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Bipolar disorder's core feature is the pathological disturbances in mood, often accompanied by disrupted thinking and behavior. Its complex and heterogeneous etiology implies that a range of inherited and environmental factors are involved. This heterogeneity and poorly understood neurobiology pose significant challenges to existing drug development paradigms, resulting in scarce treatment options, especially for bipolar depression. Therefore, novel approaches are needed to discover new treatment options. In this review, we first highlight the main molecular mechanisms known to be associated with bipolar depression-mitochondrial dysfunction, inflammation and oxidative stress. We then examine the available literature for the effects of trimetazidine in said alterations. Trimetazidine was identified without a priori hypothesis using a gene-expression signature for the effects of a combination of drugs used to treat bipolar disorder and screening a library of off-patent drugs in cultured human neuronal-like cells. Trimetazidine is used to treat angina pectoris for its cytoprotective and metabolic effects (improved glucose utilization for energy production). The preclinical and clinical literature strongly support trimetazidine's potential to treat bipolar depression, having anti-inflammatory and antioxidant properties while normalizing mitochondrial function only when it is compromised. Further, trimetazidine's demonstrated safety and tolerability provide a strong rationale for clinical trials to test its efficacy to treat bipolar depression that could fast-track its repurposing to address such an unmet need as bipolar depression.
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Transtorno Bipolar , Trimetazidina , Humanos , Trimetazidina/farmacologia , Trimetazidina/uso terapêutico , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Angina Pectoris/tratamento farmacológico , AntioxidantesRESUMO
BACKGROUND: Lifestyle factors are being increasingly studied in bipolar disorder (BD) due to their possible effects on both course of disease and physical health. The aim of this study was to jointly describe and explore the interrelations between diet patterns, exercise, pharmacological treatment with course of disease and metabolic profile in BD. METHODS: The sample consisted of 66 euthymic or mild depressive individuals with BD. Clinical and metabolic outcomes were assessed, as well as pharmacological treatment or lifestyle habits (diet and exercise). Correlations were explored for different interrelations and a factor analysis of dietary patterns was performed. RESULTS: Adherence to the Mediterranean diet was low, seen in 37.9% of the patients and was positively associated with perceived quality of life. The amount of exercise was negatively associated with cholesterol levels, with 32.8% of participants rated as low active by International Physical Activity Questionnaire. There was a high prevalence of obesity (40.6%) and metabolic syndrome (29.7%). Users of lithium showed the best metabolic profile. Interestingly, three dietary patterns were identified: "vegetarian," "omnivore" and "Western." The key finding was the overall positive impact of the "vegetarian" pattern in BD, which was associated with reduced depression scores, better psychosocial functioning, and perceived quality of life, decreased body mass index, cholesterol, LDL and diastolic blood pressure. Nuts consumption was associated with a better metabolic profile. CONCLUSIONS: A vegetarian diet pattern was associated with both, better clinical and metabolic parameters, in patients with BD. Future studies should prioritize prospective and randomized designs to determine causal relationships, and potentially inform clinical recommendations.
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Transtorno Bipolar , Dieta Vegetariana , Exercício Físico , Síndrome Metabólica , Humanos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/terapia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Síndrome Metabólica/dietoterapia , Síndrome Metabólica/terapia , Dieta Mediterrânea , Qualidade de Vida , Estilo de Vida , Antimaníacos/uso terapêutico , Compostos de Lítio/uso terapêutico , Compostos de Lítio/administração & dosagem , Padrões DietéticosRESUMO
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 disorder (BD) is a chronic and recurrent disease characterized by acute mood episodes and periods of euthymia. The available literature postulates that a biphasic dysregulation of mitochondrial bioenergetics might underpin the neurobiology of BD. However, most studies focused on inter-subject differences rather than intra-subject variations between different mood states. To test this hypothesis, in this preliminary proof-of-concept study, we measured in vivo mitochondrial respiration in patients with BD during a mood episode and investigated differences compared to healthy controls (HC) and to the same patients upon clinical remission. METHODS: This longitudinal study recruited 20 patients with BD admitted to our acute psychiatric ward with a manic (n = 15) or depressive (n = 5) episode, and 10 matched HC. We assessed manic and depressive symptoms using standardized psychometric scales. Different mitochondrial oxygen consumption rates (OCRs: Routine, Leak, electron transport chain [ETC], Rox) were assessed during the acute episode (T0) and after clinical remission (T1) using high-resolution respirometry at 37°C by polarographic oxygen sensors in a two-chamber Oxygraph-2k system in one million of peripheral blood mononuclear cells (PMBC). Specific OCRs were expressed as mean ± SD in picomoles of oxygen per million cells. Significant results were adjusted for age, sex, and body mass index. RESULTS: The longitudinal analysis showed a significant increase in the maximal oxygen consumption capacity (ETC) in clinical remission (25.7 ± 16.7) compared to the acute episodes (19.1 ± 11.8, p = 0.025), and was observed separately for patients admitted with a manic episode (29.2 ± 18.9 in T1, 22.3 ± 11.9 in T0, p = 0.076), and at a trend-level for patients admitted with a depressive episode (15.4 ± 3.9 in T1 compared to 9.4 ± 3.2 in T0, p = 0.107). Compared to HC, significant differences were observed in ETC in patients with a bipolar mood episode (H = 11.7; p = 0.003). Individuals with bipolar depression showed lower ETC than those with a manic episode (t = -3.7, p = 0.001). Also, significant differences were observed in ETC rates between HC and bipolar depression (Z = 1.000, p = 0.005). CONCLUSIONS: Bioenergetic and mitochondrial dysregulation could be present in both manic and depressive phases in BD and, importantly, they may restore after clinical remission. These preliminary results suggest that mitochondrial respiratory capacity could be a biomarker of illness activity and clinical response in BD. Further studies with larger samples and similar approaches are needed to confirm these results and identify potential biomarkers in different phases of the disease.
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Transtorno Bipolar , Doenças Mitocondriais , Humanos , Transtorno Bipolar/psicologia , Mania , Estudos Longitudinais , Leucócitos Mononucleares , Biomarcadores , OxigênioRESUMO
BACKGROUND: Affective states influence the sympathetic nervous system, inducing variations in electrodermal activity (EDA), however, EDA association with bipolar disorder (BD) remains uncertain in real-world settings due to confounders like physical activity and temperature. We analysed EDA separately during sleep and wakefulness due to varying confounders and potential differences in mood state discrimination capacities. METHODS: We monitored EDA from 102 participants with BD including 35 manic, 29 depressive, 38 euthymic patients, and 38 healthy controls (HC), for 48 h. Fifteen EDA features were inferred by mixed-effect models for repeated measures considering sleep state, group and covariates. RESULTS: Thirteen EDA feature models were significantly influenced by sleep state, notably including phasic peaks (p < 0.001). During wakefulness, phasic peaks showed different values for mania (M [SD] = 6.49 [5.74, 7.23]), euthymia (5.89 [4.83, 6.94]), HC (3.04 [1.65, 4.42]), and depression (3.00 [2.07, 3.92]). Four phasic features during wakefulness better discriminated between HC and mania or euthymia, and between depression and euthymia or mania, compared to sleep. Mixed symptoms, average skin temperature, and anticholinergic medication affected the models, while sex and age did not. CONCLUSION: EDA measured from awake recordings better distinguished between BD states than sleep recordings, when controlled by confounders.
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BACKGROUND: Deficits in emotional intelligence (EI) were detected in patients with bipolar disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients. METHODS: The Emotional Intelligence Quotient (EIQ) was calculated with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model. RESULTS: In total, 184 subjects were included (FEM n = 48, euthymic chronic BD type I n = 75, HC n = 61). BD patients performed significantly worse than HC on the EIQ [mean difference (MD) = 10.09, standard error (s.e.) = 3.14, p = 0.004] and on the understanding emotions branch (MD = 7.46, s.e. = 2.53, p = 0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex (ß = -0.293, p = 0.034) and verbal memory performance (ß = 0.374, p = 0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains. CONCLUSIONS: Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness.
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Transtorno Bipolar , Humanos , Feminino , Transtorno Bipolar/psicologia , Mania , Inteligência Emocional , Emoções , CogniçãoRESUMO
BACKGROUND AND AIMS: Patients with severe mental disorders (SMD) have been classically considered as a particularly high-risk population for bloodborne virus infections. We performed a systematic screening of hepatitis B and C virus among the population with SMD in the area of influence of Hospital Clínic (Barcelona) in order to evaluate the real prevalence of these infections and achieve HCV microelimination in this subpopulation. METHODS: We screened two cohorts for anti-HCV and HBsAg: Cohort A (hospitalized patients with SMD, done systematically) and Cohort B (outpatients, mental health centre-CSMA, done voluntarily). Risk factors and socio-demographic variables were collected. In positive cases, telematic review was activated by Hepatology, calculation of FIB-4 and prescription of direct-acting agents (DAA) in HCV or follow-up in HBV. RESULTS: In Cohort A, 404 patients were screened. 3 HBV patients were detected (0.7%). In all of them, there was a history of drug use. 12 anti-HCV positive patients were detected (3%); 8 of them had a history of drug use. Among the HCV positive, only 2 patients were viraemic (received DAA, both achieving SVR) as most of them (n = 6) had already been cured with DAA. In cohort B, 305 patients were screened, after 542 (64% of the target population) declined to participate. No cases of HCV or HBV were detected. CONCLUSIONS: HCV/HBV prevalence among SMD population with no history of drug use does not seem to be different from the general population. These data may be of interest for defining health policies.
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Hepatite B , Transtornos Mentais , Humanos , Antivirais/uso terapêutico , Hepatite B/complicações , Hepatite B/epidemiologia , Hepatite B/tratamento farmacológico , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Transtornos Mentais/epidemiologia , Transtornos Mentais/complicações , Transtornos Mentais/tratamento farmacológicoRESUMO
INTRODUCTION: Psychiatric patients are considered at risk for malnutrition due to pharmacological treatments, lifestyle habits and the mental illness by itself. Even though metabolic risk factors have been related to worse outcomes in certain conditions, the evidence regarding the nutritional status and its impact on the length of stay in psychiatric inpatients is scarce. This study aims to characterize the nutritional status in acute psychiatric patients, to correlate it with the length of stay, and to find specific potential indicators of malnutrition. METHODS: Adult patients admitted to the Hospital Clínic of Barcelona acute psychiatric ward throughout a 1-year period were included in this cross-sectional study. Sociodemographic and clinical variables were registered, including length of stay and the nutritional status measured with the CONUT score. RESULTS: Malnutrition was observed in 42.5% of patients. Plasmatic transferrin saturation, protein and iron levels were inversely correlated with length of stay, having low iron levels an association with longer hospitalizations. The length of stay was not influenced by diagnosis or treatment. Negative correlations with the nutritional status were found in: BMI, cholesterol, triglycerides, albumin, total proteins, prealbumin, iron, lymphocytes and zinc levels, and transferrin saturation. The multivariate analysis showed a significant association for cholesterol and zinc levels, lymphocyte count, and BMI. CONCLUSIONS: Our results suggest that nutritional status might influence the course of psychiatric admissions. Cholesterol and zinc levels, lymphocyte count, and BMI might be factors strongly associated with malnutrition. This consideration might allow the identification of profiles in which lifestyle interventions could be implemented.
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Desnutrição , Unidade Hospitalar de Psiquiatria , Adulto , Humanos , Avaliação Nutricional , Estudos Transversais , Desnutrição/epidemiologia , Desnutrição/diagnóstico , Desnutrição/etiologia , Colesterol , Ferro/metabolismo , Transferrinas , Zinco/metabolismoRESUMO
Bipolar depression is the most prevalent phase of bipolar disorder (BD). There is a risk of inducing treatment-emergent affective switches (TEAS) with antidepressants (ADs). Hence, clinical guidelines do not recommend their use in monotherapy. Cariprazine is a dopamine-serotonin partial agonist, with a recent FDA approval as a monotherapy for BD type 1 (BD-I) depression. To our knowledge, there is no significant evidence of cariprazine-induced TEAS in bipolar depression. We describe three clinical cases of patients admitted to our acute psychiatric ward who developed manic episodes after the introduction of low doses of cariprazine. Two of the patients met the DSM-5 criteria for BD-I, and one for schizoaffective disorder, bipolar type. All patients were initially treated with low doses of cariprazine (1.5 mg) during a depressive phase. All three cases were simultaneously treated with mood stabilizers, regardless of which they switched to a manic episode when cariprazine was initiated. In our review of previous studies assessing the efficacy and side effects profile of cariprazine in BD-I, TEAS have not been found to be significant. However, according to our experience, cariprazine may induce affective switches in BD-I patients. Patients and psychiatrists should receive information regarding early warning symptoms and monitor possible cariprazine-induced mood switching.
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Antipsicóticos , Transtorno Bipolar , Antipsicóticos/efeitos adversos , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Humanos , Mania , Piperazinas/uso terapêuticoRESUMO
OBJECTIVE: This study was aimed at identifying differences in the prodromal symptoms and their duration, risk factors and markers of vulnerability in patients presenting a first episode mania (FEM) or psychosis (FEP) with onset in late adolescence or adulthood in order to guide tailored treatment strategies. METHODS: Patients with a FEM or FEP underwent a clinical assessment. Prodromes were evaluated with the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R). Chi-squared tests were conducted to assess specific prodromal symptoms, risk factors or markers of vulnerability between groups. Significant prodromal symptoms were entered in a stepwise forward logistic regression model. The probabilities of a gradual versus rapid onset pattern of the prodromes were computed with logistic regression models. RESULTS: The total sample included 108 patients (FEM = 72, FEP = 36). Social isolation was associated with the prodromal stage of a FEP whilst Increased energy or goal-directed activity with the prodrome to a FEM. Physically slowed down presented the most gradual onset whilst Increased energy presented the most rapid. The presence of obstetric complications and difficulties in writing and reading during childhood were risk factors for FEP. As for markers of vulnerability, impairment in premorbid adjustment was characteristic of FEP patients. No specific risk factor or marker of vulnerability was identified for FEM. CONCLUSION: Early characteristics differentiating FEP from FEM were identified. These findings might help shape early identification and preventive intervention programmes.
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Sintomas Prodrômicos , Transtornos Psicóticos , Adolescente , Adulto , Humanos , Mania , Transtornos Psicóticos/diagnóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
The role of caregivers is essential during home hospitalization since they act as co-therapists, being the level of responsibility experienced by them higher than usual.
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Satisfação Pessoal , Psiquiatria , Humanos , Satisfação do Paciente , Cuidadores , HospitalizaçãoRESUMO
OBJECTIVES: This systematic review aimed at providing a critical, comprehensive synthesis of international guidelines' recommendations on the long-term treatment of bipolar disorder type I (BD-I). METHODS: MEDLINE/PubMed and EMBASE databases were searched from inception to January 15th, 2019 following PRISMA and PICAR rules. International guidelines providing recommendations for the long-term treatment of BD-I were included. A methodological quality assessment was conducted with the Appraisal of Guidelines for Research and Evaluation-AGREE II. RESULTS: The final selection yielded five international guidelines, with overall good quality. The evaluation of applicability was the weakest aspect across the guidelines. Differences in their updating strategies and the rating of the evidence, particularly for meta-analyses, randomized clinical trials (RCTs) and observational studies, could be responsible of some level of heterogeneity among recommendations. Nonetheless, the guidelines recommended lithium as the 'gold standard' in the long-term treatment of BD-I. Quetiapine was another possible first-line option as well as aripiprazole (for the prevention of mania). Long-term treatment should contemplate monotherapy, at least initially. Clinicians should check regularly for efficacy and side effects and if necessary, switch to first-line alternatives (i.e. Valproate), combine first-line compounds with different mechanisms of action or switch to second-line options or combinations. CONCLUSIONS: The possibility to monitor improvements in long-term outcomes, namely relapse prevention and inter-episode subthreshold depressive symptoms, based on the application of their recommendations is an unmet need of clinical guidelines. In terms of evidence of clinical guidelines, there is a need for more efficacious treatment strategies for the prevention of bipolar depression.
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Antipsicóticos , Transtorno Bipolar , Algoritmos , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Humanos , Fumarato de Quetiapina/uso terapêutico , Ácido Valproico/uso terapêuticoRESUMO
OBJECTIVE: Seasonal pattern (SP) is a bipolar disorder (BD) specifier that indicates a tendency towards affective relapses during specific moments of the year. SP affects 15%-25% of BD patients. In the past, SP was applied only to depressive relapses while, in DSM-5, SP may be applied to both depressive and (hypo)manic episodes. We examined the association between different clinical correlates of BD and SP according to its current definition in a cohort of patients with BD type I (BDI) and II (BDII). METHODS: Patients were recruited from a specialized unit and assessed according to the season of relapse and type of episode per season. SP and non-SP patients were compared looking into sociodemographic and clinical correlates. Significant variables at univariate comparisons were included in multivariate logistic regression with SP as the dependent variable. RESULTS: 708 patients were enrolled (503 BDI, 205 BDII), and 117 (16.5%) fulfilled DSM-5 criteria for SP. The mean age was 45.3 years (SD = 14.18), and 389 were female (54.9%). The logistic regression model included a significant contribution of BDII (OR = 2.23, CI 1.4-3.55), family history of mood disorder (OR = 1.97, CI 1.29-3.01), undetermined predominant polarity (OR = 0.44, CI 0.28-0.70), and aggressive behavior (OR = 0.42, CI 0.23-0.75). CONCLUSION: Our results outline a novel positive association of SP with undetermined predominant polarity, BDII, family history of mood disorder, and with fewer aggressiveness-related symptoms. Seasonality is associated with a biphasic pattern with similar dominance of (hypo)mania and depression and is more frequent in BDII as compared to BDI. Seasonal episodes may be easier to predict, but difficult to prevent.
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Transtorno Bipolar , Transtorno Bipolar/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos do Humor , Recidiva , Estações do AnoRESUMO
BACKGROUND: Despite an increasing number of smartphone apps, such therapeutic tools have not yet consistently demonstrated their efficacy and many suffer from low retention rates. To ensure the development of efficient apps associated with high adherence, we aimed to identify, through a user-centred design approach, patient and physician expectations of a hypothetical app dedicated to depression. METHODS: We conducted semi-structured interviews with physicians (psychiatrists and general practitioners) and patients who had experienced a major depressive episode during the last 12 months using the focus group method. The interviews were audio recorded, transcribed and analysed using qualitative content analysis to define codes, categories and emergent themes. RESULTS: A total of 26 physicians and 24 patients were included in the study. The focus groups showed balanced sex and age distributions. Most participants owned a smartphone (83.3% of patients, 96.1% of physicians) and were app users (79.2% of patients and 96.1% of physicians). The qualitative content analysis revealed 3 main themes: content, operating characteristics and barriers to the use of the app. Expected content included the data collected by the app, aiming to provide information about the patient, data provided by the app, gathering psychoeducation elements, therapeutic tools and functionalities to help with the management of daily life and features expected for this tool. The "operating characteristics" theme gathered aims considered for the app, its potential target users, considered modalities of use and considerations around its accessibility and security of use. Finally, barriers to the use of the app included concerns about potential app users, its accessibility, safety, side-effects, utility and functioning. All themes and categories were the same for patients and physicians. CONCLUSIONS: Physician and patient expectations of a hypothetical smartphone app dedicated to depression are high and confirmed the important role it could play in depression care. The key points expected by the users for such a tool are an easy and intuitive use and a personalised content. They are also waiting for an app that gives information about depression, offers a self-monitoring functionality and helps them in case of emergency.
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Transtorno Depressivo Maior , Aplicativos Móveis , Médicos , Depressão , Transtorno Depressivo Maior/terapia , Humanos , SmartphoneRESUMO
OBJECTIVES: Electroconvulsive therapy (ECT) is an effective and safe treatment of certain severe mental disorders, but there are some barriers to the implementation of continuation/maintenance ECT courses in some cases. Repeated difficulties in achieving intravenous access before each session may contribute to premature ECT discontinuation. The placement of a totally implantable venous-access device (TIVAD) could be an alternative to overcome these difficulties in certain subjects. METHODS: For the present study we retrospectively identified all patients treated with continuation/maintenance ECT in our facilities during a 13-year period to which a TIVAD was implanted, paying attention to specific factors related to clinical characteristics, treatment course, and ECT technique. RESULTS: We identified a TIVAD in 16 (3.33%) of 481 patients receiving ECT in our unit, of whom 87.5% were female. Half of the cases met the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for schizophrenia, 6 for bipolar disorder, and 2 for major depression disorder. Age of the study cases ranged from 17 to 87 years. A total of 1957 ECT sessions were registered in this group of cases during the observation period. Patients had undergone a mean of 124.06 ± 132.41 ECT sessions before the TIVAD was implanted, with the device mean time of utilization being 5.39 ± 3.46 years. In 2 cases, the device was removed after ECT discontinuation. Few incidents associated with the implantation and operation of the TIVAD were registered, comparable to the use of this device in other clinical contexts. CONCLUSIONS: This case series suggest that a TIVAD placement can be an effective and safe solution for patients in continuation/maintenance ECT courses with difficult intravenous access. Future studies will need to carefully monitor the benefit and the potential complications of TIVAD placement in patients undergoing continuation/maintenance ECT programs.
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Transtorno Bipolar , Transtorno Depressivo Maior , Eletroconvulsoterapia , Esquizofrenia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno Depressivo Maior/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Esquizofrenia/terapia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Psychomotor agitation (PA) or retardation (PR) during major depressive episodes (MDEs) have been associated with depression severity in terms of treatment-resistance and course of illness. OBJECTIVES: We investigated the possible association of psychomotor symptoms (PMSs) during a MDE with clinical features belonging to the bipolar spectrum. METHODS: The initial sample of 7689 MDE patients was divided into three subgroups based on the presence of PR, PA and non-psychomotor symptom (NPS). Univariate comparisons and multivariate logistic regression models were performed between subgroups. RESULTS: A total of 3720 patients presented PR (48%), 1971 showed PA (26%) and 1998 had NPS (26%). In the PR and PA subgroups, the clinical characteristics related to bipolarity, along with the diagnosis of bipolar disorder (BD), were significantly more frequent than in the NPS subgroup. When comparing PA and PR patients, the former presented higher rates of bipolar spectrum features, such as family history of BD (OR = 1.39, CI = 1.20-1.61), manic/hypomanic switches with antidepressants (OR = 1.28, CI = 1.11-1.48), early onset of first MDE (OR = 1.40, CI = 1.26-1.57), atypical (OR = 1.23, CI = 1.07-1.42) and psychotic features (OR = 2.08, CI = 1.78-2.44), treatment with mood-stabilizers (OR = 1.39, CI = 1.24-1.55), as well as a BD diagnosis according to both the DSM-IV criteria and the bipolar specifier criteria. When logistic regression model was performed, the clinical features that significantly differentiated PA from PR were early onset of first MDE, atypical and psychotic features, treatment with mood-stabilizers and a BD diagnosis according to the bipolar specifier criteria. CONCLUSIONS: Psychomotor symptoms could be considered as markers of bipolarity, illness severity, and treatment complexity, particularly if PA is present.
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Transtorno Depressivo Maior/diagnóstico , Agitação Psicomotora , Adulto , Antidepressivos/uso terapêutico , Antimaníacos/uso terapêutico , Transtorno Bipolar/diagnóstico , Estudos Transversais , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-IdadeRESUMO
The chronic, long-term evolution of bipolar disorder (BD) requires a careful clinical characterization with prognostic implications in terms of symptom and functional control. The OPTHYMUM multicenter study was conducted in France with the objective of evaluating residual symptoms on overall functioning of BD patients during inter-episodic period. The aims of the present study were to identify the potentially modifiable (e.g., treatable) and non-modifiable variables associated with functional impairment during the inter-episodic periods of BD. Sample was divided into two groups according to level of functioning (adequate vs. impaired), based on the FAST scale total score. FAST cut-off for functional impairment is a score >11. The two subgroups were compared as per sociodemographic and clinical variables with standard univariate analyses, and a logistic regression model was created. The model as a whole contained independent non-modifiable factors (age, gender, BD type, illness duration) and modifiable factors (illness severity, predominant polarity, depressive and manic residual symptoms, comorbidities). The final model was statistically significant (χ 2 = 53.89, df = 5, p < 0.001). Modifiable factors most strongly associated with functional impairment were manic predominant polarity (OR = 1.79, CI 95% 1.09-2.96, p = 0.022), residual depressive symptoms (OR = 1.30, CI 95% 1.18-1.43, p < 0.001) and illness severity (OR = 1.24, CI 95% 1.01-1.52, p = 0.037), whilst non-modifiable factor was illness duration (OR = 1.03, CI 95% 1.01-1.05, p = 0.017). Despite intrinsic and non-modifiable illness characteristics, a clinical-wise choice of treatment may help to improve control of manic relapses. Potential improvement of residual depressive symptoms may alleviate the functional burden associated with bipolar disorder.
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Transtorno Bipolar/diagnóstico , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Adolescente , Adulto , Transtorno Bipolar/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores Socioeconômicos , Adulto JovemRESUMO
OBJECTIVES: The pathophysiology of bipolar disorder is likely to involve both genetic and environmental risk factors. In our study, we aimed to perform a systematic search of environmental risk factors for BD. In addition, we assessed possible hints of bias in this literature, and identified risk factors supported by high epidemiological credibility. METHODS: We searched the Pubmed/MEDLINE, EMBASE and PsycInfo databases up to 7 October 2016 to identify systematic reviews and meta-analyses of observational studies that assessed associations between putative environmental risk factors and BD. For each meta-analysis, we estimated its summary effect size by means of both random- and fixed-effects models, 95% confidence intervals (CIs), the 95% prediction interval, and heterogeneity. Evidence of small-study effects and excess of significance bias was also assessed. RESULTS: Sixteen publications met the inclusion criteria (seven meta-analyses and nine qualitative systematic reviews). Fifty-one unique environmental risk factors for BD were evaluated. Six meta-analyses investigated associations with a risk factor for BD. Only irritable bowel syndrome (IBS) emerged as a risk factor for BD supported by convincing evidence (k=6; odds ratio [OR]=2.48; 95% CI=2.35-2.61; P<.001), and childhood adversity was supported by highly suggestive evidence. Asthma and obesity were risk factors for BD supported by suggestive evidence, and seropositivity to Toxoplasma gondii and a history of head injury were supported by weak evidence. CONCLUSIONS: Notwithstanding that several environmental risk factors for BD were identified, few meta-analyses of observational studies were available. Therefore, further well-designed and adequately powered studies are necessary to map the environmental risk factors for BD.