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BACKGROUND: Monoamine oxidase inhibitors (MAOIs) are considered third-line treatments for treatment resistant depression; however, they are underused in clinical practice. AIMS: This study aimed to assess the efficacy, tolerability, and acceptability of MAOIs for the treatment of depression in comparison with other antidepressant treatments. METHODS: A systematic review and network meta-analysis of randomised clinical trials was performed to compare the efficacy, tolerability and acceptability between MAOIs and other antidepressant treatments for the treatment of depressive episodes. RESULTS: A total of 83 double-blinded, randomised controlled trials were included in the analysis, with 7765 participants assigned to an active treatment and 1844 assigned to placebo. Several MAOIs, including isocarboxazid, phenelzine, tranylcypromine and moclobemide, showed significantly higher efficacy compared with placebo. The tolerability and acceptability of MAOIs was comparable to other antidepressants. LIMITATIONS: A disproportionate number of studies investigating the most commonly used MAOIs, such as moclobemide and phenelzine, and a lack of specific studies focusing on treatment-resistant and atypical depression. CONCLUSIONS: MAOIs are similar in efficacy to other antidepressants for the treatment of depression. However, more studies are needed comparing MAOI treatment in people with treatment-resistant, atypical and bipolar depression.
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BACKGROUND: Bipolar disorders (BD) are chronic, debilitating disorders. The blood-brain barrier (BBB) has been increasingly investigated in BD. This systematic review aimed to assess the available evidence on the relationship between BD and markers of BBB dysfunction. METHODS: A systematic search in PubMed, Embase, PsycINFO, CINAHL and Web of Science was run where the primary outcomes were BBB markers such as S100B, albumin ratio, matrix metalloproteinase (MMP), cell adhesion molecule (CAM), and tight junction proteins. Techniques included blood, cerebrospinal fluid (CSF), post-mortem, genetic and imaging methods in BD compared to healthy controls. RESULTS: 55 studies were identified, 38 of which found an association between BD and markers of BBB dysfunction. 16/29 studies found increased blood/CSF albumin ratio, S100B, CAMs or MMP levels in BD participants compared to controls. 5/19 post-mortem studies found increased levels of chondroitin sulphate proteoglycans, intercellular CAM, neurexin or claudin-5 mRNA in distinct locations throughout the brain in BD compared to controls. One imaging study identified extensive BBB leakage in 30 % of BD participants, compared to 0 % in controls. LIMITATIONS: The diversity in methodologies used in the included studies makes direct comparison of results challenging. Furthermore, imaging methods are the gold standard, but only one study used them. Other markers are only indicative of BBB permeability. CONCLUSIONS: This review suggests an association between BD and BBB dysfunction. Further research is needed to provide definite answers considering the existing literature's limitations, and to clarify whether this association provides a pathogenic mechanism, or is an epiphenomenon of BD.
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Transtorno Bipolar , Barreira Hematoencefálica , Subunidade beta da Proteína Ligante de Cálcio S100 , Humanos , Biomarcadores/sangue , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/metabolismo , Transtorno Bipolar/sangue , Moléculas de Adesão Celular/genética , Metaloproteinases da Matriz/metabolismo , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/líquido cefalorraquidiano , Proteínas de Junções Íntimas/metabolismoRESUMO
BACKGROUND: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD. METHODS: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. RESULTS: Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias. CONCLUSIONS: Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno Bipolar , Estimulantes do Sistema Nervoso Central , Disfunção Cognitiva , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Uso Off-Label , Metilfenidato/efeitos adversos , Metilfenidato/uso terapêuticoRESUMO
BACKGROUND: Preclinical animal and preliminary human studies indicate that 5-HT7 antagonists have the potential as a new treatment approach for mood and anxiety disorders. In this systematic review, we aimed to review the relationship between the 5-HT7 receptor system and mood and anxiety disorders, and to explore the pharmacology and therapeutic potential of medications that target the 5-HT7 receptor for their treatment. METHODS: Medline, Cochrane Library, EMBASE, PsycINFO databases, the National Institute of Health website Clinicaltrials.gov, controlled-trials.com, and relevant grey literature were used to search for original research articles, and reference lists of included articles were then hand searched. RESULTS: Sixty-four studies were included in the review: 52 animal studies and 12 human studies. Studies used a variety of preclinical paradigms and questionnaires to assess change in mood, and few studies examined sleep or cognition. Forty-four out of 47 (44/47) preclinical 5-HT7 modulation studies identified potential antidepressant effects and 20/23 studies identified potential anxiolytic effects. In clinical studies, 5/7 identified potential antidepressant effects in major depressive disorder, 1/2 identified potential anxiolytic effects in generalized anxiety disorder, and 3/3 identified potential antidepressant effects in bipolar disorders. CONCLUSION: While there is some evidence that the 5-HT7 receptor system may be a potential target for treating mood and anxiety disorders, many agents included in the review also bind to other receptors. Further research is needed using drugs that bind specifically to 5-HT7 receptors to examine treatment proof of concept further.
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Transtornos de Ansiedade , Animais , Humanos , Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológicoRESUMO
The Hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the pathophysiology of mood disorders, and preliminary data suggests that glucocorticoid receptor (GR) antagonism may be an important therapeutic mechanism. The effects of modulating HPA axis function on emotional processing related brain activity, which may be abnormal in depressed mood, is poorly understood. This study used a pharmacological functional magnetic resonance imaging (fMRI) design to determine the effects of the GR and progesterone receptor antagonist mifepristone on emotional faces processing task related brain activations in 19 right-handed healthy male participants. Each participant received 600 mg mifepristone or placebo on two separate imaging days and then performed an emotional processing fMRI task four hours later. The effect of mifepristone on task related brain activations was determined using Region-of-Interest (ROI) analyses and an exploratory whole brain voxel-wise analyses. No significant changes were observed in the defined ROIs (amygdala, anterior cingulate cortex, insula) or in the exploratory whole brain analyses that was associated with mifepristone administration in either the angry vs happy faces or angry and happy faces vs implicit baseline contrasts. Task reaction times and accuracy were similar in both mifepristone and placebo conditions (all p > 0.05). Our study failed to show significant evidence of modulation of emotional processing related brain activity associated with acute mifepristone administration. Future research should use fMRI to investigate the longer-term administration effects of mifepristone on mood in healthy participants and people with mood disorders to provide a deeper understanding of the potential effects on depressive symptoms.
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Sistema Hipotálamo-Hipofisário , Mifepristona , Humanos , Masculino , Mifepristona/farmacologia , Sistema Hipófise-Suprarrenal , Emoções/fisiologia , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Expressão FacialRESUMO
Bidirectional relationship between sleep disturbances and affective disorders is increasingly recognised, but its underlying mechanisms are far from clear, and there is a scarcity of studies that report on sleep disturbances in recurrent depressive disorder (RDD) and bipolar affective disorder (BPAD). To address this, we conducted a retrospective study of polysomnographic and clinical records of patients presenting to a tertiary sleep disorders clinic with affective disorders. Sixty-three BPAD patients (32 female; mean age ± S.D.: 41.8 ± 12.4 years) and 126 age- and gender-matched RDD patients (62 female; 41.5 ± 12.8) were studied. Whilst no significant differences were observed in sleep macrostructure parameters between BPAD and RDD patients, major differences were observed in comorbid sleep and physical disorders, both of which were higher in BPAD patients. Two most prevalent sleep disorders, namely obstructive sleep apnoea (OSA) (BPAD 50.8.0% vs RDD 29.3%, P = 0.006) and insomnia (BPAD 34.9% vs RDD 15.0%, P = 0.005) were found to be strongly linked with BPAD. In summary, in our tertiary sleep clinic cohort, no overt differences in the sleep macrostructure between BPAD and RDD patients were demonstrated. However, OSA and insomnia, two most prevalent sleep disorders, were found significantly more prevalent in patients with BPAD, by comparison to RDD patients. Also, BPAD patients presented with significantly more severe OSA, and with higher overall physical co-morbidity. Thus, our findings suggest an unmet/hidden need for earlier diagnosis of those with BPAD.
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Transtorno Bipolar , Transtorno Depressivo , Distúrbios do Início e da Manutenção do Sono , Humanos , Feminino , Transtorno Bipolar/complicações , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/diagnóstico , Estudos Retrospectivos , SonoRESUMO
BACKGROUND: Cognitive impairment experienced by people with bipolar disorders (BD) or major depressive disorder (MDD) is associated with impaired psychosocial function and poorer quality of life. Sleep disturbance is another core symptom of mood disorders which may be associated with, and perhaps worsen, cognitive impairments. The aim of this systematic review was to critically assess the relationship between sleep disturbance and cognitive impairment in mood disorders. METHODS: In this systematic review, relevant studies were identified using electronic database searches of PsychINFO, MEDLINE, Embase and Web of Science. FINDINGS: Fourteen studies were included; eight investigated people with BD, five investigated people with MDD, and one included both people with MDD and people with BD. One study was an intervention for sleep disturbance and the remaining thirteen studies used either a longitudinal or cross-sectional observational design. Ten studies reported a significant association between subjectively measured sleep disturbance and cognitive impairment in people with MDD or BD after adjusting for demographic and clinical covariates, whereas no such association was found in healthy participants. Two studies reported a significant association between objectively measured (actigraphy or polysomnography) sleep abnormalities and cognitive impairment in mood disorders. One study of cognitive behavioural therapy for insomnia modified for BD (CBTI-BD) found an association between improvements in sleep and cognitive performance in BD. INTERPRETATION: There is preliminary evidence to suggest a significant association between sleep disturbance and cognitive impairment in mood disorders. These findings highlight the need for further research of sleep disturbances and cognitive impairment in people with mood disorders.
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Disfunção Cognitiva , Transtorno Depressivo Maior , Transtornos do Sono-Vigília , Humanos , Transtornos do Humor , Estudos Transversais , Qualidade de Vida , Sono , Transtornos do Sono-Vigília/psicologiaRESUMO
BACKGROUND: Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain-based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neuroimaging studies of pro-cognitive interventions. METHODS: We included magnetic resonance imaging (MRI) studies of candidate interventions in people with mood disorders or healthy individuals, following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE, Cochrane Library, and Clinicaltrials.gov from inception to 30th April 2021. Two independent authors reviewed the studies using the National Heart, Lung, Blood Institutes of Health Quality Assessment Tool for Controlled Intervention Studies and the quality of neuroimaging methodology assessment checklist. RESULTS: We identified 26 studies (N = 702). Six investigated cognitive remediation or pharmacological treatments in mood disorders (N = 190). In healthy individuals, 14 studies investigated pharmacological interventions (N = 319), 2 cognitive training (N = 73) and 4 neuromodulatory treatments (N = 120). Methodologies were mostly rated as 'fair'. 77% of studies investigated effects with task-based fMRI. Findings varied but most consistently involved treatment-associated cognitive control network (CCN) activity increases with cognitive improvements, or CCN activity decreases with no cognitive change, and increased functional connectivity. In mood disorders, treatment-related default mode network suppression occurred. CONCLUSIONS: Modulation of CCN and DMN activity is a putative efficacy biomarker. Methodological recommendations are to pre-declare intended analyses and use task-based fMRI, paradigms probing the CCN, longitudinal assessments, mock scanning, and out-of-scanner tests.
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Transtorno Bipolar , Disfunção Cognitiva , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/tratamento farmacológico , Cognição , Disfunção Cognitiva/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Transtornos do Humor/diagnóstico por imagem , Transtornos do Humor/tratamento farmacológicoRESUMO
BACKGROUND: Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations. METHODS: The review included RCTs of candidate pro-cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials. RESULTS: We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre-screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking. CONCLUSIONS: Evidence for pro-cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre-screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real-world functioning, investigate multimodal interventions and include neuroimaging.
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Transtorno Bipolar , Disfunção Cognitiva , Transtorno Bipolar/psicologia , Transtorno Bipolar/terapia , Cognição , Disfunção Cognitiva/terapia , Humanos , Cloridrato de Lurasidona , Transtornos do Humor/etiologia , Transtornos do Humor/terapiaRESUMO
BACKGROUND: Bipolar disorders (BD) are serious mental health disorders that impacts on cognitive and social functioning. We aimed to systematically review and conduct a meta-analysis of fMRI correlates of working memory in euthymic people with BD compared to healthy participants. METHOD: Web of Science, Embase and PubMed databases were systematically searched to identify studies which examined the fMRI correlates of working memory function in euthymic people with BD and healthy participants. Relevant demographic, behavioral and functional MRI (fMRI) data was qualitatively and quantitatively assessed, and the quality of the included studies evaluated. Comparable studies which used the same working memory task were included in a meta-analysis using Seed-Based D Mapping software (SDM). RESULTS: Twenty-four studies were included in this systematic review. Consistent brain fMRI activity differences were found in key brain areas of the working memory network in euthymic people with BD compared to healthy participants including the ventromedial and dorsolateral prefrontal cortices. Cognitive performance was not significantly different between the two groups. Six studies were suitable to be included in the meta-analysis. There was no significant overlap in areas of brain activation after family-wise correction for multiple comparisons. LIMITATIONS: Heterogeneity of task paradigms, small sample sizes and inherent difficulty in the interpretation of functional brain activity due to variations between studies were all limitations. CONCLUSION: The differences in working memory related fMRI activity identified by this study between people with BD and healthy participants are consistent with existing literature reporting impaired working memory performance in BD. This was not accompanied by significant differences in cognitive performance in the reviewed studies, likely due to small sample sizes. Further studies are needed to investigate the relationship between differential brain activity and working memory performance in people with BD.
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Transtorno Bipolar , Memória de Curto Prazo , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtorno Ciclotímico , Córtex Pré-Frontal Dorsolateral , Humanos , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: Abnormalities in spontaneous brain activity, measured with resting-state functional magnetic resonance imaging (rs-fMRI), may be key biomarkers for bipolar disorders. This systematic review compares rs-fMRI findings in people experiencing a bipolar depressive or (hypo)manic episode to bipolar euthymia and/or healthy participants. METHODS: Medline, Web of Science and Embase were searched up until April 2021. Studies without control group, or including minors, neurological co-morbidities or mixed episodes, were excluded. Qualitative synthesis was used to report results and risk of bias was assessed using the National Heart, Lung and Blood Institute tool for case-control studies. RESULTS: Seventy-one studies were included (3167 bipolar depressed/706 (hypo)manic). In bipolar depression, studies demonstrated default-mode (DMN) and frontoparietal network (FPN) dysfunction, altered baseline activity in the precuneus, insula, striatum, cingulate, frontal and temporal cortex, and disturbed regional homogeneity in parietal, temporal and pericentral areas. Functional connectivity was altered in thalamocortical circuits and between the cingulate cortex and precuneus. In (hypo)mania, studies reported altered functional connectivity in the amygdala, frontal and cingulate cortex. Finally, rs-fMRI disturbances in the insula and putamen correlate with depressive symptoms, cerebellar resting-state alterations could evolve with disease progression and altered amygdala connectivity might mediate lithium effects. CONCLUSIONS: Our results suggest DMN and FPN dysfunction in bipolar depression, whereas local rs-fMRI alterations might differentiate mood states. Future studies should consider controlling rs-fMRI findings for potential clinical confounding factors such as medication. Considerable heterogeneity of methodology between studies limits conclusions. Standardised clinical reporting and consistent analysis approaches would increase coherence in this promising field.
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Biomarcadores , Transtorno Bipolar/patologia , Encéfalo/patologia , Imageamento por Ressonância Magnética , Mania/patologia , Tonsila do Cerebelo , Rede de Modo Padrão , Giro do Cíngulo , Humanos , Neostriado , Lobo Parietal , Lobo TemporalRESUMO
BACKGROUND: People with bipolar disorders (BD) may be at increased risk of Human Immunodeficiency Virus (HIV) infection but our understanding of the impacts of HIV infection on psychiatric outcomes is poor. This study aimed to examine the prevalence, temporal relationship, and clinical impact of HIV infection in people with BD. METHODS: In this retrospective case-control study, anonymised electronic case records of patients with BD who had been under the care of South London and Maudsley mental health services were used for data extraction. 54 HIV+ people with BD were identified and compared to a matched control group of 54 HIV- people with BD. RESULTS: The prevalence of HIV co-morbidity in the BD population was around 1%. 76% of HIV+ BD men identified as men who have sex with men (MSM). 65% of the HIV+ BD group were diagnosed with BD before becoming HIV+. The HIV+ BD group experienced significantly higher rates of stimulant, GBL/GHB and psychedelic use compared to the HIV- BD group. 85% of the HIV+ BD group were recorded as taking antiretroviral medications. LIMITATIONS: Retrospective and cross-sectional study design, and a relatively small sample size CONCLUSIONS: The prevalence of HIV comorbidity in BD was comparable to the local general population. HIV infection in BD is associated with MSM status and stimulant, GHB/GBL and psychedelics use suggesting that HIV prevention strategies should particularly target these groups. Lower use of antiretroviral medications by people with BD underlines the importance of engaging HIV+ BD people in HIV services.
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Transtorno Bipolar , Infecções por HIV , Minorias Sexuais e de Gênero , Transtorno Bipolar/epidemiologia , Estudos de Casos e Controles , Estudos Transversais , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Prevalência , Estudos RetrospectivosRESUMO
Background: Following the success of Cognitive Behavioral Therapy (CBT) for insomnia, there has been a growing recognition that similar treatment approaches might be equally beneficial for other major sleep disorders, including non-rapid eye movement (NREM) parasomnias. We have developed a novel, group-based, CBT-program for NREM parasomnias (CBT-NREMP), with the primary aim of reducing NREM parasomnia severity with relatively few treatment sessions. Methods: We investigated the effectiveness of CBT-NREMP in 46 retrospectively-identified patients, who completed five outpatient therapy sessions. The outcomes pre- and post- CBT-NREMP treatment on clinical measures of insomnia (Insomnia Severity Index), NREM parasomnias (Paris Arousal Disorders Severity Scale) and anxiety and depression (Hospital Anxiety and Depression Scale), were retrospectively collected and analyzed. In order to investigate the temporal stability of CBT-NREMP, we also assessed a subgroup of 8 patients during the 3 to 6 months follow-up period. Results: CBT-NREMP led to a reduction in clinical measures of NREM parasomnia, insomnia, and anxiety and depression severities [pre- vs. post-CBT-NREMP scores: P (Insomnia Severity Index) = 0.000054; P (Paris Arousal Disorders Severity Scale) = 0.00032; P (Hospital Anxiety and Depression Scale) = 0.037]. Improvements in clinical measures of NREM parasomnia and insomnia severities were similarly recorded for a subgroup of eight patients at follow-up, demonstrating that patients continued to improve post CBT-NREMP. Conclusion: Our findings suggest that group CBT-NREMP intervention is a safe, effective and promising treatment for NREM parasomnia, especially when precipitating and perpetuating factors are behaviorally and psychologically driven. Future randomized controlled trials are now required to robustly confirm these findings.
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BACKGROUND: Treatment Resistant Bipolar Depression (TRBD) is a major contributor to the burden of disease associated with Bipolar Disorder (BD). Treatment options for people experiencing bipolar depression are limited to three interventions listed by National Institute for Health and Care: lamotrigine, quetiapine and olanzapine, of which the latter two are often not well tolerated. The majority of depressed people with BD are therefore prescribed antidepressants despite limited efficacy. This demonstrates an unmet need for additional interventions. Pramipexole has been shown to improve mood symptoms in animal models of depression, in people with Parkinson's Disease and two proof of principle trials of pramipexole for people with BD who are currently depressed. METHODS: The PAX-BD study, funded by the United Kingdom (UK) National Institute for Health Research, aims to extend previous findings by assessing the efficacy, safety and health economic impact of pramipexole in addition to mood stabilisers for patients with TRBD. A randomised, double-blind, placebo controlled design is conducted in a naturalistic UK National Health Service setting. An internal pilot study to examine feasibility and acceptability of the study design is included. Participants with TRBD are screened from National Health Service secondary care services in up to 40 mental health trusts in the UK, with the aim of recruiting approximately 414 participants into a pre-randomisation phase to achieve a target of 290 randomised participants. Primary safety and efficacy measures are at 12 weeks following randomisation, with follow up of participants to 52 weeks. The primary outcome is depressive symptoms as measured by Quick Inventory for Depressive Symptomatology - Self Report. Secondary outcomes include changes in anxiety, manic symptoms, tolerability, acceptability, quality of life and cost-effectiveness. Outcome measures are collected remotely using self-report tools implemented online, and observer-rated assessments conducted via telephone. ANCOVA will be used to examine the difference in rating scale scores between treatment arms, and dependent on compliance in completion of weekly self-report measures. A mixed effects linear regression model may also be used to account for repeated measures. TRIAL REGISTRATION: ISRCTN72151939. Registered on 28 August 2019, http://www.isrctn.com/ISRCTN72151939 Protocol Version: 04-FEB-2021, Version 9.0.
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Transtorno Bipolar , Transtorno Bipolar/tratamento farmacológico , Análise Custo-Benefício , Humanos , Projetos Piloto , Pramipexol , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Medicina Estatal , Reino UnidoRESUMO
Glucocorticoid receptor (GR) antagonism is a promising new treatment for cognitive dysfunction in psychiatric disorders but the effects of GR antagonism on cognition related brain activity is poorly understood. This study examines the effects of the GR and progesterone receptor antagonist mifepristone on the neural correlates of visuospatial learning and working memory in healthy male participants. The study used a pharmacological functional magnetic resonance imaging (fMRI) design to determine mifepristone effects on visuospatial paired associates learning (vPAL) and n-back working memory (WM) fMRI task related brain activations. 20 right-handed healthy male participants received 600 mg mifepristone or placebo on two separate imaging days and each participant performed fMRI tasks four hours later. The effect of mifepristone on task related brain activations was determined using Region of Interest (ROI) fMRI analyses and an exploratory whole brain voxel-wise fMRI task analyses was also conducted. The vPAL task ROI analysis found that mifepristone administration was significantly associated with decreased fusiform cortex activations in first and second encoding blocks (p = 0.007, p = 0.04) and decreased angular and precuneal cortices activations in the first recall block (p = 0.01, p = 0.02). There were no significant differences in fMRI brain activations associated with mifepristone administration in the n-back task ROI's (all p > 0.05). Mifepristone administration did not significantly affect fMRI brain activations in the whole brain voxel-wise analyses for both tasks. N-back and vPAL task reaction times and accuracy were similar in both mifepristone and placebo conditions (all p > 0.05). Our finding of decreased fusiform, angular and precuneal vPAL task related brain activity associated with mifepristone administration for the same behavioural performance as found in the placebo condition may represent improved efficiency of visuospatial memory encoding and recall. These findings provide evidence that mifepristone may enhance the efficiency of human visuospatial memory and calls for further studies in patient populations using an fMRI approach to provide proof of concept for new treatments.
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Imageamento por Ressonância Magnética , Mifepristona , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Masculino , Memória de Curto Prazo , Rememoração Mental , Mifepristona/farmacologiaRESUMO
Our article depicts and interrogates the claims for seeing coaching and mentoring as being distinct from each other, and rather suggests that context is agentic in determining which aspects of these two helping orientations are likely to be used by practitioners. To start with, our article traces the development of coaching and mentoring as two separate discourses. Traditionally, coaching has been associated with a shorter term performance focus, with the coach portrayed as a process- rather than a content knowledge-based expert. By contrast, mentoring has a longer-term holistic focus, where the mentor has direct experience and knowledge in the setting that the mentee is operating in. Then, we discuss some limitations of seeking conceptual distinctiveness in purely theoretical terms, including accentuating differences of practices that cannot easily be disentangled from each other in practice. Therefore, on the basis of a case study, where coaching and mentoring behaviors are used by leaders and managers, we argue that context plays an agentic role and influences which of the helping orientations is used by practitioners. We conclude that, context being multifaceted, it leads to a kaleidoscope of coaching/mentoring behaviors, which supports a practice-based approach to the debate.
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Liderança , Tutoria , Mentores , HumanosRESUMO
OBJECTIVE: Addiction comorbidity is an important clinical challenge in mood disorders, but the best way of pharmacologically treating people with mood disorders and addictions remains unclear. The aim of this study was to assess the efficacy of pharmacological treatments for mood and addiction symptoms in people with mood disorders and addiction comorbidity. METHODS: A systematic search of placebo-controlled randomized controlled trials investigating the effects of pharmacological treatments in people with bipolar disorder (BD) or major depressive disorder (MDD), and comorbid addictions was performed. Treatment-related effects on mood and addiction measures were assessed in a meta-analysis, which also estimated risks of participant dropout and adverse effects. RESULTS: A total of 32 studies met systematic review inclusion criteria. Pharmacological therapy was more effective than placebo for improving manic symptoms (standardized mean difference [SMD] = -0.15; 95% confidence interval [95% CI], -0.29 to -0.02; P = 0.03) but not BD depressive symptoms (SMD = -0.09; 95% CI, -0.22 to 0.03; P = 0.15). Quetiapine significantly improved manic symptoms (SMD = -0.23; 95% CI, -0.39 to -0.06; P = 0.008) but not BD depressive symptoms (SMD = -0.07; 95% CI, -0.23 to 0.10; P = 0.42). Pharmacological therapy was more effective than placebo for improving depressive symptoms in MDD (SMD = -0.16; 95% CI, -0.30 to -0.03; P = 0.02). Imipramine improved MDD depressive symptoms (SMD = -0.58; 95% CI, -1.03 to -0.13; P = 0.01) but Selective serotonin reuptake Inhibitors (SSRI)-based treatments had no effect (SMD = -0.06; 95% CI, -0.30 to 0.17; P = 0.60). Pharmacological treatment improved the odds of alcohol abstinence in MDD but had no effects on opiate abstinence. CONCLUSIONS: Pharmacological treatments were significantly better than placebo in improving manic symptoms, MDD depressive symptoms, and alcohol abstinence but were not better for bipolar depression symptoms. Importantly, quetiapine was not more effective than placebo in improving bipolar depression symptoms nor were SSRI's for the treatment of MDD depression. Our findings highlight the need for further high-quality clinical trials of treatments for mood disorders and comorbid addictions.
Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Comorbidade , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/epidemiologia , Humanos , Transtornos do Humor , Inibidores Seletivos de Recaptação de SerotoninaRESUMO
BACKGROUND: Unipolar mania is a putative subtype of bipolar disorder (BD) in which individuals experience recurrent manic but not major depressive episodes. Few studies of unipolar mania have been conducted in developed countries and none in the UK. This study aimed to identify and characterise people with unipolar mania in the UK and France. METHODS: People with unipolar mania were ascertained using a South London UK electronic case register and a French BD case series. Each unipolar mania group was compared to a matched group of people with BD who have experienced depressive episodes. RESULTS: 17 people with unipolar mania were identified in South London and 13 in France. The frequency of unipolar mania as a percentage of the BD clinical population was 1.2% for the South London cohort and 3.3% for the French cohort. In both cohorts, people with unipolar mania experienced more manic episodes than people with BD, and in the French cohort were more likely to experience a psychotic illness onset and more psychiatric admissions. Treatment and self-harm characteristics of people with unipolar mania were similar to people with BD. LIMITATIONS: The relatively small number of people with unipolar mania identified by this study limits its power to detect differences in clinical variables. CONCLUSIONS: People with unipolar mania can be identified in France and the UK, and they may experience a higher frequency of manic episodes but have similar treatment and self-harm characteristics as people with BD.