Montgomery-Asberg Depression Rating Scale Scores Research Articles

An observational study on variations of serum uric acid level in patients of depression and healthy controls and its correlation with hidden bipolarity

Background: Bipolar disorder (BD) is one of the most studied psychiatric disorders, this being one of the leading causes of disability in young individuals. In search for its predictive biomarker, serum uric acid (UA) level was seen to have a pathophysiologic role in the genesis of BD through oxidative stress and other mechanism. Aims and Objectives: The aim of the study was to estimate serum UA levels in patients with 1st episode depression, to compare serum UA levels between patients and matched healthy controls and to compare serum UA levels between patients with and without hidden bipolarity and therefore, and to evaluate whether it can be used as a predictor of bipolarity. Materials and Methods: A study was conducted in a tertiary care center in Eastern India for a duration of 3 months with a sample size of 92, comprising 46 cases with major depressive disorder (MDD) and 46 control groups of healthy subjects. Their serum UA levels were estimated. The study population was subjected to a mood disorder questionnaire (MDQ) and Montgomery–Asberg Depression Rating Scale (MADRS) scoring. All these data were tabulated in a master sheet and analyzed using Statistical Packages for the Social Sciences 25 software. Results: The mean age of the study population was 32 years with 46 males and 46 females. The mean UA levels for MDD group was 5.27±1.14 mg/dL and for control group was 4.6±1.2 mg/dL, which was seen to be statistically significant (P=0.001). No statistically significant association was seen between the group with a high likelihood of bipolarity versus a low chance of bipolarity with respect to UA levels. A positive correlation was seen between MDQ scores and UA levels of depressed individuals (using Spearmen’s rho: rs=0.345, P=0.019), but not with their MADRS scores. Conclusion: Serum UA levels are significantly higher in depressed patients as compared to healthy subjects. A non-statistical association was seen between UA levels and their bipolar tendencies, owing to a small sample size of comparable groups. However, a higher MDQ score was associated with high UA levels. A larger study population is needed to conclusively establish the predictive role of UA with respect to BD.

Repetitive Transcranial Magnetic Stimulation for the Treatment of Depression in a Real-World Setting: Findings from a Cohort Study.

In the past two decades, significant advancements in neuromodulation techniques have occurred, such as transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD). According to the assumption that repeated stimulation within a condensed timeframe can yield sustained efficacy, an accelerated protocol may be more effective in reducing time to response. With those premises, this study aimed to evaluate a sample of TRD patients treated with standard repetitive TMS (rTMS) and accelerated rTMS (arTMS). Nine subjects were treated with standard rTMS and 19 with arTMS. Psychometric assessment was made at the baseline and one week, one month, and three months after the treatment. A linear mixed-effect regression was performed along with other appropriate statistical analyses. A significant improvement over time was observed for both depressive and cognitive symptoms. Moreover, considering the reduction in the Montgomery-Asberg Depression Rating Scale scores, a better treatment response was observed in subjects treated with arTMS (p < 0.05). Our findings showed a significant difference between the two protocols in terms of clinical response. Although further studies are needed to confirm the superiority of arTMS, the better cost-effectiveness of this technique should be considered.

Relationship between Patient Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS) total scores in older adults with major depressive disorder: An analysis of the OPTIMUM clinical trial

BackgroundThe Patient Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS) are commonly used scales to measure depression severity in older adults. MethodsWe utilized data from the Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM) clinical trial to produce conversion tables relating PHQ-9 and MADRS total scores. We split the sample into training (N = 555) and validation samples (N = 187). Equipercentile linking was performed on the training sample to produce conversion tables for PHQ-9 and MADRS. We compared the original and estimated scores in the validation sample with Bland-Altman analysis. We compared the depression severity level using the original and estimated scores with Chi-square tests. ResultsThe Bland-Altman analysis confirmed that differences between the original and estimated scores for at least 95 % of the sample fit within 1.96 standard deviations of the mean difference. Chi-square tests showed a significant difference in the proportion of participants at each depression severity category determined using the original and estimated scores. LimitationsThe conversion tables should be used with caution when comparing depression severity at the individual level. ConclusionsOur conversion tables relating PHQ-9 and MADRS scores can be used to compare treatment outcomes using aggregate data in studies that only used one of these scales.

Improved implicit self-esteem is associated with extended antidepressant effects following a novel synergistic intervention.

In a previously published randomized controlled trial, automated self-association training (ASAT), a novel digital intervention, was found to extend the rapid antidepressant effect of a single infusion of ketamine for at least 30 days. In this secondary analysis, we aimed to understand the potential role of implicit self-esteem in the combined antidepressant effect of ketamine and ASAT training, by investigating the novel synergistic treatment's effects on implicit self-associations and their relation to symptom improvement. A total of 154 adults (ages 18-60) with treatment-resistant unipolar depression and lower-than-normative explicit self-esteem were randomized in a double-blind, parallel-arm design to receive one of three treatment allocations: an active/active treatment combination consisting of one infusion of ketamine (0.5 mg/kg) followed by four days of ASAT ( ~ 30-40 min/day), or one of two control arms that lacked either the active drug or the active behavioral component. The Implicit Association Test (IAT) was used to behaviorally assess the strength of association between self-related stimuli and negative concepts. Linear regression models were used to test the relationship between group assignment, IAT scores acquired immediately post-treatment, and both acute and extended clinical outcomes (% change in Montgomery-Asberg Depression Rating Scale scores, relative to pre-treatment baseline) in the trial. The group assigned to ketamine + ASAT intervention, compared to the other groups, had a pattern of IAT scores indicating more positive self-associations immediately after treatment relative to the control arms (F(1, 131) = 3.979; p = 0.048). In regression models, IAT scores tracked with concurrent (acute post-treatment) % change in MADRS scores across all treatment arms (p = 0.001), and mediated more extended (Day 30) depression improvements specifically for the ketamine+ASAT arm (group * IAT interaction term: β = -0.201; p = 0.049). Our findings suggest that changing implicit self-worth during a post-ketamine 'plasticity window' is one key mechanism whereby the novel ketamine+ASAT treatment combination exerts its antidepressant benefit, confirming the intended treatment target at the level of implicit cognition. Future studies should seek to further enhance the reliability of the biobehavioral intervention's impact on implicit cognition, as this mechanism appears linked to the intervention's enduring clinical benefits.

Protocol for a randomised controlled trial of ketamine versus ketamine and behavioural activation therapy for adults with treatment-resistant depression in the community

IntroductionAlthough short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of ketamine by clinicians. These include acute dissociative effects of parenteral...

Possible Role of Correlation Coefficients and Network Analysis of Multiple Intracellular Proteins in Blood Cells of Patients with Bipolar Disorder in Studying the Mechanism of Lithium Responsiveness: A Proof-Concept Study.

Background: The mechanism of lithium treatment responsiveness in bipolar disorder (BD) remains unclear. The aim of this study was to explore the utility of correlation coefficients and protein-to-protein interaction (PPI) network analyses of intracellular proteins in monocytes and CD4+ lymphocytes of patients with BD in studying the potential mechanism of lithium treatment responsiveness. Methods: Patients with bipolar I or II disorder who were diagnosed with the MINI for DSM-5 and at any phase of the illness with at least mild symptom severity and received lithium (serum level ≥ 0.6 mEq/L) for 16 weeks were divided into two groups, responders (≥50% improvement in Montgomery-Asberg Depression Rating Scale and/or Young Mania Rating Scale scores from baseline) and non-responders. Twenty-eight intracellular proteins/analytes in CD4+ lymphocytes and monocytes were analyzed with a tyramine-based signal-amplified flow cytometry procedure. Correlation coefficients between analytes at baseline were estimated in both responders and non-responders and before and after lithium treatment in responders. PPI network, subnetwork, and pathway analyses were generated based on fold change/difference in studied proteins/analytes between responders and non-responders. Results: Of the 28 analytes from 12 lithium-responders and 11 lithium-non-responders, there were more significant correlations between analytes in responders than in non-responders at baseline. Of the nine lithium responders with pre- and post-lithium blood samples available, the correlations between most analytes were weakened after lithium treatment with cell-type specific patterns in CD4+ lymphocytes and monocytes. PPI network/subnetwork and pathway analyses showed that lithium response was involved in four pathways, including prolactin, leptin, neurotrophin, and brain-derived neurotrophic factor pathways. Glycogen synthase kinase 3 beta and nuclear factor NF-kappa-B p65 subunit genes were found in all four pathways. Conclusions: Using correlation coefficients, PPI network/subnetwork, and pathway analysis with multiple intracellular proteins appears to be a workable concept for studying the mechanism of lithium responsiveness in BD. Larger sample size studies are necessary to determine its utility.

Therapeutic Potential of Buprenorphine in Depression: A Meta-Analysis of Current Evidence.

Emerging research indicates buprenorphine, used in management of opioid use disorder, has attracted interest for its potential in treating a variety of psychiatric conditions. This meta-analysis aimed to determine the efficacy of buprenorphine in treating symptoms of depression. Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a search was conducted of several databases until April 25, 2022, for English language articles related to buprenorphine and its use in treating various mental health conditions. Standardized mean differences (SMDs) and its 95% confidence intervals (CIs) were reported for the Hamilton Rating Scale for Depression (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS) scores. Statistical analyses were performed using Cochrane RevMan 5. Of the 1,347 identified studies, six clinical trials were included. MADRS-10 least square mean difference (LSMD) inter-group assessment favored buprenorphine over placebo, but it lacked statistical significance. Similarly, MADRS scores as well as HAM-D inter-group assessment were in favor of buprenorphine, however, were not statistically significant. These findings suggest a potential therapeutic role for buprenorphine in treating depression, albeit with caution due to the observed lack of statistical significance and the potential for confounding factors. Preliminary evidence suggests potential efficacy of buprenorphine at lower doses in improving improving outcomes specifically related to depression. However, due to limitations in statistical significance and possible confounding factors, entail cautious interpretation. Further rigorous research is needed to investigate the long-term effects, optimal dosing, and determine the role of adjuvant drug therapy.

Exploring Esketamine's Therapeutic Outcomes as an FDA-Designated Breakthrough for Treatment-Resistant Depression and Major Depressive Disorder With Suicidal Intent: A Narrative Review.

The expansive spectrum of major depressive disorder (MDD) continues to pose challenges for psychiatrists to treat effectively. Oral antidepressant (OAD) medications that alter monoamine neurotransmitters,mainly selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), have been the mainstay of therapy for decades. Although these drugs have been largely beneficial, a considerable subset of patients do not respond adequately to multiple conventional therapies administered for an appropriate length of time, leading to a diagnosis of treatment-resistant depression (TRD). Ketamine, a non-monoaminergic drug, has long been known for its beneficial effects on TRD when given intravenously (IV). Between 2019 and 2020, an intranasal formulation of the S (+) enantiomer of racemic ketamine, esketamine (ESK), was granted "breakthrough designation" by the FDA and approved for the indicationsof TRD and MDD patients exhibiting acute suicidal intent. The objective of this narrative review was to review the academic literature and collect clinical evidence that may corroborate intranasal ESK's effectiveness for its approved indications while addressing its safety and tolerability profile, adverse effects, andimpact on cognition. An overview ofthe drug'sorigins,pharmacology, and standard treatment regimen are provided. Theoutcomes from double-blinded randomized control trials (DB-RCTs) of ESK are outlinedto demonstrate the efficacy and safety data leading to its FDA approval, along with its long-term post-market safety outcomes. Comparative trials between ESK and ketamine are then evaluated to highlight ESK's consideration as a more practical alternative toketamine in common clinical practice. The authors further discuss currently approved and developing therapies for TRD,propose future research directions, and identify the inherent limitations of the review and further research. To conduct the research required, three digital databases (PubMed, Medline, and ClinicalTrials.gov) were queried to search for key terms, includingketamine, esketamine, treatment-resistant depression, and biomarkers,using automation toolsalong with selective search engine results.After streamlining the results by title and abstract and removing duplicates, a total of 37 results were chosen, of which 18 are clinical trials. A reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) score was the primary efficacy endpoint for most of these clinical trials. In conclusion, intranasal ESK, when used as an adjunct to market OADs, shows greater efficacy in treating TRD and MDD with suicidal intent compared to OADs and placebo alone and provides a more suitable alternative to IV ketamine. It is important to note that further research is required to fully understand the novel mechanism of action of ESK, as well as the establishment of a consensus definition of TRD, which may facilitate better detection and treatment protocols. More focused quantitative and qualitative ESK studies are needed, as well as those pertaining to its use in patients with co-existing mental illnesses.

Clinical outcomes in the biomarkers of ketamine (Bio-K) study of open-label IV ketamine for refractory depression

ObjectiveWe conducted an open-label clinical trial (“Bio-K”) using IV ketamine for treatment-resistant depression to identify biomarkers linked to remission. Here, we report the clinical efficacy and side effect outcomes of Bio-K. MethodsAcross 4 US sites, 75 patients ages 18–65 with treatment-refractory unipolar or bipolar depression received 3 IV ketamine infusions over an 11-day period. Key exclusion criteria were psychotic symptoms, significant substance abuse, unstable medical conditions, and any use of cannabis. Pre-existing antidepressant medication was maintained. Primary outcome was remission as measured by Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcome of 50 % reduction in Beck Suicide Scale score. Safety monitoring and varying durations of infusions were also key parameters. ResultsUsing remission as MADRS score <10, after 3 infusions 52 % achieved remission, with 67 % achieving response. Of those achieving response after a single infusion, 66 % (22 of 33) reached remission after 3 infusions, while 40 % (16 of 40) non-responders after the first infusion went on to achieve remission after 3 infusions. Only 20 % of non-responders after 2 infusions achieved remission. Most (81 %) participants had significant suicidal ideation at baseline; of these, two-thirds (67 %) experienced at least a 50 % reduction in suicidality. Side effects were minimal. Uniquely, we had three different types of infusion categories, with individuals receiving: (1) slow (100-min) infusions only or (2) regular (40-min) infusions only or (3) a mix of infusion durations. These three infusion groups showed comparable safety and efficacy. Exploration of clinical factors revealed no link between BMI, age, or gender to remission. ConclusionsThe consistency of outcomes across 4 clinical sites and across multiple instruments, suggests high acute efficacy and safety of IV ketamine for serious depressive episodes. Duration of infusion did not alter outcomes. Meaningfully, 40 % of non-responders after a single infusion did reach remission subsequently, while only 20 % of non-responders after 2 infusions achieved remission, suggesting early response is suggestive for eventual remission. Our data on varying ketamine infusion duration adds novel insights into the clinical administration of this new treatment for refractory and severe patients. Our limitations included a lack of a control group, necessitating caution about conclusions of efficacy, balanced by the utility of reporting “real-world” outcomes across multiple clinical sites. We could also not separately analyze results for bipolar disorder due to small numbers. Together, the Bio-K clinical results are promising and provide significant sample sizes for forthcoming biological markers analyses.

Is intravenous valproate more efficacious than oral valproate for inpatients with bipolar I disorder with a manic or depressive episode and concomitant symptoms of opposite polarity?

Valproic acid (VPA) is a commonly prescribed mood stabilizer, available in both oral (OS) and intravenous (IV) formulations. However, few studies have compared their safety and efficacy. This retrospective study aimed to investigate the safety and efficacy of and IV-VPA in patients with Bipolar Disorder. Fifty patients with Bipolar Disorder experiencing a manic or depressive episode, with concomitant symptoms of opposite polarity, admitted to our inpatient unit and treated with IV-VPA were included in a retrospective, single-centre, non-randomized, open-label, parallel-group comparative study. Fifty patients experiencing a manic or depressive episode, with concomitant symptoms of opposite polarity, treated with oral-VPA and selected among those who were admitted to the inpatient unit prior to the introduction of IV-VPA in our clinical practice, were included as the control group (matched based on age, gender and clinical scales score at baseline). The Clinical Global Impression (CGI), Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) scores were recorded at baseline, after 3 days of treatment and discharge from the inpatient unit. Patients were asked to respond on the basis of the symptoms present on the day the scale was administered. Response rate and the presence of adverse effects were also recorded. Both patients treated with oral and IV-VPA demonstrated significant improvements in all psychometric scales (p < 0.001). However, the IV group exhibited superior efficacy, with significantly lower scores on the CGI, YMRS, MADRS and HAM-A scales on Day 3 and at discharge from the inpatient unit. The IV-VPA treatment showed higher response rates on all psychometric scales, and no adverse effects were reported in either group. This retrospective study supports the use of IV-VPA as a more efficacious treatment option for patients with Bipolar Disorder, particularly in acute settings where rapid symptom improvement is crucial. Both oral and IV-VPA were found to be safe and well-tolerated.

Omega-3 supplementation improves depressive symptoms, cognitive function and niacin skin flushing response in adolescent depression: A randomized controlled clinical trial

BackgroundDepressive disorder in adolescents is a major health problem with inadequate treatment. Omega-3 (ω3) polyunsaturated fatty acids are a promising adjuvant therapy in adult depression. The primary objective of this study was to investigate the efficacy of adjuvant ω3 treatment on depressive symptoms in adolescent depression. Secondarily, we explored the effects of ω3 on cognitive function and memory and niacin skin flushing response (NSFR), as their robust associations with adolescent depression. MethodsA total of 71 adolescents with depression (aged 13–24; 59.2 % female) were randomly assigned to receive ω3 plus Paxil (n = 34) or Paxil alone (n = 37) for 12 weeks. Primary outcome was depression severity according to scores on Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes were cognitive function and memory, and NSFR. ResultsSignificant improvements in depressive symptoms over time (p = 0.00027 at week 12) were observed in the ω3 + Paxil group compared with Paxil group. Additionally, in the ω3 + Paxil group, significant improvements in memory over time, and greater cognitive function and NSFR were also observed compared with the Paxil group; the NSFR was negatively correlated with MADRS scores at baseline. LimitationsThe trial was open label; thus, the outcome measures should be viewed as preliminary since inherent bias in outcomes due to the potential of a placebo effect. ConclusionsOur results demonstrate that adjuvant ω3 treatment is effective for reducing depressive symptoms as well as improving cognitive function, memory and the NSFR; these results suggest ω3 is a promising adjuvant treatment for adolescent depression.

Single-Dose Psilocybin Treatment for Major Depressive Disorder

Psilocybin shows promise as a treatment for major depressive disorder (MDD). To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. ClinicalTrials.gov Identifier: NCT03866174.

The efficacy of oral ketamine in severely depressed patients at high risk of suicide.

Ketamine is most easily and inexpensively administered by the oral route and in racemic form. Oral racemic ketamine may be an important approach to the emergency management of suicide risk in clinical settings, especially in third world countries, that have a limited range of available healthcare resources. In a prospective, uncontrolled, open-label investigation, we studied 30 severely depressed inpatients who consented to participate in a pilot hospital service offering ketamine for management of high suicide risk. Patients sipped a solution of racemic ketamine (150mg) across 10-15min in 3 alternate day sessions. Patients were assessed using the Modified Scale for Suicidal Ideation (MSSI), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Improvement-Severity (CGI-S) scale at baseline and 1day after the last ketamine session. There was statistically and clinically significant improvement on all outcomes. Mean (standard deviation) MSSI scores dropped from 25.1(1.8) to 17.3(5.6), MADRS scores from 28.8(3.4) to 21.9(3.6), and CGI-S scores from 6.0(0.2) to 3.6(0.9). At endpoint, MSSI scores had dropped from severe to low or mild-to-moderate in 67% of patients. The 90 ketamine sessions were uneventful; the treatment was well tolerated and no patient dropped out. Oral racemic ketamine may be a useful and potentially life-saving approach to the emergency management of severely depressed patients at high risk of suicide.

An Open-Label Study of Adjunctive Dextromethorphan/Quinidine in Treatment-Resistant Depression.

Approximately one third of individuals with major depressive disorder have treatment-resistant depression (TRD). Glutamatergic modulators such as the N -methyl- d -aspartate receptor antagonist ketamine have rapid and robust antidepressant effects, but their use has been limited by accessibility and route of administration. This open-label pilot study assessed the adjunctive antidepressant efficacy of dextromethorphan/quinidine (DM/Q) in TRD. Inpatients with TRD (n = 17, 40.8 ± 12.3 years; 9 females/8 males) received adjunctive open-label DM/Q (20 mg/10 mg) up to 3 times daily. The study had no set endpoint; participants were followed until they discontinued DM/Q or were discharged. Montgomery-Asberg Depression Rating Scale (MADRS) scores were obtained at baseline (before DM/Q administration) and regularly during hospitalization. Full response was defined as a ≥50% reduction in baseline MADRS score, partial response as a 25% to 50% decrease in baseline MADRS score, and nonresponse as a <25% reduction or an increase in baseline MADRS score. The 17 inpatients received open-label DM/Q for 5.1 ± 2.7 weeks. Forty-seven percent of participants responded to DM/Q-12% achieved a full response and 35% achieved a partial response. The largest MADRS difference observed at any time point was -6.4 ± 8.4 (-21.0% ± 29.9%), and the MADRS difference observed at time of DM/Q discontinuation or hospital discharge was -4.8 ± 8.4 (-15.9% ± 29.7%). Twenty-four percent of participants experienced a nonserious adverse event; none experienced a serious adverse event. In this open-label pilot study, 47% of participants responded to adjunctive DM/Q, which was well tolerated. Larger placebo-controlled trials are needed to determine the real-world efficacy of DM/Q.

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).

The Influence of Probiotic Supplementation on Depression, Anxiety, and Stress Level, as well as Inflammation, Anthropometric and Metabolic Parameters in Patients with Depressive Disorders - preliminary results of an RCT

IntroductionThere is a huge need to search for new treatment options for depression but as well as its comorbidities. Particularly, depression and metabolic abnormalities often coexist, while a pathophysiological overlap, including microbiota changes, may play a role. Thus, the trials of microbiota interventions (e.g., probiotics) may establish a safe and easy-to-use treatment option as an adjunctive therapy in patients only partially responsive to pharmacological treatment.ObjectivesThe paper presents preliminary results of an RCT on the effect of probiotic supplementation on depression, anxiety and stress level, anthropometric, metabolic, and inflammatory parameters in adult patients with depressive disorders.MethodsThe trial was a two-arm, parallel-group, prospective, randomized, double-blind, controlled design that included 43 participants and lasted 60 days. The probiotic preparation contained Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 in the amount of 3 × 109 colony forming units (CFU). We assessed depression level with Montgomery-Asberg Depression Rating Scale (MADRS), depressiveness, anxiety and stress level with 21-item version of Depression, Anxiety and Stress Scale (DASS-21), quality of life, blood pressure, body mass index and waist circumference, complete blood count, serum levels of C-reactive protein, high-density lipoprotein cholesterol, triglycerides, fasting glucose, selected secondary markers of inflammation and metabolic risk, as well as noninvasive biomarkers of liver fibrosis (APRI and FIB-4).ResultsThere were no differences in sociodemographic traits and psychometric questionnaires scores, as well as in anthropometric and basic laboratory findings between placebo and probiotic group at the start of the intervention period. Interestingly, there was a statistically significant improvement in MADRS score in both, placebo (p=0,010) and probiotic group (p=0,037) after intervention (see figure). The same finding was observed in total DASS-21 score as well as anxiety subscale of DASS-21. However, there were no differences in anthropometric, inflammation or metabolic laboratory parameters at the end of the study regardless of intervention.Image:ConclusionsWhilst probiotics may benefit some individuals who do not fully respond to antidepressant medications, our study did not show the superiority of probiotics over placebo in managing depressive and anxiety symptoms. However, the target clinical sample, as well as the intervention period and dosage of preparation for this intervention is not fully recognized. Moreover, larger clinical sample may be needed to detect differences between placebo and probiotics.Disclosure of InterestNone Declared

Engelli Bakımevlerinde Covid-19 Salgınının Bakım Veren Yükü Üzerine Etkilerinin İncelenmesi

It is very well documented that the number of patients residing in nursing homes has increased in recent years due to disabilities related with mental diseases. There is mounting evidence of the enormous burden placed on caregivers who care for people suffering from mental illness. Throughout the Covid-19 pandemic, the working conditions of personnel caring for mentally ill patients in nursing homes have deteriorated. Shifts with 14-day intervals and quarantine have been implemented in order to minimize the risk of transmission. We designed this study to ascertain the impact of the pandemic and the associated regulations, as well as the issues encountered in the routine work system, on the mental health of personnel. We used sociodemographic data form to determine the personnel's sociodemographic and clinical characteristics, the Coronavirus Anxiety Scale (CAS) to determine anxiety levels associated with Covid-19, the Zarit Burden Interview (ZBI) to determine caregiver burden, and the Montgomery–Asberg Depression Rating Scale (MADRS) to determine depressive symptoms. The participants' mean CAS score was found to be 2.72±2.91, their mean ZBI score was 41.6±10.6, and their mean MADRS score was 11.55±7.70. Nurses had significantly higher MADRS and ZBI scores than caregivers. There was a positive and significant correlation between ZBI scores, and CAS and MADRS scores (p&amp;lt;0.05). By using multiple regression analysis, it was determined that MADRS scores and the wage received was sufficient or insufficient to predict ZBI scores. The outcomes of our study indicated that the depressive symptom levels of nursing home personnel were higher than the anxiety levels related to the pandemic, and contributed to the increase in caregiver burden. Screening personnel for depression symptoms and providing required psychological support appears to be critical for enhancing service quality.

Rapidity of Symptom Improvement With Intranasal Esketamine for Major Depressive Disorder: A Systematic Review and Meta-Analysis.

Objective: Rapid-acting treatment options are needed for major depressive disorder (MDD). The objective of this systematic review and meta-analysis was to estimate the magnitude of the treatment effect for intranasal esketamine over placebo at 24 hours after the first dose and at endpoint. Data Sources: PubMed, abstracts of major psychiatric meetings, and ClinicalTrials.gov were searched up to November 2020 with no language constraints, cross-referencing the term intranasal with esketamine and randomized. Study Selection: Of 27 studies reviewed, 8 articles, with a total of 1,437 patients with MDD, met study criteria and were included in the meta-analysis. Data Extraction: Randomized, double-blind clinical trials comparing adjunctive treatment of standard antidepressants with intranasal esketamine for MDD, using intranasal placebo augmentation as a comparator, were selected. Results: Estimates of the standardized mean difference (SMD) in change scores were pooled after examining for homogeneity using the test statistic proposed by DerSimonian and Laird. Findings of the random effects model were presented. Augmentation of standard antidepressants with intranasal esketamine resulted in greater Montgomery-Asberg Depression Rating Scale (MADRS) score reduction than adjunctive intranasal placebo at 24 hours. Across the trials, the SMD was 0.34 (95% CI = 0.11 to 0.46, P < .0001) with a 2.9-point greater mean MADRS score reduction following intranasal esketamine versus active control plus intranasal saline. A similar finding was evident at endpoint. Conclusions: This updated systematic review and meta-analysis found that augmentation of antidepressants with intranasal esketamine was statistically and clinically more effective in reducing depression severity than augmentation with placebo, at both 24 hours and study endpoint. Future studies are needed to evaluate dose-response relationship for esketamine.

Efficacy and Safety of Esketamine Combined with Antidepressants for Treatment-Resistant Depression: A Meta-Analysis.

To evaluate the efficacy and safety of esketamine + antidepressant in treatment-resistant depression. We searched PubMed, Web of Science, Embase, CNKI, and Wanfang databases to obtain published information on esketamine + antidepressant from inception to July 2022. We searched for randomized controlled studies on the treatment of depression with a double-blind induction phase. Outcome indicators included changes in Montgomery-Asberg Depression Rating Scale (MADRS) scores before and after treatment, effective response rate, remission rate, and changes in self-rating depression scale (SDS). We analyzed data using Review Manager 5.4 and assessed the quality of evidence using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) analysis. A total of seven articles were included, including 701 patients in the esketamine + antidepressant group and 551 in the placebo group. Meta-analysis results showed that esketamine + antidepressant could improve the MADRS score in patients with treatment-resistant depression (MD = -2.68, 95% CI -3.98 to -1.37, P < 0.0001), SDS (MD = -2.9, 95% CI -4.01 to -1.79, P < 0.00001), response rate at the end of the double-blind induction period (RR = 1.28, 95% CI 1.12 to 1.46, P = 0.0002), remission rate at the end of the double-blind induction period (RR = 1.39, 95% CI 1.18 to 1.63, P < 0.0001), Five-Dimensional Health Scale (EQ-5D-5L) (MD = 0.05, 95% CI 0.02 to 0.08, P = 0.00009), Visual Analogue Scale of Health Status (EQ-VAS) (MD = 5.54, 95% CI 2.37 to 8.71, P = 0.0006). Esketamine + antidepressant has an obvious curative effect in treatment-resistant depression and can rapidly improve depression in patients, quality of life and satisfaction, but minor adverse reactions can occur.

Bad Dreams and Nightmares Preceding Suicidal Behaviors.

Objective: Nightmares seem to predict suicidal behaviors, and the aim of this study is to explore the chronology and trajectories of alterations in dream contents before a suicidal crisis, distinguishing 3 different experiences: bad dreams, nightmares, and suicidal scenarios during dreams. Methods: This naturalistic study included individuals hospitalized between January 2021 and May 2021 in a psychiatric post–emergency room unit for suicidal crisis (thoughts and attempts). Results: The study observed that 80% (n = 32/40) of patients had altered dreams (AD) before the suicidal crisis, including 27 (67.5%) with bad dreams, 21 (52.5%) with nightmares (bad dreams that awaken the sleeper), and 9 (22.5%) with suicidal scenarios during dreams. No differences were observed between the AD group versus patients with no altered dreams (ND) regarding sociodemographic characteristics. We observed a progression of dream content alterations: bad dreams appear 111 days (4 months) before the suicidal crisis, then nightmares appear 87.3 days before (3 months), and suicidal scenarios during dreams were reported 45.2 days before (1.5 months). For the AD and ND populations in suicidal crisis, 80% had at least 1 subtype of dream alterations, 40% had bad dreams and nightmares, and 17.5% had all 3 subtypes. The AD group, compared to the ND group, had significantly more family history of insomnia (P = .046). Almost all patients (97.5%) had depressive symptoms (Montgomery-Asberg Depression Rating Scale score ≥ 7; 82.5% had moderate to severe symptoms, MADRS ≥ 20), 60% had insomnia (Insomnia Severity Index > 14), 92.5% had altered sleep quality (Pittsburgh Sleep Quality Index > 5), and 57.5% reported sleepiness (Epworth Sleepiness Scale > 10). Conclusions: Dream alterations and their progression can be readily assessed and may help to better identify prodromal signs of suicidal behaviors.