The latest medical research on Depression
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Request AccessPredicting remission after acute phase pharmacotherapy in patients with bipolar I depression: A machine learning approach with cross-trial and cross-drug replication.
Bipolar DisordersInterpatient variability in bipolar I depression (BP-D) symptoms challenges the ability to predict pharmacotherapeutic outcomes. A machine learning workflow was developed to predict remission after 8 weeks of pharmacotherapy (total score of ≤8 on the Montgomery Åsberg Depression Rating Scale [MADRS]).
Supervised machine learning models were trained on data from BP-D patients treated with olanzapine (N = 168) and were externally validated on patients treated with olanzapine/fluoxetine combination (OFC; N = 131) and lamotrigine (LTG; N = 126). Top predictors were used to develop a prognosis rule informing how many symptoms should change and by how much within 4 weeks to increase the odds of achieving remission.
An AUC of 0.76 (NIR:0.59; p = 0.17) was established to predict remission in olanzapine-treated subjects. These trained models achieved AUCs of 0.70 with OFC (NIR:0.52; p < 0.03) and 0.73 with LTG (NIR:0.52; p < 0.003), demonstrating external replication of prediction performance. Week-4 changes in four MADRS symptoms (reported sadness, reduced sleep, reduced appetite, and concentration difficulties) were top predictors of remission. Across all pharmacotherapies, three or more of these symptoms needed to improve by ≥2 points at Week-4 to have a 65% chance of achieving remission at 8 weeks (OR: 3.74, 95% CI: 2.45-5.76; p < 9.3E-11).
Machine learning strategies achieved cross-trial and cross-drug replication in predicting remission after 8 weeks of pharmacotherapy for BP-D. Interpretable prognoses rules required only a limited number of depressive symptoms, providing a promising foundation for developing simple quantitative decision aids that may, in the future, serve as companions to clinical judgment at the point of care.
What is known about suicide prevention gatekeeper training and directions for future research.
Suicide Life ThreatSuicide prevention training that teaches skills to support a person experiencing thoughts of suicide and create community support networks, often termed, "gatekeeper" training (GKT), has been a longstanding pillar of international, national, and local suicide prevention efforts. GKT aims to improve knowledge, attitudes, and self-efficacy in identifying individuals at risk for suicide, hopefully enhancing one's willingness and ability to intervene with a person experiencing a crisis. However, little is known about GKT's effectiveness in creating the essential behavior change (e.g., increase in intervening behaviors) it sets out to accomplish.
This paper explores the history and theoretical background of GKT, reviews the current state of research on GKT, and provides framing and recommendations for next steps to advance research and practice around GKT.
Through positioning GKT appropriately within the field of suicide prevention, we argue that the field of suicide prevention needs more rigorous research around GKT that includes long-term follow-up data on usage of skills learned during training, data on outcomes of those who have received an intervention from a trained gatekeeper, and the integration of implementation science to further our understanding of which trainings are appropriate for which helpers.
Contact resolution among Veterans Crisis Line phone and text contacts regarding Veterans Health Administration enrollees.
Suicide Life ThreatTo expand access to suicide prevention and support services, the Veteran Crisis Line (VCL) added text capabilities in 2011. It is unknown whether the likelihood of a contact being terminated by the user varies by contact type. We aimed to assess whether contact resolution varies by contact type after accounting for Veterans' sociodemographic and clinical characteristics, contact risk, and reasons for contact.
A retrospective cohort study of VCL phone and text contacts regarding identified VHA enrollees between 2016 and 2021 was performed. To examine differences in contact resolution between contact types, inverse probability of treatment weights were used to balance characteristics of text and phone contacts.
Relative to phone contacts, text contacts were associated with 3.39 percentage point (PP) (95% CI, 3.27-3.50; p < 0.001) lower likelihood of receiving an emergency dispatch/welfare check, 2.65 PP (95% CI, 2.55-2.76; p < 0.001) lower likelihood of requiring arrangement for same-day care, and 9.47 (95% CI, 9.34-9.59; p < 0.001) PP higher likelihood of being terminated by the user.
VCL text contact was associated with an increased likelihood of being terminated by the user. Further investigation is needed to understand the reasons for terminating contact for those who texted VCL.
Mood regulation in euthymic patients with a history of antidepressant-induced mania.
Bipolar DisordersThe use of antidepressants in bipolar disorder (BD) remains contentious, in part due to the risk of antidepressant-induced mania (AIM). However, there is no information on the architecture of mood regulation in patients who have experienced AIM. We compared the architecture of mood regulation in euthymic patients with and without a history of AIM.
Eighty-four euthymic participants were included. Participants rated their mood, anxiety and energy levels daily using an electronic (e-) visual analog scale, for a mean (SD) of 280.8(151.4) days. We analyzed their multivariate time series by computing each variable's auto-correlation, inter-variable cross-correlation, and composite multiscale entropy of mood, anxiety, and energy. Then, we compared the data features of participants with a history of AIM and those without AIM, using analysis of covariance, controlling for age, sex, and current treatment.
Based on 18,103 daily observations, participants with AIM showed significantly stronger day-to-day auto-correlation and cross-correlation for mood, anxiety, and energy than those without AIM. The highest cross-correlation in participants with AIM was between mood and energy within the same day (median (IQR), 0.58 (0.27)). The strongest negative cross-correlation in participants with AIM was between mood and anxiety series within the same day (median (IQR), -0.52 (0.34)).
Patients with a history of AIM have a different underlying mood architecture compared to those without AIM. Their mood, anxiety and energy stay the same from day-to-day; and their anxiety is negatively correlated with their mood.
The Suicide Status Form-4 (SSF-IV) as a potentially therapeutic suicide risk assessment tool.
Suicide Life ThreatEmpirically supported suicide risk assessment and conceptualization is a central aim of the Zero Suicide model. The Suicide Status Form (SSF) is the essential document and scaffolding of the Collaborative Assessment and Management of Suicidality-Brief Intervention (CAMS-BI) and is hypothesized as an example of a psychological assessment as therapeutic intervention (PATI). However, this hypothesis has never been directly tested.
N = 57 patients deemed at risk for outpatient suicidal behavior and treated as part of an inpatient psychiatric consultation and liaison service were recruited to participate in CAMS-BI at a Level 1 trauma center in the southeastern United States. During the CAMS-BI process, patients were asked to rate their subjective units of distress (SUDS) at five time points throughout the intervention (k = 285).
The omnibus random intercept multilevel model revealed a significant difference in pre- to post-session ratings of SUDS across patients. Post hoc pairwise comparisons revealed no significant differences between SSF sections (e.g., Section A, Section B, and Section C) and relative reductions in SUDS; however, there was an observable trend toward a favorable effect of Section A of the SSF.
The SSF may represent an example of PATI pending replication and extension of the current results.
Effects of long-term lithium therapy on kidney functioning in mood disorders: A population-based historical cohort study.
Bipolar DisordersLithium is Food and Drug Administration-approved for bipolar disorder (BD) and is also used in depressive disorders but is underutilized due to concerns about chronic kidney disease (CKD). We explored clinical and demographic profiles of patients on long-term lithium therapy (LTLT) and assessed kidney function. Our aims were to identify the predictors for CKD stage ≥3 and the impact of lithium discontinuation post-CKD diagnosis.
We conducted a population-based historical cohort study of adult patients with mood disorders on LTLT at the Marshfield Clinical Health System from 1990 to 2019. Data on lithium therapy and kidney-related information (estimated glomerular filtration rate and CKD) were extracted from electronic medical records.
Among 1603 patients with mood disorders (mean age 42.1 years, 60% females), 15.3% (n = 246) developed CKD stage ≥3. Patients without CKD were on lithium for 4.5 years, compared to 6.6 years for those with CKD. Hypertension, age, and BD were significant CKD risk factors. Kidney function declined linearly with lithium duration, returning to pre-treatment trajectory in patients without CKD but showed no improvement in those with CKD after lithium discontinuation.
The findings suggest that CKD occurs in 15% of patients with mood disorder receiving LTLT, with its progression potentially influenced by existing comorbidities rather than lithium alone. These results underscore the importance of monitoring kidney function in patients on LTLT and considering individual risk factors for CKD development. In patients who developed CKD, Li discontinuation did not impact change in kidney function.
Recent trends in hospital admission due to bipolar disorder in 10-19-year-olds in Spain: A nationwide population-based study.
Bipolar DisordersBipolar disorder (BD) hospitalization rates in children and adolescents vary greatly across place and over time. There are no population-based studies on youth BD hospitalizations in Spain.
We identified all patients aged 10-19 hospitalized due to BD in Spain between 2000 and 2021, examined their demographic and clinical characteristics, and assessed temporal trends in hospitalizations - overall and stratified by age and presence of additional psychiatric comorbidity. We used Joinpoint regressions to identify inflection points and quantify whole-period and annual percentage changes (APCs) in trends.
Of 4770 BD hospitalizations in 10-19-year-olds between 2000 and 2021 (average annual rate: 4.8 per 100,000), over half indicated an additional psychiatric comorbidity, most frequently substance abuse (62.2%), mostly due to cannabis (72.4%). During the study period, admissions increased twofold with an inflection point: Rates increased annually only between 2000 and 2008, for APCs 34.0% (95% confidence interval: 20.0%, 71.1%) among 10-14-year-olds, 10.3% (6.4%, 14.3%) among 15-19-year-olds, and 15.5% (11.5%, 22.7%) among patients with additional psychiatric comorbidity. Between 2009 and 2021, rates decreased moderately among 10-14-year-olds - APC: -8.3% (-14.1%, -4.4%) and slightly among 15-19-year-olds without additional psychiatric comorbidity - APC: -2.6(-5.7, -1.0), remaining largely stable among 15-19-year-olds overall.
Recent trends in hospitalization due to BD in 10-19-year-olds in Spain indicate salient increases in the early 2000s - especially among (i) patients aged 10-14 (decreasing moderately after 2009 among 10-14-year-olds and plateauing among 15-19-year-olds) and (ii) patients with additional psychiatric comorbidity (i.e., cannabis use disorder). These findings suggest links with recent changes in clinical practices for children and recent trends in substance use among Spanish youth.
A 6-month, prospective, randomized controlled trial of customized adherence enhancement versus a bipolar-specific educational control in poorly adherent adolescents and young adults living with bipolar disorder.
Bipolar DisordersFew studies have addressed medication adherence in adolescents and young adults (AYAs) with bipolar disorder (BD). This 6-month prospective randomized-controlled trial (RCT) tested customized adherence enhancement for adolescents and young adults (CAE-AYA), a behavioral intervention for AYAs versus enhanced treatment as usual (ETAU).
Inclusion criteria were AYAs age 13-21 with BD type I or II with suboptimal adherence defined as missing ≥20% of medications. Assessments were conducted at Screening, Baseline, and weeks 8, 12 and 24. Primary outcome was past 7 day self-reported Tablets Routine Questionnaire (TRQ) validated by electronic pillbox monitoring (SimpleMed). Symptom measures included the Hamilton Depression Rating Scale (HAM-D) and Young Mania Rating Scale (YMRS).
The mean sample age (N = 36) was 19.1 years (SD = 2.0); 66.7% (N = 24) female, BD Type I (81%). The mean missed medication on TRQ for the total sample was 35.4% (SD = 28.8) at screening and 30.4% (SD = 30.5) at baseline. Both CAE-AYA and ETAU improved on TRQ from screening to baseline. Baseline mean missed medication using SimpleMed was 51.6% (SD = 38.5). Baseline HAM-D and YMRS means were 7.1 (SD = 4.7) and 6.0 (SD = 7.3), respectively. Attrition rate at week 24 was 36%. Baseline to 24-week change on TRQ, adjusting for age, gender, educational level, living situation, family history, race, and ethnicity, showed improvement favoring CAE-AYA versus ETAU of 15%. SimpleMed interpretation was limited due to substantial missing data. There was a significant reduction in depression favoring CAE-AYA.
CAE-AYA may improve adherence in AYAs with BD, although conclusions need to be made cautiously given study limitations.
ClinicalTrials.gov identifier: NCT04348604.
Suicide decision-making: Differences in proximal considerations between individuals who aborted and attempted suicide.
Suicide Life ThreatThe transition from suicidal thoughts to behaviors often involves considering the consequences of suicide as part of the decision-making process. This study explored the relationship between this consideration process and the decision to either abort or carry out a suicide attempt.
Among inpatients with a suicide-related event in the past 2 weeks (suicide attempt n = 30 or aborted attempt n = 16), we assessed the degree to which they considered six domains of consequences, the impact of these considerations on their inclination to attempt suicide, and the duration of their decision-making.
All the participants who aborted and 87% of those who attempted considered consequences of suicide. Participants who aborted took longer to progress through decision-making stages and considered more suicide-hindering factors, especially interpersonal ones, though these differences were no longer significant after correction. Group status moderated the relationship between the balance of suicide-facilitating and suicide-hindering considerations and decision-making duration. Considering the consequences of suicide more favorably was related to a shorter ideation-to-action period before a suicide attempt and a longer ideation period before aborting an attempt.
This study highlights the complexity of suicide decision-making and its role in better understanding the progression from ideation to action.
Predictors and patterns of suicidal ideation disclosures among American adults.
Suicide Life ThreatWhen experiencing suicidal thoughts, many individuals do not tell others, making it difficult to ensure suicide prevention resources reach those who need it.
The current study utilizes a large sample of US adults who have experienced suicidal ideation in their lifetime (n = 1074) to examine predictors of disclosures. We also explore who participants disclose to and how helpful these disclosures are rated.
A majority (n = 812, 75.6%) reported disclosing. Black and Hispanic participants were less likely to disclose than White participants. Those who were never married were more likely to disclose, as were those who have attempted suicide. Mental healthcare utilization and favorable attitudes toward mental healthcare were also positive predictors of disclosure. More participants reported disclosing to a personal connection (n = 532, 65.5%) than a mental health professional (n = 282, 34.8%). On average, most sources were rated as neither helpful nor harmful.
The study highlights those who may be at a higher risk of experiencing suicidal thoughts but going unidentified. To increase helpfulness of disclosures, suicide prevention programming should emphasize training for laypersons and professionals on how to effectively respond when someone reveals that they are thinking of suicide.
Concept article: Antidepressant-induced destabilization in bipolar illness mediated by serotonin 3 receptor (5HT3).
Bipolar DisordersAntidepressants used by patients with bipolar disorder have been associated with destabilization with an increase in mania, depression, and cycling. The most commonly proposed mechanism, that antidepressants 'overshoot' their antidepressant effect to create a manic or mixed state, is unlikely since antidepressants have actually been found to be ineffective in treating bipolar depression. Beginning with known bipolar-specific pathophysiologic abnormalities provides the greatest likelihood of insight.
PubMed was queried with 'bipolar', 'sodium', 'intracellular sodium', 'serotonin 3', '5HT3', '5-hydroxytryptamine type 3 receptors', and 'antidepressant' either individually or in combination.
Pathologic mood states (both mania and depression) are associated with increased intracellular sodium (Na) concentrations that depolarize the resting membrane potential to increase cellular excitability (mania) or cause depolarization block (depression). Stimulation of the serotonin (5HT) receptors depolarizes the post-synaptic neuron. Stimulation of 5HT3 may be of particular importance since it is coupled to a cation channel that directly depolarizes the membrane. These effects directly impact the physiology of patients with bipolar disorder to alter neuronal excitability in a fashion that worsens both mania and depression.
The most consistently observed biological abnormality in individuals going through mania or bipolar depression involves a decline in Na pump activity, with consequent elevation of intracellular Na levels. Antidepressant treatment potentiates this, particularly by activation of 5HT3. This hypothesis can be tested by coadministering a 5HT3 antagonist (e.g., vortioxetine or ondansetron) to achieve blockade of that receptor while treating bipolar depression with a serotoninergic antidepressant.
Nonresponse to an item assessing firearm ownership: Associations with suicide risk and emotional distress.
Suicide Life ThreatFirearms account for more than half of suicide deaths in the United States (US) and both ownership and access are associated with increased risk of intentional and unintentional injury. Despite evidence linking ownership and access to suicide risk, individuals may be reticent to answer questionnaire items assessing ownership. The current study examined characteristics of individuals who do not provide a response (nonresponders) to a firearm ownership item in a community sample.
Data were collected from a cross-sectional online survey of 10,625 US adults. Univariate and multivariate analyses were conducted to examine demographic, emotional distress, and suicide risk differences across three groups (firearm owners, nonowners, and nonresponders).
Nonresponders were significantly younger, more likely to be female and non-White than firearm owners and nonowners. Nonresponders were less likely to endorse recent suicidal ideation and probable PTSD than firearm owners, but more likely to endorse probable PTSD than nonowners. Firearm owners were significantly more likely to report several correlates of suicide risk than nonowners.
Nonresponders may be a unique subgroup with distinct demographic, emotional distress, and suicide risk profiles compared to both firearm owners and nonowners. Implications of these findings for future directions are discussed.