Background:
Brexpiprazole is a dopamine/serotonin receptor partial agonist (D2, 5-HT1A) and antagonist (5-HT2A) approved for treatment of schizophrenia and major depressive disorder (adjunct to ...antidepressants).
Aims:
This study aimed to investigate brexpiprazole as monotherapy in acute mania (bipolar I disorder) in two short-term (ST) studies (study 080 and study 081) and one open-label (OL) extension (study 083).
Methods:
ST studies were three-week randomized, double-blind, flexible dose (2–4 mg/day), placebo-controlled studies. The primary endpoint was mean change in Young Mania Rating Scale (YMRS) total score from baseline to day 21. The OL study was a 26-week flexible dose (2–4 mg/day) study for patients completing the ST studies.
Results:
A total of 164 and 158 (study 080) and 170 and 162 (study 081) inpatients with DSM-5 mania with/without mixed features were randomized to placebo or brexpiprazole, respectively. The primary analyses did not show a statistically significant difference between brexpiprazole and placebo: study 080: least squares mean difference (95% confidence limits): 0.14 (−1.74, 2.03), p = 0.8797; study 081: −1.62 (−3.56, 0.32), p = 0.1011. OL study patients (n = 381) demonstrated a gradual improvement in YMRS total score. Akathisia was the only adverse event, with an incidence of ⩾5% with brexpiprazole and more than placebo in the ST studies, or ⩾5% in the OL study. Brexpiprazole was more efficacious in patients with impaired or no insight (predominantly EU patients) than in patients with excellent insight (predominantly US patients).
Conclusions:
Further studies are necessary to address the potential efficacy of brexpiprazole in acute mania, which should ensure that the study sample is severe enough (especially with regard to insight), and that the dose/titration schedule is not too modest.
Mitochondria are cellular organelles involved in several biological processes, especially in energy production. Several studies have found a relationship between mitochondrial dysfunction and mood ...disorders, such as major depressive disorder and bipolar disorder. Impairments in energy production are found in these disorders together with higher levels of oxidative stress. Recently, many agents capable of enhancing antioxidant defenses or mitochondrial functioning have been studied for the treatment of mood disorders as adjuvant therapy to current pharmacological treatments. A better knowledge of mitochondrial physiology and pathophysiology might allow the identification of new therapeutic targets and the development and study of novel effective therapies to treat these specific mitochondrial impairments. This could be especially beneficial for treatment-resistant patients. In this article, we provide a focused narrative review of the currently available evidence supporting the involvement of mitochondrial dysfunction in mood disorders, the effects of current therapies on mitochondrial functions, and novel targeted therapies acting on mitochondrial pathways that might be useful for the treatment of mood disorders.
Abstract
Objectives. These guidelines are based on a first edition that was published in 2004, and have been edited and updated with the available scientific evidence up to October 2012. Their ...purpose is to supply a systematic overview of all scientific evidence pertaining to the long-term treatment of bipolar disorder in adults. Methods. Material used for these guidelines are based on a systematic literature search using various data bases. Their scientific rigor was categorised into six levels of evidence (A-F) and different grades of recommendation to ensure practicability were assigned. Results. Maintenance trial designs are complex and changed fundamentally over time; thus, it is not possible to give an overall recommendation for long-term treatment. Different scenarios have to be examined separately: Prevention of mania, depression, or an episode of any polarity, both in acute responders and in patients treated de novo. Treatment might differ in Bipolar II patients or Rapid cyclers, as well as in special subpopulations. We identified several medications preventive against new manic episodes, whereas the current state of research into the prevention of new depressive episodes is less satisfactory. Lithium continues to be the substance with the broadest base of evidence across treatment scenarios. Conclusions. Although major advances have been made since the first edition of this guideline in 2004, there are still areas of uncertainty, especially the prevention of depressive episodes and optimal long-term treatment of Bipolar II patients.
Recent years have seen major developments in psychotherapy research that suggest the need to address critical methodological issues. These recommendations, developed by an international group of ...researchers, do not replace those for randomized controlled trials, but rather supplement strategies that need to be taken into account when considering psychological treatments. The limitations of traditional taxonomy and assessment methods are outlined, with suggestions for consideration of staging methods. Active psychotherapy control groups are recommended, and adaptive and dismantling study designs offer important opportunities. The treatments that are used, and particularly their specific ingredients, need to be described in detail for both the experimental and the control groups. Assessment should be performed blind before and after treatment and at long-term follow-up. A combination of observer-and self-rated measures is recommended. Side effects of psychotherapy should be evaluated using appropriate methods. Finally, the number of participants who deteriorate after treatment should be noted according to the methods that were used to define response or remission.
Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine ...learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47-67.00, ROC-AUC = 71.49%, 95% CI = 69.39-73.59), followed by leave-one-site-out cross-validation (accuracy = 58.67%, 95% CI = 56.70-60.63). Meta-analysis of individual site accuracies did not provide above chance results. There was substantial agreement between the regions that contributed to identification of BD participants in the best performing site and in the aggregate dataset (Cohen's Kappa = 0.83, 95% CI = 0.829-0.831). Treatment with anticonvulsants and age were associated with greater odds of correct classification. Although short of the 80% clinically relevant accuracy threshold, the results are promising and provide a fair and realistic estimate of classification performance, which can be achieved in a large, ecologically valid, multi-site sample of BD participants based on regional neurostructural measures. Furthermore, the significant classification in different samples was based on plausible and similar neuroanatomical features. Future multi-site studies should move towards sharing of raw/voxelwise neuroimaging data.
Abstract Cognitive reserve (CR) refers to the hypothesized capacity of an adult brain to cope with brain pathology in order to minimize symptomatology. CR was initially investigated in dementia and ...acute brain damage, but it is being applied to other neuropsychiatric conditions. The present study aims at examining the fit of this concept to a sample of euthymic bipolar patients compared with healthy controls in order to investigate the role of CR in predicting psychosocial and cognitive outcome in bipolar disorder (BD). The sample included 101 subjects: 52 patients meeting DSM-IV-TR criteria for BD type I or II and 49 healthy controls (HC) matched for age and gender. They were all assessed with a cognitive battery tapping into executive and memory functioning. CR was obtained using three different proxies: education–occupation, leisure activities and premorbid IQ. Psychosocial functioning was evaluated by means of the Functioning Assessment Short Test (FAST). MANCOVAs were performed to determine differences in cognitive and functioning variables. Linear regression analyses were carried out to predict neuropsychological and psychosocial outcomes. Euthymic bipolar patients showed worse neuropsychological performance and psychosocial functioning than HC. The linear regression models revealed that CR was significantly predictive of FAST score ( β= −0.47, p <0.0001), Executive Index ( β= 0.62, p <0.0001) and Visual Memory Index ( β= 0.44, p =0.0004), indicating that CR is a significant predictor of cognitive and psychosocial functioning in euthymic bipolar outpatients. Therefore, CR may contribute to functional outcome in BD and may be applied in research and clinical interventions to prevent cognitive and functional impairment.
Objectives: Although clinically highly relevant, the recognition and treatment of bipolar mixed states has played only an underpart in recent guidelines. This WFSBP guideline has been developed to ...supply a systematic overview of all scientific evidence pertaining to the acute and long-term treatment of bipolar mixed states in adults.
Methods: Material used for these guidelines is based on a systematic literature search using various data bases. Their scientific rigour was categorised into six levels of evidence (A-F), and different grades of recommendation to ensure practicability were assigned. We examined data pertaining to the acute treatment of manic and depressive symptoms in bipolar mixed patients, as well as data pertaining to the prevention of mixed recurrences after an index episode of any type, or recurrence of any type after a mixed index episode.
Results: Manic symptoms in bipolar mixed states appeared responsive to treatment with several atypical antipsychotics, the best evidence resting with olanzapine. For depressive symptoms, addition of ziprasidone to treatment as usual may be beneficial; however, the evidence base is much more limited than for the treatment of manic symptoms. Besides olanzapine and quetiapine, valproate and lithium should also be considered for recurrence prevention.
Limitations: The concept of mixed states changed over time, and recently became much more comprehensive with the release of DSM-5. As a consequence, studies in bipolar mixed patients targeted slightly different bipolar subpopulations. In addition, trial designs in acute and maintenance treatment also advanced in recent years in response to regulatory demands.
Conclusions: Current treatment recommendations are still based on limited evidence, and there is a clear demand for confirmative studies adopting the DSM-5 specifier with mixed features concept.
Three articles in this issue detail the process and results of reliability tests for proposed DSM-5 diagnoses and cross-diagnosis symptom domains. The editorial highlights the good reliability of ...borderline personality disorder and relates the questionable reliability of major depressive disorder to its heterogeneity. The editorial is also available in Spanish, Traditional Chinese, and Simplified Chinese.
Cognitive impairment in bipolar II disorder Torrent, Carla; Martínez-Arán, Anabel; Daban, Claire ...
British journal of psychiatry,
09/2006, Letnik:
189, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Persistent impairments in neurocognitive function have been described in bipolar disorder.
To compare the cognitive performance of patients with bipolar II disorder with that of patients with bipolar ...I disorder and a healthy control group.
The study included 71 euthymic patients with bipolar disorder (38 bipolar I, 33 bipolar II), who were compared on clinical and neuropsychological variables (e.g. executive function, attention, verbal and visual memory) and contrasted with 35 healthy controls on cognitive performance.
Compared with controls, both bipolar groups showed significant deficits in most cognitive tasks including working memory (DigitSpan Backwards, P=0.002) and attention (DigitSpan Forwards, P=0.005; Trail Making Test, P=0.001). Those with type II disorders had an intermediate level of performance between the bipolar I group and the control group in verbal memory (P<0.005) and executive functions (Stroop interference task, P=0.020).
Cognitive impairment exists in both subtypes of bipolar disorder, although more so in the bipolar I group. The best predictors of poor psychosocial functioning in bipolar II disorder were subclinical depressive symptoms, early onset of illness and poor performance on a measure related to executive function.
Psychotherapists need effective tools to monitor changes in the patient's affective perception of the therapist and the therapeutic relationship during sessions to tailor therapeutic interventions ...and improve treatment outcomes. This study aims to evaluate the factor structure, reliability, and validity of the
(SPARQ), a concise self-report measure designed for practical application in real-world psychotherapy settings.
Validation data was gathered from (
= 700) adult patients in individual psychotherapy. These patients completed the SPARQ in conjunction with additional measures capturing sociodemographic details, characteristics of therapeutic interventions, individual personality traits, mental health symptom severity, elements of the therapeutic relationship, and session outcomes. This comprehensive approach was employed to assess the construct and criterion-related validity of the SPARQ.
The SPARQ has a two-factor structure: Positive Affect (
= 4,
total = .87) and Negative Affect (
= 4,
total = .75). Bifactor confirmatory factor analysis (CFA) yielded the following fit indices:
= 2.53, CFI = .99; TLI = .98; RMSEA = .05; and SRMR = .02. Multi-group CFAs demonstrated measurement invariance (i) across patients who attended psychotherapy sessions in person
in remote mode, and (ii) across patients with and without psychiatric diagnoses confirmed metric invariance. Furthermore, the SPARQ showed meaningful correlations with concurrently administered measures.
The SPARQ proves to be a valuable instrument in clinical, training, and research contexts, adept at capturing patients' session-level affective responses towards their therapist and perceptions of the therapeutic alliance. Comprehensive descriptive statistics and a range of score precision indices have been reported, intended to serve as benchmarks for future research.
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