Montgomery-Asberg Depression Rating Scale Research Articles

Mental disorders during the pandemic of a new coronavirus infection: clinical features

Objective: to study the clinical features of mental disorders during the COVID-19 epidemic in those who turned to psychiatrist for the first time, as well as in patients with already diagnosed mental illness.Material and methods. We examined 100 patients who turned to psychiatrist due to deterioration of their mental state on the background of a pandemic. Of these, 50 were new cases (1st group; 23 women and 27 men, mean age 34 years) and 50 were cases with previously diagnosed mental disorders (2nd group; 25 women and 25 men, mean age 37 years). 80% of patients of the 1st group, 54% of patients of the 2nd group had coronavirus infection. Anxiety and depressive disorders prevailed in the 1st group, endogenous diseases prevailed in the 2nd group: bipolar affective disorder, recurrent depressive disorder, schizophrenia. The study was conducted by the clinical method using a specially designed map; the severity of depression was assessed using the Montgomery-Asberg Depression Rating Scale, and the severity of anxiety was assessed using the Hamilton Anxiety Rating Scale.Results. The clinical picture of primary and recurrent depressive episodes after infection was characterized by the presence of motor and associative retardation, severe apathy, hypersomnia and lack of sleep, fatigue, increased appetite, and complaints of impaired attention and memory. Depression in SARS-CoV-2 survivors was characterized by anxiety, anhedonia, irritability, somatic complaints, and hypochondriacal inclusions. Anxiety symptoms in those who were not ill included severe anxiety, reaching agitation, disturbed sleep with frequent awakenings, irritability, somatic complaints, and hypochondriacal fixation on one’s condition. In recovering patients, anxiety was accompanied by control of somatic functions, cognitive impairments, and fear of retention or even intensification.Conclusion. The results obtained indicate the existing differences between the mental disorders that first appeared and worsened during the pandemic, as well as the differences in the structure of the depressive and anxiety syndrome depending on the presence or absence of coronavirus infection.

Beneficial effect of digoxin-specific Fab fragments in bipolar disorder- a preliminary study

A vast amount of experimental data supports the notion that Na+, K+-ATPase and endogenous cardiac steroids (ECS) such as digoxin and ouabain are involved in bipolar disorders. The aim of the study was to examine the possible beneficial effect of Digoxin-specific antibody Fab fragments Digibind, in bipolar disorder (BD) patients. In a pilot, open-label study without a control group, BD inpatient subjects received a single dose of Digibind, injected intravenously. During the 72 hrs following the intervention. the response to Digibind was measured using the Montgomery-Asberg Depression Rating Scale (MADRS). A total 6 patients with a moderate to severe bipolar depressive episode (MADRS 30.3, 24–38) participated in the study. We found a significant clinical improvement at all time points after Digibind administration, manifested by a maximal decrease in the MADRS score of 8.3 points at 24 hrs, followed by a gradual rebound to baseline scores. No control group was included, treatment was open-label, and only 6 patients were studied. This preliminary study showed that a one-time injection of Digibind resulted in a transient significant beneficial effect on depression symptoms in BD patients.

Long term efficacy of psilocybin in patients with cancer and major depressive disorder (MDD).

12021 Background: Up to 25% of people living with cancer have depression. Existing psychological interventions have limited efficacy in treating depression. Psilocybin, a 5-hydroytrptamintergic psychedelic, coupled with group therapy is safe and effective in ameliorating symptoms of depression (Agrawal et al, ASCO 2022). Response to psilocybin treatment was observed in 83.3% of patients at 8 weeks, and 50% of patients showed full remission of depressive symptoms. This study evaluates the efficacy of psilocybin-assisted group therapy in relieving depression in cancer patients over 18 months. Methods: Adults with curable or metastatic cancer and MDD (according to DSM-5) underwent psychological assessments at baseline. They were treated with single-dose psilocybin 25 mg administered simultaneously in group cohorts of 3-4, supported with group and individual psychological therapy, and evaluated at 8 weeks and 18 months. Primary objectives were long-term effectiveness on depression and anxiety severity (as measured by change in Montgomery Asberg Depression Rating Scale [MADRS] and Hamilton Depression Rating Scale [HAM-A] scores by independent rater assessments) as well as clinical response (≥50% decrease in MADRS total score from baseline to 18 months) and remission (defined as patients with a MADRS total score ≤10 at 18 months). Results: Of 30 patients enrolled in the parent study, 2 died and 4 were lost to follow-up. Clinical response was demonstrated in 18/28 patients (64.2%) from baseline to 18 months follow-up (see table); 16/28 patients (57.1%) demonstrated remission of depression at 18 months. In 24 evaluable patients, continued reduction in mean depression severity scores was also demonstrated from baseline to week 8 (MADRS by 20.6 points [95% CI 23.2, 18.0, p < 0.001] and HAMA-A by 16.7 points [95% CI 19.7, 13.7, p < 0.001]) and from baseline to 18 months (MADRS by 16.7 points [95% CI 20.4, 12.9, p < 0.001] and HAMA-A by 14.4 points [95% CI 17.3, 11.4, p < 0.001]). Conclusions: Long-term follow-up suggests continued robust clinical response and remission from depression with a single dose of psilocybin and simultaneous psychological support in patients with cancer and MDD. These findings indicate psilocybin may play a role in treatment of depression in cancer patients, and further investigations are ongoing. [Table: see text]

Validation and psychometric properties of the Arabic version of Hamilton Depression Rating Scale 7 items (HAMD-7) among non-clinical and clinical samples of Lebanese adults.

The Hamilton Depression Rating Scale (HDRS or HAMD) is widely used scale for depression assessment. A shortened version of the HDRS, composed of 7 items, was implemented. The latter is timesaving compared to the original version, while still providing similar precision. Our objective in this study was to assess the psychometric properties of the Arabic HAMD-7 scale among non-clinical and clinical samples of Lebanese adults. In study 1, 443 Lebanese citizens enrolled in this cross-sectional study (June-September 2021). The total sample in study 1 was divided into two subsamples to conduct the exploratory-to-confirmatory factor analysis (EFA-to-CFA). Another cross-sectional study was conducted in September 2022 on another sample of Lebanese patients (independent from the sample of study 1) and included 150 patients attending two psychology clinics. The Montgomery-Asberg Depression Rating Scale (MADRS), Lebanese Depression Scale (LDS), Hamilton Anxiety Scale (HAM-A) and Lebanese Anxiety Scale (LAS) were used to assess the validity of the HAMD-7 scale. The results of the EFA (subsample 1; study 1) showed that the HAM-D-7 items converged into a one-factor solution (McDonald's ω = .78). The CFA (subsample 2; study 1) confirmed the one-factor solution obtained in the EFA (ω = .79). CFA indicated that fit of the one-factor model of the HAM-D-7 was acceptable: χ2/df = 27.88/14 = 1.99, RMSEA = .066 (90% CI = .028, .102), SRMR = .043, CFI = .960, TLI = .939. All indices suggested that configural, metric, and scalar invariance was supported across gender. The HAMD-7 scale score positively correlated with the MADRS (r = 0.809; p<0.001), LDS (r = 0.872; p<0.001), HAM-A (r = 0.645; p<0.001) and LAS (r = 0.651; p<0.001) scales scores. The optimal cutoff score between healthy individuals and depressive patients for the HAMD-7 was at a value = 5.50 (Se = 82.8% and Sp = 62.4%). The positive and negative predicted values for the HAMD-7 were 25.1% and 96.0%, respectively. The positive and negative likelihood ratios were 2.20 and 0.28 respectively. No significant difference was found between the non-clinical total sample (study 1) and the clinical sample (study 2) in terms of HAM-D-7 scores (5.24 ± 4.43 vs 4.54 ± 5.06; t(589) = 1.609; p = .108). Psychometric properties of the Arabic HAMD-7 scale are satisfactory, warranting its use clinically and in research. This scale seems highly efficient for ruling out depression; however, those with positive scores need a referral to a mental health professional for deeper evaluation. HAMD-7 might be self-administered by non-clinical subjects. Future studies are recommended to additionally confirm our results.

Reliability and validity of the telephone-based version of the Montgomery-Asberg depression rating scale for assessing depression in individuals with primary brain tumour

Purpose This study aimed to examine interrater reliability and construct validity of the Montgomery-Asberg Depression Rating Scale (MADRS) semi-structured interview for assessing depression in adults with a primary brain tumour. Materials and methods Fifty adults with a primary brain tumour (mean age = 45.86, SD = 12.48) reporting at least mild distress (Distress Thermometer [DT] ≥ 4) were recruited from a multidisciplinary brain tumour clinic and administered a telephone-based cognitive screener, MADRS, Depression Anxiety Stress Scales (DASS) depression subscale and Generalised Anxiety Disorder-7 (GAD-7). Audiotaped interviews were transcribed and then scored by two independent raters. Results Interrater reliability for the MADRS total score was excellent (ICC = 0.98) and ranged from good to excellent (ICC = 0.83–0.96) for MADRS items. The MADRS total score was significantly associated with the DT, DASS depression, and GAD-7 (r = 0.50–0.76, p < 0.001), thus providing evidence of construct validity. Individuals with poorer cognitive function reported higher levels of depression. Conclusions The findings provide psychometric support for the MADRS as a semi-structured interview for assessing depression after brain tumour. Further research investigating the sensitivity and specificity of the MADRS is recommended.

Right dorsolateral prefrontal cortex volumetric reduction is associated with antidepressant effect of low-dose ketamine infusion: A randomized, double-blind, midazolam-controlled PET-MRI clinical trial

BackgroundEvidence has shown a rapid antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression (TRD) and prominent suicidal ideation (SI). The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in the TRD pathomechanisms. ObjectiveWhether the structural and functional changes of the DLPFC, particularly Brodmann area 46, are associated with the antidepressant and antisuicidal effects of ketamine infusion among such patients is unknown. MethodsWe randomized 48 patients with TRD and SI into groups receiving a single infusion of 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. The Hamilton Depression Rating Scale and the Montgomery–Asberg Depression Rating Scale were used to assess symptoms. Positron emission tomography (PET)–magnetic resonance imaging was conducted prior to infusion and on Day 3 postinfusion. We performed longitudinal voxel-based morphometry (VBM) analysis to evaluate the gray matter (GM) volume changes of the DLPFC. The standardized uptake value ratio (SUVr) of 18F-fluorodeoxyglucose PET images was calculated using the SUV of the cerebellum as a reference region. ResultsThe VBM analysis revealed a small but significant volumetric reduction in the right DLPFC in the ketamine group compared with that in the midazolam group. A greater reduction in depressive symptoms was associated with a smaller decrease in right DLPFC volumes (p = 0.025). However, we found no SUVr changes of the DLPFC between baseline and post-Day 3 ketamine infusion. DiscussionThe optimal modulation of the right DLPFC GM volumes may play an essential role in the antidepressant neuromechanisms of low-dose ketamine.

Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression

Intravenous ketamine is posited to rapidly reverse depression by rapidly enhancing neuroplasticity. In human patients, we quantified gray matter microstructural changes on a rapid (24-h) timescale within key regions where neuroplasticity enhancements post-ketamine have been implicated in animal models. In this study, 98 unipolar depressed adults who failed at least one antidepressant medication were randomized 2:1 to a single infusion of intravenous ketamine (0.5 mg/kg) or vehicle (saline) and completed diffusion tensor imaging (DTI) assessments at pre-infusion baseline and 24-h post-infusion. DTI mean diffusivity (DTI-MD), a putative marker of microstructural neuroplasticity in gray matter, was calculated for 7 regions of interest (left and right BA10, amygdala, and hippocampus; and ventral Anterior Cingulate Cortex) and compared to clinical response measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR). Individual differences in DTI-MD change (greater decrease from baseline to 24-h post-infusion, indicative of more neuroplasticity enhancement) were associated with larger improvements in depression scores across several regions. In the left BA10 and left amygdala, these relationships were driven primarily by the ketamine group (group * DTI-MD interaction effects: p = 0.016–0.082). In the right BA10, these associations generalized to both infusion arms (p = 0.007). In the left and right hippocampus, on the MADRS only, interaction effects were observed in the opposite direction, such that DTI-MD change was inversely associated with depression change in the ketamine arm specifically (group * DTI-MD interaction effects: p = 0.032–0.06). The acute effects of ketamine on depression may be mediated, in part, by acute changes in neuroplasticity quantifiable with DTI.

Esketamine in treatment-resistant depression patients comorbid with substance-use disorder: A viewpoint on its safety and effectiveness in a subsample of patients from the REAL-ESK study

Esketamine, the S-enantiomer of ketamine, has recently emerged as a therapy for treatment-resistant depression (TRD), showing both rapid antidepressant action and good efficacy and high safety. It is also indicated for the acute short-term treatment of psychiatric emergency due to major depressive disorder (MDD) and for depressive symptoms in adults with MDD with acute suicidal thoughts/behavior. We here provide preliminary insights on esketamine nasal spray (ESK-NS) effectiveness and safety among patients with a substance use disorder (SUD) within the sample of patients with TRD collected for the observational, retrospective, multicentre REAL-ESK study. Twenty-six subjects were retrospectively selected according to the presence of a SUD in comorbidity. Subjects enrolled completed the three different follow-up phases (T0/baseline, T1/after one month, and T2/after three months) and there were no dropouts. A decrease in Montgomery-Asberg depression rating scale (MADRS) scores was recorded, thus highlighting the antidepressant efficacy of ESK-NS (MADRS decreased from T0 to T1, t = 6.533, df=23, p<0.001, and from T1 to T2, t = 2.029, df=20, p = 0.056). Considering tolerability and safety issues, one or more side effects were reported by 19/26 subjects (73%) after treatment administration. All reported side effects were time-dependent and did not cause significant sequelae; among them, dissociative symptoms (38%) and sedation (26%) were the most frequently reported. Finally, no cases of abuse or misuse of ESK-NS were reported. Despite study limitations related to the inherent nature of the study, a limited number of patients, and a short follow-up period, ESK-NS showed to be effective and safe in patients diagnosed with TRD comorbid with a SUD.

노년기 우울 증상 평가에서 주관적 척도와 객관적 척도 간 상관성 연구

Objective: The aim of this study was to investigate the correlation between subjective and objective depression rating scale for the elderly with depressive symptoms.&#x0D; Methods: Thirty three outpatients aged more than 55 with depressive symptoms were assessed with the Patient Health Questionnare-9 (PHQ-9) and the Montgomery-Asberg Depression Rating Scale (MADRS). Similar items from each scale were paired to investigate their correlations. The level of agreement between the PHQ-9 and the MADRS was also assessed for subjects by using discrepancy-score.&#x0D; Results: Correlation between total scores of the PHQ-9 and the MADRS was significant (r=0.85, p&lt;0.001). There were significant correlations between the paired items except for the item about volition. These results were the same in the group whose total education years are 7 or more. However, in the group whose total education years are 6 or less, there was no significant correlation between the paired items about sleep, concentration and volition.&#x0D; Conclusion: These results demonstrate that using the PHQ-9 in elderly patients is reliable and education level might be considered when interpreting the scale.

The course of insomnia symptoms during the acute treatment of major depressive disorder: A CAN-BIND-1 report

Despite considerable efforts to study the relationship between insomnia and depression, there is minimal research investigating whether insomnia symptoms change over time during a course of antidepressant pharmacotherapy. This study investigated the course of insomnia symptoms during the acute treatment of major depressive disorder (MDD) using a secondary analysis of data from MDD patients (N = 180) who were treated with open-label escitalopram (10–20 mg/day) for 8-weeks. Montgomery-Asberg Depression Rating Scale without sleep item (modified-MADRS) assessed depression and Self-reported Quick Inventory Depressive Scale (QIDS-SR) measured subjective sleep-onset, mid-nocturnal, and early-morning insomnia throughout 8-weeks of treatment. Pittsburgh Sleep Quality Index (PSQI) was used to assess subjective sleep quality, duration, onset latency, and efficiency throughout 8-weeks of treatment. Remission of depression was defined as modified-MADRS ≤10 at week-8. Mixed model repeated measures (MMRMs) were conducted with remission status as an independent variable and each sleep variable as a dependent variable. MMRMs demonstrated that remitters had significantly lower QIDS-SR sleep-onset and mid-nocturnal insomnia scores as well as a significantly lower PSQI sleep quality score than non-remitters throughout 8-weeks of treatment. Monitoring subjective sleep-onset and mid-nocturnal insomnia during the course of treatment with serotonergic antidepressants may be useful for predicting acute remission of depression.

Ghrelin Modifies the Impact of Life Stress on Suicidality in Patients With Acute Coronary Syndrome.

This study investigated associations of life stressors and serum ghrelin levels with suicidal ideation (SI), and evaluated the potential mediating effect of ghrelin on associations between life stressors and SI in patients with acute coronary syndrome (ACS). In total, 969 ACS patients recruited from a tertiary university hospital in Korea within 2 weeks of disease onset were evaluated in terms of life stressors (using the List of Threatening Events Questionnaire), serum ghrelin levels, and SI (using the "suicidal thoughts" item of the Montgomery-Asberg Depression Rating Scale). Covariates included sociodemographics, depression, vascular risk factors, and disease severity. After 1 year, 711 patients were re-evaluated in terms of SI; logistic regression was performed with adjustment for covariates. Life stressors were significantly associated with SI at baseline and follow-up. Serum ghrelin showed no such associations, but high levels thereof mediated associations of life stressors with SI; significant interaction terms were also observed after adjustment for covariates. By evaluating life stressors and serum ghrelin levels, clinical prediction of SI in the acute and chronic phases of ACS could be improved.

The Efficacy of Lumateperone in Patients With Bipolar Depression With Mixed Features.

Objective: A post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled outpatient study investigated efficacy of lumateperone 42 mg in patients with bipolar I or bipolar II disorder and experiencing a major depressive episode (MDE) stratified by the presence of mixed features.Methods: Adults (18-75 years) with bipolar I or bipolar II disorder experiencing an MDE, defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria, were randomized 1:1 to 6-week oral lumateperone 42 mg/d or placebo (conducted November 2017-March 2019). Montgomery-Asberg Depression Rating Scale (MADRS) total score, Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) total score, and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) were analyzed in patients (N = 376) categorized as having mixed features (Young Mania Rating Scale [YMRS] score ≥ 4 and ≤ 12, 41.5%) or not having mixed features (YMRS < 4, 58.5%) at baseline. Treatment-emergent adverse events (TEAEs) including mania/hypomania were assessed.Results: At day 43, lumateperone significantly improved MADRS and CGI-BP-S total scores change from baseline compared with placebo for patients with mixed features (MADRS least squares mean difference [LSMD] = -4.4, P < .01; CGI-BP-S LSMD = -0.7, P < .05) and without mixed features (MADRS LSMD = -4.2, P < .001, CGI-BP-S LSMD = -1.0, P < .001). Q-LES-Q-SF percent score significantly improved at day 43 with lumateperone vs placebo in patients with mixed features (LSMD = 5.9, P < .05), with numerical improvements in patients without mixed features (LSMD = 2.6, P = .27). TEAEs of mania/hypomania were rare.Conclusions: Lumateperone 42 mg significantly improved symptoms of depression and disease severity in patients with an MDE associated with bipolar I or bipolar II disorder, with or without mixed features.Trial Registration: ClinicalTrials.gov identifier: NCT03249376.

Structured physical exercise for bipolar depression: an open-label, proof-of concept study

BackgroundPhysical exercise (PE) is a recommended lifestyle intervention for different mental disorders and has shown specific positive therapeutic effects in unipolar depressive disorder. Considering the similar symptomatology of the depressive phase in patients with bipolar disorder (BD) and unipolar depressive disorder, it is reasonable to suggest that PE may also be beneficial for bipolar depression. However, there is an absence of studies evaluating the antidepressant effect of a structured PE intervention in BD.MethodsThis is an open-label, single-arm study trial. Fifteen patients with a diagnosis of BD Type I or Type II, presenting a depressive episode were included in the study. After physical and functional evaluation, patients participated in supervised training sessions with aerobics followed by strength exercises, three times per week, for 12 weeks (36 training sessions). Depressive and manic symptoms were assessed at baseline and 2, 4, 8, and 12 weeks. Additionally, quality of Life and functioning were assessed at baseline and 4, 8, and 12 weeks). Finally, we tested cardiorespiratory fitness, muscle strength and body composition at baseline and week-12.ResultsThe mean (± SD) Montgomery Asberg Depression Rating Scale (MADRS) score at baseline was 23.6 ± 8.3 points and after 12 weeks of PE the mean score was 10.2 ± 4.8 points. Nine patients (82%) presented an antidepressant response defined as a reduction of more than 50% of depressive symptoms at week 12 with five of those patients (45%) presenting criteria for full remission. A large and significant Cohen’s D Effect Size (pre-post) was verified for MADRS reduction [1.98 (95% Confidence interval = 0.88 to 3.08)]. We did not detect a significant change in manic symptoms, functioning, and quality of life during the 12-week follow-up. At week-12, all patients increased their muscular strength (one repetition maximal test − 1RM) and reduced the percentage of body fat (spectral bioelectrical impedance analysis).ConclusionsThis study, using rigorous criteria and a structured intervention, provides valid pilot data, showing the feasibility of a structured PE intervention for the treatment of depressive symptoms in BD, and suggesting a potential adjunctive antidepressant effect. Moreover, PE showed a positive impact on muscle strength and body composition. This should be further verified by randomized controlled studies.

Psychological features of patients with Takotsubo syndrome: cross-sectional study

Objective. We aimed to assess the psychological state and personality-adaptive potential in patients with Takotsubo syndrome (TS), and to use the results to construct a prognostic model for the risk of developing the disease.&#x0D; Materials and methods. A total of 38 patients with TS were examined 1014 days after the disease onset. The mean age of the men was 63.814.73 years, and the women, 33 (86.8%) years. The control group included 40 people; their average age was 66.610.4 years, of which 39 (97.5%) were women. Their psychological state and stress resistance were assessed using the following tests and questionnaires: G. Eysenck's personality questionnaire; the hardiness survey; the N.V. Kirsheva and N.V. Ryabchikov personality stress resistance self-test; the scale of perceived stress; the PSM-25 LemurTessierFillion psychological stress measure; the SpielbergerKhanin anxiety scale; the Hamilton Anxiety Scale; the Hospital Anxiety and Depression scale; the Beck Depression Scale; and the MontgomeryAsberg depression rating scale.&#x0D; Results. G. Eysenck's personality questionnaire showed that patients with TS had a higher level of neuroticism (14.63.7 and 11.44.1, respectively; p 0.01) and tendency to introversion (9.43.3 and 12.43.5, respectively; p 0.001) than the control group. According to the SpielbergerKhanin psychometric scale, reactive anxiety was higher in the TS group (46.49.1 and 37.011.4, respectively; p 0.0001), and there was also a tendency toward personal anxiety (45.17.3 and 41.811.1, respectively; p 0.05). For all three analyzed scales designed to assess internal anxiety, it was found that in patients with TS, this component of the psyche was more pronounced (HARS: 21.84.8 and 16.15.4, respectively; p 0.0001; HADS: 13.13.6 and 7.43.0, respectively; p 0.0001). Depression, ranging from mild to severe, was more common in patients with TS, according to all questionnaires (HADS: 100% and 40%, respectively; p 0.05; BDI: 73.7% and 27%, respectively; p 0.05; MADRS: 97.4% and 62.5%, respectively, p 0.05). According to the hardiness test, the TS group had low indicators of overall hardiness (71.418.0 and 82.619.7, respectively; p 0.05), involvement (32.59.1 and 36.88.9, respectively; p 0.05), and control (23.37.3 and 29.27.8, respectively; p 0.01) compared to the control group. Stress resistance was also significantly lower in patients with TS (38.96.4 and 34.17.3, respectively; p 0.001). Based on the data from the questionnaires and scales, using the classification tree method, an integral model for predicting the development of TS with a high predictive value (96%) was built.&#x0D; Conclusion. Anxiety and depressive disorders make a significant contribution to the development of TS. Personality traits like introversion, neuroticism, and increased susceptibility to stress with low stress resistance and hardiness also play a role. This suggests the need for timely diagnosis of psychological disorders and their correction in people with this personality type, especially postmenopausal women. Prompt intervention may help prevent or reduce the risk of developing the disease.

Targeting Slow Wave Sleep Deficiency in Late-Life Depression: A Case Series With Propofol

Slow wave sleep (SWS), characterized by large electroencephalographic oscillations, facilitates crucial physiologic processes that maintain synaptic plasticity and overall brain health. Deficiency in older adults is associated with depression and cognitive dysfunction, such that enhancing sleep slow waves has emerged as a promising target for novel therapies. Enhancement of SWS has been noted after infusions of propofol, a commonly used anesthetic that induces electroencephalographic patterns resembling non-rapid eye movement sleep. This paper 1) reviews the scientific premise underlying the hypothesis that sleep slow waves are a novel therapeutic target for improving cognitive and psychiatric outcomes in older adults, and 2) presents a case series of two patients with late-life depression who each received two propofol infusions. One participant, a 71-year-old woman, had a mean of 2.8 minutes of evening SWS prior to infusions (0.7% of total sleep time). SWS increased on the night after each infusion, to 12.5 minutes (5.3% of total sleep time) and 24 minutes (10.6% of total sleep time), respectively. Her depression symptoms improved, reflected by a reduction in her Montgomery-Asberg Depression Rating Scale (MADRS) score from 26 to 7. In contrast, the other participant, a 77-year-old man, exhibited no SWS at baseline and only modest enhancement after the second infusion (3 minutes, 1.3% of total sleep time). His MADRS score increased from 13 to 19, indicating a lack of improvement in his depression. These cases provide proof-of-concept that propofol can enhance SWS and improve depression for some individuals, motivating an ongoing clinical trial (ClinicalTrials.gov NCT04680910).

Effectiveness of Repetitive Transcranial Magnetic Stimulation (rTMS) Add-On Therapy to a Standard Treatment in Individuals with Multiple Sclerosis and Concomitant Symptoms of Depression-Results from a Randomized Clinical Trial and Pilot Study.

Compared to the general population, persons with multiple sclerosis (MS) are at increased risk of suffering from major depressive disorder (MDD). Repetitive Transcranial Magnetic Stimulation (rTMS) was used successfully to treat individuals with MDD. Here, we conducted a randomized clinical trial and pilot study, and tested the effectiveness of rTMS adjuvant to a standard pharmacological treatment among persons with MS, compared to a sham condition. A total of 40 persons with MS (mean age: 32 years; 42.5% females; median EDSS score: 4) and with moderate to severe symptoms of depression were randomly assigned to the rTMS or to the rTMS sham condition, always as adjuvant intervention to the standard treatment with sertraline, a selective serotonin reuptake inhibitor (SSRI). rTMS consisted of 10 sessions each of 37.5 min; the sham condition was identical to the active condition except for the absence of rTMS stimuli. At the beginning and two weeks after the end of the study, participants reported on their fatigue, while experts rated the severity of participants' depressive symptoms (Montgomery-Asberg Depression Rating Scale; MADRS), cognitive performance (Montreal Cognitive Assessment; MoCA), and degree of disability (Expanded Disability Status Scale; EDSS). Data were analyzed per intent-to-treat. Scores for depression, fatigue, and EDSS declined significantly over time (large effect sizes), but more so in the rTMS condition than in the sham condition (large effect sizes for the time by group-interactions). Compared to the sham condition, scores for depression were significantly lower in the rTMS condition. Scores for cognition improved over time in both study conditions (large effect size). Compared to a sham condition, adjuvant rTMS to a standard pharmacological treatment ameliorated typical MS-related symptoms (depression; fatigue; EDSS scores). Results from this pilot study suggested that rTMS might be routinely applied in persons with MS displaying symptoms of depression and fatigue.

Safety and effectiveness of vortioxetine for major depressive disorder: Real-world evidence from a population-based study in South Korea

A post-marketing surveillance study was conducted to assess the real-world safety and effectiveness of vortioxetine for the treatment of major depressive disorder (MDD) in South Korea. Adult patients aged 19-94 years receiving vortioxetine for MDD at 72 hospitals and clinics in South Korea between 19th August 2014 and 18th August 2020 were included. Patients were followed for up to 24±2 weeks, at up to three visits. Adverse events (AEs) and effectiveness, assessed by both clinician and patient-reported measures, were analyzed. A total of 3,263 patients (mean age: 51.28 years) were included in the safety set; 1,095 were aged ≥65 years. The majority of the safety set (61.97%) were female. The overall rate of any AEs and serious AEs were 17.13 and 1.56%, respectively. The majority of AEs were mild (88.32%). The rates of AEs did not differ statistically by age (≥65 years: 16.89% [185/1,095] versus <65 years: 17.25% [374/2,168)], p=0.7989), sex (male: 15.95% [198/1,241] versus female: 17.85% [361/2,022], p=0.1623), or liver impairment (with liver impairment: 20.90% [14/67] versus without liver impairment: 17.05% [545/3,196], p=0.4087). Effectiveness was assessed in 1,918 patients. By 24±2 weeks, there were significant clinical improvements from baseline, assessed by change in Montgomery-Asberg Depression Rating Scale total score (mean±standard deviation [SD]: -10.49±9.42 points, p <0.0001), the proportion of patients with improved symptoms using the Clinical Global Impression - Improvement scores (79.29%), and in both patient-reported measures, with a significant improvement in the Korean Version of the Perceived Deficits Questionnaire-Depression (mean±SD: -6.06±13.23, p <0.0001) and Digit Symbol Substitution Test (mean±SD: 4.83±9.81, p <0.0001) total scores from baseline. Similar to the safety profiles, the proportions of patients with improved symptoms compared with baseline using the Clinical Global Impression - Improvement scores did not differ by age (≥65 years: 82.09% versus <65 years: 78.32%, p=0.0511), sex (male: 77.45% versus female: 81.01%, p=0.0587), or liver impairment (with liver impairment: 67.57% versus without liver impairment: 79.85%, p=0.0663). Vortioxetine appears to be well-tolerated and effective for treating MDD patients in the real-world setting in South Korea, irrespective of age, sex, and liver impairment, reflecting the known profile of vortioxetine based on studies worldwide.

The Chinese Version of Oxford Depression Questionnaire: A Validation Study in Patients with Mood Disorders.

Emotional blunting is prevalent in patients with mood disorders and adversely affects the overall treatment outcome. The Oxford Depression Questionnaire is a validated psychometric instrument for assessing emotional blunting. We aimed to evaluate the reliability and validity of the Chinese version of the ODQ (ODQ) in Chinese patients with mood disorders. 136 mood disorders patients and 95 healthy control participants were recruited at the First Affiliated Hospital of Zhejiang University, School of Medicine. Patients were assessed using the ODQ, Beck Depression Inventory-II (BDI-II), and Montgomery-Asberg Depression Rating Scale (MADRS). Internal consistency reliability and test-retest reliability were analyzed. Confirmatory factor analysis and correlation analysis were used to evaluate construct and convergent validity. A total of 136 patients with mood disorders and 95 healthy controls participated in this study. Cronbach α values were 0.928 (ODQ-20) and 0.945 (ODQ-26). Test-retest reliability coefficients were 0.798 (ODQ-20) and 0.836 (ODQ-26) (p<0.05); intraclass correlation coefficient values were 0.777 (ODQ-20) and 0.781 (ODQ-26) (p<0.01). The score of ODQ was positively correlated with BDI-II and MADRS (r=0.326~0.719, 0.235~0.537, p<0.01). The differences in the ODQ scores between the patient and control groups were statistically significant. The reliability, structural validity, and criterion validity of the ODQ applied to patients with mood disorders meet the psychometric requirements, and the scale can be used to assess emotional blunting in Chinese patients with mood disorders.

A Prospective, Multi-center Randomized, Controlled, Blinded Trial of Vagus Verve Stimulation for Difficult to Treat Depression: the RECOVER Trial

Abstract Introduction: Therapeutic Vagus Nerve Stimulation (VNS) has been FDA-approved for treatment-resistant depression (TRD). In 2007, the US Centers for Medicare and Medicaid Services (CMS) issued a non-coverage decision, making access difficult for patients. In 2019, CMS requested a “coverage with evidence development trial” to determine potential VNS efficacy in the US Medicare TRD population. This trial, RECOVER, is co-sponsored by CMS and the device maker (LivaNova) to assess VNS efficacy over 12 months is large, multi-centered (N=71, US sites), randomized, and placebo-controlled. Methods: Inclusion criteria include: ≥18 years old, diagnosis of Major Depressive Disorder (MDD) or Major Depressive Episode (MDE) in bipolar disorder, chronic (2 years) or recurrent (≥ 4 MDEs), failure of four medical record-verified AD treatments in the current MDE, a score of ≥ 22 on the Montgomery Asberg Depression Rating Scale (MADRS). Exclusion criteria include: substance use and psychotic disorders, acute suicidal ideation/intention, severe personality disorder. All subjects undergo VNS implantation then randomized to active treatment (device on) or sham (implanted, not activated) for 12 months. Depression ratings are performed by blinded, offsite raters. The trial’s primary measure is number of months in response (active –vs- placebo). Results: 480 patients enrolled; subject mean age is 54.0, 34.6 mean MADRS, mean age of onset is 20.9, and 20.4 years of lifetime MDE. Average failed lifetime ADs is 14.1, with many receiving aggressive treatments: ECT (41.9%), TMS (46.7%), and ketamine (21.3%). Many report psychiatric hospitalizations (64.0%); attempted suicide (43.8%). To date, 222 patients (including 40 early terminated) have completed the trial’s first year. Conclusions: RECOVER is the largest prospective, randomized, device-based, placebo-controlled MDD trial ever undertaken; enrolling severe TRD patients not studied in most MDD clinical trials. It will provide a thorough understanding of the nature of VNS response (e.g., onset of response and potential baseline outcome predictors). Research Category and Technology and Methods Clinical Research: 12. Vagus Nerve Stimulation (VNS) Keywords: Treatment-Resistant Depression, Vagus Nerve Stimulation, Difficult to Treat Depression, Major Depressive Disorder

Expectation focused and frequency enhanced cognitive behavioural therapy for patients with major depression (EFFECT): a study protocol of a randomised active-control trial

IntroductionThe effectiveness of psychotherapy in depression is subject of an ongoing debate. The mechanisms of change are still underexplored. Research tries to find influencing factors fostering the effect of psychotherapy....