Hamilton Rating Scale For Depression Total Score Research Articles

Sleep Problems and Gambling Disorder: Cross-Sectional Relationships in a Young Cohort.

To investigate the potential association between gambling disorder and symptoms of sleep problems (including insomnia and excessive daytime sleepiness). It was hypothesised that, compared to controls, individuals with gambling disorder would have significantly greater disturbance of sleep, as indicated by increased scores in: (1) sleep items on the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Rating Scale for Depression (HAM-D); (2) total score on the HAM-A and HAM-D; and (3) the Epworth Sleepiness Scale (ESS). Secondary analysis of previously published data from 152 young adults, aged 18-29 years. Individuals were stratified into three groups: controls, those at risk of gambling disorder, and those with gambling disorder. One-way ANOVAs with post-hoc tests were conducted to determine whether groups differed significantly in sleep item scores and total scores of the HAM-A and HAM-D, and the ESS. HAM-D scale insomnia item scores were significantly higher in the disorder group, when compared to controls, this being particularly marked for middle and late insomnia. The HAM-A item score indicated significantly worse sleep quality in the disorder group, compared to at risk and control groups. Total HAM-A and HAM-D scores were significantly higher in the disorder group, but ESS scores did not differ significantly. Measures of disruptions in sleep were significantly higher in gambling disorder than controls. Anxiety and depressive symptom severity was also significantly higher in the gambling disorder group. Further research could have implications for identification and treatment of sleep disorders and psychiatric comorbidities in gambling disorder.

Rapid improvements and subsequent effects in major depressive disorder patients with somatic pain using rTMS combined with sertraline

This study aims to explore changes in depression and pain for major depressive disorder (MDD) patients with somatic pain after repetitive transcranial magnetic stimulation (rTMS) using the event-related potentials (ERPs) technique. Eighty MDD patients with somatic pain were randomly assigned to drug therapy (DT) and combined therapy (CT) groups. CT group underwent intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (DLPFC) with 800 pulses and 1 Hz over the right DLPFC with 800 pulses, 5 times a week for 3 weeks. All patients were given sertraline at 50–100 mg per day. All subjects were evaluated at baseline and at weeks three and six of therapy using the Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Scale (HAMA), and Numerical Rating Scales (NRS), and the latency and amplitude of P300 and mismatch negativity (MMN) were measured. There were no significant differences in all indices between groups at baseline. At 3 weeks, HAMD subscale scores of Cognitive Impairment and NRS scores were significantly lower in the CT group than in the DT group. At 6 weeks, NRS and HAMD total scores in the CT group decreased significantly in the CT group compared with the DT group, especially for anxiety and pain, and the MMN and P300 latencies and P300 amplitude showed greater improvements. Our findings highlight that rTMS in combination with antidepressants is a rapid method of symptom improvement in patients with somatic pain with MDD and is helpful for cognitive impairment and anxiety.

Serum levels of high mobility group box-1 protein (HMGB1) and soluble receptors of advanced glycation end-products (RAGE) in depressed patients treated with electroconvulsive therapy.

High mobility group box-1 (HMGB1) is one of the damage-associated molecular patterns produced by stress and induces inflammatory responses mediated by receptors of advanced glycation end-products (RAGE) on the cell surface. Meanwhile, soluble RAGE (sRAGE) exhibits an anti-inflammatory effect by capturing HMGB1. Animal models have shown upregulation of HMGB1 and RAGE in the brain or blood, suggesting the involvement of these proteins in depression pathophysiology. However, there have been no reports using blood from depressed patients, nor ones focusing on HMGB1 and sRAGE changes associated with treatment and their relationship to depressive symptoms. Serum HMGB1 and sRAGE concentrations were measured by enzyme-linked immunosorbent assay in a group of patients with severe major depressive disorder (MDD) (11 males and 14 females) who required treatment with electroconvulsive therapy (ECT), and also in a group of 25 age- and gender-matched healthy subjects. HMGB1 and sRAGE concentrations were also measured before and after a course of ECT. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAMD). There was no significant difference in HMGB1 and sRAGE concentrations in the MDD group compared to healthy subjects. Although ECT significantly improved depressive symptoms, there was no significant change in HMGB1 and sRAGE concentrations before and after treatment. There was also no significant correlation between HMGB1 and sRAGE concentrations and the HAMD total score or subitem scores. There were no changes in HMGB1 and sRAGE in the peripheral blood of severely depressed patients, and concentrations had no relationship with symptoms or ECT.

Tau deposition in the locus coeruleus and depression in cognitively unimpaired older adults

AbstractBackgroundDepression is a common manifestation of Alzheimer’s disease (AD) and frequently observed at the early phase of the disease. Several postmortem studies demonstrated that tau deposition was found at the brainstem nuclei including the locus coeruleus (LC) and dossal raphe nucleus (DRN) (3, 4), even before early Braak stages of neurofibrillary tangle pathology. Given the disturbance of monoaminergic system is related to depression in general, tau deposition in the LC or DRN may underlie depression in late‐life, as suggested in a couple of postmortem studies. In this context, we tried to examine the hypothetical association between in vivo tau depostion at the brain stem monoaminergic nuclei and depression in cognitively unimpaired older adults.MethodA total of 69 cognitively unimpaired older adults from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) were included. All participants underwent comprehensive clinical assessment including the Hamilton Rating Scale for Depression (HRSD) and [18F] AV‐1451 positron emission tomography. Tau deposition in the LC and DRN was measured using the Harvard Ascending Arousal Network Atlas (AAN). Tau deposition in the pons was also assessed as a non‐monoaminergic control for comparison. Age, education, sex, and apolipoprotein E ε4 positivity were controlled as covariates in the analyses for the association between brain stem tau and HRSD score.ResultTau deposition in the LC was significantly associated with HRSD total score (β = 3.861, P = .009). In contrast, there was no significant association between tau deposition in the DRN and HRSD score (β = 2.229, P = .090). Tau deposition in the pons was also not related to HRSD score (β = 1.632, P = .207).ConclusionThe findings support the possibility that alteration of the noradrenergic neurons in the LC by tau pathology may underlie depressive manifestation in cognitively unimpaired older individuals.

Effect of adverse childhood experiences on hypothalamic–pituitary–adrenal (HPA) axis function and antidepressant efficacy in untreated first episode patients with major depressive disorder

Adverse childhood experiences (ACEs) has been associated not only with an increased vulnerability for stress-related psychiatric disorders but also with distinct alterations of the hypothalamic–pituitary–adrenal (HPA) axis function and the immune system. The aim of this study is to examine differences in the HPA axis between major depressive disorder (MDD) patients with and without ACEs, and to explore differences in efficacy and HPA changes after long term antidepressant treatment between these two groups. A cohort of 803 patients with MDD were recruited. After the determination of cortisol (COR) and adrenocorticotropic hormone (ACTH), Hamilton Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety (HAMA), the Childhood Trauma Questionnaire (CTQ), 403 subjects were recruited for the following treatment study. Finally 330 MDD patients finished the monotherapy treatments of four antidepressants (Fluoxetine, Sertraline, Venlafaxine-extended release (XR), Duloxetine hydrochloride) for 12 weeks. Of 403 patients, 226 (56%) patients reported ACEs. Total score of HAMD in MDD with ACEs were higher than those in MDD without ACEs. There were significant differences for both ACTH and COR between MDD patients with and without ACEs that MDD patients with any types of maltreatment had higher level. Both COR and ACTH was positively and significantly correlated with the total scores of CTQ, HAMD, HAMA. After 12 weeks treatment of antidepressants monotherapy, the mean (SD) changes in HAMD and HAMA total scores was greater in MDD without ACEs than those in MDD with ACEs. At the 12-week end point, response was achieved by 37.2% in the MDD with ACEs group, 59.0% in the MDD without ACEs group respectively, with significant difference. Remission was achieved by 15.2% in the MDD with ACEs group and 32.2% in the MDD without ACEs group, with significant difference. The change in ACTH level in MDD without ACEs was also greater than that in MDD with ACEs, which was positively and significantly correlated with the HAMD total score only in MDD patient without ACEs. Logistic regression analysis showed that the total scores of CTQ, level of COR and ACTH at baseline were significantly associated with the response and remission. These findings indicated that exposure to ACEs for MDD could influence the HPA function and severity of symptoms. ACEs, ACTH and COR could be used as predictors of long term antidepressant treatment, suggested that are poor prognostic signs for antidepressants monotherapy in MDD with ACEs.

1068: Insights on GABAergic mechanism of postpartum depression from pivotal studies of brexanolone injection and SAGE-217

Postpartum depression (PPD) is one of the most common medical complications during and after pregnancy. One proposed etiology involves dysfunctional GABAergic signaling. The safety, tolerability, and antidepressant activity of brexanolone injection (BRX) and SAGE-217, two neuroactive steroid GABAA receptor (GABAAR) positive allosteric modulators with a pharmacology distinct from benzodiazepines were evaluated in 4 RCTs. Study inclusion criteria were similar: adult women, ≤6 months postpartum, diagnosed with PPD, and with a qualifying Hamilton Rating Scale for Depression (HAM-D) total score (BRX Studies A and B, ≥26; BRX Study C, 20-25; SAGE-217, ≥26). BRX study randomization was 1:1:1 to BRX 90 ug/kg/h (BRX90):BRX 60 ug/kg/h:placebo in Study B and 1:1 BRX90:placebo in Studies A and C. Study drug was administered as a continuous 60-hour infusion, with follow-up through Day 30. SAGE-217 study randomization was 1:1 to SAGE-217 30 mg capsules or placebo for 14 days, with 4 weeks follow-up. Primary endpoints were change in HAM-D total score at Hour 60 (BRX studies) or Day 15 (SAGE-217 study). Safety and tolerability were evaluated by adverse events (AEs) and standard clinical assessments. Both BRX90 and SAGE-217 achieved their primary endpoints (p< 0.0001 and p=0.0028 respectively). Significant improvement with BRX90 versus placebo was sustained through Day 30 (p=0.0213) and favoring SAGE-217 were observed from Day 3 (p=0.0252) through Day 45 (p=0.0027). AEs occurring in all BRX groups (n=140) in ≥5% of BRX and ≥2x the rate of placebo were sedation/somnolence, dry mouth, loss of consciousness, and flushing/hot flush. The most common (≥5%) with SAGE-217 were somnolence, headache, dizziness, upper respiratory tract infection, diarrhea, and sedation. BRX and SAGE-217 achieved their primary endpoints of statistically significant and clinically meaningful reductions in depressive symptoms versus placebo in pivotal RCTs in PPD and were generally well tolerated. These results support the role of GABAergic signaling in PPD.

Putative Antidepressant Effect of Chamomile (Matricaria chamomilla L.) Oral Extract in Subjects with Comorbid Generalized Anxiety Disorder and Depression.

Objectives: This exploratory analysis examined the putative antidepressant effect of Matricaria chamomilla L. (chamomile) extract in subjects with generalized anxiety disorder (GAD) with or without comorbid depression. It was hypothesized that chamomile extract would demonstrate similar anxiolytic activity in both subgroups, but superior antidepressant activity in GAD subjects with comorbid depression. Design: As part of a randomized double-blind placebo-controlled trial of chamomile extract for relapse prevention of GAD, 179 subjects received initial therapy with open-label chamomile extract 1500 mg daily for 8 weeks. Linear mixed-effect models were used to identify clinically meaningful changes in anxiety and depression symptoms between diagnostic subgroups. Settings/Location: The study took place at the University of Pennsylvania in Philadelphia, PA. Subjects: Subjects were ≥18 years old with a primary DSM IV-TR diagnosis of GAD. They were subcategorized into two diagnostic groups: GAD without comorbid depression (n = 100) and GAD with comorbid depression (n = 79). Interventions: Open-label chamomile extract 1500 mg was given daily for 8 weeks. Outcome measures: Generalized anxiety disorder (GAD-7), Hamilton rating scale for anxiety, Beck anxiety inventory, Hamilton rating scale for depression (HRSD), the six-item core HRSD (items 1, 2, 3, 7, 8, and 13), and the Beck depression inventory (BDI). Results: The authors observed similar anxiolytic effects over time in both diagnostic subgroups. However, there was a greater reduction in HRSD core symptom scores (p < 0.023), and a trend level reduction in HRSD total scores (p = 0.14) and in BPI total scores (p = 0.060) in subjects with comorbid depression. Conclusions: M. chamomilla L. may produce clinically meaningful antidepressant effects in addition to its anxiolytic activity in subjects with GAD and comorbid depression. Future controlled trials in subjects with primary major depressive disorder are needed to validate this preliminary observation.

PMH51 BREXANOLONE INJECTION FOR THE TREATMENT OF POSTPARTUM DEPRESSION: MINIMAL IMPORTANT DIFFERENCE AND MEANINGFUL CHANGE

Brexanolone injection (BRX) is the first FDA-approved postpartum depression (PPD)-specific treatment, based on a primary endpoint supported by the Hamilton Rating Scale for Depression (HAM-D) total score at hour 60. The most common adverse events (≥10%) with BRX were headache, dizziness, and somnolence. While BRX has shown significant improvement over placebo (-4.1, 95% CI: -6.0, -2.3, p<0.0001) little is known about the interpretation of the HAM-D in a PPD population. Thus, the objectives of the analysis were to: (1) establish a HAM-D minimal important difference (MID) and patient-level meaningful change thresholds (MCT) for PPD, and (2) calculate the proportion of BRX and placebo patients who met the MCTs at hour 60. The HAM-D MID was estimated based on two distribution-based methods: one-half standard deviation (SD) for the pooled sample at baseline and one standard error of measurement (SEM; using a test re-test intra-class correlation coefficient). Thresholds for HAM-D MCTs (minimal, moderate, and large) were estimated based on Clinician Global Impression of Improvement (CGI-I) response category (minimally improved, much improved, and very much improved, respectively). 209 subjects were included at baseline. The HAM-D MID estimates were -1.8 and -2.4 based on one-half SD and one SEM, respectively. Integrated analysis estimates of least-squared mean difference between BRX and placebo at hour 60 exceeded both MID estimates. Minimal, moderate and large MCTs were estimated to be -9, -15 and -20 points, respectively. Significantly more BRX-treated patients achieved minimal (87% vs 68%, p<0.01), moderate (67% vs 42% p<0.001), and large change (30% vs 15%, p<0.05) at hour 60. HAM-D total score improvements at hour 60 with BRX were both statistically significant and clinically importantly different from placebo. This analysis has provided the first estimates of PPD-specific MID and MCTs for the HAM-D in this clinically important outcome.

86: Brexanolone iv efficacy in postpartum depression in three pivotal trials: montgomery-åsberg depression rating scale assessment

The investigational, positive allosteric modulator of ɣ-aminobutyric acid A (GABAA) receptors, brexanolone iv (BRX), was evaluated for efficacy and safety in women with postpartum depression (PPD) in 3 double-blind, placebo-controlled, randomized trials. BRX met the primary efficacy endpoint with a significantly greater change from baseline in Hamilton Rating Scale for Depression (HAM-D) total score at Hour 60 than placebo (PBO). This abstract presents the results of a secondary measure, the Montgomery-Åsberg Depression Rating Scale (MADRS). An umbrella protocol for the 3 studies allowed integrated dataset analysis. Women aged 18-45 years, ≤ 6 months postpartum, with PPD (i.e. major depressive episode no earlier than third trimester and no later than 4 weeks post-delivery) and a qualifying 17-item HAM-D total score (≥ 26 in Studies A and B; 20-25 in Study C) were enrolled. Randomized subjects received a single, continuous 60-hour infusion of PBO, BRX 60 μg/kg/hour (BRX60), or 90 μg/kg/hour (BRX90) and were followed through Day 30. Change from baseline in MADRS total score (MADRSts) was a secondary endpoint, analyzed by a mixed effects model for repeated measures (BRX90). Safety and tolerability were assessed by adverse event (AE) reporting and clinical laboratory testing (BRX60 and BRX90). Least squares mean (SE) change from baseline in MADRSts at Hour 60 in the PBO (N=107) or BRX90 (N=102) groups was -17.7 (1.2) or -23.5 (1.2) respectively. A significantly greater mean reduction versus PBO was achieved with BRX90 starting at Hour 24 and maintained through Day 7 (Figure). At Day 30, the mean reduction of BRX90 versus PBO was numerically greater. The most common AEs (≥ 10%) reported in all BRX subjects included headache, dizziness, and somnolence. Brexanolone iv was generally well tolerated and showed statistically significant greater reductions of depressive symptoms in women with PPD compared to PBO, as measured by MADRSts. The proposed mechanism of action of brexanolone iv (i.e., positive allosteric modulation of GABAA receptors) is a novel approach in the development of a therapeutic agent for PPD and, if regulatory approval is obtained, has the potential to provide meaningful new treatment options for women with PPD.

Characteristics of and factors influencing cognitive impairment in adolescent patients with first-episode depression

ABSTRACTThis study aims to explore the characteristics and risk factors of cognitive impairment in adolescent patients with first-episode depression. In total, 128 adolescents with first-episode depression were selected (patient group). Clinical factors, including gender, educational level, suicide risk, sleep status based on the Pittsburg Sleep Quality Index scale (PSQI), and disease duration based on Hamilton Rating Scale for Depression (HRSD), were assessed to identify risk factors. The MATRICS Consensus Cognitive Battery (MCCB) was used to assess 50 health subjects (control group). Data were statistically analyzed using the t test, χ2 test, Pearson’s correlation analysis, and stepwise multiple regression analysis in SPSS 22.0. The total MCCB score in the control group was higher than that in the patient group (P < 0.05), while no differences were observed on the maze test, semantic fluency, and continuous operation results (P > 0.05). Cognitive functional impairment in adolescent patients with first-episode depression was related to gender, educational level, suicide risk, sleep disorder, total HRSD score, and disease duration. The stepwise multiple-linear regression analysis obtained the regression equation as follows: Y1 (total MCCB points) = 82.741 + 11.897 × X3 (educational level) – 8.914 × X6 (total HRSD score) – 8.457 × X7 (total disease duration). Cognitive impairment in adolescent patients with first-episode depression was related to their gender, educational level, suicide risk, sleep disorders, HRSD score, and disease duration. Further, educational level, HRSD score, and disease duration were identified as high-risk factors.

Circadian preferences are associated with vegetative symptoms and comorbid medical diseases in patients with major depression

ABSTRACTCircadian preferences may affect the severity and symptom structure of depression and could influence specific symptom clusters of depression. This study aims to examine the relationship between chronotypes and symptomatology in patients with major depression. One hundred and one drug-naïve outpatients with major depression were evaluated through the use of the Hamilton Rating Scale for Depression (HRSD). The Morningness–Eveningness Questionnaire (MEQ) was used to the define chronotypes and the quality of subjective sleep was measured with Pittsburgh Sleep Quality Index (PSQI). The medical records of patients were evaluated retrospectively to determine the presence of another medical illness. HRSD total score and cognitive and vegetative factor scores were significantly higher in the evening chronotype than in the morning and intermediate chronotypes (p < .001). In the regression analysis, MEQ total score was inversely related to HRSD-vegetative factor score (p < .001). The ratio of comorbid illness was found to be statistically significant among depressed patients with evening chronotype (p = .001). Additionally, binary logistic regression analysis was performed to ascertain the likelihood of participants having comorbid medical illness; only age (p = .010) and MEQ total score (p = .011) were associated with exhibiting comorbid illness. General and psychiatric clinical examinations need to be considered with the understanding of circadian preference.

Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials

Post-partum depression is associated with substantial morbidity, and improved pharmacological treatment options are urgently needed. We assessed brexanolone injection (formerly SAGE-547 injection), a positive allosteric modulator of γ-aminobutyric-acid type A (GABAA) receptors, for the treatment of moderate to severe post-partum depression. We did two double-blind, randomised, placebo-controlled, phase 3 trials, at 30 clinical research centres and specialised psychiatric units in the USA. Eligible women were aged 18-45 years, 6 months post partum or less at screening, with post-partum depression and a qualifying 17-item Hamilton Rating Scale for Depression (HAM-D) score (≥26 for study 1; 20-25 for study 2). Women with renal failure requiring dialysis, anaemia, known allergy to allopregnanolone or to progesterone, or medical history of schizophrenia, bipolar disorder, or schizoaffective disorder were excluded. Patients were randomly assigned (1:1:1) to receive a single intravenous injection of either brexanolone 90 μg/kg per h (BRX90), brexanolone 60 μg/kg per h (BRX60), or matching placebo for 60 h in study 1, or (1:1) BRX90 or matching placebo for 60 h in study 2. Patients, the study team, site staff, and the principal investigator were masked to treatment allocation. The primary efficacy endpoint was the change from baseline in the 17-item HAM-D total score at 60 h, assessed in all patients who started infusion of study drug or placebo, had a valid HAM-D baseline assessment, and had at least one post-baseline HAM-D assessment. The safety population included all randomised patients who started infusion of study drug or placebo. Patients were followed up until day 30. The trials have been completed and are registered with ClinicalTrials.gov, numbers NCT02942004 (study 1) and NCT02942017 (study 2). Participants were enrolled between Aug 1, 2016, and Oct 19, 2017, in study 1, and between July 25, 2016, and Oct 11, 2017, in study 2. We screened 375 women simultaneously across both studies, of whom 138 were randomly assigned to receive either BRX90 (n=45), BRX60 (n=47), or placebo (n=46) in study 1, and 108 were randomly assigned to receive BRX90 (n=54) or placebo (n=54) in study 2. In study 1, at 60 h, the least-squares (LS) mean reduction in HAM-D total score from baseline was 19·5 points (SE 1·2) in the BRX60 group and 17·7 points (1·2) in the BRX90 group compared with 14·0 points (1·1) in the placebo group (difference -5·5 [95% CI -8·8 to -2·2], p=0·0013 for the BRX60 group; -3·7 [95% CI -6·9 to -0·5], p=0·0252 for the BRX90 group). In study 2, at 60 h, the LS mean reduction in HAM-D total score from baseline was 14·6 points (SE 0·8) in the BRX90 group compared with 12·1 points (SE 0·8) for the placebo group (difference -2·5 [95% CI -4·5 to -0·5], p=0·0160). In study 1, 19 patients in the BRX60 group and 22 patients in the BRX90 group had adverse events compared with 22 patients in the placebo group. In study 2, 25 patients in the BRX90 group had adverse events compared with 24 patients in the placebo group. The most common treatment-emergent adverse events in the brexanolone groups were headache (n=7 BRX60 group and n=6 BRX90 group vs n=7 placebo group for study 1; n=9 BRX90 group vs n=6 placebo group for study 2), dizziness (n=6 BRX60 group and n=6 BRX90 group vs n=1 placebo group for study 1; n=5 BRX90 group vs n=4 placebo group for study 2), and somnolence (n=7 BRX60 group and n=2 BRX90 group vs n=3 placebo group for study 1; n=4 BRX90 group vs n=2 placebo group for study 2). In study 1, one patient in the BRX60 group had two serious adverse events (suicidal ideation and intentional overdose attempt during follow-up). In study 2, one patient in the BRX90 group had two serious adverse events (altered state of consciousness and syncope), which were considered to be treatment related. Administration of brexanolone injection for post-partum depression resulted in significant and clinically meaningful reductions in HAM-D total score at 60 h compared with placebo, with rapid onset of action and durable treatment response during the study period. Our results suggest that brexanolone injection is a novel therapeutic drug for post-partum depression that has the potential to improve treatment options for women with this disorder. Sage Therapeutics, Inc.

The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome, functional diarrhea and functional constipation: An open-label observational study

BackgroundsThe intestinal microbiota is considered as a potential common underpinning pathophysiology of Functional Gastrointestinal Disorders (FGIDs) and psychiatric disorders such as depression and anxiety. Fecal Microbiota Transplantation (FMT) has been reported to have therapeutic effects on diseases related to dysbiosis, but few studies have evaluated its effect on psychiatric symptoms. MethodsWe followed 17 patients with either Irritable Bowel Syndrome (IBS), Functional Diarrhea (FDr) or Functional Constipation (FC) who underwent FMT for the treatment of gastrointestinal symptoms and observation of psychiatric symptoms. Changes in Hamilton Rating Scale for Depression (HAM-D) and subscale of sleep-related items, Hamilton Rating Scale for Anxiety (HAM-A) and Quick Inventory for Depressive Symptoms (QIDS) between baseline and 4 weeks after FMT, and relationship with the intestinal microbiota were measured. ResultsAt baseline, 12 out of 17 patients were rated with HAM-D ≥ 8. Significant improvement in HAM-D total and sleep subscale score, HAM-A and QIDS were observed (p = 0.007, p = 0.007, p = 0.01, p = 0.007, respectively). Baseline Shannon index indicated that microbiota showed lower diversity in patients with HAM-D ≥ 8 compared to those of healthy donors and patients with HAM-D < 8. There was a significant correlation between baseline Shannon index and HAM-D score, and a correlation between Shannon index change and HAM-D improvement after FMT. LimitationsThe small sample size with no control group. ConclusionsOur results suggest that depression and anxiety symptoms may be improved by FMT regardless of gastrointestinal symptom change in patients with IBS, FDr and FC, and the increase of microbiota diversity may help to improve patient's mood.

Depression and associated factors in nondemented Chinese patients with Parkinson’s disease

ObjectivesDepression is more common in Parkinson’s disease (PD) than other chronic and disabling disorders. This study aimed to estimate the prevalence and identify potential risk factors influencing depression in 519 consecutive nondemented Chinese PD patients. Patients and methodsDepression was assessed using the Hamilton Rating Scale for Depression (HAMD), PD severity was assessed using Hoehn and Yahr (H&Y) staging, motor symptoms were measured with the Unified PD Rating Scale (UPDRS) part III, and the Non-Motor Symptoms Questionnaire (NMS-Quest) was used to evaluate the global non-motor symptoms (NMS). The PD Sleep Scale (PDSS), and Mini-Mental State Examination (MMSE) were also administered. ResultsThe mean total HAMD score was 12.60±9.29, and the most prevalent depressive domain was retardation (84.4%). There were significant correlations between the total HAMD score and sex, PD-duration, UPDRS-III, H&Y stage, PD-NMS, PDSS, and MMSE. Non-motor symptoms, poor sleep quality, younger age, and cognitive dysfunction are independent predictors of depression. Among these, non-motor symptoms or sleep disturbances are the most powerful predictors of each depressive domain. We observed a significantly higher total HAMD score and domains of anxiety/somatization, mental disorder, and hopelessness in female patients. However, there was no difference in HAMD total scores and HAMD sub-items between young-onset PD and late-onset PD patients when adjusted by potential confounding factors. ConclusionsThe prevalence rate of depression among nondemented Chinese PD patients is high and similar to those reported in previous studies. The presence of depression in PD patients should be routinely assessed in clinical practice.

Dose Escalation of Antidepressants in Unipolar Depression: A Meta-Analysis of Double-Blind, Randomized Controlled Trials

Background: As many patients with unipolar depression do not respond sufficiently to initial antidepressant monotherapy, a dose increase of the current administered antidepressant (dose escalation, high-dose treatment) is frequently carried out as next treatment measure. Methods: We conducted a meta-analysis which included all double-blind randomized controlled trials (RCTs) comparing a dose increase of antidepressants directly to continuation of standard-dose treatment in unipolar depressive patients who were non- responders to standard-dose pharmacotherapy. A mean change in the Hamilton Rating Scale for Depression (HAM-D) total score was the primary outcome. Secondary outcomes were response rates and discontinuation rates due to any reason, inefficacy, and adverse effects. Hedges g and risk ratios were calculated as effect sizes. Results: Seven double-blind RCTs (8 study arms) representing 1,208 participants were included. Fluoxetine (N [number of studies] = 2, n [number of patients] = 448), sertraline (N = 2, n = 272), paroxetine (N = 2, n = 146), duloxetine (N = 1, n = 255), and maprotiline (N = 1, n = 87) were investigated. Dose escalation was not more efficacious in HAM-D total score reduction than maintaining standard-dose treatment, neither for the pooled antidepressant group (N = 7, n = 999; Hedges g = -0.04, 95% CI: -0.20 to 0.12; p = 0.63) nor the individual antidepressants. No differences could be determined for response rates, all-cause discontinuation, and drop-outs due to inefficacy. Significantly more patients in the dose escalation group dropped out due to adverse effects than in the standard-dose continuation group. The metaregressions indicate no influence of baseline symptom severity or amounts of dose increments on effect sizes. Conclusions: According to our meta-analytic findings, dose escalation after initial non-response to standard-dose pharmacotherapy cannot be regarded as general evidence-based treatment option in unipolar depression.

Cross-national differences in hypochondriasis symptoms between Korean and American outpatients with major depressive disorder.

Hypochondriasis is defined as the tendency to worry excessively about having a serious illness. This study aimed to investigate cross-national differences in hypochondriasis symptoms between Korean and American patients with major depressive disorder (MDD). This study examined 1592 Korean and 3744 American MDD outpatients of age ≥18 years using the Hamilton Rating Scale for Depression (HAM-D) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). Korean MDD patients exhibited significantly higher scores for hypochondriasis than Americans after controlling for total HAM-D scores and demographic variables (p<0.0001), even though Americans had significantly higher total HAM-D scores (p<0.0001). Multivariate logistic regression analyses revealed that hypochondriasis was significantly associated with somatic and psychic anxiety, insomnia-middle, and suicide for both Korean and American MDD patients after adjusting for demographic covariates. Among all factors, somatic anxiety was the most strongly associated with hypochondriasis in both Korean (AOR=2.14, 95% CI 1.31-3.52) and American (AOR=1.98, 95% CI 1.69-2.31) MDD outpatients. Hypochondriasis symptoms are more prevalent among Korean than American MDD patients but appear to be associated with high levels of somatic anxiety regardless of culture. This suggests that cultural and personal factors play a shared role in the presentation of hypochondriasis symptoms.

Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder.

Vortioxetine was approved by the U.S. Food and Drug Administration (FDA) in September 2013 for treating major depressive disorder (MDD). Thus far, a number of randomized, double-blind, placebo-controlled clinical trials (RCTs) of vortioxetine have been conducted in patients with MDD. We performed a meta-analysis to increase the statistical power of these studies and enhance our current understanding of the role of vortioxetine in the treatment of MDD. We performed an extensive search of databases and the clinical trial registry. The mean change in total scores on the 24-item Hamilton Rating Scale for Depression (HAM-D) and the Montgomery- Åsberg Depression Rating Scale (MADRS) from the baseline were the primary outcome measures. The secondary efficacy measures were the response and remission rates, as defined by a 50% or greater reduction in HAM-D/MADRS total scores and as a score of 10 or less in the MADRS and 7 or less in the HAM-D total scores at the end of treatment. We included 7 published and 5 unpublished short-term (6-12 wk) RCTs in our meta-analysis. Vortioxetine was significantly more effective than placebo, with an effect size (standardized mean difference [SMD]) of -0.217 (95% confidence interval [CI] -0.313 to -0.122) and with odds ratios (ORs) for response and remission of 1.652 (95% CI 1.321 to 2.067) and 1.399 (95% CI 1.104 to 1.773), respectively. Those treated with vortioxetine did not differ significantly from those treated with selective norepinephrine reuptake inhibitors/agomelatine with regard to the SMD of the primary outcome measure (0.081, -0.062 to 0.223) or for response (OR 0.815, 95% CI 0.585 to 1.135) and remission (OR 0.843, 95% CI 0.575 to 1.238) rates. Discontinuation owing to lack of efficacy (OR 0.541, 95% CI 0.308 to 0.950) was significantly less common among those treated with vortioxetine than among those who received placebo, whereas discontinuation owing to adverse events (AEs; OR 1.530, 95% CI 1.144 to 2.047) was significantly more common among those treated with vortioxetine than among those receiving placebo. There was no significant difference in discontinuation rates between vortioxetine and comparators owing to inefficacy (OR 0.983, 95% CI 0.585 to 1.650), whereas discontinuation owing to AEs was significantly less common in the vortioxetine than in the comparator group (OR 0.728, 95% CI 0.554 to 0.957). Studies examining the role of vortioxetine in the treatment of MDD are limited. Although our results suggest that vortioxetine may be an effective treatment option for MDD, they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of heterogeneous RCTs.

Bupropion for interferon-alpha-induced depression in patients with hepatitis C viral infection: an open-label study.

Interferon (IFN)-α therapy for chronic hepatitis C virus (HCV) infection is frequently associated with major depressive episodes. Bupropion, a commonly used antidepressant agent, has recently found to have strong anti-inflammatory effects in animal models. Despite of the theoretical relevancy, the antidepressant effect of bupropion in IFN-alpha-induced depression has never been studied. Ten HCV patients with IFN-α-induced depression were recruited to receive 8-week bupropion treatment and were assessed every 2 weeks for depressive symptoms by the Hamilton rating scale for depression (HAMD) and somatic symptoms by the Neurotoxicity Rating Scale (NRS). Four of the 10 patients met the criteria for remission (total HAMD scores≤7), and 5 patients met the criteria for response (at least 50% reduction in total HAMD scores). In addition, 5 patients had 50% decreases in NRS for neuropsychiatric symptoms. This preliminary open-label study suggests that bupropion is effective in treating IFN-alpha-induced depressive and somatic symptoms.

P-55 * TRYPTOPHAN ACUTE DEPLECTION TEST IN COCAINE DEPRESSED PATIENTS

Introduction. Major depression is a common comorbidity in cocaine dependent (CD) subjects. A major challenge is to know if the comorbid depression episode is primary (PMD) or induced by the substance. Serotonergic system is implicated in both pathologies. Acute tryptophan depletion (ATD) has been used to evaluate serotonin function. The aim of the study is to observe differences in ATD response between PMD and cocaine-induced major depression (C-IMD). Methods. 23 CD patients (DSM-IV-TR) (14 with PMD and 9 with C-IMD) and 21 healthy controls have been assessed by ATD in a randomized double-blind crossover study. Mood changes during ATD by the Hamilton Rating Scale for Depression (HRSD) and tryptophan (TRP) plasma levels were evaluated at baseline (T0) and at 5hs (T5). Results. Those subjects with PMD showed changes in HRSD total scores in T5 (T0 mean = 1,57 ± 1,55 vs. T5 mean= 3,07 ± 2,058; p = 0.001), but not in C-IMD group (T0 mean =0,2 ± 0,6 and T5 mean = 0,5 ± 0,88) and in control group (T0 mean = 0,42 ± 0,76 and T5 mean =0,73 ± 1,1). In TRP plasma levels decreased in TDA-session and in Control-session behave as expected [1] but there were no differences between the controls and CD group. Conclusions. These results show a different response to ATD test between PMD and C-IMD in HRSD scores. These data support differences in the serotonergic system.

Older age is associated with rapid remission of depression after electroconvulsive therapy: a latent class growth analysis.

This study aims to empirically identify latent course trajectories of depressive symptoms during electroconvulsive therapy (ECT) within a cohort of patients suffering from a depressive disorder and to examine putative predictors of course. Using a prospective cohort multicenter collaborative ECT design, 120 patients fulfilling the Mini International Neuropsychiatric Interview criteria for major depressive disorder and referred for ECT were selected. Ratings of the 17-item Hamilton Rating Scale for Depression (HRSD) were obtained weekly during the course of ECT. Latent class growth analysis was used to identify trajectories of course during 6-week follow-up, based on weekly total HRSD scores. Characteristics of the identified classes were examined, and putative predictors for class membership were tested. Data-driven techniques identified distinct course trajectories during 6-week follow-up ECT treatment, consisting of "rapid remission," "moderate response," and "nonremitting" course trajectories. Remission rates were as high as 80.1% in the rapid remission class. Older age was associated with rapid remission, even after adjustment for putative confounders. Our results strongly confirm the favorable outcome of ECT among elderly depressed inpatients.