Agitated Depression Associated With Flurazepam Discontinuation.

Agitated depression, also known as melancholia agitata, is a variant of depression characterized by severe symptoms of psychomotor agitation, inner unrest, anxiety, restlessness, prominent vegetative symptoms, and a high risk of suicide. This form of depression is reported to worsen with antidepressants and potentially improve with the use of ECT, lithium, antiepileptics, antipsychotics, and benzodiazepines. We describe a case of a 73-year-old female with a prior history of depression and generalized anxiety disorder who was maintained on flurazepam for 44 years and was admitted for severe depression with psychomotor agitation, prominent vegetative symptoms, thought perseveration, indecisiveness, and psychotic features that emerged following the discontinuation of flurazepam. Symptoms did not resolve with the use of alternative benzodiazepines such as nitrazepam and temazepam and further worsened with the use of several antidepressants. She finally had a complete resolution of these symptoms with a combination of alprazolam, zopiclone, and olanzapine. This case provides insight into this unique variant of depression and the role of GABA agonists in its pathology and management.

The longitudinal patterns of depression subtypes and stressors in depression severity in the Canadian longitudinal study on aging (CLSA).

AIM: The current study aims to characterize the longitudinal patterns of depression subtypes and investigate the associations among the stability of depression subtypes, COVID-19-related stressors, and depression severity. METHODS: The study utilized data from the Canadian Longitudinal Study on Aging, which is a national, long-term study of Canadian adults aged 45 and older (n = 12,957). Latent profile analysis was used to identify latent depression subtypes. Latent transition analysis was then applied to assess the stability of these subtypes over time. Hierarchical multivariate linear regression was used to explore the relationships among these identified depression subtypes, COVID-19-related stressors, and depression severity among males and females, respectively. RESULTS: Distinct depression subtypes were identified. Except for atypical depression, other depression subtypes showed greater stability over time. We also found that melancholic depression (B = 9.432) and typical depression (B = 6.677) were strongly associated with depression severity during the pandemic. Health-related stressors (B = 0.840), conflict (B = 3.639), difficulties accessing resources (B = 0.927), separation from family (B = 0.840), and caregiving experience (B = 0.764), were significantly associated with increased depression severity. Sex-specific analyses also revealed differences in the associations between stressors and depression severity between males and females. CONCLUSIONS: This study contributes valuable insights into the latent clustering of depression subtypes and their stability. Stressors were associated with increased depression severity, with distinct associations observed among males and females. These findings have implications for targeted early interventions and integrated clinical management strategies by providing the evidence base for tailored mental health care during and after the pandemic.

Depression Severity, Slow- versus Fast-Wave Neural Activity, and Symptoms of Melancholia.

Melancholia is a major and severe subtype of depression, with only limited data regarding its association with neurological phenomena. To extend the current understanding of how particular aspects of melancholia are correlated with brain activity, electroencephalographic data were collected from 100 adults (44 males and 56 females, all aged 18 y or more) and investigated for the association between symptoms of melancholia and the ratios of alpha/beta activity and theta/beta activity at parietal-occipital EEG sites PO1 and PO2. The results indicate differences in these associations according to the depressive status of participants and the particular symptom of melancholia. Depressed participants exhibited meaningfully direct correlations between alpha/beta and theta/beta activity and the feeling that "Others would be better off if I was dead" at PO1, whereas non-depressed participants had significant inverse correlations between theta/beta activity and "Feeling useless and not needed" and "I find it hard to make decisions" at PO1. The results are discussed in terms of the relative levels of fast-wave (beta) versus slow-wave (alpha, theta) activity exhibited by depressed and non-depressed participants in the parietal-occipital region and the cognitive activities that are relevant to that region.

"Mourning and Melancholia" Meets The Babadook: Emptiness and its Relation to Absence.

This paper explores how the film The Babadook illuminates psychoanalytic understandings of melancholia and mourning. The author attempts to unwind the complicated character of melancholia, using Freud as an initial point of orientation, then relying on a few ideas from Klein and later writers. The paper attempts to refine our understanding of the difference between absence and emptiness, especially the difference between being captured in the nothing or deadness of melancholic emptiness, on the one hand, and being alive enough to suffer the absence of a lost object, which bears a potential for mourning, on the other. The possibility of psychic tension between these states is explored. Some implications of the relationship between absence and emptiness for the mourning process are considered. The author uses the film as a resource throughout.

Mourning, melancholia and machines: An applied psychoanalytic investigation of mourning in the age of griefbots.

Death and mourning are being shaped by posthumous opportunities for the dead to affect current life in ways not possible in pre-digital generations. The psychological and sociological impact of the dead 'online' and of 'grief tech' is only beginning to be understood. It has not yet been explored psychoanalytically until this paper that examines one type of grief tech, namely the griefbot. This development is critically explored through a psychoanalytic reading of an episode of Black Mirror. I suggest that a psychoanalytic model of mourning provides an invaluable perspective to help us to think about this technology's potential as well as the psychological and ethical risks it poses. I argue that the immortalisation of the dead through digital permanence works against facing the painful reality of loss and the recognition of otherness, which is fundamental to psychic growth and to the integrity of our relationships with others. Drawing on Derrida's conceptualization of 'originary mourning', I suggest that mourning is an interminable process that challenges us to preserve within the self the otherness of the lost object. The tools we use for mourning need to be assessed first and foremost against this psychological and fundamentally ethical process.

Entrenched grievance as a harbour for the unmourned.

This paper hopes to enhance understanding about entrenched grievance in a couple of ways: (a) Initially, the paper reviews how entrenched grievance reflects melancholic states of mind in terms of its avoidance of the pain of loss and change. But the main contribution of the paper is likely to be found in (b), that is, via detailed clinical material, the paper illustrates how earnest efforts on the part of the analyst to bring understanding may lead to cognitive entrapments such as the convictions incumbent in the "knowing" analyst. Further, that this knowing analyst may need to become aggrieved, that is, narrow, impatient and concrete towards her patient's entrenchment, and then to recogize this plight in herself before she can genuinely hear her patient's grievance about her from a wider view, that is as a complaint from the "lively self", deserving recognition. The clinical detail demonstrates that such recognition softened the patient's grievance, allowing both members of the dyad to become more collaborative and open to the pains and growth available from mourning states of mind.

Catatonia and melancholia interface: exploring a new paradigm for evaluation and treatment. A case series and literature review.

Background: Catatonia has been increasingly associated with mood disorders and is recognized as a specifier in the DSM-5 and DSM-5-TR. The DSM-5-TR recognizes melancholia as a specifier for depressive episodes in major depressive disorder and bipolar disorder. It is characterized by severe anhedonia, lack of reactivity, excessive or delusional guilt, and significant vegetative symptoms. As the conceptualization of melancholia expanded beyond its mood components to include psychomotor disturbances, its overlap with psychomotor symptoms or catatonia becomes evident. This overlap was also described in Kahlbaum's original literature, where he describes the transition between states of melancholia, mania, and catatonia. Method: Case summary of six patients with major depressive disorder or depressed phase of bipolar disorder who were admitted for severe depression, anhedonia, intense anxiety, psychomotor agitation or retardation, indecisiveness, perseveration, and vegetative symptoms such as poor sleep, appetite, and significant weight loss. Results: All patients demonstrated rapid and complete resolution of their mood and psychomotor symptoms, indecisiveness, perseveration, as well as psychosis shortly after administration of lorazepam, with recurrence of the above symptoms upon lorazepam discontinuation and resolution upon resumption, in an on-and-off manner. Conclusion: The present study argues for a closer relationship between melancholia and catatonia based on our case series, historical review, overlap in phenomenology, and response to treatment. We propose provisional [Mahgoub] criteria for patients with severe depression and melancholia. The role of GABA agonists, such as lorazepam, can be explored as an option for patients with treatment-resistant depression who meet these criteria for melancholia. Limitations: Absence of a standardized, systematic assessment tool and a small sample size.

'Detention is morally exhausting': melancholia of detention centres in France.

How are ethics articulated in the organization of migrants' detention in France? While state agents enjoy discretionary power, it is the third sector that claims legal knowledge and good practice, exposing an unresisting and reverent attitude towards the 'rule of law'. This legalistic gaze on the state attests to the impasse in questioning (the moral grounds of) laws and flaunting intense emotions on a daily basis, an expression of their moral dilemma. In doing so, police officers, legal practitioners and other service providers display contrasting ideological disapproval but practical compliance, creating an environment infused with melancholy. Melancholy enables them to be humble operators of state rules and regulations and, at the same time, to suffer endless (moral and emotional) pain. This article analyses inter-organizational and inter-personal affective experiences in order to demonstrate how melancholy reflects the morale that is manifest in the organization of migrants' detention.

Joseph Guislain's writings on melancholia from 1835 and 1852.

Over the course of the 19th century, the concept of melancholia morphed from a partial insanity defined by disorders of judgment to a disorder characterized primarily by mood disturbances. The francophone Belgian psychiatrist Joseph Guislain, whose work has not been previously translated into English, played an important role in this transition. We translate and comment upon two of his key descriptions of melancholia from 1835 and 1852, emphasizing the following 5 features. First, his concept of melancholia is quite "modern" meeting all DSM-5 criteria for major depression. Second, his clinical descriptions are vivid, often giving voice to his patients. Third, other aspects of his text reflect older concepts, including 17th century melancholic subtypes. Fourth, and of particular historical import, he was, in 1835, likely the first major European alienist to argue that nonpsychotic melancholia was an important form of the disorder and a legitimate mental illness. This represented key step in the transition of melancholia from a psychotic to a mood disorder and also helped expand the 18th century model of insanity which was as restricted solely to disturbances of judgment/imagination. Fifth, beginning with his 1835 writings, but more prominently in his 1852 text, Guislain emphasizes that melancholia is a form of phrenalgia - mental pain. In so doing, he played an important role in helping initiate this influential psychophysiological theory of melancholia that was championed by Wilhelm Griesinger and other important German and English psychiatrists later in the 19th century.

Does theta burst stimulation have differential benefit for those with melancholic or non-melancholic depression?

BACKGROUND: To determine if theta burst stimulation (TBS) is of preferential benefit to those with melancholic or non-melancholic depression as an adjunctive treatment for treatment resistant depression (TRD). METHODS: Fifty-two patients receiving TBS at a private psychiatric hospital participated in a naturalistic study. Four diagnostic strategies were used to assign melancholic versus non-melancholic depression subtype status. Depression symptoms were assessed at baseline, mid-treatment, and end of treatment using the Montgomery-Ǻsberg Depression Rating Scale - Self-Assessment (MADRS-S). Forty-one participants also completed the MADR-S at a six-week follow-up assessment. RESULTS: We quantified poor correlations between the four study measures of melancholia; a finding suggesting that valid measurement of melancholia is likely to remain problematic. TBS led to significant reductions in depression symptoms from baseline to end of treatment, with this effect maintained at follow up. Response rates for the whole sample were 61.5 % at end of treatment and 53.7 % at follow-up, while remission rates were 34.6 % at end of treatment and 31.7 % at follow-up. Improvement rates as well as responder and remission rates were comparable for the melancholic and non-melancholic groups, irrespective of the diagnostic strategy used. LIMITATIONS: The study was naturalistic (i.e., there being no control group, and concomitant medication changes were allowed), depression severity was assessed only by use of self-report measures, and the sample size was relatively small. CONCLUSION: TBS appears to be non-specific, in that we failed to quantify any statistically significant differential benefit for those with melancholic compared to those with non-melancholic depression.

Melancholic features and treatment outcome to selective serotonin reuptake inhibitors in major depressive disorder: A re-analysis of the STAR*D trial.

BACKGROUND: Melancholia has been positioned as a qualitatively different form of Major Depressive Disorder (MDD). Some studies have suggested that melancholic MDD patients may show lower remission when receiving treatment with Selective Serotonin Reuptake Inhibitors, but this has not yet been explored in large, representative samples of MDD. METHODS: We used data from the STAR*D, a multisite randomized controlled trial (n = 4041). We defined melancholia status through the BA Melancholia Empirical Index, constructed using items from the Inventory of Depressive Symptomatology (IDSC). The main outcome of interest was symptomatic remission defined as a Quick Inventory of Depressive Symptoms (Clinician version) (QIDS-C) below or equal to 5. Inverse probability weighting was used to control for confounding. RESULTS: 3827 patients were eligible for this study. Melancholic patients were more likely to be unemployed, never married, to self-report an African American race, and to have a higher depressive severity. The adjusted 4-month probability of remission was 26.9 % (22.0, 45.5) for melancholic and 53.8 % (53.2, 58.5), for nonmelancholic patients. Compared with nonmelancholic, the difference in 4-month probability of remission was -26.9 % (-37.0, -15.6). Results were consistent across sensitivity analyses. LIMITATIONS: Items from IDSC were used as a surrogate measure of the BA Melancholia Index, and extrapolation of the results to agents other than citalopram and to psychotic MDD patients requires caution. CONCLUSIONS: Melancholic MDD patients showed lower probabilities of remission at 4-months receiving treatment with citalopram. The results of this study show how validly subtyping episodes could contribute to the personalized treatment of depression.

Methods for quantifying the heterogeneity of psychopathology.

OBJECTIVES: Specifiers for a major depressive disorder (MDE) are supposed to reduce diagnostic heterogeneity. However, recent literature challenges the idea that the atypical and melancholic specifiers identify more homogenous or coherent subgroups. We introduce the usage of distance metrics to characterize symptom heterogeneity. We attempt to replicate prior findings and explore whether symptom heterogeneity is reduced using specifier subgroups. METHODS: We used data derived from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC Wave I; N = 5,749) and the Sequenced Treatment Alternatives to Relieve Depression study (STAR*D; N = 2,498). We computed Hamming and Manhattan distances from study participants' unique symptom profiles. Distances were standardized from 0-1 and compared by their within- and between-group similarities to their non-specifier counterparts for the melancholic and atypical specifiers. RESULTS: There was no evidence of statistically significant differences in heterogeneity for specifier (i.e., melancholic or atypical) vs. non-specifier designations (i.e., non-melancholic vs. non-atypical). CONCLUSION: Replicating prior work, melancholic and atypical depression specifiers appear to have limited utility in reducing heterogeneity. The current study does not support the claim that specifiers create more coherent subgroups as operationalized by similarity in the number of symptoms and their severity. Distance metrics are useful for quantifying symptom heterogeneity.

Chronic pain predicts a worse response to depression treatment, regardless of thyroid function or psychotropics prescribed.

BACKGROUND: Chronic pain (CP) and thyroid hormones' (TH) abnormalities are associated with depression, but the impact of pain and TH fluctuation on the response to depression treatment is uncertain. METHODS: Eighty-eight patients with major depression were evaluated before and after 6 months of specific treatment, through scales of symptoms' severity (HAM-D-17), psychomotor disturbance (CORE), and quality of life (WHOQOL-Bref). We reviewed psychiatric medications and measured TSH, T3 and T4. We used Generalized Estimating Equations to assess the interaction effect between CP and treatment time on depression severity and TH levels, and Bonferroni to compare means. RESULTS: 47.7 % of the patients had CP. Patients with and without CP did not differ at baseline. At follow-up, those with CP experienced a more modest decrease in symptoms' severity and no improvement in any domain of psychomotor disturbance, contrasting with a decrease of over 40 % from the baseline values of CORE in patients without CP (non-CP). Initial and final scores were respectively: HAM-D CP 24.06 and 19.3, Δ = -4.75; HAM-D non-CP 22.92 and 14.7, Δ = -8.21; CORE CP 5.36 and 5.24, Δ = -0.12; CORE non-CP 5.8 and 3.22, Δ = -2.57. There was no interaction with TH or life quality. Model adjustments for psychotropic drugs received and sensitivity analysis excluding somatic symptoms from severity scales did not impact the results. LIMITATIONS: Findings may not replicate in mildly depressed patients from primary care. Pain scales were not applied. CONCLUSIONS: Individuals with chronic pain showed a suboptimal response to depression treatment, regardless of the medications used or TH levels.

On the Origins of MAOI Misconceptions: Reaffirming their Role in Melancholic Depression.

The first monoamine oxidase inhibitors (MAOIs) used for the treatment of depression in the 1950-60s were credited with treating severe melancholic depression (MeD) successfully and greatly reducing the need for electroconvulsive therapy (ECT). Following the hiatus caused by the then ill-understood cheese reaction, MAOI use was relegated to atypical and treatment-resistant depressions only, based on data from insufficiently probing research studies suggesting their comparatively lesser effectiveness in MeD. The siren attraction of new 'better' drugs with different mechanisms amplified this trend. Following a re-evaluation of the data, we suggest that MAOIs are effective in MeD. Additionally, the broad unitary conceptualisation of major depressive disorder (MDD) in the DSM model diminished the chance of demonstrating distinctive responses to different antidepressant drugs (ADs) such as SSRIs, TCAs, and MAOIs, thereby further reducing the interest in MAOIs. More reliable categorical distinction of MeD, disentangling it from MDD, may be possible if more sensitive measuring instruments (CORE, SMPI) are used. We suggest these issues will benefit from re-appraisement via an inductive reasoning process within a binary (rather than a unitary) model for defining the different depressive disorders, allowing for the use of more reliable diagnostic criteria for MeD in particular. We conclude that MAOIs remain essential for, inter alia, TCA-resistant MeD, and should typically be used prior to ECT; additionally, they have a role in maintaining remission in cases treated with ECT (and ketamine/esketamine). We suggest that MAOIs should be utilized earlier in treatment algorithms and with greater regularity than is presently the case.

Alpha wave asymmetry is associated with only one component of melancholia, and in different directions across brain regions.

Alpha wave asymmetry inconsistently correlates with Major Depressive Disorder (MDD). One possible reason for this inconsistency is the heterogeneity of MDD, leading to study of depressive 'subtypes', one of which is Melancholia. To investigate the correlation between Melancholia and alpha-wave asymmetry, 100 community participants (44 males, 56 females; aged at least 18 yr) completed the Zung self-rated Depression Scale, and underwent 3 min of eyes closed EEG recording from 24 scalp sites. There was no significant correlation between EEG data and Melancholia total score for the entire sample, but there was for those participants who had clinically significant depression (n = 33). When examined at the level of individual Melancholia scale items, significant EEG data correlations were found for some of the items but not for others. Factor analysis revealed a two-factor structure for the Melancholia scale, only one of which exhibited significant correlations with EEG AA data. Further exploration of those data identified two subcomponents of that Melancholia factor, one which was inversely correlated with frontal alpha asymmetry, and another which was directly correlated with parietal-occipital alpha wave asymmetry. These findings suggest that Melancholia may itself be heterogeneous, similarly to MDD, and rely upon different aspects of cognitive function.

Differentiating melancholic and non-melancholic depression via biological markers: A review.

OBJECTIVES: Melancholia is a severe form of depression that is typified by greater genetic and biological influence, distinct symptomatology, and preferential response to physical treatment. This paper sought to broadly overview potential biomarkers of melancholia to benefit differential diagnosis, clinical responses and treatment outcomes. Given nuances in distinguishing melancholia as its own condition from other depressive disorder, we emphasised studies directly comparing melancholic to non-melancholic depression. METHODS: A comprehensive literature search was conducted. Key studies were identified and summarised qualitatively. RESULTS: 105 studies in total were identified. These studies covered a wide variety of biomarkers, and largely fell into three domains: endocrinological (especially cortisol levels, particularly in response to the dexamethasone suppression test), neurological, and immunological (particularly inflammatory markers). Less extensive evidence also exists for metabolic, genetic, and cardiovascular markers. CONCLUSIONS: Definitive conclusions were predominantly limited due to substantial heterogeneity in how included studies defined melancholia. Furthermore, this heterogeneity could be responsible for the between- and within-group variability observed in the candidate biomarkers that were examined. Therefore, clarifying these definitional parameters may help identify underlying patterns in biomarker expression to improve diagnostic and therapeutic precision for the depressive disorders.

Cortisol and the Dexamethasone Suppression Test as a Biomarker for Melancholic Depression: A Narrative Review.

The dexamethasone suppression test (DST) assesses the functionality of the HPA axis and can be regarded as the first potential biomarker in psychiatry. In 1981, a group of researchers at the University of Michigan published a groundbreaking paper regarding its use for diagnosing melancholic depression, reporting a diagnostic sensitivity of 67% and a specificity of 95%. While this study generated much enthusiasm and high expectations in the field of biological psychiatry, subsequent studies produced equivocal results, leading to the test being rejected by the American Psychiatric Association. The scientific reasons leading to the rise and fall of the DST are assessed in this review, suggestions are provided as to how the original test can be improved, and its potential applications in clinical psychiatry are discussed. An improved, standardized, and validated version of the DST would be a biologically meaningful and useful biomarker in psychiatry, providing a tool for clinicians caring for depressed patients in the areas of diagnosis, treatment, and prognosis, and predicting the risk of suicide. Additionally, such a test could be a crucial part in the generation of biologically homogenous patient cohorts, necessary for the successful development of new psychotropic medications.

Incidence of melancholic depression by age of onset and gender in the Lundby population, 1947-1997.

Whether melancholic depression is a distinct syndrome or not has long been debated. There are few studies providing information about the epidemiology of melancholic depression. In this study, we investigate the incidence rates, overall as well as by gender and age of onset of melancholic depression according to Taylor and Fink and corresponding DSM-IV disorders: major depressive disorder (MDD) with melancholic specifier, MDD with psychotic features, MDD with postpartum debut and bipolar depression in the Lundby population. Incidence rates with 95% confidence intervals were calculated. The incidence rate of melancholic depression was 0.48 (CI 0.36-0.61) per 1000 person-years under risk. The rates of the corresponding DSM-IV disorders were as follows: MDD with melancholic specifier 0.38 (CI 0.27-0.49), MDD with psychotic features 0.13 (CI 0.07-0.21), MDD with postpartum debut 0.02 (CI 0.00-0.06) and bipolar depression 0.04 (CI 0.01-0.10). Females had a significantly higher incidence rate, with a peak in age group 40-49, in melancholic depression according to Taylor and Fink and MDD with melancholic specifier. There was no gender difference in incidence rates of MDD with psychotic features or bipolar depression. The diagnoses were set in retrospect and the number of subjects with MDD with postpartum debut and bipolar depression was low. Incidence of melancholia was low in the Lundby Study. There was a female preponderance to become melancholically depressed in line with research on undifferentiated depression.

Neurocognitive function of patients with melancholic and non-melancholic major depressive episodes: An exploratory study.

OBJECTIVE: The aim of this exploratory study was to compare the neurocognitive performance of patients undergoing melancholic and non-melancholic major depressive episodes. Considering potential limitations of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) specifier, we employed an additional tool that has proven useful in identifying melancholia (the Sydney Melancholia Prototype Index). METHODS: One hundred forty-one depressed inpatients were classified as melancholic or non-melancholic according to the Sydney Melancholia Prototype Index and the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria and compared on a neurocognitive battery selected to assess attention and processing speed, verbal memory, working memory and executive functions. Results were controlled for several potential confounders. RESULTS: Patients diagnosed as melancholic by the two diagnostic systems displayed lower scores in executive measures, semantic verbal fluency and phonological verbal fluency. On attention and processing speed, patients with melancholia underperformed those with non-melancholic depression only when diagnosed by the Sydney Melancholia Prototype Index. After controlling for confounders, associations between melancholic status and executive dysfunction remained significant for the Sydney Melancholia Prototype Index but not for the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) diagnosis. CONCLUSION: In this study, melancholia diagnosed by the Sydney Melancholia Prototype Index (but not by the Diagnostic and Statistical Manual of Mental Disorders [5th ed.] criteria) was characterized by a greater compromise of tests assessing executive functions than non-melancholic depressions, even after controlling for depressive severity. These preliminary results might contribute to generating hypotheses about differences in the cognitive profile and pathophysiological substrate between melancholic and non-melancholic depressions. Likewise, the pattern of findings supports the hypothesis that the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) melancholia specifier might identify more severe forms of depressive episodes rather than a qualitatively different subtype.

Cotard delusion in a depressed patient: "My throat is missing!"

Cotard's syndrome is a rare neuropsychiatric disorder characterized by marked nihilistic delusions. This report describes an Indonesian woman from a small town in Malaysia who was diagnosed with depression and Cotard's delusion. The diagnosis was confirmed after thorough history-taking, clinical examination, and relevant laboratory tests. Herein, we highlight the unique psychopathology of a possible Cotard's syndrome subtype and efficacy of pharmacological combination strategies, rather than monotherapy and electroconvulsive therapy, for its treatment.