Interictal Dysphoric Disorder in Epilepsy and Its Relationship with Specific Clinical and Demographic Variables.

Patients with epilepsy present a variety of psychiatric comorbidities, with mood disorders and anxiety disorders as well as interictal dysphoric disorder as the most frequent and often associated with comorbid mental conditions. Interictal dysphoric disorderand ictal and peri-ictal changes may contribute to overall clinical symptomatology in epilepsy, as well as subjective and objective adverse effects of anti-epileptic drugs. We performed a post-hoc analysis to verify the relation of interictal dysphoric disorder with specific clinical and demographic variables in people with epilepsy, including the correlation between interictal dysphoric disorder and anti-epileptic drugs. We found no correlation between the incidence of interictal dysphoric disorder and drug-resistant epilepsy, and no correlation between the incidence of interictal dysphoric disorder and sex was observed. The results of our analysis indicate that patients with interictal dysphoric disorder, compared with those with no interictal dysphoric disorder, had epilepsy onset at a later age, had had a history of psychiatric treatment and had distinctly lower, but not statistically significant, percentage of active employment status. Another finding was the frequent suicide attempts in people with epilepsy (11.5%). However, there was no relationship with interictal dysphoric disorder. We also did not find any evidence supporting the impact of epileptic medication on the incidence of interictal dysphoric disorder nor did the data contribute to support the evidence of interictal dysphoric disorder as a standing-alone phenomenon. An essential issue in epilepsy is awareness and understanding of interictal dysphoric disorder and concomitant mental health abnormalities as this is crucial for clinical practice and may significantly determine the progression and management of epilepsy if it remains ignored, and hence lead to a severe decline in life quality.

Anhedonia in bipolar depression treated with ketamine.

BACKGROUND: Bipolar depression is the major cause of morbidity in patients with bipolar disorder. It affects psychosocial functioning and markedly impairs occupational productivity. Anhedonia is one of the most debilitating symptoms of depression contributing to treatment resistance. It correlates with suicidality, low quality of life, social withdrawal, and poor treatment response. Currently, there is no approved treatment specifically targeting anhedonia. Emerging evidence suggests that ketamine possesses anti-anhedonic properties in individuals with depression. OBJECTIVES: The aim of this naturalistic open-label study was to investigate the effect of add-on ketamine treatment on anhedonia in treatment resistant bipolar depression. METHODS: Our main interest was the change in patient-reported (Snaith-Hamilton Pleasure Scale) and rater-based anhedonia measure (Montgomery-Åsberg Depression Rating Scale-anhedonia subscale). The secondary aim was to analyze the score change in three Inventory of Depressive Symptomatology-Self Report (IDS-SR) domains: mood/cognition, anxiety/somatic, and sleep. Patients underwent assessments at several time points, including baseline, after the third, fifth, and seventh ketamine infusions. Additionally, a follow-up assessment was conducted 1 week following the final ketamine administration. RESULTS: We found improvement in anhedonia symptoms according to both patient-reported and rater-based measures. The improvement in IDS-SR domains was most prominent in anxiety/somatic factor and mood/cognition factor, improvement in sleep factor was not observed. No serious adverse events occurred. CONCLUSION: Add-on ketamine seems to be a good choice for the treatment of anhedonia in treatment resistant bipolar depression. It also showed a good effect in reducing symptoms of anxiety in this group of patients. Considering unmet needs and the detrimental effect of anhedonia and anxiety, more studies are needed on ketamine treatment in resistant bipolar depression.

Exploring the Relationship between Mood Disorders and Coexisting Health Conditions: The Focus on Nutraceuticals.

Major depressive disorder and bipolar disorder are the leading causes of global disability. Approximately 50% of patients fail to attain remission, prompting a pronounced focus on the significance of dietary patterns and specific nutrients within the pathophysiology of mood disorders. The connection between chronic diseases and mood disorders follows a bidirectional pattern: physical ailments are interrelated with affective disorders, and, concurrently, mood symptoms often precede chronic diseases and have the potential to worsen their prognosis. Nutraceuticals affect factors that could potentially impact the onset of mood disorders: monoamines and brain-derived neurotrophic factor (BDNF) concentrations, neuroinflammation, oxidative stress, and sleep quality. Furthermore, mood disorders rarely manifest in isolation. Typically, such patients concurrently experience other mental disorders or somatic comorbidities: obesity, hypertension, diabetes, polycystic ovary syndrome (PCOS), etc., where providing nutritional support is also pertinent. To optimize the therapeutic approach for individuals with mood disorders, incorporating nutritional support may not solely ameliorate symptoms stemming directly from the mental condition, but also indirectly through interventions targeting comorbidities.

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.

Ketamine as Add-On Treatment in Psychotic Treatment-Resistant Depression.

Psychotic treatment-resistant depression is a complex and challenging manifestation of mood disorders in the clinical setting. Psychotic depression is a subtype of major depressive disorder characterized by mood-consistent hallucinations and/or delusions. Psychotic depression is often underdiagnosed and undertreated. Ketamine appears to have rapid and potent antidepressant effects in clinical studies, and the Federal Drug Agency approved the use of ketamine enantiomer esketamine-nasal spray for treatment-resistant depression pharmacotherapy in 2019. This study aimed to assess the usage of ketamine for major depressive disorder with psychotic features as an add-on treatment to the standard of care. Here we present four inpatients suffering from treatment-resistant depression with psychotic features, including one with severe suicidal crisis, all treated with 0.5 mg/kg intravenous infusion of ketamine. Subsequent monitoring revealed no exacerbation of psychotic symptoms in short and long-term observation, while stable remission was observed in all cases with imminent antisuicidal effect. Results suggest ketamine may benefit individuals with treatment-resistant depression with psychotic features.

Ketamine and Lamotrigine Combination in Psychopharmacology: Systematic Review.

BACKGROUND AND OBJECTIVES: Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been published, there is still not enough data on the effect of ketamine in combination with other medications. Particularly interesting is the combination of ketamine and lamotrigine, and its potential role in bipolar depression. The aim of this review was to identify animal and human studies in which ketamine and lamotrigine were used together in order to find out if there is scientific ground for combining ketamine and lamotrigine in the treatment of mood disorders. Directions for future studies are presented. MATERIALS AND METHODS: PubMed and Web of Science were searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 methodology was applied. RESULTS: Seventeen studies were included for review. Animal studies using models of depression suggested a synergistic effect of ketamine and lamotrigine in combination. Studies on healthy humans showed a reduction in ketamine-induced dissociative symptoms with lamotrigine pretreatment. In a study on patients with depression, ketamine and lamotrigine did not have a stronger antidepressant effect than ketamine alone, but in this study only one ketamine infusion was administered. One case series described the antidepressant and anti-suicidal effect of the combination in two bipolar patients. Available clinical studies on patients with mood disorders did not support the hypothesis that lamotrigine reduces ketamine-induced dissociative symptoms. CONCLUSIONS: The results of the analyzed studies were not sufficient to answer any of the stated questions; however, they allowed us to delineate future research directions. The identified animal studies suggested a possible synergistic antidepressant effect of ketamine and lamotrigine. The available clinical studies were not conclusive. No controlled studies on large groups of bipolar patients with multiple ketamine infusions combined with lamotrigine treatment have been published so far. There is some evidence for the reduction of ketamine's side effects by lamotrigine, and there are reports suggesting that lamotrigine can reduce ketamine craving. More studies with follow-up are needed in order to investigate the ketamine-lamotrigine combination in bipolar patients.

Antianhedonic Effect of Repeated Ketamine Infusions in Patients With Treatment Resistant Depression.

Anhedonia constitutes one of the main symptoms of depressive episode. It correlates with suicidality and significantly effects the quality of patient's lives. Available treatments are not sufficient against this group of symptoms. Ketamine is a novel, rapid acting strategy for treatment resistant depression. Here we report the change in symptoms of anhedonia measured by Snaith-Hamilton Pleasure Scale as an effect of eight ketamine infusions as an add-on treatment in 42 patients with treatment resistant depression. We also determined the effect of this change on the severity of depressive symptoms measured by Inventory for Depression Symptomatology-Self Report 30-Item (IDS-SR 30). We have observed statistically significant decrease in the level of anhedonia during ketamine treatment. After adjusting for potential confounders we have found that significant reduction in Snaith-Hamilton Pleasure Scale (SHAPS) after each infusion and 1 week post treatment was observed only among patients who did not use benzodiazepines. The reduction in symptoms of anhedonia mediates the antidepressive effect of ketamine. The results need replication in a larger randomized placebo controlled trial.

Dysphoria and Irritability-Diagnostic Pitfalls in the Assessment of Interictal Dysphoric Disorder in Epilepsy.

This article aims to review the concept of epilepsy-specific psychiatric disturbance, Interictal Dysphoric Disorder (IDD), focusing on issues related to its core symptoms and methodological pitfalls. In the psychiatric literature, an epilepsy-specific pleomorphic mood disorder has been long recognized and described as IDD, a condition characterized by eight symptoms, which are grouped into four labile depressive symptoms, two labile affective symptoms, and two specific symptoms. The existence of IDD is still a matter of debate because of several methodological issues. The main features of IDD, such as dysphoria and irritability, lack precise and clear definition. This review article explores the different definitions and approaches towards both terms described in the psychiatric literature and the rationale for modifying the diagnostic process of IDD.

Multiple Comorbidity Profile of Psychiatric Disorders in Epilepsy.

The co-occurrence of psychiatric disorders in people with epilepsy (PWE) is not well documented or studied. Anxiety and depressive disorders are the most frequent comorbid disorders in PWE. In this paper, we characterized the rates of multiple psychiatric disorder comorbidity by reanalyzing data from a study sample of PWE. A total of 96 outpatient PWE completed the self-report symptom scale, and were diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) Axis I disorders (SCID-I). For analyses, patients were assigned to a comprehensive diagnostic group of anxiety and depressive disorders. In order to determine comorbidity across psychiatric diagnoses for the DSM-IV categories, Pearson's chi-squared test (χ2) was used. In the study sample, eight patients (8.3% of the study sample, n = 96) had comorbid major depressive disorder and anxiety disorder. When looking at comorbidity of each diagnosis separately, it was determined that 50% of individuals with an anxiety disorder had comorbid Major Depressive Disorder (MDD) and 38% patients with MDD had comorbid anxiety disorder. This finding encourages a more systematic reporting of psychiatric prevalence data in epilepsy, especially taking into account the high ratio of multiple comorbid anxiety and depressive disorders in PWE.

Intravenous Ketamine Infusions in Treatment-Resistant Bipolar Depression: An Open-Label Naturalistic Observational Study.

PURPOSE: Bipolar disorder is a chronic and recurrent condition often associated with treatment resistance and suicidality. There is an unmet need for effective treatment in this group of patients. Ketamine has been demonstrated to have antidepressant and antisuicidal properties in unipolar depression. Most of the available studies concern unipolar depression. Here, we present the efficacy and safety of IV ketamine as an add-on treatment in patients with bipolar I and bipolar II depression. PATIENTS AND METHODS: Thirteen patients with treatment-resistant bipolar depression (TRBD) received eight IV infusions of 0.5 mg/kg ketamine twice a week over four weeks. This is an open-label naturalistic observational study. Ketamine is an add-on treatment. Depressive symptoms were measured with the Montgomery-Asberg Depression Rating Scale (MADRS), and manic symptoms were measured with the Young Mania Rating Scale (YMRS). Psychomimetic symptoms were assessed with the Clinician-Administered Dissociative States Scale (CADSS) and the Brief Psychiatric Rating Scale (BPRS). RESULTS: The rates of response and remission after the seventh infusion of ketamine were 61.5% and 46.2%, respectively. A significant antisuicidal effect was observed in responders at the 7th infusion. Suicidality was measured with item 10 on the MADRS scale. The average time to respond was between 21.1 and 23.2 days to remission. There was an increase in the CADSS scores during the treatment compared to baseline and follow-up, but no differences between responders and non-responders were observed. No affective switch was observed according to the YMRS scale scores. Ketamine treatment was associated with a transient increase in arterial blood pressure. No serious adverse events, however, were observed. CONCLUSION: This report presents the preliminary results of IV ketamine effectiveness and safety in treatment-resistant bipolar depression. The findings suggest that it is a feasible, safe and well-tolerated treatment option in this group of patients. There is a definite need for more studies in this field.

Magnesium in Ketamine Administration in Treatment-Resistant Depression.

Relationship between depression and magnesium levels is reported. This observational study examined whether serum magnesium concentration change over time of ketamine treatment course, also whether association between magnesium concentrations and treatment response measured with Montgomery-Åsberg Depression Rating Scale (MADRS) score occurs. Moreover, interlink between changes in Young Mania Rating Scale (YMRS) score, somatic comorbidities, and magnesium concentration was studied. Inpatients with major depressive disorder or bipolar disorder were rated weekly by clinician using MADRS and YMRS. Magnesium levels assessments were carried out weekly, before start of ketamine treatment and then every second infusion and one week after last ketamine infusion. The concentration of Mg2+ ions differs depending on the measurement. The Mg2+ concentration in pre-measurement was significantly higher than in measurement after five infusions (p = 0.031) and after seven infusions (p = 0.003). No significant correlation was observed between changes in magnesium serum levels and MADRS or YMRS. The concentration of Mg2+ ion in course of the treatment was not associated with somatic comorbidities. The study supports data for role of magnesium in treatment-resistant depression, particularly related to ketamine treatment, but provides no clear evidence of straightforward association between magnesium serum concentration and treatment response or comorbidity.

Screening and diagnosis for mood and anxiety disorders in epilepsy: Polish population reference values.

INTRODUCTION: Epilepsy is one of the world's most prevalent noncommunicable diseases and tends to have a chronic course, often with comorbid psychiatric disorders, of which depressive disorders (DDs) and anxiety disorders (ADs) are the most common. BACKGROUND: As anxiety and depressive disorders are underdiagnosed and so undertreated in people with epilepsy (PWE), this could have implications for the course of both of these medical conditions and the response to treatment and health outcomes. Thus it is crucial to perform screening for psychiatric disorders in populations with epilepsy using specific psychometric screening instruments optimised for that group of patients. Polish versions of the Hospital Anxiety and Depression Scale (HADS), the Hamilton Rating Scale for Depression (HRSD), the Hamilton Anxiety Rating Scale (HARS), the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI) and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) were validated against 'gold standards' in a Polish population with epilepsy. CLINICAL IMPLICATIONS: Using well-validated screening instruments that can be easily implemented in a clinical setting may contribute to better diagnosis, and consequently treatment, of comorbid psychiatric disorders, which would have a great impact on the course and prognosis of epilepsy management. CONCLUSIONS: Based on the outcomes of Polish studies aimed at validating psychometric instruments for screening for mood and anxiety disorders, HADS is recommended as a first-choice screening tool.

Affective Switch Associated With Oral, Low Dose Ketamine Treatment in a Patient With Treatment Resistant Bipolar I Depression. Case Report and Literature Review.

There is a growing evidence for the rapid and robust antidepressive effect of ketamine in unipolar and bipolar treatment resistant depression although evidence for the risk of affective switch is still limited. This case presents bipolar I disorder patient with treatment resistant depressive episode experiencing a switch to manic episode with mixed features shortly after receiving eight subanaesthetic doses of oral ketamine as an add-on treatment preceded by 2-day period of manic symptoms.