illness which is closely leagued with inflammation. Crocin is a natural product that exhibits both anti-inflammatory and anti-oxidant activities. However, little is known about anti-inflammatory mechanisms of crocin on LPS-induced anxiety and depressive-like behaviors. The objective of this study is emphasized on neuroprotective role of crocin against LPS-induced anxiety and depressive-like behaviors in mice. It is observed that crocin inhibited LPS-induced production of NO, TNF-α, IL-1β and ROS in BV-2 microglial cells. Moreover, crocin significantly declined the expression of iNOS, NF-κB p65 and CD16/32 (M1 marker), as well as elevated the expression of CD206 (M2 marker) in BV-2 cell line with decreased LPS-induced anxiety and depressive-like behaviors by improved locomotor activity, reduced sucrose intake, and decreased immobility time in forced swim and tail suspension test in Kunming mice. Expression of NLRP3, ASC and caspase-1 by i.p administration of LPS found to be neutralized with reduction in level of IL-1β, IL-18 and TNF-α in mouse hippocampus. In conclusion, these results suggested that crocin as a potential therapeutic candidate for neuro-inflammation and depressive-like behaviors induced by LPS. The effect was found to be due to inhibition of NLRP3 inflammasome and NF-κB and its promoted M1 to M2 phenotypic conversion of microglia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Somatic complications account for the majority of the 13-30 years shortened life expectancy in psychiatric patients compared to the general population. The study aim was to assess to which extent patients visiting outpatient departments for mood and anxiety disorders were monitored for relevant somatic comorbidities and (adverse) effects of psychotropic drugs-more specifically a) metabolic parameters, b) lithium safety and c) ECGs-during their treatment., Methods: We performed a retrospective clinical records review and cross-sectional analysis to assess the extent of somatic monitoring at four outpatient departments for mood and anxiety disorders in The Netherlands. We consecutively recruited adult patients visiting a participating outpatient department between March and November 2014. The primary outcome was percentage of patients without monitoring measurements. Secondary outcomes were number of measurements per parameter per patient per year and time from start of treatment to first measurement., Results: We included 324 outpatients, of whom 60.2% were female. Most patients were treated for depressive disorders (39.8%), anxiety disorders (16.7%) or bipolar or related disorders (11.7%) and 198 patients (61.1%) used at least one psychotropic drug. For 186 patients (57.4%), no monitoring records were recorded (median treatment period 7.3 months, range 0-55.6). The median number of measurements per parameter per year since the start of outpatient treatment for patients with monitoring measurements was 0.31 (range 0.0-12.9). The median time to first monitoring measurement per parameter for patients with monitoring measurements was 3.8 months (range 0.0-50.7)., Discussion: Somatic monitoring in outpatients with mood and anxiety disorders is not routine clinical practice. Monitoring practices need to be improved to prevent psychiatric outpatients from undetected somatic complications., Competing Interests: The authors have declared that no competing interests exist.

Depression and anxiety disorders are debilitating diseases resulting in substantial economic costs to society. Traditional antidepressants often take weeks to months to positively affect mood and are ineffective for about 30% of the population. Alternatives, such as ketamine, a dissociative anesthetic capable of producing hallucinations, and the psychoactive tisane ayahuasca, have shown great promise due to their fast-acting nature and effectiveness in treatment-resistant populations. Here, we investigate the effects of N, N-dimethyltryptamine (DMT), the principle hallucinogenic component of ayahuasca, in rodent behavioral assays relevant to anxiety and depression using adult, male, Sprague-Dawley rats. We find that while DMT elicits initial anxiogenic responses in several of these paradigms, its long-lasting effects tend to reduce anxiety by facilitating the extinction of cued fear memory. Furthermore, DMT reduces immobility in the forced swim test, which is a characteristic behavioral response induced by many antidepressants. Our results demonstrate that DMT produces antidepressant and anxiolytic behavioral effects in rodents, warranting further investigation of ayahuasca and classical psychedelics as treatments for depression and post-traumatic stress disorder.

Introduction: Measurement-based care (MBC) transfers the scientific principle from controlled clinical trials to the daily routine treatment to improve the care of patients with anxiety and depression., Aim: Within the pharmacopsychometric triangle in which the domain of desired clinical effect of treatment is balanced against the domain of undesired treatment side effects in terms of the domain of restored well-being. The relevance of these domains both in the controlled clinical trials and in the MBC trials will be tested., Methods: The MBC trials are compared with the controlled clinical trials focusing on the health domains of symptoms reduction (anxiety/depression), side effects of treatment, self-reported quality of life and social functioning., Results: The amount of MBC trials was found rather sparse but information emerged demonstrating that the full clinician-rated Hamilton Depression Scale (HAM-D 17 ) was sufficient for the identification of patients being in need of treatment and the HAM-D 6 subscale was valid as outcome measure. From the patient-reported domains, the full Symptom Checklist (SCL-90), the 10-item anxiety/depression subscale (SCL-10) was found valid as symptom outcome. From the full Patient Reported Inventory of Side-Effects (PRISE), a subscale including Clinician Action of Response (CAR) for side effects to antidepressants was found valid (PRISE-CAR), as was the World Health Organization subscale (WHO-5) for the measure of quality of life., Conclusion: The pharmacopsychometric triangle is also important in the MBC trials for improving the care of patients with anxiety and depression. However, the amount of MBC trials is still rather sparse.

Objective: Reward positivity (RewP), a neurophysiologic index of reward responsivity, is consistently reduced in participants with depression and, to a lesser extent, anxiety. It remains unknown, however, whether RewP can be altered as psychiatric symptoms change with treatment. The current study addressed this question by examining differences in RewP within patients before and after 12 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI) or cognitive-behavioral therapy (CBT). We also examined the utility of RewP as a predictor of symptom change during CBT and SSRI treatment., Methods: Participants were recruited between 2014 and 2017 and included adults with a primary DSM-5 anxiety or depressive disorder (n = 63) and healthy controls (n = 25). At baseline and 12 weeks, participants completed a monetary award task while electroencephalogram (EEG) was recorded. Between EEG sessions, patients completed CBT or SSRI treatment., Results: At baseline, higher levels of depressive symptoms were associated with a more attenuated RewP. We found no significant differences between patients and healthy controls in the degree of RewP change across the 12 weeks; however, among patients, the extent of increase in RewP robustly correlated with the extent of decline in depressive (t = -2.21, P = .03) and anxiety (t = -2.57, P = .02) symptoms following CBT and SSRI treatment. Additionally, a more attenuated RewP at baseline predicted a greater reduction in depressive symptoms following treatment with SSRIs (t = -2.04, P < .05), but not after CBT., Conclusions: These findings highlight neural responsiveness to reward as both a mechanism and a predictor of depressive symptom change that may be used serve as an objective index of symptom improvement., Trial Registration: ClinicalTrials.gov identifier: NCT01903447., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

Background: It has been suggested that antidepressant benefits are smaller for mild than severe depression. Because antidepressants are also used for anxiety disorders, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD), we examined the influence of severity for these disorders., Methods: We used individual patient data of eight trials (3,430 participants) for generalized anxiety disorder (GAD); four trials (1,195 participants) for social anxiety disorder (SAD); four trials (1,132 participants) for OCD; three trials (1,071 participants) for PTSD; and 10 trials (2,151 participants) for panic disorder (PD). Mixed-effects models were used to investigate an interaction between severity and treatment group., Results: For GAD and PD, severity moderated antidepressant efficacy. The antidepressant-placebo difference was 1.4 (95% CI: 0.4-2.5; SMD: 0.21) Hamilton Anxiety Rating Scale (HAM-A) points for participants with mild GAD (baseline HAM-A = 10), increasing to 4.0 (3.4-4.6; SMD: 0.45) or greater for severely ill participants (HAM-A ≥ 30). For PD, the difference was 0.4 (0.3-0.6) panic attacks/2 weeks for participants with 10 panic attacks/2 weeks at baseline, increasing to 4.7 (3.0-6.4) for participants with 40. For SAD, OCD, and PTSD, no interaction was found. Across severity levels, the differences were 16.1 (12.9-19.3; SMD: 0.59) Liebowitz Social Anxiety Scale points, 3.4 (2.5-4.4, SMD: 0.39) Yale-Brown Obsessive-Compulsive Scale points, and 10.3 (6.9-13.6; SMD: 0.41) Clinician-Administered PTSD Scale points., Conclusions: Antidepressants are equally effective across severity levels for SAD, OCD, and PTSD. For GAD and PD, however, benefits are small at low severity, and the benefit-risk ratio may be unfavorable for these patients., (© 2018 Wiley Periodicals, Inc.)

Background: Mothers have increased mental illness such as anxiety and depression after the death of a child. We examine the duration of this worsening of mental health., Methods: The mental health of all mothers who experience the death of an infant (< 1 years old) in Manitoba, Canada between April 1, 1999 and March 31, 2011 (n = 534) is examined in the 4 years leading up to, and the 4 years following, the death of their child. Mental health-related outcomes of these mothers are compared with a matched (3:1) cohort of mothers who did not experience the death of a child (n = 1,602). Three mental health-related outcomes are examined: depression diagnoses, anxiety diagnoses, and use of psychotropic medications., Results: Compared with mothers who did not experience the death of a child, mothers experiencing this event had higher rates of anxiety diagnoses and psychotropic prescriptions starting 6 months before the death. Elevated rates of anxiety continued for the first year and elevated rates of psychotropic prescriptions continued for 6 months after the death of the child. Mothers who experienced the death of a child had higher rates of depression diagnoses in the year after the death. Relative rates (RR) of depression (RR = 4.94), anxiety (RR = 2.21), and psychotropic medication use (RR = 3.18) were highest in the 6 months after the child's death., Conclusions: Elevated rates of depression, anxiety, and psychotropic medication use after the death of a child end within 1 year of the child's death., (© 2018 Wiley Periodicals, Inc.)

Objective: To investigate early evolution, tolerability, and predictors of antidepressant-emergent sexual dysfunction in patients with anxiety or depressive disorder., Methods: Patients with anxiety or depressive disorders who were prescribed antidepressant monotherapy (mirtazapine, sertraline, desvenlafaxine, escitalopram, or fluoxetine) at the discretion of the treating clinician were recruited from July 2012 to June 2014 from a hospital outpatient service. All were free of psychotropic medication for least 1 month. Sexual function was assessed at baseline, week 2, and week 6 using the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ). A PRSexDQ score of ≥2 was considered to indicate sexual dysfunction. Sexual function was dichotomised to 'favourable' or 'impaired'., Results: Of 230 patients recruited, 209 were assessed at baseline of whom 184 were assessed at week 2; of these, 154 were also assessed at week 6. At baseline, 138 (66%) of the 209 patients were diagnosed with depressive disorder and 71 (34%) with anxiety disorder; 29% of patients had sexual dysfunction (in any domain of PRSexDQ). By week 6, the percentage had increased to 41%, although the change in the mean PRSexDQ score was only marginal (from 1.04 at baseline to 1.55 at week 6). With regard to individual questionnaire items, by week 6, sexual desire improved, but erectile and ejaculatory function in men and orgasmic function in women worsened. Fluoxetine and sertraline were associated with impaired sexual function, whereas mirtazapine was associated with favourable sexual function. In a logistic regression analysis, at week 2, mirtazapine and desvenlafaxine were predictors of favourable sexual outcome, whereas fluoxetine and higher baseline PRSexDQ score were predictors of impaired sexual outcome. At week 6, mirtazapine remained a predictor of favourable sexual outcome, whereas fluoxetine, higher 2-week PRSexDQ score, and adequate dose were predictors of impaired sexual outcome., Conclusions: In patients with anxiety or depressive disorder, the risk of antidepressant-emergent sexual dysfunction at 6 weeks is low when drug doses are initially low with gradual up-titration. Baseline sexual dysfunction was independently associated with impaired sexual outcome. Men may be more likely than women to experience impaired sexual outcome. In patients with baseline sexual dysfunction, prescription of mirtazapine might be preferable to fluoxetine.

Objectives: A pilot of clinical services provided by psychiatric clinical pharmacists in an outpatient clinic are described and evaluated. The primary objective was to evaluate the difference in change of Patient Health Questionnaire (PHQ)-9 and/or Generalized Anxiety Disorder (GAD) Questionnaire scores between the two groups. Secondary objectives were to assess time patients spent in clinic, time to target psychotropic medication dose, and patient self-reported medication adherence., Experimental Design: Data were collected from January 2014 to November 2015 for patients with depression and/or anxiety who had an appointment within an outpatient psychiatric clinic with either a provider (control) or both a provider and clinical pharmacist (case)., Principle Observations: A total of 217 patients were included in the study; 117 patients served as controls and 100 patients received clinical pharmacist intervention. No statistical difference was detected in the primary outcome. However, patients in the case group had higher baseline PHQ-9/GAD scores, and the frequency of measured values was lower than anticipated, limiting power to detect a difference. All secondary outcomes achieved statistical significance. Both time in clinic and time to reach a stabilized psychotropic medication regimen were shorter in the control group. Patient self-reported adherence favored a higher adherence rate in the intervention group., Conclusion: While this study found no significant difference in the change in PHQ-9/GAD scores between groups, it demonstrated the need for enhanced utilization of measurement-based outcomes in the psychiatric setting. Pharmacists provide a range of services to patients and providers and can serve as key partners to enhance measurement-based care., Competing Interests: Conflicts of Interest None.

Significant advances have been made in the application of pharmacogenomic testing for the treatment of patients with psychiatric disorders. Over the past decade, a number of studies have evaluated the utility of pharmacogenomic testing in pediatric patients with psychiatric disorders. The evidence base for pharmacogenomic testing in youth with depressive and anxiety disorders as well as attention/deficit hyperactivity disorder (ADHD) is reviewed in this article. General pharmacogenomic principles are summarized and functional polymorphisms in P450 enzymes (and associated metabolizer phenotypes), the serotonin transporter promoter polymorphisms, serotonin 2A receptor genes (e.g., HT2AR) and catecholamine pathway genes (e.g., COMT) are reviewed. These commonly tested pharmacogenomic markers are discussed with regard to studies of drug levels, efficacy and side effects. The translation of pharmacogenomics to individualized/precision medicine in pediatric patients with ADHD, anxiety and depressive disorders has accelerated; however, its application remains challenging given that there are numerous divergent pathways between medication/medication dose and clinical response and side effects. Nonetheless, by leveraging variations in individual genes that may be relevant to medication metabolism or medication target engagement, pharmacogenomic testing may have a role in predicting treatment response, side effects and medication selection in youth with ADHD, depressive and anxiety disorders., (Copyright © 2018 Mosby, Inc. All rights reserved.)

Aims: To establish recommendations for the management of psychological problems affecting patients with inflammatory bowel disease (IBD)., Methods: A meeting of a group of IBD experts made up of doctors, psychologists, nurses and patient representatives was held. The following were presented: 1) Results of a previous focal group, 2) Results of doctor and patient surveys, 3) Results of a systematic review of tools for detecting anxiety and depression. A guided discussion was then held about the most important psychological and emotional problems associated with IBD, appropriate referral criteria and situations to be avoided. The validated instrument most applicable to clinical practice was selected. A recommendations document and a Delphi survey were designed. The survey was sent to the group and to a scientific committee of the GETECCU group in order to establish the level of agreement with these recommendations., Results: Fifteen recommendations were established linked to 3 key processes: 1) What steps should be taken to identify psychological problems at an IBD appointment; 2) What are the criteria for referring patients to a mental health specialist; 3) How to approach psychological problems., Conclusions: Resources should be made available to healthcare professionals so that they can treat these problems during consultations, identify the disorders which could affect the clinical course of the disease and determine their impact on the patient's life in order that these can be treated and followed up by the most suitable professional. These recommendations could serve as a basis for redesigning IBD services or processes and as justification for the training of healthcare personnel., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)