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This article discusses a study that examines the relationship between the acute dissociative effects of ketamine and changes in depression severity or suicidal thinking in individuals with major depressive disorder (MDD). The study found no association between the dissociative effects of ketamine and subsequent changes in depression severity or suicidal thinking. The article also explores the potential implications of this finding and discusses the question of what makes ketamine "special" in terms of its therapeutic benefits. The study acknowledges its limitations, such as a small sample size and lack of control for multiplicity. The article concludes by mentioning the use of ketamine-assisted psychotherapy and the need for further research in this area. [Extracted from the article]

Current treatment of major depressive disorder (MDD) warrants critical reexamination. Initial treatment response rates are modest and drop dramatically after 3 months. Meanwhile, MDD is emerging as the leading cause of disease burden worldwide. We searched PubMed (up to June 2021) for randomized controlled trials comparing antidepressant combinations versus monotherapy. We discuss findings from these studies in light of current treatment guidelines for MDD. These recommend a sequence of single, six-week-long, medication trials, before trying antidepressant combinations. The result leaves one third of patients still depressed after six months of treatment. Optimizing the first three months of MDD treatment is crucial because response rates during this period are five times better than in the second three months. We propose a new, evidence-based algorithm of sequential antidepressant treatment steps, termed Accelerated Sequential Antidepressant Protocol (ASAP), that may offer better response rates than current guidelines. ASAP involves shorter duration medication trials (2–4 weeks) and earlier use of antidepressant combinations, seeking additive antidepressant effects without worsening side effects. Future research should compare ASAP to current treatment guidelines. Research is also needed on the role of rapidly acting antidepressants like ketamine for acutely ill and suicidal depressed patients. [ABSTRACT FROM AUTHOR]

Neuroinflammation is implicated in the pathophysiology of depression. Toxoplasma gondii (T. gondii) causes chronic brain inflammatory process and may thus contribute to both depression and its most serious complication, suicidal behavior. In this study, we hypothesized that latent toxoplasmosis may underlie current depression and/or suicidal behavior. Currently depressed individuals (N = 384) and age, sex, and residence-matched healthy controls (HC) (N = 400) were tested for latent toxoplasmosis (i.e., positive serum T. gondii IgG antibodies). Exclusions included positive IgM and negative IgG antibodies indicating acute T. gondii infection and history of cognitive problems. Depression severity and history of lifetime suicide attempts were assessed using Beck Depression Inventory (BDI) and Columbia Suicide Severity Rating Scale, respectively. Participants with seropositive anti-T. gondii IgG antibody had a significantly higher odds of being depressed compared with seronegative participants (OR = 2.9, 95% CI: 1.9–4.3; p < 0.001). BDI score was significantly different between depressed seropositive and depressed seronegative individuals (IgG＋: mean (SD)= 39.65 (11.83) vs. IgG−: mean (SD)= 33.44(9.80); t = 5.03, p < 0.001). Further, seropositive depressed participants were more likely to have prior history of actual suicide attempts compared with seronegative participants (OR= 6.2, 95% CI: 3.4–11.2, p < 0.001). Latent toxoplasmosis may represent be a risk factor for depression and suicidal behavior. Screening for, and treatment of, underlying T. gondii infection may help improve depression and curb the increasing suicide rates. Future studies should prospectively test these hypotheses to be adequately implemented. Latent toxoplasmosis has been linked to history of psychiatric disorders. Depressed individuals have higher positivity rate of T. gondii IgG antibody than healthy controls. Depressed T. gondii seropositive individuals have increased likelihood to have history of suicidal behavior. [ABSTRACT FROM AUTHOR]

In the article, the authors present a brain-centric model of suicidal behavior called stress-diathesis model to help explain the pathogenesis of the diathesis elements of suicidal behavior. Also cited are the high rate of suicide in the U.S. and around the world, some proven suicide prevention measures like improved training of nonpsychiatrist physicians in the diagnosis and treatment of depression, as well as the prevalence of suicidal ideation as compared to suicidal behavior.

Objective: Suicidal ideation (SI) is heterogeneous with different patterns and risk factors. SI can be persistent with stable severity, but may also fluctuate rapidly over a short period of time. The latter pattern is likely associated with affective instability and may consist of activation of SI at times of stress, that then subside. Although affective instability is a hallmark of borderline personality disorder (BPD), little is known about SI variability in BPD. We hypothesized that SI variability would be associated with affective instability in BPD suicide attempters. Method: Sample included 38 females with BPD and history of suicidal behavior. SI was assessed over 1 week using ecological momentary assessment (EMA) at six epochs daily. The relationship between SI variability (i.e., change of SI from one epoch to another) and SI severity (i.e., average scores across epochs), and affective instability, assessed using the Affective Lability Scale (ALS), were examined. Possible confounding effects of depression severity and impulsiveness were tested. Results: Participants demonstrated high ALS scores and wide range of SI variability. ALS scores predicted SI variability, even after controlling for depression severity. Although ALS also predicted SI severity, this association was driven by depression severity. ALS did not correlate with impulsiveness score. Conclusions: Affective instability may predict SI variability in BPD suicide attempters independent of depression severity. This supports our model of suicidal subgroups with different constellations of clinical aspects and risk factors. Future studies could examine these associations in larger samples and different populations to determine implications for suicide prevention. [ABSTRACT FROM AUTHOR]

Background: Identifying brain activity patterns that are associated with suicidal ideation (SI) may help to elucidate its pathogenesis and etiology. Suicide poses a significant public health problem, and SI is a risk factor for suicidal behavior.Methods: Forty-one unmedicated adult participants in a major depressive episode (MDE), 26 with SI on the Beck Scale for Suicidal Ideation and 15 without SI, underwent resting-state functional magnetic resonance imaging scanning. Twenty-one healthy volunteers (HVs) were scanned for secondary analyses. Whole brain analysis of both amplitude of low-frequency fluctuations (ALFFs) and fractional ALFF was performed in MDE subjects to identify regions where activity was associated with SI.Results: Subjects with SI had greater ALFF than those without SI in two clusters: one in the right hippocampus and one in the thalamus and caudate, bilaterally. Multi-voxel pattern analysis distinguished between those with and without SI. Post hoc analysis of the mean ALFF in the hippocampus cluster found it to be associated with a delayed recall on the Buschke memory task. Mean ALFF from the significant clusters was not associated with depression severity and did not differ between MDE and HV groups.Discussion: These results indicate that SI is associated with altered resting-state brain activity. The pattern of elevated activity in the hippocampus may be related to how memories are processed. [ABSTRACT FROM AUTHOR]

Importance: Increasing evidence suggests a potential role of immune-modulatory drugs for treatment-resistant depression. This scoping review explores the emerging evidence regarding the antidepressant effects of monoclonal antibodies (mAbs), a relatively newer class of immune therapeutics with favorable safety profile., Observations: PubMed was searched up to November 2023 for English publications addressing the antidepressant effects of mAbs, including meta-analyses, randomized controlled trials, open-label, single-arm studies, and case series. Several mAbs have shown potential antidepressant effects, but most studies in primary inflammatory disorders included patients with mild depression. Only infliximab and sirukumab were directly examined in individuals with primary depression. mAbs that do not require laboratory monitoring, such as ixekizumab and dupilumab, could hold potential promise if future studies establish their safety profile regarding suicide risk., Conclusions and Relevance: The use of several mAbs for the treatment of primary inflammatory disorders has been associated with improvement of comorbid depressive symptoms. Given their unique mechanisms of action, mAbs may offer a new hope for depressed patients who do not respond to currently available antidepressants. Further research addressing individuals with more severe depressive symptoms is essential. Direct examination of antidepressant effects of mAbs in people with primary depressive disorders is also crucial to refine their clinical use in the treatment of depression., (© Copyright 2024 Physicians Postgraduate Press, Inc.)