HDRS Scores Research Articles

Differential Placebo Responses for Pharmacotherapy and Neurostimulation in Late-Life Depression

BackgroundThe magnitude of the placebo response depends on both the modality used as the “placebo” and the intervention with which it is compared, both of which can complicate the interpretation of randomized controlled trials (RCTs) for depression in late life. Given that neurostimulation and pharmacotherapy are among the most common interventions studied for late-life depression, comparing the relative placebo responses in studies of these interventions can aid interpretation of relative effect sizes. Materials and MethodsWe analyzed data from two RCTs of adults aged ≥60 years in an episode of treatment-resistant major depression, one comparing aripiprazole and matching placebo pills and the other comparing deep repetitive transcranial magnetic stimulation (rTMS) and sham rTMS. In both RCTs, depression was assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17). The primary comparison occurred after four weeks using analysis of covariance (ANCOVA) of HDRS-17 scores in participants who received placebo pills or sham rTMS. Relevant covariates included years of education, duration of depressive episode, and baseline HDRS-17 score. ResultsAccounting for covariates, there was a larger reduction of HDRS-17 after four weeks in the sham rTMS group (estimated marginal mean ± SE: −5.90 ± 1.45; 95% CI: [−8.82, 2.98]) than in the placebo pills group (−1.07 ± 1.45; [−3.98, 1.85]). There were no significant differences between these groups in the binary outcome analysis of response and remission rates at four weeks or any outcome at trial end point comparison. ConclusionsSham rTMS may have a larger placebo response than placebo pills early in the treatment of older adults with treatment-resistant depression. Differential placebo responses should be considered in both the interpretation and design of RCTs.

The course of postpsychotic depressions in adolescence

To identify psychopathological features of postpsychotic depressions formed within the achievement of remission after the first psychotic episode in adolescence. Fifty-six male patients of adolescent age (average age 19.7±2.5 years) with postpsychotic depression (F20, F25) were enrolled. The study used clinical-psychopathological, psychometric and statistical methods. HDRS-21 was used for psychometric assessment of depressive symptoms, and suicidal risk was assessed using SSI. There were two types of post-psychotic depression: type 1 with a positive affectivity (58.93%, n=33) and type 2 with negative affectivity (41.07%, n=23). Significant differences in the structure of the first psychosis were found (χ2=7.8; p=0.02). In the case of depression type 1, the HDRS-21 score was 17.49±7.49 points with the largest number of points on the sub-scales «low mood» (2.81±0.83) and «mental anxiety» (2.88±0.45). The SSI average score was 7.81±6.46. Anti-vital thinking was noted by 75.76% (n=25). In the case of depression type 2, the HDRS-21 average score was 23.68±9.24 points (the largest number of points was fixed in the sub-scales «low mood» - 2.44±0.73, «work and activity» - 3.19±0.89). The SSI average score was 12.30±8.47. The study showed the heterogeneity of the course of postpsychotic depressions that occur after a manifest psychotic episode of adolescence. Differences in the structure of depression were identified, which are important for therapeutic tactics and prognosis of the disease.

Activity of enzymes of glutamate, energy and glutathione metabolism in the first juvenile depression with attenuated symptoms of schizophrenia

To reveal clinical and biological correlations in patients with attenuated symptoms of schizophrenia in the first juvenile depression, namely, the correlation between SOPS and HDRS-21 scores and the levels of activities of glutathione, glutamate and energy metabolism enzymes in the blood of patients. The study included 81 young men, aged 16-25 years, with the first depressive episode (ICD-10 items F32.1, F32.2, F32.38, F32.8), from which the groups with predominantly attenuated positive symptoms (group 1, n=36) and predominantly attenuated negative symptoms (group 2, n=24), and a group without attenuated schizophrenia symptoms (group 3, n=21) were selected. The control group consisted of 20 mentally healthy men aged 19-25 years. Psychometric methods (SOPS and HDRS-21) and psychopathological methods were used. Activities of cytochrome c oxidase (COX), glutamate dehydrogenase (GDH), glutathione reductase (GR), and glutathione S-transferase (GST) enzymes were determined spectrophotometrically in blood cells. When compared with the control group, activities of platelet GDH, GR, and GST (before and after treatment) were significantly reduced in groups 1, 2, 3 (Mann-Whitney U-test, p<0.0002, p<0.001 and p<0.0001, respectively); the activity of erythrocyte GST was reduced in group 1, and the activities of erythrocyte GR and GST were reduced in group 3 (p<0.05). In group 1, baseline COX (before treatment) was positively correlated with post-treatment SOPS-N scores (R=0.580, p=0.0003), while baseline erythrocyte GR was negatively correlated with post-treatment HDRS-21 scores (R=-0.591, p=0.0004). In group 2, baseline GDH levels were positively correlated with post-treatment scores on SOPS-P (R=0.425, p=0.0384), SOPS-N (R=0.500, p=0.0129), SOPS total (R=0.526, p=0.0083) and HDRS-21 (R=0.479, p=0.0180). The discovery of clinical and biological correlations in groups of patients with attenuated symptoms of schizophrenia in the structure of juvenile depression contributes to understanding the pathogenetic mechanisms of the formation of a high clinical risk of psychosis and contributes to the search for markers of the initial stages of schizophrenia.

Treatment aspects of youth depression with attenuated schizophrenic symptoms

To analyze main aspects of the treatment of patients with youth depression with attenuated schizophrenic symptoms (ASS). Two hundred and nineteen young in-patients (median age 19.6±2.4) with the first depressive episode (F32.1, F32.2, F32.38, F32.8.) and ASS were examined. The comparison group included 52 patients with depression without ASS with similar socio-demographic and age characteristics (average age 19.8±2.7 years). The efficacy of the therapy was assessed by the reduction of HDRS, SOPS and SANS scores. The Drug Compliance Scale was used to assess the compliance of patients. The average duration of in-patient treatment did not differ between groups (56.3 days in the main group and 54.2 days in the comparison group). The most effective therapy was found in the depression reduction on HDRS (67.9% and 76.6% respectively), the ASS reduction was 46.1% on the SOPS and 31.2% on the SANS. The combination of antidepressants (46.0±28.9 mg/day for fluoxetine equivalents) and antipsychotics (385.4±210.7 mg/day for chlorpromazine equivalents) were required to achieve this efficacy. The average duration of continued treatment was 7.4±9.6 months that was significantly lower (p<0.05) than in the comparison group (11.7±9.0 months), which was determined by the low compliance of such patients. The results show that a combination treatment and the implementation of measures, increasing the degree of compliance are required to increase the efficacy of treatment in patients with youth depression and ASS.

A Cross-sectional Study of the Patterns and Impact of Socio-demographic Factors in Anxious and Depressed Alcohol Dependent Patients

Introduction: Socio-demographic factors may play a pivotal role in anxious and depressed alcohol dependent patients. Identifying the patterns and impact of these factors may be important in the successful management of Alcohol Use Disorders (AUDs). Aim: To assess the patterns and impact of socio-demographic factors in anxious and depressed alcohol dependent patients. Materials and Methods: This cross-sectional study was conducted at Rama Medical College Hospital and Research Center Hapur, Uttar Pradesh, India, from August 2018 to January 2020. Patients with history of substance dependence, gross brain damage, severe medical complications, or evidence of drinking during the hospital stay were excluded. Severity of Alcohol Dependence Questionnaire (SADQ) was used to rate the extent of alcohol dependence and Hamilton Depression Rating Scale (HAM-D or HDRS) to rate depression. Sociodemographic data was recorded in each patient which included age, gender, background, education level, employment status, occupation, marital status, and family type. The severity of anxiety symptoms was measured on Hamilton Anxiety Rating Scale (HAM-A). Independent t-tests, Chi-square tests, oneway Analysis of Variance (ANOVA) and Pearson’s correlation analysis were used for statistical analysis. A p-value &lt;0.05 was considered statistically significant. Results: The total of 90 alcohol dependent patients with mean age of 37.6±9.3 years and mean HDRS score was 8.5±4.3. The overall prevalence of depression cohort was. Out of these 30 (33.3%) had mild and 6 (6.7%) had moderate depression, respectively. The mean Hamilton anxiety scale score was 18.6±5.2. Patients who had a lower Socio-economic Status (SES) (p-value= 0.049 and 0.004), were martially separated (p-value&lt;0.001 and 0.027), living in a nuclear family (p-value=0.005 and &lt;0.001) and were unemployed (p-value&lt;0.001 and p-value&lt;0.001) had significantly higher depression and anxiety scores, respectively. Conclusion: In anxious and depressed alcohol dependent patients, lower SES, martial separation, living as a single family and unemployment significantly influenced depression and anxiety

Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression

BackgroundRecent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role in the interaction between the central and peripheral inflammation. Here we aimed to investigate CP volume alterations in depression and their associations with inflammation. Methods51 depressed participants (HDRS score > 13) and 25 age- and sex-matched healthy controls (HCs) from the Wellcome Trust NIMA consortium were re-analysed for the study. All the participants underwent full peripheral cytokine profiling and simultaneous [11C]PK11195 PET/structural MRI imaging for measuring neuroinflammation and CP volume respectively. ResultsWe found a significantly greater CP volume in depressed subjects compared to HCs (t(76) = +2.17) that was positively correlated with [11C]PK11195 PET binding in the anterior cingulate cortex (r = 0.28, p = 0.02), prefrontal cortex (r = 0.24, p = 0.04), and insular cortex (r = 0.24, p = 0.04), but not with the peripheral inflammatory markers: CRP levels (r = 0.07, p = 0.53), IL-6 (r = -0.08, p = 0.61), and TNF-α (r = -0.06, p = 0.70). The CP volume correlated with the [11C]PK11195 PET binding in CP (r = 0.34, p = 0.005). Integration of transcriptomic data from the Allen Human Brain Atlas with the brain map depicting the correlations between CP volume and PET imaging found significant gene enrichment for several pathways involved in neuroinflammatory response. ConclusionThis result supports the hypothesis that changes in brain barriers may cause reduction in solute exchanges between blood and CSF, disturbing the brain homeostasis and ultimately contributing to inflammation in depression. Given that CP anomalies have been recently detected in other brain disorders, these results may not be specific to depression and might extend to other conditions with a peripheral inflammatory component.

Repeated, low-dose oral esketamine in patients with treatment-resistant depression: pilot study.

Intravenous infusion of ketamine can produce rapid and large symptom reduction in patients with treatment-resistant depression (TRD) but presents major obstacles to clinical applicability, especially in community settings. Oral esketamine may be a promising addition to our TRD treatment armamentarium. To explore the safety, tolerability and potential clinical effectiveness of a 3-week treatment with repeated, low-dose oral esketamine. Seven patients with chronic and severe TRD received 1.25 mg/kg generic oral esketamine daily, over 21 consecutive days. Scores on the Systematic Assessment for Treatment Emergent Events (SAFTEE), Community Assessment of Psychic Experiences (CAPE), Clinician Administered Dissociative States Scale (CADSS) and Hamilton Rating Scale for Depression (HRSD) instruments, as well as blood pressure and heart rate, were repeatedly assessed. Treatment with oral esketamine was well-tolerated. No serious side-effects occurred, and none of the participants discontinued treatment prematurely. Psychotomimetic effects were the most frequently reported adverse events. Mean HDRS score decreased by 16.5%, from 23.6 to 19.7. Three participants showed reductions in HDRS scores above the minimum clinically important difference (eight-point change), of whom two showed partial response. No participants showed full response or remission. These results strengthen the idea that oral esketamine is a safe and well-tolerated treatment for patients with chronic and severe TRD, but therapeutic effects were modest. Results were used to design a randomised controlled trial that is currently in progress.

Abstract 11284: Relationship of Inflammatory Cytokines and Six-Month Hospital Readmission in Heart Failure

Hospital readmission rates (HRR) in heart failure (HF) remains high. Psychosocial and clinical factors are linked with HF hospital readmission. Brain natriuretic peptide (BNP) is strongly associated with acute decompensated HF. However, the relationships of inflammatory cytokines (i.e. tumor necrosis factor-alpha [TNFα], interleukin-6 [IL6], interleukin-10 [IL10]) and HRR in HF are rarely evaluated. Objective: Evaluate the relationship of BNP, TNF-α, IL6 and IL10 with all-cause HRR within 6 months post-HF hospital discharge. Methods: A cross-sectional study was conducted in 104 HF patients: age 68.4 ± 11.7 years, left ventricular ejection fraction 37.9% ± 17%, Specific Activity Scale (SAS) I/II- 40 (39%), and III/IV- 64 (61%) , Charlson Comorbidity Index (CCI) score: 0-1= 24%, 2-3= 26%, and =/&gt;4= 50%. Hospital readmission rate is the number of hospital readmissions of all causes occurring 2 weeks to 6 months after HF hospital discharge. Initially, we analyzed bivariate correlations of HRR with sociodemographic, depression (via Hamilton depression rating scale [HDRS] score), functional status, comorbidities, BNP, and inflammatory cytokines (i.e. TNF-α, IL-6 and IL10). A multiple linear regression was performed, with important and significant psychosocial and clinical variables entered first as a block, followed by BNP and inflammatory cytokines. Results: Incidence of 6-month HRR: 0= 49 (47%); 1-2= 43 (41%); 3-6= 12 (12%). Bivariate correlation of HRR with: 1) sociodemographic: age- ( r = .21, p= .02), non-white- 37% ( r = .04, p= .36), living alone- 42% ( r = .17, p= .04); 2) functional status: SAS ( r = .28, p= .002); 3) CCI score ( r = .21, p= .02); 3) HDRS score ( r = .14, p= .07); 4) BNP: ( r = .14, p= .08); and 5) inflammatory cytokines: IL6 ( r = .41, p= &lt;.001, and IL10 ( r = .16, p= .06). Together, age, living alone, being non-white, HDRS score, SAS, CCI score, and IL6 accounted for 24% of the variance in HRR (p= .001). Specific variables contributing significant variance to HRR were: higher IL6- 34% (p= .001), and living alone= 14% (p= .10). Conclusion: Six-month HRR in HF remains high. Higher IL6 is associated with high HRR. After HF hospital discharge, patients with high inflammatory cytokines may require more frequent monitoring and intervention.

Baseline Working Memory Predicted Response to Low-Dose Ketamine Infusion in Patients with Treatment-Resistant Depression.

Pretreatment neurocognitive function may predict the treatment response to low-dose ketamine infusion in patients with treatment-resistant depression (TRD). However, the association between working memory function at baseline and the antidepressant efficacy of ketamine infusion remains unclear. A total of 71 patients with TRD were randomized to one of three treatment groups: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, or normal saline. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HDRS) at baseline and after treatment. Cognitive function was evaluated using working memory and go-no-go tasks at baseline. A generalized linear model with adjustments for demographic characteristics, treatment groups, and total HDRS scores at baseline revealed only a significant effect of working memory function (correct responses and omissions) on the changes in depressive symptoms measured by HDRS at baseline (F=12.862, p<0.05). Correlation analysis further showed a negative relationship (r=0.519, p=0.027) between pretreatment working memory function and changes in HDRS scores in the 0.5 mg/kg ketamine group. An inverse relationship between pretreatment working memory function and treatment response to ketamine infusion may confirm that low-dose ketamine infusion is beneficial and should be reserved for patients with TRD.

Long-term outcome in patients with myasthenia gravis: one decade longitudinal study.

Even treated, myasthenia gravis (MG) continues to represent a significant burden and might continuously affect patients' quality of life (QoL). The aim of our longitudinal study was to analyze QoL in a large cohort of MG patients after a 10-year follow-up period. This study comprised 78 MG patients (60% females, 50 ± 16years old at baseline, 70% AchR positive) who were retested after 10 years. Disease severity was evaluated by MGFA classification. QoL was assessed using SF-36 questionnaire and Myasthenia Gravis-specific Questionnaire (MGQ). Hamilton rating scales for depression and anxiety (HDRS and HARS), Multidimensional Scale of Perceived Social Support (MSPSS) and Acceptance of Illness Scale (AIS) were also used. Similar percentage of patients was in remission at both time points (42% and 45%). However, at baseline all patients were treated, while 32% were treatment-free at follow-up. SF-36, MGQ, MSPSS and AIS scores were similar at baseline and retest. Mean HDRS and HARS scores worsened during time (p < 0.05), although percentage of patients with depression and anxiety did not change significantly. Significant predictors of worse SF-36 score at retest were depression (β = -0.45, p < 0.01), poor disease acceptance (β = -0.44, p < 0.01) and older age (β = -0.30, p < 0.01). Significant predictors of worse MGQ score at retest were poor disease acceptance (β = -0.40, p < 0.01), retirement (β = -0.36, p < 0.01), lower education (β = 0.25, p < 0.01), and depression (β = -0.18, p < 0.05). Although after 10 years, a significant number of MG patients were in remission, their QoL was still reduced. Neurologists should be aware that patients' perception of poor QoL may persist even if MG is well treated from a physician's perspective.

Theta burst deep TMS for the treatment of major depression

Background: Intermittent theta burst stimulation (iTBS) is a promising transcranial magnetic stimulation (TMS) protocol that can induce neuroplastic changes in short stimulation time and was FDA-cleared recently for MDD. Deep TMS (dTMS) enables activation of deeper and broader brain volume, and with high frequency (HF) protocol was found to be highly effective in MDD. This study investigates dTMS with iTBS in MDD.Methods: 69 MDD patients received dTMS iTBS treatment at a clinical setting, composed of bursts of 3 pulses at 50 Hz, 5 Hz burst frequency, 2s on and 8 s off, 1800 pulses per session. The primary endpoint was the change from baseline in HDRS-21 scores after 4-weeks (20 treatment sessions). Secondary endpoints included response and remission rates based on HDRS-21 scores, after 4-weeks and 6-weeks (30 sessions), change in CGI-S score from baseline to 6-weeks and response and remission rates based on CGI-S scores at the 6-week visit.Results: The treatment was well-tolerated with no adverse events. The mean HDRS-21 change from baseline to week 4 was -9.82 (p<0.0001), and to week 6 was -11.91 (p<0.0001). Response and remission rates based on HDRS-21 after 4 weeks were 51.5% and 52.9%, respectively, and after 6 weeks (were 81.4% and 76.3%, respectively. The mean CGI-S change from baseline to week 6 was -2.91 (p<0.0001). Response and remission rates after 6 weeks based on CGI-S were 79.3% and 67.2%, respectively.Conclusions: Deep TMS iTBS was found to be a safe and highly effective treatment alternative for major depression.Conflicts of Interests: Dr. Roth and Dr. Zangen are key inventors of deep TMS technology and have financial interest in BrainsWay. Dr. Tendler serves as the chief medical officer of and has a financial interest in BrainsWay, and he has ownership interest in Advanced Mental Health Care, Inc. Dr. Pell and Dr. Zibman are BrainsWay employees.Funding: This work was supported by BrainsWay Ltd. Background: Intermittent theta burst stimulation (iTBS) is a promising transcranial magnetic stimulation (TMS) protocol that can induce neuroplastic changes in short stimulation time and was FDA-cleared recently for MDD. Deep TMS (dTMS) enables activation of deeper and broader brain volume, and with high frequency (HF) protocol was found to be highly effective in MDD. This study investigates dTMS with iTBS in MDD. Methods: 69 MDD patients received dTMS iTBS treatment at a clinical setting, composed of bursts of 3 pulses at 50 Hz, 5 Hz burst frequency, 2s on and 8 s off, 1800 pulses per session. The primary endpoint was the change from baseline in HDRS-21 scores after 4-weeks (20 treatment sessions). Secondary endpoints included response and remission rates based on HDRS-21 scores, after 4-weeks and 6-weeks (30 sessions), change in CGI-S score from baseline to 6-weeks and response and remission rates based on CGI-S scores at the 6-week visit. Results: The treatment was well-tolerated with no adverse events. The mean HDRS-21 change from baseline to week 4 was -9.82 (p<0.0001), and to week 6 was -11.91 (p<0.0001). Response and remission rates based on HDRS-21 after 4 weeks were 51.5% and 52.9%, respectively, and after 6 weeks (were 81.4% and 76.3%, respectively. The mean CGI-S change from baseline to week 6 was -2.91 (p<0.0001). Response and remission rates after 6 weeks based on CGI-S were 79.3% and 67.2%, respectively. Conclusions: Deep TMS iTBS was found to be a safe and highly effective treatment alternative for major depression. Conflicts of Interests: Dr. Roth and Dr. Zangen are key inventors of deep TMS technology and have financial interest in BrainsWay. Dr. Tendler serves as the chief medical officer of and has a financial interest in BrainsWay, and he has ownership interest in Advanced Mental Health Care, Inc. Dr. Pell and Dr. Zibman are BrainsWay employees. Funding: This work was supported by BrainsWay Ltd.

An open label prospective clinical trial assessing the role of individualized homoeopathic medicine in management of adolescent depression

Background: “Depression–Let’s talk” was the slogan for World Health Day 2017. Depression is an extremely common illness which contributes to significant disease burden at national and global levels, especially of the adolescent age group. Objectives: To ascertain the role of homoeopathic medicines in the management of moderate depression in adolescent age group. Material and Methods: 44 patients were enrolled. An open observational clinical trial was conducted at Out Patient Department of National Institute of Homoeopathy, Kolkata. HDRS-17 and PHQ-9 Score level was recorded at baseline, at 3 months and after 6 months of treatment for assessing the primary and secondary outcomes respectively. Medicines were prescribed on the basis of strict homoeopathic principles. Result: 12 patients dropped-out, 32 patients completed the trial. Protocol–compliant sample (n=32) was analyzed at the end. HDRS-17 Score Baseline Vs HDRS-17 Score at 3 months Vs HDRS-17 Score at 6 months: Mean was reduced from 15.5 (SD 3.464) to 8.81 (SD 2.78), to 8.71 (SD 3.87) 95% CI 1.29 to 1.02 to 1.42, P

Neuron-specific enolase during the therapy in patients with alcohol use disorder and mood disorders

IntroductionStudies of the pathophysiology of mental disorders indicate the involvement of neurobiological processes, including the release of neurospecific proteins in biological substances.ObjectivesThe purpose of this study was to research the level of neuron-specific enolase in patients with alcohol use disorder and mood disorders during the therapy.MethodsThe studied groups included patients with alcohol use disorder (AUD, F10.2, ICD-10; n=41), patients with mood disorders (MD, F32, F33, ICD-10; n=39), patients with co-morbidity of AUD and MD (n=31) and 20 healthy controls. Severity of depressive symptoms was assessed with HDRS-17 and CGI-S scales. The concentration of NSE were measured in serum by enzyme immunoassay. Рarticipants of the study were examined with clinical scales and laboratory analysis at baseline and on the 28th day of treatment. For statistical analysis we used the SPSS software.ResultsThe results of the study showed that all patients are characterized by an increased level of NSE (p&gt;0.005 compared with control). Patients with AUD characterized by changes in the concentration of NSE during therapy (p&gt;0.005 compared with patients after therapy). In patients with MD revealed correlation between the level of NSE on the 28th day of antidepressive therapy and the HDRS-17 score before treatment (r=0,421; p=0,018). In patients with co-morbidity correlation between the level of NSE and the CGI-S score before therapy was found (r=-0,537; p=0,001).ConclusionsThe revealed correlations indicate the relationship between the severity of depressive symptoms and the level of NSE. Disclosure statement: This study was supported by the Russian Science Foundation, grant No. 19-15-00023.Conflict of interestDisclosure statement: This study was supported by the Russian Science Foundation, grant No. 19-15-00023.

Impact of residual thymic symptoms in quality of life in bipolar patients in euthymia

IntroductionSeveral studies have shown that residual mood symptoms affect the psychosocial functioning of patients with bipolar disorder (BD) in euthymia.ObjectivesTo evaluate specific areas of functioning in this population and to explore the relationship with residual mood symptoms.MethodsThis is a descriptive and analytical cross-sectional study including patients with BD (DSM V) in euthymia followed on ambulatory basis to the Mood Disorders Unit of the Psychiatry A Department at Hedi Chaker Hospital in Sfax between January and April 2019. Patients were considered euthymic if they scored below 7 on the Young Mania Assessment Scale (YMRS) and under 8 on the Hamilton Depression scale (HDRS-17). Residual manic and depressive mood symptoms were assessed using YMRS and HDRS-17. The Short Function Evaluation Test (FAST) was used to evaluate the overall and specific functionning domains.The alteration of the domain-specific functioning is defined by the following thresholds: autonomy&gt;1, professional functioning&gt;1, cognitive functioning&gt;2, financial problems&gt;1, interpersonal relations&gt;3 and leisure time&gt;3.ResultsWe recruited 62 patients with a mean age of 45.65 years (SD = 13.3) and a sex ratio 1.13.The medians of YMRS and HDRS scores were respectively 2[0-5] and 2[0-7]. Global functionning impairment was observed in 85.5% of patients. Marked impairment of professional and cognitive functioning was observed in 98.4% and 77.4%, respectively. Alteration of the relational sphere was significantly more frequent in patients with residual depressive symptoms (p=0.009); impairment of autonomy was significantly more frequent in subjects with manic residual symptoms (p=0.005).ConclusionsResidual symptoms should be considered as specific targets of treatment to improve functioning.

Baseline EEG-correlates of responders/non-responders to combined antidepressive treatment including transcranial magnetic stimulation

IntroductionUse of combined antidepressive treatment included high-frequency rhythmic transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is one of the ways for overcoming of pharmaco-resistance in depressive patients.ObjectivesThe aim of the study was the search for possible EEG predictors of antidepressive effects of rTMS of the left DLPFC in combined treatment of depression.Methods30 female in-patients (F31.3, F33.0, F33.1, by ICD-10; 20-50 years, mean age 36.9±10.3) with pharmaco-resistant depression were enrolled in the study. Treatment included antidepressants (mainly SSRI) and a 3-week course of rTMS (20 Hz) of the left DLPFC. Correlations between pre-treatment EEG spectral power values, and post-treatment quantitative clinical assessments of patients were analyzed. Responders/non-responders were determined by standard criteria of 50% decrease in HDRS-17 scale total scores after treatment course.ResultsResponders (23 out of 30) revealed significant (p&lt;0.05) negative correlations between post-treatment HDRS-17 scores and pre-treatment EEG spectral power in theta-2 (6-8 Hz) and alpha-1 (8-9 Hz) frequency sub-bands in the parietal-occipital-posterior temporal leads. Non-responders (7 out of 30) showed negative correlations between the post-treatment HDRS-17 scores and pre-treatment theta-2 EEG spectral power in the frontal-central-temporal regions of the right hemisphere.ConclusionsEven brief course of rTMS of the left DLPFC enhances the action of antidepressants, and allows overcoming partially the pharmaco-resistance in depressive patients. Baseline values of theta-2 and alpha-1 EEG spectral power may serve as possible predictors of the effects of combined antidepressive therapy including rTMS. The study supported by RBRF grant No.18-01-00029a.DisclosureNo significant relationships.

Impact of gender, depression severity and type of depressive episode on efficacy and safety of escitalopram: an observational study on major depressive disorder patients in southern India

BackgroundAntidepressant response is a complex trait influenced by clinical, demographic and genetic factors.ObjectivesTo explore the influences of baseline depression severity, gender and type of depressive episode on efficacy and safety of escitalopram (10–20 mg/day) in South Indian patients with major depressive disorder (MDD).MethodsThe study was conducted on 18–65-year-old patients (n = 151) suffering from a first or recurrent episode of MDD with a 17-item Hamilton Depression Rating Scale (HDRS-17) score of ≥ 18 at baseline. Efficacy assessments were done using HDRS-17, Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression (CGI) at baseline and weeks 4, 8 and 12. Patients were monitored for adverse drug reactions (ADRs). Clinical outcomes were compared among various groups based on gender, type of depressive episode (first or recurrent episode) and baseline HDRS-17 scores (moderate depression—score between 17 and 23; severe depression—score ≥ 24).ResultsAmong the 148 subjects who completed the 12-week study, 43.9% and 42.6% achieved response and remission, respectively. The decline in HDRS-17 and MADRS scores from baseline was significant (p value < 0.05) at all follow-up visits and a similar pattern was seen with CGI. Efficacy outcomes were better in the moderate baseline depression group compared with severe depression. There were no associations of efficacy with gender and type of depressive episode. A total of 247 adverse drug reactions (ADR) were reported and 119 (80.41%) subjects experienced at least one ADR during the study period. No serious ADR was reported. Male patients experienced more ADRs compared with females. The safety profile of escitalopram was similar across various groups based on baseline depression severity and type of depressive episode.ConclusionThe study revealed that escitalopram is efficacious in south Indian MDD patients with a favourable safety profile. The efficacy was influenced by baseline depression severity whereas more ADRs were reported by male patients.

Depressive symptoms in involuntary hospitalized patients in Cyprus: Socio-demographic and psychopathological characteristics.

Τhe severity and variation of depressive symptoms (DS), among psychotic individuals under involuntary hospitalization is unclear. We investigated the socio-demographic and clinical characteristics of psychotic adults with DS involuntarily hospitalized for compulsory treatment in Cyprus. We also evaluated the psychometric properties (internal consistency, known-group and discriminant validity) of the HDRS-17 and HAM-A for the assessment of depressive and anxiety symptoms, respectively. A descriptive correlational study with cross-sectional comparisons was applied. Data on demographics, cognitive functioning (MoCA scale), depressive (HDRS-17 scale), anxiety (HAM-A scale) and psychotic (PANSS scale) symptoms were collected (December 2016 -February 2018). Following informed consent, the sample included 406 patients. Among them, 21 males and 23 females reported DS (HDRS-17 total score ≥8). The latter were mainly Greek-Cypriots (61.4%), 45-65 years old (38.6%), single (77.3%), unemployed (72.7%), mainly admitted due to aggressiveness towards others (47.7%), most frequently diagnosed with a bipolar disorder (59.1%). The mean score (M) in the HDRS-17 was 30.72 (scale range: 8-50; Standard Deviation [SD]: 10.42). The highest mean score (M) per item was in the variables "Suicide behavior"'(M:3.09; SD:1.09) and "Depressive mood" (M=2.95; SD=1.07). The DS group (HDRS-17 score≥8) reported higher PANSS positive symptoms subscale score (t-test, p=0.003) and HAM-A total score (t-test, p=0.05) compared to the non-DS group (HDRS-17 score<8). In multivariable logistic regression analysis only female sex [OR (95%CI) = 3.28 (1.33.-8.04), p=0.01)] and a mood disorder diagnosis [OR95% CI: 15.22(4.13.-56.14), p<0.0001)] retained a statistically significant association with DS. Cronbach' s alpha was 0.827 for the HDRS, and 0.763 for the HAM-A. The present findings partially support the known-group validity of the HDRS-17 and the ΗΑΜ-Α, and the discriminant validity of the HDRS-17 in psychotic patients under involuntary hospitalization. Additionally, the most frequent diagnosis in the DS group was a bipolar disorder, and the most frequent admission cause was aggressiveness towards others; it is possible that the majority of the DS group participants were patients with a bipolar disorder in episodes with mixed features, presenting simultaneously depressive symptoms and aggressiveness. Further studies on relapse prevention regarding this clinical group are proposed, as well as studies on specificity and sensitivity of the HDRS-17 and HAM-A.

A Bio-Psychosocial Framework for Chronic Daily Headaches: A Mixed Methods Study.

Chronic daily headaches (CDH) are primarily understood from a psychophysiological formulation. A broad biopsychosocial understanding, where there is equal importance given to biological, psychological and socio-cultural factors, is underexplored in headache. Socio-cultural factors, such as gender, socio-economic factors can perpetuate and worsen the condition. For an effective and sustainable intervention, these factors need to be considered. The current study aims to explore and develop a biopsychosocial framework for headache disorders. A convergent parallel mixed methods design was used and participants were recruited from a tertiary referral care hospital, Bengaluru, India. Headache Assessment Sheet, GAD 7, HDRS, PSS and B COPE were used in the quantitative phase. The data was analysed using r software. Qualitative phase of the study, in depth interview guide was used and data analysed thematically. Quantitative phase, 38 participants were recruited. The average age, was 38.02 (±10.17), majority of the participants being females 31 (81.58%). The mean duration of illness was 8.63 (±4.73) years. The anxiety scores positively correlated with pain intensity (r = 0.50 at P ≤ .001) and the median anxiety scores varied with photophobia (P ≤ .03). The anxiety scores correlated with PSS (r = 0.428 at P ≤ .007) and HDRS (r = 0.428 at P ≤ .007) scores. Gender variations in coping were seen, avoidant coping having higher median scores in women. (P ≤ .08). In qualitative phase of the study, six participants were recruited. Three main themes emerged from the qualitative phase of the study: headache - an illness, headache factors and the impact. Chronic daily headaches are influenced by biological, psychological, environmental and socio-cultural factors. A bio-psychosocial framework will help to understand and develop targeted interventions.

Monitoring Changes in Depression Severity Using Wearable and Mobile Sensors.

Background: While preliminary evidence suggests that sensors may be employed to detect presence of low mood it is still unclear whether they can be leveraged for measuring depression symptom severity. This study evaluates the feasibility and performance of assessing depressive symptom severity by using behavioral and physiological features obtained from wristband and smartphone sensors.Method: Participants were thirty-one individuals with Major Depressive Disorder (MDD). The protocol included 8 weeks of behavioral and physiological monitoring through smartphone and wristband sensors and six in-person clinical interviews during which depression was assessed with the 17-item Hamilton Depression Rating Scale (HDRS-17).Results: Participants wore the right and left wrist sensors 92 and 94% of the time respectively. Three machine-learning models estimating depressive symptom severity were developed–one combining features from smartphone and wearable sensors, one including only features from the smartphones, and one including features from wrist sensors–and evaluated in two different scenarios. Correlations between the models' estimate of HDRS scores and clinician-rated HDRS ranged from moderate to high (0.46 [CI: 0.42, 0.74] to 0.7 [CI: 0.66, 0.74]) and had moderate accuracy with Mean Absolute Error ranging between 3.88 ± 0.18 and 4.74 ± 1.24. The time-split scenario of the model including only features from the smartphones performed the best. The ten most predictive features in the model combining physiological and mobile features were related to mobile phone engagement, activity level, skin conductance, and heart rate variability.Conclusion: Monitoring of MDD patients through smartphones and wrist sensors following a clinician-rated HDRS assessment is feasible and may provide an estimate of changes in depressive symptom severity. Future studies should further examine the best features to estimate depressive symptoms and strategies to further enhance accuracy.

Resveratrol Adjunct Therapy for Negative Symptoms in Patients With Stable Schizophrenia: A Double-Blind, Randomized Placebo-Controlled Trial.

BackgroundPatients with schizophrenia can generally manifest a broad variety of primary negative symptoms. The current study aimed to assess the efficacy and tolerability of resveratrol add-on therapy in the treatment of negative symptoms in patients with stable schizophrenia.MethodsIn a randomized, double-blind, and placebo-controlled setting, schizophrenia patients were assigned to receive either 200 mg/d resveratrol or matched placebo in addition to a stable dose of risperidone for 8 weeks. Patients were assessed using the positive and negative syndrome scale, the extrapyramidal symptom rating scale, and Hamilton Depression Rating Scale over the trial period. The primary outcome was considered as the change in positive and negative subscale score from baseline to week 8 between the treatment arms.ResultsA total 52 patients completed the trial (26 in each arm). Baseline characteristics of both groups were statistically similar (P > .05). Despite the statistically similar behavior of positive symptoms between the groups across time (Greenhouse-Geisser corrected: F = 1.76, df = 1.88, P = .180), the resveratrol group demonstrated greater improvement in negative, general psychopathology, and total scores (Greenhouse-Geisser corrected: F = 12.25, df = 2.04, P < .001; F = 5.42, df = 1.56, P = .011; F = 7.64, df = 1.48, P = .003). HDRS scores and its changes, ESRS score, and frequency of other complications were not significantly different between resveratrol and placebo groups.ConclusionAdding resveratrol to risperidone can exhibit remarkable efficacy and safety in terms of management of schizophrenia-related negative symptoms.