Treatment-emergent symptoms during short-term ketamine administration in treatment-resistant bipolar depression: A retrospective cross-sectional descriptive study.

Symptoms that emerge during pharmacological treatment of bipolar depression are frequently observed, underscoring the necessity for comprehensive treatment monitoring. This observational study sought to observe the correlation of eight intravenous ketamine infusions with treatment-emergent depressive symptoms in treatment-resistant bipolar depression patients who maintained their baseline psychotropic and chronic somatic treatments. Depressive symptoms were evaluated using the Inventory of Depressive Symptomatology Self-Report 30 (IDS-SR30). Treatment-emergent symptoms TES were defined as symptoms absent at baseline but present at the conclusion of the study. The most common TES included decreased appetite, increased weight, hypersomnia, and diurnal mood variation. Conversely, feelings of sadness, altered perceptions of the future, decreased interest in sex, and physical discomfort were absent in all patients. Notably, 13.6 % of patients reported thoughts of death or suicide. Larger-scale studies, integrating clinician-rated and patient-reported outcome measures, are essential to deepen our understanding of treatment-emergent symptoms. Establishing regulatory or professional definitions for treatment-emergent symptoms is warranted to improve the robustness of future research endeavors.

Worldwide internet trends in the public interest related to skin whitening and bleaching creams.

Skin whitening is a practice that is used to obtain lighter skin tone and is most prevalent in Africa and Asia. Substances used for this procedure, such as hydroquinone or mercury have a variety of side effects and are banned in several countries. This study examined the popularity of internet searches for terms related to skin whitening and bleaching creams with the use of GoogleTrends (GT). GT was searched globally for the topic "skin whitening" and two terms "hydroquinone cream" and "mercury cream" throughout a 10-year period (01.09.2013-31.08.2023). The popularity of searches increased during the analyzed period. The topic "skin whitening" was most popular in Sudan, Vietnam, and Sri Lanka. The searches were higher for "hydroquinone cream" than "mercury cream" in almost all countries, besides the Philippines and Indonesia. Our study confirms that skin whitening practices are popular, especially among populations with darker skin tone. Despite potentially toxic side effects, creams with hydroquinone and mercury are increasingly searched worldwide. Education about skin whitening and the usage of bleaching substances should be implemented, especially in the regions of Africa and Asia.

Ketamine treatment for anhedonia in unipolar and bipolar depression: a systematic review.

Ketamine, an N-methyl-D-aspartate receptor antagonist, is a racemic mixture of esketamine and arketamine used to treat unipolar and bipolar depression. Preliminary reports indicate that it may be beneficial for depressed patients reporting symptoms of anhedonia. In this systematic review we aim to assess and analyze the existing body of evidence regarding the therapeutic effects of ketamine on the domain of anhedonia. Electronic databases (PubMed, APA Psycinfo and Web of Science) were searched from inception to November 2023. Protocol was registered in PROSPERO under the identifier CRD42023476603. A total of twenty-two studies, including four randomized-controlled trials and eighteen open-label trials were included. All studies reported alleviation of anhedonia symptoms following ketamine or esketamine administration, regardless of the number of infusions. Several important limitations were included, first and foremost low number of placebo-controlled randomized-controlled trials. This review indicates a potential anti-anhedonic effect of ketamine in patients with depression. Several trials used neuroimaging techniques which confirm ketamine's effect on functional connectivity correlating with the improvement in anhedonia. Despite considerable variations in methodology and the specific brain regions investigated, these studies collectively point towards ketamine's neuroplastic effects in mitigating anhedonia.

Anhedonia and depression severity measures during ketamine administration in treatment-resistant depression.

Background: Anhedonia is a core symptom of depression characterized by a diminished ability to experience pleasure. Currently available treatments for depression often fall short in adequately addressing anhedonia that often presents as a chronic and debilitating symptom. Ketamine is known to possess antianhedonic properties. Methods: This post-hoc analysis of a naturalistic observational study of treatment-resistant depression inpatients (n=28) analyzed antianhedonic response patterns measured by Snaith-Hamilton Pleasure Scale and changes in Inventory of Depressive Symptomatology in responders (n=6) and non-responders (n=22) stratified per Montgomery-Åsberg Depression Rating Scale during short-term ketamine treatment. Results: Results show that responders significantly improve in anhedonia over time (p=0.0084) and at the 7th infusion and follow-up (both p<0.05). Non-responders reported significant reduction in anhedonia over time (p=0.0011) and at the 5th, 7th infusion and at the follow-up (all p's<0.05). Non-responders were also observed to improve significantly in self-reported depression at the 7th infusion (p=0.0219) but not at the follow-up. Discussion: There is no complete overlap between change in depressive symptoms and anhedonia. Therefore, it might be assumed ketamine alleviates anhedonia as an individual symptom domain regardless of formal treatment outcome.

Low-carbohydrate diet as a nutritional intervention in a major depression disorder: focus on relapse prevention.

Objectives: Mood disorders are trending to be among the leading causes of years lived with disability. Despite multiple treatment options, around 30% patients with major depressive disorder (MDD) develop treatment resistant depression (TRD) and fail to respond to current pharmacological therapies. This study aimed to explore the potential benefits of nutritional treatment strategies, along with their molecular mechanisms of action, focusing especially on low-carbohydrate diet (LCHD), ketogenic diet (KD) and other strategies based on carbohydrates intake reduction.Methods: A comprehensive literature review was conducted to determine the impact of LCHD on alleviating depressive symptoms in patients with MDD, along with an explanation of its mode of action.Results: The study revealed significant impact of nutritional interventions based on restriction in carbohydrate intake such as LCHD, KD or sugar-sweetened beverages (SSB) exclusion on anxiety or depression symptoms reduction, mood improvement and lower risk of cognitive impairment or depression. The efficacy of these approaches is further substantiated by their underlying molecular mechanisms, mainly brain-derived neurotrophic factor (BDNF) which is a potential key target of sugar restriction diets in terms of neuroplasticity.Discussion: Healthcare professionals may consider implementing LCHD strategies for MDD and TRD patients to modify the disease process, maintain euthymia, and prevent depressive episode relapses. Ranging from the exclusion of SSB to the adherence to rigorous LCHD regimens, these nutritional approaches are safe, straightforward to implement, and may confer benefits for well-being and relapse prevention in this specific patient population.

Predictive Performance of Neuron-Specific Enolase (NSE) for Survival after Resuscitation from Cardiac Arrest: A Systematic Review and Meta-Analysis.

The prediction of outcomes following cardiac arrest continues to provide significant difficulties. A preferred strategy involves adopting a multimodal approach, which encompasses the careful evaluation of the biomarker neuron-specific enolase (NSE). This systematic review and meta-analysis aimed to gather and summarize new and existing evidence on the prediction effect of neuron-specific enolase for survival to hospital discharge among adult patients with cardiac arrest. We searched PubMed Central, Scopus, EMBASE databases, and the Cochrane Library without language restrictions from their inceptions until 30 October 2023 and checked the reference lists of the included studies. Pooled results were reported as standardized mean differences (SMDs) and were presented with corresponding 95% confidence intervals (CIs). The primary outcome was survival to hospital discharge (SHD). Eighty-six articles with 10,845 participants were included. NSE showed a notable degree of specificity in its ability to predict mortality as well as neurological status among individuals who experienced cardiac arrest (p < 0.05). This study demonstrates the ability to predict fatality rates and neurological outcomes, both during the time of admission and at various time intervals after cardiac arrest. The use of NSE in a multimodal neuroprognostication algorithm has promise in improving the accuracy of prognoses for persons who have undergone cardiac arrest.

Short-term ketamine use in bipolar depression: a review of the evidence for short-term treatment management.

Bipolar depression constitutes a major problem in psychiatry. It correlates with high suicidality, treatment resistance, chronicity, and poor quality of life. Registered treatment for bipolar depression is limited and insufficient. There is an urgent need for implementing new therapeutic strategies. Intranasal ketamine's enantiomer-esketamine is a novel rapid-acting antidepressant with proven efficacy in treatment-resistant depression. Research on bipolar depression, although not as comprehensive, indicates that it may be a viable and safe substitute with minimal risk for mood polarity changes. Reports suggest that ketamine treatment in bipolar depression may reduce suicidal tendencies, decrease anhedonia, and alleviate anxiety. Ketamine's mood-stabilizing properties are also hypothesized. In this narrative review, we focus on ketamine use as an add-on to standard medication for the acute treatment of bipolar depression.

Residual insomnia in major depressive disorder: a systematic review.

Introduction: The ultimate goal in major depressive disorder (MDD) treatment is recovery. A proportion of MDD patients with formal remission experience persistent difficulties, which impair their daily functioning. Residual insomnia is one of the most common residual symptoms. Patients with residual insomnia experience relapse significantly earlier and have a poor prognosis. Little is known about possible ways of treatment and what subtype of insomnia is mostly reported. Methods: A systematic literature review was carried out in PubMed and Web of Science to synthesize the current status of knowledge about effective treatment methods and insomnia subtypes in residual insomnia in MDD. Results: A few non-pharmacological treatment methods e.g., Cognitive Behavioral Therapy for Insomnia (CBT-I), Mindfulness-Based Cognitive Therapy (MBCT), behavioral activation (BA) and pharmacological methods (gabapentin, clonazepam) have proven to mitigate residual insomnia. Cognitive Behavioral Therapy for Depression (CBT-D) ameliorates insomnia complaints to a limited extent. Mid-nocturnal insomnia is the most common residual insomnia subtype in MDD patients. Conclusion: Residual insomnia is a very common complaint and most often appears as mid-nocturnal insomnia. Scarce data points out the benefits from pharmacotherapy, psychotherapy, and BA. More research is needed.

Central nervous system-related safety and tolerability of add-on ketamine to standard of care treatment in treatment-resistant psychotic depression in patients with major depressive disorder and bipolar disorder.

Background: Psychotic treatment-resistant depression represents a complex and challenging form of mood disorder in clinical practice. Despite its severity, psychotic depression is frequently underdiagnosed and inadequately treated. Ketamine has demonstrated rapid and potent antidepressant effects in clinical studies, while exhibiting a favorable safety and tolerability profile. Although there is limited literature available on the use of ketamine in psychotic TRD, reports on its efficacy, safety, and tolerability profile are of great interest to clinicians. The aim of this study is to investigate the relationship between dissociative symptomatology and psychomimetic effects in inpatients with treatment-resistant major psychotic depression and treatment-resistant bipolar psychotic depression, who receive intravenous ketamine treatment alongside psychotropic medication, both during and after treatment. Materials and methods: A total of 36 patients diagnosed with treatment-resistant unipolar (17 patients) or bipolar (18 patients) depression with psychotic features were treated with eight intravenous infusions of 0.5 mg/kg ketamine twice a week over 4 weeks. Ketamine was given in addition to their standard of care treatment. The severity of depressive symptoms was evaluated using the MADRS, while dissociative and psychomimetic symptoms were assessed using the CADSS and BPRS, respectively. Results: There were no statistically significant changes observed in MADRS, CADSS, and BPRS scores within the study group during ketamine infusions. However, significant improvements in MADRS, CADSS, and BPRS scores were observed during ketamine infusions in both the unipolar and bipolar depression groups. Conclusion: This study provides support for the lack of exacerbation of psychotic symptoms in both unipolar and bipolar depression.

Short term ketamine treatment in patient with bipolar disorder with comorbidity with borderline personality disorder: Focus on impulsivity.

OBJECTIVES: Borderline personality disorder (BPD) and bipolar disorder (BD) often co-occur and frequently do not respond adequately to traditional antidepressant treatments. Ketamine has shown rapid antidepressant and anti-suicidal effects. However, there is limited literature on the safety and tolerance of using ketamine to treat patients with comorbid BD and BPD. METHODS: This case presents a female patient diagnosed with both Bipolar Disorder (BD) and Borderline Personality Disorder (BPD) who received intravenous ketamine treatment to alleviate acute depressive symptoms. RESULTS: Initially, ketamine ameliorated depressed symptoms. However, as the ketamine treatment continued, the patient showed an increase in nonsuicidal self-injury (NSSIs) and impulsive conduct with a aggravation of dissociative symptoms. As a result, intravenous ketamine was discontinued, and the patient received the medication, which proved helpful. CONCLUSIONS: Although ketamine presents antidepressant properties, reports on its impact on emotional dysregulation and impulsive conduct are unclear and not alike to its antidepressant effect. Therefore, there is a need for more studies investigating the effectiveness and safety of this rapid-acting medicine in this patient population.

Safety and Tolerability of the Acute Ketamine Treatment in Treatment-Resistant Depression: Focus on Comorbidities Interplay with Dissociation and Psychomimetic Symptoms.

There is evidence for ketamine use in treatment-resistant depression (TRD). Several safety concerns arise regarding adverse drug reactions in specific subpopulations. The aim of this study was to investigate the safety of intravenous ketamine treatment in relation to dissociative and psychotic measures in TRD inpatients with Major Depressive Disorder (MDD) and Bipolar depression (BP) with comorbidities. In total, 49 inpatients with MDD or BP were treated with ketamine following the registered naturalistic observational protocol in a tertiary reference unit for mood disorders (NCT04226963). This dataset represents an intermittent analysis of an observational study performed for interim modeling of observational learning. The observations were applied to the inhomogeneous TRD population in a single site with no blinding and were limited to acute administration. The presence of epilepsy was significantly associated with an elevation in the BPRS over time (p = 0.008). Psychotic symptomatology with BPRS scores for comorbid conditions excluding epilepsy turned out to be insignificant (p = 0.198) regardless of the diagnosis. However, for a subgroup of patients with epilepsy (n = 6), a substantial fluctuation was seen across all administrations in the time course of the study. The study results contribute to the literature on the safety and tolerability profile of CNS adverse drug reactions in short-term treatment with intravenous ketamine as an add-on intervention to current standard-of-care psychotropic medication in TRD-MDD and TRD-BP inpatients with comorbidities. The careful consideration of comorbidities and concomitant medication is needed with ketamine administration along with close-clinical supervision at every visit.

Effect of Ketamine on Sleep in Treatment-Resistant Depression: A Systematic Review.

BACKGROUND: Depression is a debilitating disease with a high socioeconomic burden. Regular antidepressants usually require several weeks to ameliorate symptoms; however, numerous patients do not achieve remission. What is more, sleep disturbances are one of the most common residual symptoms. Ketamine is a novel antidepressant with rapid onset of action with a proven antisuicidal effect. Little is known about its impact on sleep-wake and circadian rhythm alterations. The aim of this systematic review is to research the impact ketamine has on sleep disturbances in depression. METHODS: PubMed, Web of Science, and APA PsycINFO were searched for relevant studies on ketamine's impact on sleep disturbances in depression. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA2020 methodology was applied. The systematic review protocol was registered in the PROSPERO Registry (CRD42023387897). RESULTS: Five studies were included in this review. Two studies reported significant improvement in sleep measured by MADRS (Montgomery-Åsberg Depression Rating Scale) and QIDS-SR16 (Quick Inventory of Depressive Symptomatology Self-Report (16-item)) scales after intravenous ketamine and intranasal esketamine administration. One case report showed mitigation of symptoms in PSQI (Pittsburgh Sleep Quality Index) and ISI (Insomnia Severity Index) during 3-month treatment with esketamine. In two studies, sleep was objectively measured by nocturnal EEG (electroencephalography) and showed a decrease in nocturnal wakefulness accompanied by an increase in slow wave (SWS) and rapid eye movement (REM) sleep. CONCLUSION: Ketamine reduces the severity of sleep insomnia in depression. Robust data are lacking. More research is needed.

The Downstaging Concept in Treatment-Resistant Depression: Spotlight on Ketamine.

Treatment-resistant depression is a pleomorphic phenomenon occurring in 30% of patients with depression. The chance to achieve remission decreases with every subsequent episode. It constitutes a significant part of the global disease burden, causes increased morbidity and mortality, and is associated with poor quality of life. It involves multiple difficult-to-treat episodes, with increasing resistance over time. The concept of staging captures the process of changes causing increasing treatment resistance and global worsening of functioning in all areas of life. Ketamine is a novel rapid-acting antidepressant with neuroplastic potential. Here, we argue that ketamine use as an add-on treatment of resistant major depressive disorder, based on its unique pharmacological properties, can reverse this process, give hope to patients, and prevent therapeutic nihilism.

The Brief Assessment of Cognition in Affective Disorders - Novel Tool Is the Neuropsychological Assessment in Mood Disorders - Polish Translation.

Mood disorders are chronic disorders accompanied by cognitive impairment. They impair the adaptability and daily functioning of patients, also during remission and justify implementing pharmacological treatment and psychotherapeutic interactions in these patients to improve their quality of life. The recommended method for assessing the charcter of cognitive deficits in affective disorders is the BAC-A (Brief Assessment of Cognition In Affective Disorders) test battery. This scale is a short, simple instrument of the "paper-and-pencil test" type, based on the BAC (Brief Assessment of Cognition) inventory and the Short Scale for Assessment of Cognitive Functions in Schizophrenia (BAC-S). The BAC-A consists of eight subtests measuring: verbal memory and learning, affective control, working memory, motor functions, verbal fluency, executive functions. This paper presents the Polish version of the BAC-A along with instructions about its use and interpretation. The BAC-A scale is a method designed to monitor the cognitive functioning of people with mood disorders, enabling early detection of existing deficits to improve the effectiveness of the diagnostic and treatment process.

Dietary Patterns of Treatment-Resistant Depression Patients.

Depression is a common mental disorder that occurs all over the world with treatment resistance commonly seen in clinical practice. Ketamine exhibits an antidepressant that is more often used in the case of treatment-resistant depression (TRD) in MDD and BP. Research emphasizes that a healthy diet and the nutrients it contains can lower the risk of developing depression and form a strategy that supports conventional treatment. The aim of the study was to evaluate the patients' diet and to analyze the effect of ketamine on food intake among patients with TRD. The study involved 15 patients suffering from treatment-resistant depression and 15 healthy volunteers. The data required for the analysis were collected using the food frequency questionnaire (FFQ) and 4-day food diaries. The study group was statistically significantly less likely to consume milk and plain milk beverages, plain white cheese, wholemeal bread, various vegetables, wine, and drinks. Our results show several disorders in the eating habits of patients with treatment-resistant depression. After the administration of ketamine, the patients consumed significantly less protein, fats, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), fiber, tryptophan, vitamins, and minerals compared to the control group. There is a lack of research describing the effects of ketamine on nutrition. In order to confirm the results of the study, more participants are required, and the assessment of food diaries filled in at the patient's home with a longer interval after the last dose of ketamine as well.

Changes in T-Cell Subpopulations and Cytokine Levels in Patients with Treatment-Resistant Depression-A Preliminary Study.

Although there is some evidence for the involvement of cytokines and T cells in the pathophysiology of treatment-resistant depression (TRD), the nature of this relationship is not entirely clear. Therefore, we compared T-cell subpopulations and serum cytokine levels in TRD patients to find relationships between their immunological profiles, clinical presentation, and episode severity. Blood samples from TRD patients (n = 20) and healthy people (n = 13) were collected and analyzed by flow cytometry. We analyzed the percentages of helper and cytotoxic T cells according to the expression of selected activation markers, including CD28, CD69, CD25, CD95, and HLA-DR. The serum levels of inflammatory cytokines IL12p70, TNF-α, IL-10, IL-6, IL-1ß, and IL-8 were also determined. TRD patients had a lower percentage of CD3+CD4+CD25+ and CD3+CD8+CD95+ cells than healthy people. They also had lower serum levels of IL-12p70 and TNF-α, whereas IL-8 levels were significantly higher. Receiver operating characteristic (ROC) analysis demonstrated that serum IL-8 values above 19.55 pg/mL were associated with a 10.26 likelihood ratio of developing TRD. No connections were found between the MADRS score and immunological parameters. These results show that TRD patients have reduced percentages of T cells expressing activation antigens (CD25 and CD95) and higher serum concentrations of proinflammatory and chemotactic IL-8. These changes may indicate reduced activity of the immune system and the important role of IL-8 in maintaining chronic inflammation in the course of depression.

Perspectives for therapy of treatment-resistant depression.

A high proportion of depressed patients fail to respond to antidepressant drug treatment. Treatment-resistant depression (TRD) is a major challenge for the psychopharmacology of mood disorders. Only in the past decade have novel treatments, including deep brain stimulation (DBS) and ketamine, been discovered that provide rapid and sometimes prolonged relief to a high proportion of TRD sufferers. In this review, we consider the current status of TRD from four perspectives: the challenge of developing an appropriate regulatory framework for novel rapidly acting antidepressants; the efficacy of non-pharmacological somatic therapies; the development of an animal model of TRD and its use to understand the neural basis of antidepressant non-response; and the potential for rapid antidepressant action from targets (such as 5-HT1A receptors) beyond the glutamate receptor. LINKED ARTICLES: This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc.

Case Report: Repeated Series of Ketamine Infusions in Patients With Treatment-Resistant Depression: Presentation of Five Cases.

Purpose: Approximately 30% of patients with major depressive disorder (MDD) are treatment resistant. There is an unquestionable need for new treatment strategies. Subanesthetic doses of intravenous (IV) ketamine have a rapid antidepressant effect in treatment-resistant depression (TRD). This paper describes the efficacy of repeated series of intravenous ketamine infusions as an add-on treatment in five TRD inpatients. Methods: Eligible patients aged 43-63 were given eight ketamine infusions as an add-on treatment for patients with MDD. The subjects have readministered the intervention due to worsening depressive symptoms. Results: Of the five inpatients given ketamine as a series of eight infusions, one underwent three, and four had two treatment series. Four patients achieved remission after first series and three after the second series of ketamine infusions. The adverse reactions were mild and transient with no sequelae. Limitations: Presented case series applies to short-term intervention with IV ketamine as an add-on therapy. The results cannot be generalized to the long-term maintenance treatment nor other ketamine formulations as well as different administration schedules and dosing. Conclusions: This case series showed efficacy and safety of the repeated series of IV ketamine treatment in TRD in MDD and bipolar disorder type I. The subsequent interventions were safe and observed adverse events were mild and transient. Interestingly, the IV ketamine treatment at successive administrations seems to alter the major depression severity of the next affective episode. There is a critical need for further research regarding IV ketamine treatment effectiveness and long-term safety in future studies.