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.

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.

Psychometric properties and diagnostic utility of the State-Trait Anxiety Inventory in epilepsy with and without comorbid anxiety disorder.

OBJECTIVE: Anxiety disorders are frequent comorbid disorder in patients with epilepsy (PWEs). The availability of validated screening instruments to detect anxiety disorders in PWEs is limited. The aim of the present study was to validate State-Trait Anxiety Inventory (STAI) in adult PWEs for the detection of anxiety disorders. METHODS: A total of 96 outpatients with epilepsy completed the self-report symptom scale and were diagnosed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition Text Revision (DSM-IV-TR) Axis I disorders (SCID-I). The sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic (ROC) curves were assessed to determine the optimal threshold scores for the State-Trait Anxiety Inventory State (STAI-S) and State-Trait Anxiety Inventory Trait (STAI-T) anxiety subscales. RESULTS: Receiver operating characteristic analyses for STAI-T showed area under the curve at 84.7%. For diagnoses of anxiety disorders, the STAI-T demonstrated the best psychometric properties for a cutoff score ≥ 52 with sensitivity of 81.3%, specificity of 77.5%, positive predictive value (PPV) of 41.9%, and negative predictive value (NPV) of 95.4%. CONCLUSIONS: The STAI-T proved to be a valid and reliable psychometric instrument in terms of screening for anxiety disorders in PWEs. In the epilepsy setting, STAI-T maintains adequate sensitivity, acceptable specificity, and high NPV but low PPV for diagnosing anxiety disorders with an optimum cutoff score ≥ 52.

Psychometric properties of the Polish version of the Hamilton Anxiety Rating Scale in patients with epilepsy with and without comorbid anxiety disorder.

OBJECTIVE: Anxiety disorders (ADs) are frequent comorbid disorder in patients with epilepsy (PWE). The availability of validated screening instruments to detect AD in PWE is limited. The aim of the present study was to validate the Polish version of the Hamilton Anxiety Rating Scale (HARS) in adult PWE for the detection of AD. METHODS: A total of 96 outpatient PWE completed the self-report symptom scale, the HARS, and were diagnosed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) Axis I disorders (SCID-I). The sensitivity, specificity, positive and negative predictive value, and receiver operating characteristic (ROC) curves were assessed to determine the optimal threshold scores for the HARS. RESULTS: Receiver operating characteristic analyses showed areas under the curve at 81.2%. For diagnoses of AD, the HARS demonstrated the best psychometric properties for a cutoff score ≥17 with sensitivity of 68.8%, specificity of 87.5%, positive predictive value of 52.4%, and negative predictive value of 93.3%. CONCLUSIONS: The Polish version of the HARS performed moderately well as a screening instrument for ADs in PWE. In the epilepsy setting, the HARS maintains moderate sensitivity, high specificity, and excellent Negative perdictive value (NPV) but low Positive perdictive value (PPV) for diagnosing ADs with an optimum cutoff score ≥17. These results suggest that the HARS performed better to rule out anxiety, however, because of moderate sensitivity, some cases of anxiety might be missed.

Interictal dysphoric disorder of epilepsy: A continuing diagnostic challenge.

OBJECTIVE: The interictal dysphoric disorder (IDD) is a proposed epilepsy-specific mood disorder characterized by a cluster of symptoms such as depressed mood, irritability, euphoria, and anxiety. Since its introduction, the concept of IDD has been a matter of debate. This study aimed to evaluate the frequency of the IDD and the association between psychiatric disorders and IDD. We also analyzed potential associations between IDD symptoms and epilepsy-related variables. METHODS: A consecutive group of 118 outpatients with epilepsy were screened. Ninety-six patients met inclusion criteria and examined by a trained psychiatrist using Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders fourth edition Text Revision (DSM-IV-TR) (SCID-I). In order to diagnose IDD, all participants completed the self-rating questionnaire consisting of a set of questions aimed to assess the eight key symptoms of IDD. On completion of the questionnaire, the psychiatrist reviewed all the data for completeness and accuracy with the patient. RESULTS: In our group with epilepsy, we observed IDD in 49.0% (47 of 96) of people with epilepsy (PWE) with substantial overlap (85%) of IDD with depressive and anxiety disorders. The frequency of depressive mood, anergia, and irritability was significantly higher in patients with IDD diagnosis. Older age at epilepsy onset was associated with IDD. STUDY LIMITATIONS: The cross-sectional study design, a consecutive sample of patients presenting to a tertiary referral center, a small sample size of the population, and applied methodology could have affected the results. CONCLUSIONS: The present study indicates that IDD occurs in high frequency in PWE with a substantial overlap of IDD with depressive and anxiety disorders. The study highlights the importance of the observer-based systematic approach for diagnosing IDD and the usage of operationalized diagnostic criteria for psychiatric comorbidities in PWE. Future research should be directed at validating whether IDD is nosologically independent of other psychiatric conditions.

Clozapine: promising treatment for suicidality in bipolar disorder.

Bipolar disorder is associated with the highest risk of completed suicide of all mental disorders. The suicide mortality of people with bipolar disorder is approximately 25 times higher than the general population. No approved pharmacological strategies for suicidality in bipolar disorder have been introduced so far. There is evidence for anti-suicidal effect of clozapine in schizophrenia. Clozapine with its unique pharmacology, anti-aggressive and anti-impulsive properties is potentially an effective strategy for suicidality in bipolar disorder.

Short-term ketamine administration in treatment-resistant depression: focus on cardiovascular safety.

Ketamine is an anaesthetic and analgesic agent that demonstrates the antidepressive effect in major depression. Several administrations routes, dosing schemas and esketamine are investigated in basic and clinical research with particular focus on treatment-resistant depression (TRD) where drug demonstrates its efficacy where very limited alternatives are available. The majority of ketamine studies in TRD treatment reported no serious adverse events regardless the administration route or regimen. However, the most commonly observed adverse events following ketamine administration in antidepressive doses include general, psychotomimetic, dissociative and hemodynamic ones. The side effects are mild or moderate, well-tolerated and transient. This paper discusses the risks regarding cardiovascular safety in MDD patients in short-term ketamine administration with particular focus on the effect on blood pressure and adverse drug reactions mitigation measures. The increase in systolic (SBP) and diastolic (DBP) blood pressure is dose-dependent and begins shortly after administration peaking at around 30 to 50 minutes with SBP and DBP rise from 10% to 50% above predose values and resolving at approximately 2 to 4 hours after the dose administration. These changes generally are primarily asymptomatic. The elevations in SBP and DBP are observed on each dosing day with multiple administration schema. The treatment with ketamine and esketamine is contradicted in subjects at risk of an increase in blood pressure or intracranial pressure. The current evidence indicates the blood pressure should be assessed prior to dosing with ketamine and hypertensive individuals shall receive effective lifestyle/pharmacologic management prior to treatment. Blood pressure should be monitored after dose administration until blood pressure returns to acceptable levels. If blood pressure remains elevated acute blood pressure management shall be delivered. In patients experiencing symptoms of hypertensive crisis immediate emergency care must be provided. The unmet need for improved pharmacotherapies for TRD means the use of ketamine and esketamine is warranted therapeutic option in patients who fail to achieve a sustained remission of depressive symptoms with drugs with monoamine-based mechanisms of action. Adequate safety measures must be applied when using ketamine/esketamine in TRD subjects with particular focus on somatic comorbidities as the transient drug effect on cardiovascular system is demonstrated and of clinical significance.

Short-term ketamine administration in treatment-resistant depression patients: focus on adverse effects on the central nervous system.

Major depressive disorder (MDD) is a recurrent, incapacitating psychiatric illness which will be the second most disabling disease worldwide by the year 2020. There is a rising promise in a N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, which may be used in the treatment of resistant depression. Many of the studies are in favor of the drug, even in single dose application, with effects appearing in minutes to hours from administration. However, there is a need to evaluate the benefits and risks regarding psychomimetic, psychiatric, neurologic, and cognitive adverse effects of ketamine administration. The most distressing symptoms which appear most frequently during ketamine administration are dissociative symptoms, which can be quantified as a CNS adverse drug reaction. Results generally show that a single infusion of ketamine is efficacious and well-tolerated, while dissociative symptoms tend to abate within 2 hours after ketamine administration. As studies show single doses of ketamine should be definitely considered as an option in TRD patients with/without suicidal thoughts, even though it could not provide remission, or the effect could be temporary, but improving patients' quality of life by reducing depressive symptomatology should be a major asset while considering this particular procedure, particularly in inpatients.

Suicidality in treatment resistant depression: perspective for ketamine use.

Suicidal ideations or attempts in patients with major depressive disorder (MDD) are emergent conditions that require immediate treatment. Numerous therapeutic interventions to reduce suicide risk in psychiatric disorders are effective in long-term suicide prevention, but there is necessity of sufficient, rapid pharmacological treatment of suicidal risk in MDD. Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, has been reported to have rapid antidepressant effect. Depressive symptoms, anxiety, hopelessness, suicidal ideation had decreased within hours after ketamine infusion. Ketamine's rapid symptoms relief and reduction of suicide thoughts has aroused growing interests in psychiatric association.

Role of copper and ketamine in major depressive disorder - an update.

Major depressive disorder is one of the most important psychiatric issues worldwide, with important prevalence of treatment-resistant depression (TRD). Non-monoaminergic agents are currently in the spotlight. Objective was to explore for information about mechanisms of action of ketamine, its connections with copper and possible importance for TRD treatment. There are at least few possible pathways for ketamine action in depression in which copper and other divalent ions may show a vital role. There is urgent need for more studies to gather information about correlation between ketamine, copper and antidepressive features of these agents.

Prevalence of anxiety disorders in epilepsy.

OBJECTIVE: Anxiety disorders (ADs) are common in patients with epilepsy (PWE). The aim of this study was to estimate the prevalence of specific ADs in outpatients with epilepsy. METHODS: A group of 118 consecutive outpatients with epilepsy were screened, and 96 patients meeting inclusion criteria were examined by a trained psychiatrist using Structured Clinical Interview (SICD-I) for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (Text Revision) (DSM-IV-TR). RESULTS: A diagnosis of any current AD was established in 16 (16.7%) out of 96 participants. Furthermore, panic disorder (PD) was the most frequent AD; it was observed in 13.5% of PWE and constituted 81.2% of the identified ADs in the study group. Older age and later age of seizure onset were associated with increased odds of AD diagnosis. STUDY LIMITATIONS: The cross-sectional study design, a consecutive sample of patients presenting to a tertiary referral center, and small sample size of the population could have affected the results. CONCLUSIONS: Panic disorder and other forms of AD are common among PWE. Age and age of seizure onset are important factors associated with AD among PWE.

Validation of the Polish version of the Hospital Anxiety and Depression Scale for anxiety disorders in patients with epilepsy.

OBJECTIVE: Anxiety disorders are frequent comorbid disorders in patients with epilepsy (PWEs). The availability of validated screening instruments to detect anxiety disorders in PWEs is limited. The aim of the present study was to validate the Polish version of the Hospital Anxiety and Depression Scale (HADS) in adult PWEs for the detection of anxiety disorders. METHODS: A total of 96 outpatients with epilepsy completed the self-reported symptom scale, the HADS, and were diagnosed using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) axis I disorders (SCID-I). The sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and receiver operating characteristic (ROC) curves were assessed to determine the optimal threshold scores for the HADS anxiety subscale (HADS-A). RESULTS: Receiver operating characteristic analyses showed areas under the curve at 80.8%. For diagnoses of anxiety disorder, the HADS-A demonstrated the best psychometric properties for a cutoff score ≥10 with sensitivity of 81.3%, specificity of 70.0%, PPV of 31.5%, and NPV of 94.9%. CONCLUSIONS: The HADS-A proved to be a valid and reliable psychometric instrument in terms of screening for anxiety disorders in our sample of PWEs. In the epilepsy setting, the HADS-A maintains adequate sensitivity, acceptable specificity, and high NPV but low PPV for diagnosing anxiety disorders with an optimum cutoff score ≥10.

Validation of the Polish version of the Beck Depression Inventory in patients with epilepsy.

BACKGROUND: Despite the fact that depressive disorders are the most common comorbidities among patients with epilepsy (PWE), such disorders often go unrecognized and untreated. In addition, the availability of validated screening instruments to detect depression in PWE is limited. The aim of the present study was thus to validate the Polish version of the Beck Depression Inventory (BDI) in adult PWE. METHODS: A group of 118 outpatient PWE were invited to participate in the study. Ninety-six patients meeting the inclusion criteria completed the Polish Version of Beck Depression Inventory-I (BDI-I) and were examined by a trained psychiatrist using the Structured Clinical Interview (SICD-I) for Diagnostic and statistical manual of mental disorders - fourth edition (Text revision) (DSM-IV-TR). Receiver operating characteristic (ROC) curves were used to determine the optimal threshold scores for BDI. RESULTS: Receiver operating characteristic analysis showed the area under the curve to be approximately 84%. For major depressive disorder (MDD) diagnosis, the BDI demonstrated the best psychometric properties for a cut-off score to be 18, with a sensitivity of 90.5%, specificity of 70.7%, positive predictive value (PPV) of 46.3%, and negative predictive value (NPV) of 96.4%. For the 'any depressive disorder' group, the BDI optimum cut-off score was 11, with a sensitivity of 82.5%, specificity of 73.2%, PPV of 68.8%, and NPV of 85.4%. CONCLUSIONS: The BDI score is a valid psychometric indicator for depressive disorders in PWE maintaining adequate sensitivity and specificity, high NPV, and acceptable PPV with an optimum cut-off score of 18 for MDD diagnosis.

Neurosyphilis presenting with cognitive deficits - a report of two cases.

BACKGROUND: Neurosyphilis is an infection of the brain or spinal cord caused by Treponema pallidum. In the third phase of syphilis involving the central nervous system it may manifest in a widespread dysfunctions including psychiatric manifestations being often underestimated in the differential diagnosis. CASE REPORTS: Two patients demonstrating rapid cognitive decline as the primary symptom for neurosyphillis are described with particular focus on the diagnostic process complexity and adequate treatment delivery. CONCLUSIONS: Clinical manifestations as well as psychiatric symptoms of syphilis are diverse and often non-specific. The symptomatology of mood disorders in neurosyphilis is frequently atypical, intermittent, and pleomorphic and fails to meet DSM-5 diagnostic categories. Neurocognitive decline although could be one of the key symptoms domains in neurosyphilis. Those two cases emphasise the importance of specific differential diagnosis with rapid onset cognitive decline with spotlight to sexually transmitted diseases as syphilis.

Neurosyphilis - the white matter disintegration? - two case reports.

BACKGROUND: There is evidence for neurosyphilis being associated with the central nervous system vasculitis involving medium and small vessels. As the hemispheric white matter is the major target of these vascular alterations the white matter axonal and myelination disruption may be observed employing measure for the rate of water molecule diffusion. High apparent diffusion coefficient (ADC) correspond to unimpeded water diffusion and indicating white matter disintegration. CASE REPORTS: In a retrospective study exploringcentral nervous system magnetic resonance (MR) images of two subjects presenting with neurosyphilis the ADC values were found to be increased as related to normal values being accompanied with normal appearing white matter of hemispheres. CONCLUSIONS: Applying ADC analysis to evaluate the brain in patients with neurosyphilis may reveal undetectable changes and explain the scale of abnormalities that occur in CNS. The increased mean ADC valuesin the normal appearing white matter of the hemispheres may correlate with neuropsychoatric symptomatology in syphilis.

Telepsychiatry and Virtual Reality an the Teatment of Patients with Intellectual and Developmental Disabilities.

BACKGROUND: Treatment and rehabilitation of people with intellectual and developmental disabilities is a multidisciplinary challenge, which require implementing new attitudes. The use of modern technology solutions like telepsychiatry or virtual reality may be a valuable addition to the traditional methods. OBJECTIVE: The objective of this review was to explore the usability of new technological solutions in this special population of patients. METHODS: The search in the PubMed was conducted using the following terms: (intellectual disability (Title/Abstract) OR developmental disability OR learning disorder (Title/Abstract)) AND virtual reality (Title/Abstract) OR telepsychiatry OR telemedicine OR e-mental health AND English (lang) AND (1995/01/01(PDAT): 2017/07/31(PDAT)). RESULTS: Telepsychiatry may be a useful tool in situations, when the direct access to professional assistance is limited, in solving particular problems like e.g. managing challenging behavior, also to support patients' parents and for diagnostic and educational purposes. Virtual reality can be a safe and effective method of improving different skills, developing physical fitness, and enriching the ways of spending the leisure time. CONCLUSIONS: Using modern technology is a relatively new and promising field in which new ideas may develop to support the already existing services for patients with intellectual and developmental disabilities.

The Role of Hormones and Inflammatory Markers in Cognitive Functioning of Schizophrenic Patients.

BACKGROUND: In the literature we can find evidence that immunological processes are involved the alterations of cognition in schizophrenic patients. Another factor, which may have an impact on cognitive domains in this clinical group are hormones. OBJECTIVE: The objective of this review was to explore studies, in which the role of both immunological and endocrine factors on cognitive functions in schizophrenia are analyzed. METHODS: The search of papers covering this topic in PubMed and Google Scholar was performed. RESULTS: The studies focusing on this co-relation are not numerous. The role such hormones like cortisol, insulin and sex hormones may be important in the immunomodulatory processes influencing cognition in schizophrenia. CONCLUSIONS: More studies are necessary to confirm these possible co-relations.

Validation of the Hospital Anxiety and Depression Scale in patients with epilepsy.

OBJECTIVE: Despite the fact that depressive disorders are the most common comorbidities among patients with epilepsy (PWEs), they often go unrecognized and untreated. The availability of validated screening instruments to detect depression in PWEs is limited. The aim of the present study was to validate the Hospital Anxiety and Depression Scale (HADS) in adult PWEs. METHODS: A consecutive group of 118 outpatient PWEs was invited to participate in the study. Ninety-six patients met inclusion criteria, completed HADS, and were examined by a trained psychiatrist using Structured Clinical Interview (SCID-I) for DSM-IV-TR. Receiver operating characteristic (ROC) curves were used to determine the optimal threshold scores for the HADS depression subscale (HADS-D). RESULTS: Receiver operating characteristic analyses showed areas under the curve at approximately 84%. For diagnoses of MDD, the HADS-D demonstrated the best psychometric properties for a cutoff score ≥7 with sensitivity of 90.5%, specificity of 70.7%, positive predictive value of 46.3%, and negative predictive value of 96.4%. In the case of the group with 'any depressive disorder', the HADS-D optimum cutoff score was ≥6 with sensitivity of 82.5%, specificity of 73.2%, positive predictive value of 68.8%, and negative predictive value of 85.4%. CONCLUSIONS: The HADS-D proved to be a valid and reliable psychometric instrument in terms of screening for depressive disorders in PWEs. In the epilepsy setting, HADS-D maintains adequate sensitivity, acceptable specificity, and high NPV but low PPV for diagnosing MDD with an optimum cutoff score ≥7.