Magnetic seizure therapy reduces suicidal ideation and produces neuroplasticity in treatment-resistant depression.
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SUBMITTER: Sun Y
PROVIDER: S-EPMC6251931 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
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Magnetic seizure therapy reduces suicidal ideation and produces neuroplasticity in treatment-resistant depression.
Sun Yinming Y Blumberger Daniel M DM Mulsant Benoit H BH Rajji Tarek K TK Fitzgerald Paul B PB Barr Mera S MS Downar Jonathan J Wong Willy W Farzan Faranak F Daskalakis Zafiris J ZJ
Translational psychiatry 20181123 1
Therapeutic seizures may work for treatment-resistant depression (TRD) by producing neuroplasticity. We evaluated whether magnetic seizure therapy (MST) produces changes in suicidal ideation and neuroplasticity as indexed through transcranial magnetic stimulation and electroencephalography (TMS-EEG) of the dorsolateral prefrontal cortex (DLPFC). Twenty-three patients with TRD were treated with MST. Changes in suicidal ideation was assessed through the Scale for Suicidal Ideation (SSI). Before an ...[more]
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Project description:Importance:There is an unmet need for effective treatments for suicidality in mental disorders. Magnetic seizure therapy (MST) has been investigated as an alternative to electroconvulsive therapy, a known effective treatment for suicidality, in the management of treatment-resistant major depressive disorder, with promising findings. Yet, there are very limited data on the association of MST with suicidality directly. It is important to explore the potential of MST as a viable treatment alternative to electroconvulsive therapy for suicidality. Objective:To determine the association of MST with suicidality in patients with treatment-resistant major depressive disorder. Design, Setting, and Participants:This nonrandomized controlled trial took place at a single tertiary care psychiatric facility in Canada. It followed an open-label study design with consecutive treatment cohorts. Consecutive groupings of 67 patients with treatment-resistant major depressive disorder and with baseline suicidality present were treated for up to 24 treatments. The study was run from February 2012 through June 2019. Patients were followed up for 6 months at the end of the treatment period. This post hoc secondary analysis of the trial was performed from January to November 2019. Interventions:MST was delivered at 100% stimulator output over the prefrontal cortex with low (25 Hz), moderate (50 or 60 Hz), or high (100 Hz) frequency, for a maximum of 24 sessions. Main Outcomes and Measures:Remission from suicidality was measured as an end point score of 0 on the Beck Scale for Suicidal Ideation. A linear mixed model was used to assess the trajectory of Beck Scale for Suicidal Ideation scores. Results:A total of 67 patients (mean [SD] age, 46.3 [13.6] years; 40 women [60.0%]) received a mean (SD) of 19.5 (5.1) MST treatments. The overall number of patients achieving remission was 32 (47.8%). Sixteen patients (55.2%) receiving low-frequency MST achieved remission, as well as 12 patients (54.5%) in the moderate-frequency group, and 4 patients (25.0%) in the high-frequency group. The linear mixed model revealed an association of time with Beck Scale for Suicidal Ideation scores (F8,293.95?=?5.73; P?<?.001). Conclusions and Relevance:These findings suggest that MST may be an effective treatment for suicidality, and sensitivity analysis shows this may be particularly so at low and moderate frequencies. Future studies should directly compare MST with electroconvulsive therapy for treating suicidality and should evaluate MST as a treatment for suicidality across mental disorders. Trial Registration:ClinicalTrials.gov Identifier: NCT01596608.
| S-EPMC7435344 | biostudies-literature
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:Background and aimsWe investigated kynurenine pathway (KP) metabolites levels and their association with suicidal ideation in patients with treatment-resistant depression (TRD) and elevated peripheral inflammation. The effect of antidepressant augmentation with minocycline on KP metabolites was tested.MethodsWe analysed data from MINocycline in DEPression, a 4-week, randomized, placebo controlled (1:1) trial of minocycline added to antidepressant treatment in 39 TRD patients (n = 18 minocycline; n = 21 placebo) with C-reactive protein (CRP) ⩾1 mg/L. At baseline and at week 4, we collected data on suicidality (Beck Depression Inventory) and blood samples to measure inflammatory markers and KP metabolites. We tested (1) the association of KP metabolites ratios with inflammatory markers and suicidal ideation at baseline and (2) the role of suicidality and treatment (minocycline vs placebo) in affecting KP changes over time.ResultsAt baseline, kynurenine/tryptophan (KYN/TRP) ratio positively correlated with high-sensitivity CRP (Spearman's ρ = 0.35, p = 0.02) and IL-10, (ρ = 0.41, p = 0.009); and tumour necrosis factor was positively correlated with quinolinic acid/3-hydroxykynurenine ratio (ρ = 0.55, p < 0.001). Moreover, participants with suicidal ideation showed higher levels of KYN/TRP (U = 143.000, p = 0.02) than those without suicidal ideation. There was no significant effect of minocycline on KP metabolites changes from baseline to week 4. However, in the minocycline group, the number of participants with suicidal thoughts decreased from 44.4% (8/18) to 22.2% (4/18).ConclusionIncreased KP neurotoxic metabolites are associated with elevated peripheral inflammation in depressed individuals, particularly in those with suicidal ideation. Targeting KP in this population could be a potential effective personalized approach. Whether this includes minocycline should be investigated in future larger trials.
| S-EPMC10291376 | biostudies-literature
Project description:ObjectivesThis study aimed to systematically review the efficacy of transcranial magnetic stimulation treatment in reducing suicidal ideation in depression.MethodsPubMed, Web of Science, CBMdisc, WanFang, Chongqing VIP, and CNKI databases were electronically searched for randomized controlled trials of transcranial magnetic stimulation (TMS) intervention in the management of suicidal ideation from inception to February 24, 2021. Two reviewers independently screened studies, extracted data, and assessed the quality of included studies. Meta-analysis was then performed using STATA 15.1 software.ResultsA total of eight articles involving 566 patients were included. The meta-analysis results showed that the suicidal ideation scores of the group who received TMS treatment were significantly lower [standardized mean difference (SMD) = -0.415, 95% confidence interval (CI): -0.741 to -0.090, P = 0.012] than those of the control group. Subgroup analysis showed that age, TMS pattern, frequency of intervention, and stimulation threshold altered the TMS efficacy.ConclusionsEvidence showed that TMS achieved superior results in reducing suicidal ideation. Because of the limited quality and quantity of the included studies, more high-quality studies are required to verify the conclusions.Systematic review registrationhttps://inplasy.com/, identifier: INPLASY202180065.
| S-EPMC8803905 | biostudies-literature
Project description:Repeated administration of subanesthetic intravenous ketamine may prolong the rapid decrease in suicidal ideation (SI) elicited by single infusions. The purpose of this secondary analysis was to evaluate reduction in SI with a single ketamine infusion compared with an active control, and prolonged suppression of SI with repeated and maintenance infusions. Thirty-seven participants with treatment-resistant depression (TRD) and baseline SI first received a single ketamine infusion during a randomized, double-blind crossover with midazolam. Following relapse of depressive symptoms, participants received six open-label ketamine infusions administered thrice-weekly over 2 weeks. Antidepressant responders (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] scores) received four further open-label infusions administered once-weekly. Changes in SI were assessed with the suicide items on the MADRS (item 10, MADRS-SI) and the Quick Inventory of Depressive Symptomatology-Self Report (item 12, QIDS-SI). Linear mixed models revealed that compared with midazolam, a single ketamine infusion elicited larger reduction in SI (P = 0.01), with maximal effects measured at 7 days postinfusion (P < 0.001, Cohen's d = 0.83). Participants had cumulative reductions in MADRS-SI scores with repeated infusions (P < 0.001), and no further change with maintenance infusions (P = 0.94). QIDS-SI results were consistent with MADRS-SI. Overall, 69% of participants had a complete alleviation of SI following repeated infusions. In TRD, single and repeated ketamine infusions resulted in decreases in SI which were maintained with once-weekly maintenance infusions. This study adds to the growing body of research suggesting ketamine as a possible novel treatment strategy for SI in mood disorders.
| S-EPMC7021716 | biostudies-literature
Project description:BackgroundDisturbed sleep may confer risk for suicidal behaviors. Polysomnographic (PSG) sleep parameters have not been systematically evaluated in association with suicidal ideation (SI) among individuals with treatment-resistant depression (TRD).MethodsThis secondary data analysis included 54 TRD individuals (N=30 with major depressive disorder (MDD) and N=24 with bipolar depression (BD)). PSG sleep parameters included Sleep Efficiency (SE), Total Sleep Time (TST), Wakefulness After Sleep Onset (WASO), REM percent/latency, and non-REM (NREM) Sleep Stages 1-4. The Hamilton Depression Rating Scale (HAM-D) was used to group participants according to presence or absence of SI. Sleep abnormalities were hypothesized among those with current SI. ANOVA analyses were conducted before (Model 1) and after adjusting for depression (Model 2) and diagnostic variables (Model 3).ResultsSignificant differences in PSG parameters were observed in Model 1; those with SI had less NREM Stage 4 sleep (p<.05). After adjusting for central covariates, Models 2 and 3 revealed significantly less NREM Stage 4 sleep, lower SE (P<.05), and higher WASO (P<.05) among those with SI. BD participants with SI also had less NREM Stage 4 and more NREM Stage 1 sleep.Limitations1) a predominantly white sample; 2) exclusion of imminent suicide risk; 3) concomitant mood stabilizer use among BD patients; and 4) single-item SI assessment.ConclusionsIndependent of depression severity, SI was associated with less NREM Stage 4 sleep, and higher nocturnal wakefulness across diagnostic groups. Sleep may warrant further investigation in the pathogenesis of suicide risk, particularly in TRD, where risk may be heightened.
| S-EPMC6502232 | biostudies-literature
Project description:To test the hypothesis that Problem Solving Therapy (PST) is more effective than Supportive Therapy (ST) in reducing suicidal ideation in older adults with major depression and executive dysfunction. We further explored whether patient characteristics, such as age, sex, and additional cognitive impairment load (e.g., memory impairments) were related to changes in suicidal ideation over time.Secondary data analysis using data from a randomized clinical trial allocating participants to PST or ST at 1:1 ratio. Raters were blind to patients' assignments.University medical centers.221 people aged 65 years old and older with major depression determined by Structured Clinical Interview for DSM-III-R diagnosis and executive dysfunction as defined by a score of 33 or less on the Initiation-Perseveration Score of the Mattis Dementia Rating Scale or a Stroop Interference Task score of 25 or less.12 weekly sessions of PST or ST.The suicide item of the Hamilton Depression Rating Scale.Of the 221 participants, 61% reported suicidal ideation (SI). The ST group had a lower rate of improvement in SI after 12 weeks (44.6%) than did the PST group (60.4%, Fisher's exact test p = 0.031). Logistic regression showed significantly greater reductions in SI in elders who received PST at both 12 weeks (OR: .50, Z = -2.16, p = 0.031) and 36 weeks (OR: 0.5, Z = -1.96, p = 0.05) after treatment.PST is a promising intervention for older adults who are at risk for suicide. ClinicalTrials.gov Identifier: NCT00052091.
| S-EPMC5730069 | 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:BackgroundClinical guidelines suggest that psychological interventions specifically aimed at reducing suicidality may be beneficial. We examined the impact of two depression treatments, cognitive therapy (CT) and interpersonal psychotherapy (IPT) on suicidal ideation (SI) and explored the temporal associations between depression and SI over the course of therapy.MethodsNinety-one adult (18-65) depressed outpatients from a large randomized controlled trial who were treated with CT (n = 37) and IPT (n = 54) and scored at least ≥1 on the Beck Depression Inventory II (BDI-II) suicide item were included. Linear (two-level) mixed effects models were used to evaluate the impact of depression treatments on SI. Mixed-effects time-lagged models were applied to examine temporal relations between the change in depressive symptoms and the change in SI.ResultsSI decreased significantly during treatment and there were no differential effects between the two intervention groups (B = -0.007, p = .35). Depressive symptoms at the previous session did not predict higher levels of SI at the current session (B = 0.016, p = .16). However, SI measured at the previous session significantly predicted depressive symptoms at the current session (B = 2.06, p < .001).ConclusionsBoth depression treatments seemed to have a direct association with SI. The temporal association between SI and depression was unidirectional with SI predicting future depressive symptoms during treatment. Our findings suggest that it may be most beneficial to treat SI first.
| S-EPMC8451935 | biostudies-literature