Montgomery-Asberg Depression Rating Scale Research Articles

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.

Serum Levels of Zinc, Albumin, Interleukin-6 and CRP in Patients with Unipolar and Bipolar Depression: Cross Sectional Study

Unipolar (UD) and bipolar depression (BDD) show a high degree of similarity in clinical presentations, which complicates the differential diagnosis of these disorders. The aim of this study was to investigate the serum levels of interleukin 6 (IL-6), C-reactive protein (CRP), albumin (Alb), and zinc (Zn) in patients with UD, BDD, and healthy controls (HC). A total of 211 samples were collected: 131 patient samples (65 UD and 68 BDD) and 80 HC. The Montgomery–Asberg Depression Rating Scale (MADRS), along with the Hamilton Depression Rating Scale (HAMD-17), were administered to patient groups to evaluate symptoms. A cross-sectional study was performed to analyse the serum levels of IL-6, CRP, albumin, and zinc. The concentration of CRP was determined using the immunoturbidimetry method, zinc using the colorimetric method, and albumin using the colorimetric method with bromocresol green on the Alinity c device. IL-6 cytokine concentration in serum samples was ascertained using a commercial enzyme immunoassay, ELISA. We found no significant differences in serum concentrations of zinc, albumin, CRP, and IL-6 between the groups of patients with unipolar and bipolar depression. There was a significant statistical difference (p < 0.001) between serum levels of all investigated parameters in both groups of depressed patients in comparison with HC. Furthermore, correlations with specific items on HAMD-17; (namely, hypochondrias, work and activities, somatic symptoms-general, and weight loss) and on MADRS (concentration difficulties, lassitude) were observed in both patient groups. These findings confirm the presence of low-grade inflammation in depression, thus adding better insight into the inflammation hypothesis directed to explain the aetiology of depressive disorders. Our results do not indicate potential biomarkers for distinguishing between unipolar and bipolar depression.

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...

Ketamine and electroconvulsive therapy for severe depression: A network meta-analysis of efficacy and safety

BackgroundKetamine, electroconvulsive therapy (ECT), and their combination are effective for treating severe depression, but few large-scale studies have compared these. MethodsWe searched databases for randomized controlled trials (RCTs) using ketamine, ECT, ketamine + ECT, or placebo for severe depression. Standardized measures were efficacy outcomes. Risk of bias was assessed. Stata and ADDIS were used for network meta-analysis (NMA) comparing efficacy and adverse reactions post-treatment. This study was registered on PROSPERO (CRD42023476740). Results17 RCTs with 1370 patients were included. NMA showed ECT and ketamine improved Hamilton Depression Rating Scale (HDRS) versus placebo; other comparisons not significant. Rank probabilities showed highest probability for ECT, followed by ketamine + ECT, ketamine, placebo. No differences in Montgomery-Asberg Depression Rating Scale (MADRS); highest rank probability again for ECT, followed by ketamine + ECT, ketamine, placebo. ConclusionsAnalysis suggests ECT superior to ketamine and their combination for improving depressive severity, but individualized treatment selection warranted. Higher adverse reactions with ketamine + ECT need further study for optimized combined use.

Efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression or major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.

To report the first and largest systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression (TRD) or major depressive disorder(MDD). We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April 2023 for RCT, which evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching for patients with TRD or MDD. Outcomes measured were changes in the Montgomery-Asberg Depression Rating Scale (MADRS), response and remission rate, and serious adverse events. Five RCTs, including 4480 patients, were included for meta-analysis. Among them, two RCTs were rated as "high risk" in three aspects (allocation concealment, blinding of participants and personnel and blinding of outcome assessment) because of the non-blind method, and the quality evaluation of the remaining works of literature was "low risk". Augmentation treatment with Aripiprazole (A-ARI) was associated with a significant higher response rate compared with augmentation treatment with bupropion (A-BUP) (RR: 1.15; 95% CI: 1.05, 1.25; P = 0.0007; I2 = 23%). Besides, A-ARI had a significant higher remission rate compared with switching to bupropion (S-BUP) (RR: 1.22; 95% CI: 1.00, 1.49; P = 0.05; I2 = 59%) and A-BUP had a significant higher remission rate compared with S-BUP (RR: 1.20; 95% CI: 1.06, 1.36; P = 0.0004; I2 = 0%). In addition, there was no significant difference in remission rate(RR: 1.05; 95% CI: 0.94, 1.17; P = 0.42; I2 = 33%), improvement of MADRS(WMD: -2.07; 95% CI: -5.84, 1.70; P = 0.28; I2 = 70%) between A-ARI and A-BUP. No significant difference was observed in adverse events and serious adverse events among the three treatment strategies. A-ARI may be a better comprehensive antidepressant treatment strategy than A-BUP or S-BUP for patients with TRD or MDD. More large-scale, multi-center, double-blind RCTs are needed to further evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching treatment strategies.

A prospective open-label study to evaluate the effectiveness of intravenous ketamine as an adjunct in treating severe depression

BackgroundKetamine, an emerging pharmacotherapeutic agent for depression, has demonstrated rapid and substantial improvement in mood and suicidal ideation, particularly in severe cases. While previous studies have established its efficacy, the current study aims to delve into the effectiveness of intravenous ketamine in treating severe depression.MethodsAn open-label prospective study enrolled 49 consecutive patients with severe depression. Baseline assessments using the Hamilton Depression Rating Scale (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS), and Modified Scale for Suicidal Ideation (MSSI) were conducted. Intravenous (IV) ketamine, administered at 0.5 mg/kg in 100-ml normal saline over 40 min, was given during sessions spaced on alternate days. Each patient received at least five sessions alongside their regular antidepressants. Close monitoring occurred during the infusion, and disease rating scale scores were recorded. Data was analyzed; employed paired Student t-test and graphical were used for visual clarity.ResultsFollowing the initiation of IV ketamine, a significant reduction in scores was observed from baseline. Response rates were achieved in over half of the patients by the third session and in nearly all by the end of fifth session. Remission rates were attained in nearly half of the patients by the fourth session and in almost all by the fifth session.ConclusionsIV ketamine could be considered as an adjunct to antidepressants in treating severe depression especially among those with suicidal ideations to obtain rapid improvement. However, the need for long-term studies is emphasized to determine the duration of its effect.

Efficacy and safety of lurasidone for schizophrenia: A systematic review and meta‑analysis of eight short‑term, randomized, double‑blind, placebo‑controlled clinical trials.

Lurasidone is an atypical anti-psychotic approved by the US Food and Drug Administration. It is mainly used to treat schizophrenia in adults through its antagonistic action on dopamine and 5-hydroxytryptamine receptors. The present study systematically assessed the efficacy and safety of lurasidone in the treatment of schizophrenia. Clinical, double-blind, parallel, randomized controlled trials (RCTs) of lurasidone in the treatment of schizophrenia were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and related clinical trial registration websites up to May 2023. A total of two investigators independently screened the included references and evaluated their quality. RevMan 5.3 software was used for meta-analysis of each measure outcome. The present systematic review was registered in PROSPERO (ID=CRD42018108178). A total of eight RCTs were included in the present study, including a total of 2,456 patients with schizophrenia. All eight references were randomized, double-blind and parallel control trials. All eight references were evaluated as high quality. The meta-analysis results demonstrated that there were no significant change in total Positive and Negative Syndrome Scale (PANSS) score, Clinical Global Impression of Severity (CGI-S) score and Montgomery-Asberg Depression Rating Scale (MADRS) between the 40 mg lurasidone group and the placebo group (P>0.05). However, as the dosage increased, the 80, 120 and 160 mg lurasidone groups had significant changes in total PANSS score, CGI-S score and MADRS Compared with placebo (P<0.05), although changes in MADRS in the 120 mg lurasidone group were not statistically significant (P>0.05). In terms of safety, the changes in the incidence of agitation in the 40 mg lurasidone group (P<0.05), vomiting in the 80 mg group (P<0.05) and akathisia in the 160 mg group (P<0.05) were statistically significant and there were also statistically significant changes in the incidence of akathisia, nausea, somnolence and extrapyramidal disorder among the 40, 80 and 120 mg lurasidone groups (P<0.05); No statistically significant changes in the in the incidence of other adverse reactions (P>0.05). In conclusion, existing evidence suggests that the initial dose of lurasidone for schizophrenia can be adjusted to 80 mg. As the condition aggravates, the dose can be incrementally increased to 160 mg. A dose of 160 mg lurasidone is recommended as the most efficacious and safe dose for acute schizophrenia and the risk of occurrence of akathisia, nausea, somnolence and extrapyramidal disorder is still high when lurasidone is administered at a dose of 80-120 mg. The dose should be promptly adjusted or the drug should be withdrawn if the aforementioned adverse reactions worsen. Multi-center, high-quality and long-term clinical RCTs influenced by the included references are still necessary to support the aforementioned conclusions.

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.

Prospective, comparative, pilot study of maintenance treatment in comorbid bipolar disorders with post-traumatic stress disorder.

There is limited real-world evidence that evaluates the impact of monotherapy vs. combination therapy as a maintenance treatment in comorbid post-traumatic stress disorder (PTSD) in bipolar disorder (BD). Our aim was to compare lithium vs. lithium plus quetiapine in maintenance treatment in a sample of comorbid BD with PTSD. An exploratory, comparative pilot study over a 28-week period in 34 comorbid BD with PTSD patients was performed to compare monotherapy (n = 18) vs. combination therapy (n = 16) during maintenance treatment. The primary outcome was the time to event of recurrence of any mood episode. The secondary outcomes were regarding change from the baseline to endpoint in the Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). A Cox regression, Kaplan-Meir survival, and mixed-effects model for repeated measures analyses were performed. Lithium plus quetiapine reduces the risk of recurrence of any mood episode. There are significant differences between baseline and endpoint for YMRS, MADRS, and CGI-BP scales in the sample. In this pilot, exploratory analysis, combination therapy during maintenance treatment for comorbid BD with PTSD may be effective in preventing recurrences of any type of mood episode.

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.

Active versus sham DLPFC-NAc rTMS for depressed adolescents with anhedonia using resting-state functional magnetic resonance imaging (fMRI): a study protocol for a randomized placebo-controlled trial

BackgroundAnhedonia, which is defined as the inability to feel pleasure, is considered a core symptom of major depressive disorder (MDD). It can lead to several adverse outcomes in adolescents, including heightened disease severity, resistance to antidepressants, recurrence of MDD, and even suicide. Specifically, patients who suffer from anhedonia may exhibit a limited response to selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT). Previous researches have revealed a link between anhedonia and abnormalities within the reward circuitry, making the nucleus accumbens (NAc) a potential target for treatment. However, since the NAc is deep within the brain, repetitive transcranial magnetic stimulation (rTMS) has the potential to modulate this specific region. Recent advances have enabled treatment technology to precisely target the left dorsolateral prefrontal cortex (DLPFC) and modify the functional connectivity (FC) between DLPFC and NAc in adolescent patients with anhedonia. Therefore, we plan to conduct a study to explore the safety and effectiveness of using resting-state functional connectivity magnetic resonance imaging (fcMRI)-guided rTMS to alleviate anhedonia in adolescents diagnosed with MDD.MethodsThe aim of this article is to provide a study protocol for a parallel-group randomized, double-blind, placebo-controlled experiment. The study will involve 88 participants who will be randomly assigned to receive either active rTMS or sham rTMS. The primary object is to measure the percentage change in the severity of anhedonia, using the Snaith-Hamilton Pleasure Scale (SHAPS). The assessment will be conducted from the baseline to 8-week post-treatment period. The secondary outcome includes encompassing fMRI measurements, scores on the 17-item Hamilton Rating Scale for Depression (HAMD-17), the Montgomery Asberg Depression Rating Scale (MADRS), the Chinese Version of Temporal Experience of Pleasure Scale (CV-TEPS), and the Chinese Version of Beck Scale for Suicide Ideation (BSI-CV). The Clinical Global Impression (CGI) scores will also be taken into account, and adverse events will be monitored. These evaluations will be conducted at baseline, as well as at 1, 2, 4, and 8 weeks.DiscussionIf the hypothesis of the current study is confirmed, (fcMRI)-guided rTMS could be a powerful tool to alleviate the core symptoms of MDD and provide essential data to explore the mechanism of anhedonia.Trial registrationClinicalTrials.gov NCT05544071. Registered on 16 September 2022.

Dextromethorphan/Bupropion: A Novel Treatment for Patients With Major Depressive Disorder.

Major depressive disorder (MDD) affects millions of people and is the leading cause of disability worldwide. Patients report decreased quality of life and ability to perform activities of daily living. It is estimated that the current standard of care, which includes pharmacologic therapy with a selective serotonin reuptake inhibitor, is effective in 40%-60%. Additional treatment options are warranted. The combination of dextromethorphan (DEX) and bupropion (BUP) (Auveulty) was approved for treatment in 2022. This unique combination offers an interesting mechanism of action and favorable onset of action for patients with MDD. The mechanism of action of DEX-BUP when used in combination is unique. DEX is a noncompetitive N-methyl-d-aspartate receptor antagonist rapidly metabolized through the CYP450 2D6. BUP is an aminoketone and CYP2D6 inhibitor, which results in increased plasma levels of DEX through competitive CYP2D6 inhibition. In a phase 2 clinical study, the efficacy of DEX-BUP was compared with BUP alone in patients with clinically diagnosed MDD. At baseline, participants had moderate-to-severe depression using the Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impressions Severity (CGI-S) scales. There was a significant overall reduction in MADRS and CGI-S scores in the treatment group compared with the BUP monotherapy with improvement observed as early as week 1 of treatment. Later, a phase 3 study was conducted comparing DEX-BUP 45 mg/105 mg with placebo in patients with moderate-to-severe MDD. Similarly, MADRS and CGI-S scores were significantly reduced in the treatment group. Adverse effects were similar in all groups. Clinical response to first line treatment options for MDD are reported to be 40%-60%. Availability of additional treatment options, particularly those with reduced time to efficacy, may improve overall treatment and patient quality of life. DEX-BUP is a combination option that has been shown to improve depression symptoms as early as 1 week after initiation.

Comparative efficacy of cognitive behavior therapy and interpersonal therapy in the treatment of depression: A randomized controlled study

Background: Depressive disorders are one of the most common psychiatric disorders that occur in people of all ages. Aim: To assess the efficacy of cognitive behavior therapy (CBT) and interpersonal therapy (IPT) in cases of depression. Materials and Methods: The sample for the study comprised 52 diagnosed cases of major depressive disorder (MDD) based on the 10th revision of the International Classification of Diseases (ICD-10) criteria in the age range of 21 to 50 years. They were randomized with the help of the app and assigned to CBT and IPT groups. Two patients had dropped out of the CBT group. Hence, finally, 50 cases were taken for study. A total of 12 therapy sessions were given. All patients were given standard treatment as prescribed. Results: Findings of paired samples t-test to assess the within-group differences in both the groups (CBT and IPT) as well as gains score statistics or difference score statistics (pre-test minus post-test) were applied to compare group differences. Results of paired samples ‘t’ test suggest that there was a statistically significant difference in the scores of both the groups from pre-test to post-test. IPT group had shown significantly better outcomes as quantified by the percentage of patients scoring less on the outcome variable of the Beck Depression Inventory (BDI), Montgomery–Asberg Depression Rating Scale (MADRS), Hopelessness Scale, and General Health Questionnaire (GHQ). Conclusion: Both CBT and IPT are efficacious in the treatment of MDD. IPT yielded better results on MADRS as compared to CBT on parameters of outcome in the present study. The findings indicate that interventions were effective in reducing the symptoms of depression.

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.

Machine learning algorithm-based estimation model for the severity of depression assessed using Montgomery-Asberg depression rating scale.

Depressive disorder is often evaluated using established rating scales. However, consistent data collection with these scales requires trained professionals. In the present study, the "rater & estimation-system" reliability was assessed between consensus evaluation by trained psychiatrists and the estimation by 2 models of the AI-MADRS (Montgomery-Asberg Depression Rating Scale) estimation system, a machine learning algorithm-based model developed to assess the severity of depression. During interviews with trained psychiatrists and the AI-MADRS estimation system, patients responded orally to machine-generated voice prompts from the AI-MADRS structured interview questions. The severity scores estimated from two models of the AI-MADRS estimation system, the max estimation model and the average estimation model, were compared with those by trained psychiatrists. A total of 51 evaluation interviews conducted on 30 patients were analyzed. Pearson's correlation coefficient with the scores evaluated by trained psychiatrists was 0.76 (95% confidence interval 0.62-0.86) for the max estimation model, and 0.86 (0.76-0.92) for the average estimation model. The ANOVA ICC rater & estimation-system reliability with the evaluation scores by trained psychiatrists was 0.51 (-0.09 to 0.79) for the max estimation model, and 0.75 (0.55-0.86) for the average estimation model. The average estimation model of AI-MADRS demonstrated substantially acceptable rater & estimation-system reliability with trained psychiatrists. Accumulating a broader training dataset and the refinement of AI-MADRS interviews are expected to improve the performance of AI-MADRS. Our findings suggest that AI technologies can significantly modernize and potentially revolutionize the realm of depression assessments.

Ketamine for postoperative avoidance of depressive symptoms: the K-PASS feasibility randomised trial

BackgroundSurgical patients with previous depression frequently experience postoperative depressive symptoms. This study's objective was to determine the feasibility of a placebo-controlled trial testing the impact of a sustained ketamine infusion on postoperative depressive symptoms. MethodsThis single-centre, triple-blind, placebo-controlled randomised clinical trial included adult patients with depression scheduled for inpatient surgery. After surgery, patients were randomly allocated to receive ketamine (0.5 mg kg−1 over 10 min followed by 0.3 mg kg−1 h−1 for 3 h) or an equal volume of normal saline. Depressive symptoms were measured using the Montgomery–Asberg Depression Rating Scale. On post-infusion day 1, participants guessed which intervention they received. Feasibility endpoints included the fraction of patients approached who were randomised, the fraction of randomised patients who completed the study infusion, and the fraction of scheduled depression assessments that were completed. ResultsIn total, 32 patients were allocated a treatment, including 31/101 patients approached after a protocol change (31%, 1.5 patients per week). The study infusion was completed without interruption in 30/32 patients (94%). In each group, 7/16 participants correctly guessed which intervention they received. Depression assessments were completed at 170/192 scheduled time points (89%). Between baseline and post-infusion day 4 (pre-specified time point of interest), median depressive symptoms decreased in both groups, with difference-in-differences of −1.00 point (95% confidence interval −3.23 to 1.73) with ketamine compared with placebo. However, the between-group difference did not persist at other time points. ConclusionsPatient recruitment, medication administration, and clinical outcome measurement appear to be highly feasible, with blinding maintained. A fully powered trial may be warranted. Clinical trial registrationNCT05233566.

Factors Associated with Psychotic and Depressive Symptoms in Methamphetamine Users.

Objective: Methamphetamine use has been recognized as a prominent public health issue, which is associated with psychotic and depressive symptoms. This study aimed to assess factors that show a significant relation with psychotic and depressive symptoms in adults who use methamphetamine. Method : We assessed 95 patients who had used methamphetamine within the last month and were admitted to the outpatient treatment clinic. Evaluation of all patients was carried out through face-to-face interviews, and their symptoms were evaluated using different scales. The Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms were employed to assess positive and negative symptoms of psychosis, respectively. Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale, while illness severity was evaluated using the Clinical Global Impression- Severity Scale. Additionally, functioning status was assessed using the Functioning Assessment Short Test, and withdrawal severity was measured by employing the Amphetamine Cessation Symptom Assessment Scale. Craving severity was evaluated using the Stimulant Craving Questionnaire, anxiety severity using the Hamilton Anxiety Rating Scale, and insight status using the Schedule for Assessment of Insight Expanded. Results: Among the demographic variables, working with family was associated with lower positive symptoms scores (OR = 6.31, P < 0.05). Parole/probation related admissions were associated with lower positive and depressive symptoms scores (OR = 15.06, P = 0.03; OR = 9.87, P = 0.02). Having suicide attempts, number of suicide attempts, and amount of methamphetamine used were found to show association with higher positive (OR = 13.59, P < 0.01; OR = 2.52, P < 0.05; OR = 3.48, P < 0.05, respectively) and depressive symptoms scores (OR = 10.35, P < 0.001; OR = 2.23, P < 0.01; OR = 2.3, P < 0.05). After adjusting for all variables, clinical impression and insight scores remained significantly associated with positive symptoms scores (AOR = 6.74, P < 0.05; AOR = 2.63, P < 0.001, respectively), while anxiety, amphetamine cessation, and positive symptoms scores remained associated with depressive symptoms scores (AOR = 0.48, P < 0.001; AOR = 0.11, P = 0.003; AOR = 0.36, P = 0.02, respectively). Conclusion: This study appears to be the first to examine the associations between clinical variables and both positive symptoms and depressive symptoms in methamphetamine users. Increased attention should be paid to suicide history, anxiety level, amount of methamphetamine use and loss of insight to provide effective treatment in patients with methamphetamine use.

P201: Effect of Virtual Reality-based Biofeedback in Highly Stressed People

Objective:Virtual Reality (VR)-based Biofeedback (BF), a relatively new intervention, is rapidly increasing for the treatment of mood disorders. However, research on whether VR-based BF is more effective than traditional BF is still lacking.Methods:A total of 131 adults from the community enrolled in the study. Participants scored ≥10 on Patient Health Questionnaire-9 (PHQ-9) or ≥9 on Panic Disorder Severity Scale (PDSS) were randomly assigned to VR or BF group. Those who have not met the criteria of PHQ-9 and PDSS were classified as the control group. All participants visited three times across 3 months and received either VR-based or conventional BF intervention. The control group received the same treatment as the VR group. Also, on each visit, the participants completed Montgomery-Asberg Depression Rating Scale (MADRS), State-Trait Anxiety Inventory (STAI), and Visual Analogue Scale (VAS).Results:The analysis included 118 participants in total (VR: 40, BF: 38, Control: 40). There was no significant difference in demographic variables among the 3 groups. After the treatment, VR and BF groups exhibited significant decreases in MADRS, PHQ-9, STAI, and VAS compared to the baseline within each group (p&lt;0.005). Importantly, compared to the BF group, the VR group showed a significantly greater decrease in STAI (p&lt;0.05). Further analyses revealed that scores of MADRD, PHQ-9, STAI, and VAS also significantly decreased in highly stressed group compared to the control group.Conclusion:Findings suggest that the application of VR-based BF was effective in reducing anxiety and depressive symptoms in highly stressed people. Compared to conventional BF, VR-based BF can be a cost-effective treatment option especially for relieving anxiety.

Comparing the efficacies of transcranial magnetic stimulation treatments using different targeting methods in major depressive disorder: protocol for a network meta-analysis

IntroductionTranscranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (lDLPFC) has been widely used as a treatment for major depressive disorder (MDD) in the past two decades. Different methods...