Pilot randomized clinical trial of an SSRI vs bupropion: effects on suicidal behavior, ideation, and mood in major depression.
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SUBMITTER: Grunebaum MF
PROVIDER: S-EPMC3260969 | biostudies-other | 2012 Feb
REPOSITORIES: biostudies-other
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Project description:ObjectiveStudies demonstrate rapid antidepressant and anti-suicidal ideation effects of subanesthetic ketamine. The specific subcomponents of depression that are most closely tied to reduction of suicidal ideation with ketamine treatment are less explored.MethodsExploratory, post hoc analysis of data from a randomized clinical trial of ketamine vs midazolam in patients with major depressive disorder (MDD) and clinically significant suicidal ideation examined changes in factor analysis-derived symptom clusters from standard measures of depression (Hamilton Depression Rating Scale, HDRS; Beck Depression Inventory, BDI) and mood disturbance (Profile of Mood States, POMS), and their relationship to severity of suicidal ideation (Beck Scale for Suicidal Ideation; SSI). Ratings obtained before and one day after blinded intravenous infusion were decomposed into component factors or published subscales. Treatment effects on factors/subscales were compared between drugs, correlations with changes in suicidal ideation were tested, and stepwise regression was used to derive predictors of change in SSI.ResultsFactor scores for HDRS Psychic Depression, HDRS Anxiety, BDI Subjective Depression, POMS Depression and POMS Fatigue improved more with ketamine than midazolam. Stepwise regression showed across both drugs that improvement in HDRS Psychic Depression, POMS Depression, and HDRS Anxiety predicted 51.6% of the variance in reduction of suicidal ideation.LimitationsSecondary analysis of clinical trial data.ConclusionsKetamine's rapid effects on suicidal ideation appear to be mostly a function of its effects on core mood and anxiety symptoms of MDD, with comparatively little contribution from neurovegetative symptoms with the potential exception of vigor/fatigue.Trial registrationData used in this secondary analysis came from ClinicalTrials.gov identifier: NCT01700829.
| S-EPMC8828686 | biostudies-literature
Project description:Suicide is the second leading cause of death among adolescents. With every fifth Indian to be an adolescent, the cost of an adolescent dying by suicide is enormous. This necessitates an understanding of the potential risk factors of suicidal ideation among adolescents. Secondary data analysis is performed on cross-sectional survey data obtained from Understanding the Lives of Adolescents and Young Adults. The survey was conducted in two Indian states of Bihar and Uttar Pradesh. Descriptive statistics, bivariate analysis and logistic regression are done to examine the results. Adolescent girls reported more suicidal ideation than boys. The odds of suicidal ideation are significantly higher among adolescents whose mother faced physical abuse and adolescents who themselves experienced sexual abuse. Adolescent boys and girls who have moderate depressive symptoms and impulsive behavior are significantly more likely to report suicidal ideation. The results help in identifying the adolescents who are at a particular risk for suicidal ideation while planning for intervention program for prevention of suicide.
| S-EPMC8722622 | biostudies-literature
Project description:BackgroundRecent analyses have described metabolomic markers for depression and suicidal ideation in non-pregnant adults. We examined the metabolomic profile of antepartum depression and suicidal ideation during mid-pregnancy, a time of high susceptibility to mood disorders.MethodsWe collected fasting blood from 100 pregnant Peruvian women and profiled 307 plasma metabolites using liquid chromatography-mass spectrometry. We used the Patient Health Questionnaire 9 to define antepartum depression (score ≥ 10) and suicidal ideation (having thoughts that you would be better off dead, or of hurting yourself). Logistic regression was used to calculate odds ratios (ORs).ResultsThree triacylglycerol metabolites (C48:5 triacylglycerol [OR = =1.89; 95% confidence interval (CI): 1.14-3.14], C50:6 triacylglycerol [OR = =1.88; 95%CI: 1.13-3.14], C46:4 triacylglycerol [OR = =1.89; 95%CI: 1.11-3.21]) were associated with higher odds of antepartum depression and 4 metabolites (betaine [OR = =0.56; 95%CI:0.33-0.95], citrulline [OR = =0.58; 95%CI: 0.34-0.98], C5 carnitine [OR = =0.59; 95%CI: 0.36-0.99], C5:1 carnitine [OR = =0.59; 95%CI: 0.35-1.00]) with lower odds of antepartum depression. Twenty-six metabolites, including 5-hydroxytryptophan (OR = =0.52; 95%CI: 0.30-0.92), phenylalanine (OR = =0.41; 95%CI: 0.19-0.91), and betaine (OR = =0.53; 95%CI: 0.28-0.99) were associated with lower odds of suicidal ideation.LimitationsOur cross-sectional study could not determine whether metabolites prospectively predict outcomes. No metabolites remained significant after multiple testing correction; these novel findings should be replicated in a larger sample.ConclusionsAntepartum suicidal ideation metabolomic markers are similar to markers of depression among non-pregnant adults, and distinct from markers of antepartum depression. Findings suggest that mood disorder in pregnancy shares metabolomic similarities to mood disorder at other times and may further understanding of these conditions' pathophysiology.
| S-EPMC6917910 | biostudies-literature
Project description:BackgroundDefining the neurobiological underpinnings of suicidal ideation (SI) is crucial to improving our understanding of suicide. This study used magnetoencephalographic gamma power as a surrogate marker for population-level excitation-inhibition balance to explore the underlying neurobiology of SI and depression. In addition, effects of pharmacological intervention with ketamine, which has been shown to rapidly reduce SI and depression, were assessed.MethodsData were obtained from 29 drug-free patients with major depressive disorder who participated in an experiment comparing subanesthetic ketamine (0.5 mg/kg) with a placebo saline infusion. Magnetoencephalographic recordings were collected at baseline and after ketamine and placebo infusions. During scanning, patients rested with their eyes closed. SI and depression were assessed, and a linear mixed-effects model was used to identify brain regions where gamma power and both SI and depression were associated. Two regions of the salience network (anterior insula, anterior cingulate) were then probed using dynamic causal modeling to test for ketamine effects.ResultsClinically, patients showed significantly reduced SI and depression after ketamine administration. In addition, distinct regions in the anterior insula were found to be associated with SI compared with depression. In modeling of insula-anterior cingulate connectivity, ketamine lowered the membrane capacitance for superficial pyramidal cells. Finally, connectivity between the insula and anterior cingulate was associated with improvements in depression symptoms.ConclusionsThese findings suggest that the anterior insula plays a key role in SI, perhaps via its role in salience detection. In addition, transient changes in superficial pyramidal cell membrane capacitance and subsequent increases in cortical excitability might be a mechanism through which ketamine improves SI.
| S-EPMC7064429 | biostudies-literature
Project description:Evaluating the severity of depression (SOD), especially suicidal ideation (SI), is crucial in the treatment of not only patients with mood disorders but also psychiatric patients in general. SOD has been assessed on interviews such as the Hamilton Rating Scale for Depression (HAMD)-17, and/or self-administered questionnaires such as the Patient Health Questionnaire (PHQ)-9. However, these evaluation systems have relied on a person's subjective information, which sometimes lead to difficulties in clinical settings. To resolve this limitation, a more objective SOD evaluation system is needed. Herein, we collected clinical data including HAMD-17/PHQ-9 and blood plasma of psychiatric patients from three independent clinical centers. We performed metabolome analysis of blood plasma using liquid chromatography mass spectrometry (LC-MS), and 123 metabolites were detected. Interestingly, five plasma metabolites (3-hydroxybutyrate (3HB), betaine, citrate, creatinine, and gamma-aminobutyric acid (GABA)) are commonly associated with SOD in all three independent cohort sets regardless of the presence or absence of medication and diagnostic difference. In addition, we have shown several metabolites are independently associated with sub-symptoms of depression including SI. We successfully created a classification model to discriminate depressive patients with or without SI by machine learning technique. Finally, we produced a pilot algorithm to predict a grade of SI with citrate and kynurenine. The above metabolites may have strongly been associated with the underlying novel biological pathophysiology of SOD. We should explore the biological impact of these metabolites on depressive symptoms by utilizing a cross species study model with human and rodents. The present multicenter pilot study offers a potential utility for measuring blood metabolites as a novel objective tool for not only assessing SOD but also evaluating therapeutic efficacy in clinical practice. In addition, modification of these metabolites by diet and/or medications may be a novel therapeutic target for depression. To clarify these aspects, clinical trials measuring metabolites before/after interventions should be conducted. Larger cohort studies including non-clinical subjects are also warranted to clarify our pilot findings.
| S-EPMC5161310 | biostudies-literature
Project description:IntroductionSeveral monoclonal antibodies (mAbs) have been linked to neuropsychiatric adverse effects in patients, including depression and suicidal ideation and behavior.ObjectiveThe aim of this study was to quantify and characterize spontaneously reported adverse drug reactions (ADRs) of depression and suicidal ideation and behavior related to mAb users, and to explore a possible association with their mechanism of action.MethodsWe included mAb ADRs that were reported in VigiBase, and identified those related to depression and suicidal ideation and behavior. Reporting odds ratios (RORs) were estimated for each mAb (bevacizumab as the reference) and according to their influence on the immune system (not directly targeting [reference], stimulating, or suppressing). Those suppressing the immune system were further divided into their intended indication (auto-immune diseases, cancer).ResultsOverall, 2,924,319 ADRs for 44 mAbs were included; 9455 ADRs were related to depression and 1770 were related to suicidal ideation and behavior. The association was strongest for natalizumab and belimumab, both for depression (ROR 5.7, 95% confidence interval [CI] 5.0-6.4; and ROR 5.1, 95% CI 4.2-6.2) and suicidal ideation and behavior (ROR 12.0, 95% CI 7.9-18.3; and ROR 20.2, 95% CI 12.4-33.0). Those suppressing the immune system showed higher ROR, i.e. 1.9 (95% CI 1.8-2.0) for depression and 3.6 (95% CI 3.0-4.4) for suicidal ideation and behavior. This finding was only seen for mAbs used for treating autoimmune diseases.ConclusionDepression and suicidal ideation and behavior are seen in patients using mAbs, particularly mAbs used for treating autoimmune diseases that suppress the immune system. For interpretation of these data, the indications for use and other characteristics require further consideration.
| S-EPMC6581921 | biostudies-literature
Project description:This study tests a novel, within-person model that reexamines depression and stress as risk factors for suicidal ideation and behavior among adolescent girls with and without sexual/physical abuse histories.This longitudinal study includes data from 220 adolescent girls between 12 and 16 years of age (M = 14.69 years, SD = 1.37; 61% White). At baseline, adolescents reported the presence or absence of prior abuse as part of a clinical interview. At baseline and every 3 months for 18 months, adolescents completed measures of suicidal ideation and behavior, depressive symptoms, and stress.Multilevel models examined within-person mean, deviations from within-person mean, depression, and stress and their interactions with abuse as predictors of suicidal ideation and behavior. In addition to within-person mean depression, higher-than-usual depression (odds ratio [OR] = 1.99) and higher-than-usual stress (OR = 1.53) predicted greater risk of suicidal ideation at each follow-up assessment. Periods of higher-than-usual stress (1 SD increase) and periods of higher-than-usual depression (1 SD increase) were associated with an 82% and 57% increase in the odds of suicidal behavior, respectively, but only among those with abuse histories.Depression, stress, and abuse are well-known risk factors for suicidal ideation and behavior; however, it has been unclear for whom, and when, these factors have their greatest impact. These results show that depression and stress are potent risk factors among those with a history of abuse and that within-person elevations in these risk factors signal increased short-term risk of suicidal ideation and behavior. (PsycINFO Database Record
| S-EPMC5477992 | biostudies-literature
Project description:Suicide attempts and suicidal ideation in adolescence are considered to be related to suicide and psychiatric adversity later in life. Secondary prevention by improving the treatment of suicidal youth is a distinct possibility. In this study, treatment with a systematised mood-regulation focused cognitive behavioural therapy (MR-CBT) (n = 15) was compared with treatment as usual (TAU) (n = 12) in a group of depressed adolescents in a clinical setting. MR-CBT focuses on mood regulation by means of counter conditioning with memory reconsolidation being the proposed mechanism of change. Subjects practice keeping emotionally positive memories to diminish the emotional impact of negative memories. Symptoms of depression were tested with a short version of the Mood and Feelings Questionnaire (SMFQ), and wellbeing with the World Health Organization 5 Wellbeing Index (WHO-5). Suicidal events were rated according to the clinical interview Columbia Suicide Severity Rating Scale (C-SSRS). Suicidal events at the end of treatment were significantly reduced in the MR-CBT group, but not in the TAU group. Depression and wellbeing improved significantly in both treatment groups. While far from conclusive, the results are encouraging enough to suggest that further studies should be undertaken to examine whether psychotherapy focusing on mood regulation for young individuals at risk might enhance secondary prevention of suicide.
| S-EPMC5981960 | biostudies-literature
Project description:BackgroundWe tested the hypothesis that, after initial improvement with intravenous ketamine in patients with bipolar disorder (BD) with severe depression and acute suicidal thinking or behavior, a fixed-dose combination of oral D-cycloserine (DCS) and lurasidone (NRX-101) can maintain improvement more effectively than lurasidone alone.MethodsThis was a multi-center, double-blind, twostage, parallel randomized trial. Adult BD patients with depression and suicidal ideation or behavior were infused with ketamine or saline (Stage 1); those who improved were randomized to a fixed-dose combination of DCS and lurasidone vs. lurasidone alone (Stage 2) to maintain the improvement achieved in Stage 1. Depression was measured by the Montgomery Åsberg Depression Rating Scale (MADRS), and suicidal thinking and behavior was measured by the Columbia Suicide Severity Rating Scale (C-SSRS); global improvement was measured by the clinical global severity scale (CGI-S).Clinicaltrialsgov NCT02974010; Registered: November 22, 2016.ResultsThirty-seven patients were screened and 22 were enrolled, randomized, and treated. All 22 patients treated in Stage 1 (17 with ketamine and 5 with saline) were enrolled into Stage 2, and 11 completed the study. The fixed-dose combination of DCS and lurasidone was significantly more effective than lurasidone alone in maintaining improvement in depression (MADRS LMS Δ-7.7; p = 0.03) and reducing suicidal ideation, as measured by C-SSRS (Δ-1.5; p = 0.02) and by CGI-SS (Δ-2.9; p = 0.03), and with a non-statistically significant decrease in depressive relapse (0% vs. 40%; p = 0.07). This sequential treatment regimen did not cause any significant safety events and demonstrated improvements in patient-reported side effects.ConclusionsSequential treatment of a single infusion of ketamine followed by NRX-101 maintenance is a promising therapeutic approach for reducing depression and suicidal ideation in patients with bipolar depression who require hospitalization due to acute suicidal ideation and behavior. On the basis of these findings, Breakthrough Therapy Designation was awarded, and a Special Protocol Agreement was granted by the FDA for a registrational trial.
| S-EPMC10423711 | biostudies-literature
Project description:BACKGROUND:This exploratory study sought to examine the effect of an acute course of high-frequency repetitive TMS on suicidal ideation in adolescents. METHODS:Data were pooled from 3 prior protocols providing a 30-session course of open-label TMS treatment for adolescents with treatment-resistant depression. All participants (n?=?19) were outpatients taking antidepressant medication, with TMS provided as adjunctive treatment. Suicidality was assessed at baseline, after 10 treatments, after 20 treatments, and after 30 treatments. Outcome measures of suicidal ideation included the Columbia Suicide Severity Rating Scale (C-SSRS) "Intensity of Ideation" subscale and Item 13 "Suicidality" on the Children's Depression Rating Scale, Revised (CDRS-R). RESULTS:The predicted odds of suicidal ideation (CDRS-R Item 13 and C-SSRS Intensity of Ideation subscale) significantly decreased over 6 weeks of acute TMS treatment without adjustments for illness (depression) severity. However, the magnitude of the decrease in the predicted odds of suicidal ideation across 6 weeks of treatment was attenuated and rendered non-significant in subsequent analyses that adjusted for illness (depression) severity. LIMITATIONS:This was an exploratory study with a small sample size and no sham control. Regulatory and ethical barriers constrained enrollment of adolescents with severe suicidality. CONCLUSIONS:The present findings suggest that open-label TMS mitigated suicidal ideation in adolescents through the treatment and improvement of depressive symptom severity. Although caution is warranted in the interpretation of these results, the findings can inform the design and execution of future interventional trials targeting suicidal ideation in adolescents.
| S-EPMC6431788 | biostudies-literature