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The COVID-19 pandemic had an unprecedented impact on global mental health and well-being, including across the Asia-Pacific. Efforts to mitigate virus spread led to far-reaching disruption in the delivery of health and social services. In response, there was a rapid shift to the use of digital mental health (DMH) approaches. Though these technologies helped to improve access to care for many, there was also substantial risk of access barriers leading to increased inequities in access to mental health care, particularly among at-risk and equity-deserving populations. The objective of this study was to conduct a needs assessment and identify priorities related to equitable DMH access among at-risk and equity-deserving populations in the Asia Pacific region during the first year of the COVID-19 pandemic. The study consisted of a modified Delphi consensus methodology including two rounds of online surveys and online consultations with stakeholders from across the region. Study participants included policy makers, clinicians and service providers, and people with lived experience of mental health conditions. Results demonstrate that vulnerabilities to negative mental health impacts and access barriers were compounded during the pandemic. Access barriers included a lack of linguistically and culturally appropriate DMH options, low mental health literacy and poor access to technological infrastructure and devices, low levels of awareness and trust of DMH options, and lack of policies and guidelines to support effective and equitable delivery of DMH. Recommendations to improve equitable access include ensuring that diverse people with lived experience are engaged in research, co-design and policy development, the development and implementation of evidence-based and equity-informed guidelines and frameworks, clear communication about DMH evidence and availability, and the integration of DMH into broader health systems. Study results can inform the development and implementation of equitable DMH as its use becomes more widespread across health systems.
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BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults. METHODS: CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process. RESULTS: The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted. CONCLUSIONS: The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD.
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Trastorno Depresivo Mayor , Adulto , Humanos , Canadá , Trastorno Depresivo Mayor/terapia , Guías de Práctica Clínica como Asunto , Revisiones Sistemáticas como Asunto , Metaanálisis como AsuntoRESUMEN
High-Harmonic Generation (HHG) spectra of randomly aligned bromoform (CHBr3) molecules have been experimentally measured and theoretically simulated at various laser pulse intensities. From the experiments, we obtained a significant number of harmonics that goes beyond the cutoff limit predicted by the three-step model (3SM) with ionization from HOMO. To interpret the experiment, we resorted to real-time time-dependent configuration interaction with single excitations. We found that electronic bound states provide an appreciable contribution to the harmonics. More in detail, we analyzed the electron dynamics by decomposing the HHG signal in terms of single molecular-orbital contributions, to explain the appearance of harmonics around 20-30 eV beyond the expected cutoff due to HOMO. HHG spectra can be therefore explained by considering the contribution at high energy of HOMO-6 and HOMO-9, thus indicating a complex multiple-orbital strong-field dynamics. However, even though the presence of the bromoform cation should be not enough to produce such a signal, we could not exclude a priori that the origin of harmonics in the H29-H45 to be due to the cation, which has more energetic ionization channels.
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BACKGROUND: Identifying neuroimaging biomarkers of antidepressant response may help guide treatment decisions and advance precision medicine. AIMS: To examine the relationship between anhedonia and functional neurocircuitry in key reward processing brain regions in people with major depressive disorder receiving aripiprazole adjunct therapy with escitalopram. METHOD: Data were collected as part of the CAN-BIND-1 study. Participants experiencing a current major depressive episode received escitalopram for 8 weeks; escitalopram non-responders received adjunct aripiprazole for an additional 8 weeks. Functional magnetic resonance imaging (on weeks 0 and 8) and clinical assessment of anhedonia (on weeks 0, 8 and 16) were completed. Seed-based correlational analysis was employed to examine the relationship between baseline resting-state functional connectivity (rsFC), using the nucleus accumbens (NAc) and anterior cingulate cortex (ACC) as key regions of interest, and change in anhedonia severity after adjunct aripiprazole. RESULTS: Anhedonia severity significantly improved after treatment with adjunct aripiprazole.There was a positive correlation between anhedonia improvement and rsFC between the ACC and posterior cingulate cortex, ACC and posterior praecuneus, and NAc and posterior praecuneus. There was a negative correlation between anhedonia improvement and rsFC between the ACC and anterior praecuneus and NAc and anterior praecuneus. CONCLUSIONS: Eight weeks of aripiprazole, adjunct to escitalopram, was associated with improved anhedonia symptoms. Changes in functional connectivity between key reward regions were associated with anhedonia improvement, suggesting aripiprazole may be an effective treatment for individuals experiencing reward-related deficits. Future studies are required to replicate our findings and explore their generalisability, using other agents with partial dopamine (D2) agonism and/or serotonin (5-HT2A) antagonism.
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OBJECTIVE: Suicide risk in bipolar disorder (BD) is estimated to be up to 20 times higher than in the general population. While there is a large body of evidence suggesting that increased sympathetic activation is associated with disease and death, there is a paucity of research on the role of autonomic nervous system (ANS) dysfunction in patients with BD who have attempted suicide. METHODS: Fifty-three participants with BD used a wearable device to assess the association between history of suicide attempt, current suicidal ideation, and ANS dysfunction, including measures of heart rate variability (HRV) and respiratory rate. Data were analyzed in a series of unadjusted and adjusted bivariate models of association controlling for relevant variables. RESULTS: A history of suicide attempts was significantly associated with an increase in respiratory rate (p < 0.01). These results remained significant after adjusting for age, BMI, and current mood state. There was no association between current suicidal ideation and heart rate or respiratory rate. In the frequency domain, HRV parameters suggest reduced parasympathetic (i.e., vagal) activity in participants with a history of suicide attempts and in those with current suicidality, suggesting changes in sympathicovagal balance in BD. CONCLUSIONS: Our results suggest that changes in the ANS in patients with BD and a history of suicide attempt are not restricted to pure vagally mediated HRV parameters, but rather signal a general ANS dysregulation. This ANS imbalance may be contributing to illness burden and cardiovascular disease. Further research on the relationship between ANS and suicidality in BD is needed.
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Trastorno Bipolar , Intento de Suicidio , Humanos , Trastorno Bipolar/epidemiología , Ideación Suicida , Violencia , Costo de Enfermedad , Factores de RiesgoRESUMEN
BACKGROUND: Electroconvulsive therapy (ECT) is a well-accepted intervention for treatment-resistant, serious mental illnesses. Its acceptability, efficacy, and tolerability are well documented in high-income settings, but less so in lower- and middle-income countries (LMICs). This report is a narrative review of ECT practice in the latter setting. METHODS: A literature search was conducted using Medline and PubMed. Initial results yielded 81 publications in English. Following the screening, 19 papers were included to evaluate the information on ECT practice and perceptions. RESULTS: Reports from LMICs on efficacy, tolerability, and perceptions of ECT were relatively sparse. In general, they confirm its use mostly for treatment-resistant major mental illnesses (i.e., depression, schizophrenia, bipolar disorder). Both modified and unmodified forms of ECT are used and considered equally effective, although the former is better tolerated. Use of unmodified ECT remains significant in LMICs due to its low cost and limited resource requirements. In general, there is satisfaction with ECT and its outcomes. The education of patients and families, content process, and research have been noted as areas to improve. CONCLUSIONS: ECT is perceived as an effective intervention in LMICs, but use of unmodified ECT remains controversial. There is a need for the development and use of global guidelines to improve clinician training, knowledge sharing with patients and their families, and outcome research.
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Trastorno Bipolar , Terapia Electroconvulsiva , Esquizofrenia , Humanos , Terapia Electroconvulsiva/métodos , Países en Desarrollo , Esquizofrenia/terapia , Trastorno Bipolar/terapia , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Stroke is a common neurological condition and among the leading causes of death and disability worldwide. Depression is both a risk factor for and complication of stroke, and the two conditions may have a complex reciprocal relationship over time. However, the secondary effects of depression on stroke are often overlooked, resulting in increased morbidity and mortality. In the previous concept of 'poststroke depression', stroke and depression were considered as two independent diseases. It often delays the diagnosis and treatment of patients. The concept 'stroke depression' proposed in this article will emphasise more the necessity of aggressive treatment of depression in the overall management of stroke, thus to reduce the incidence of stroke and in the meantime, improve the prognosis of stroke. Hopefully, it will lead us into a new era of acute stroke intervention.
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Background: Knowledge brokering is a knowledge translation strategy used in healthcare settings to facilitate the implementation of evidence into practice. How healthcare providers perceive and respond to various knowledge translation approaches is not well understood. This qualitative study used the Theoretical Domains Framework to examine healthcare providers' experiences with receiving one of two knowledge translation strategies: a remote knowledge broker (rKB); or monthly emails, for encouraging delivery of mood management interventions to patients enrolled in a smoking cessation program. Methods: Semi-structured interviews were conducted with 21 healthcare providers recruited from primary care teams. We used stratified purposeful sampling to recruit participants who were allocated to receive either the rKB, or a monthly email-based knowledge translation strategy as part of a cluster randomized controlled trial. Interviews were structured around domains of the Theoretical Domains Framework (TDF) to explore determinants influencing practice change. Data were coded into relevant domains. Results: Both knowledge translation strategies were considered helpful prompts to remind participants to deliver mood interventions to patients presenting depressive symptoms. Neither strategy appeared to have influenced the health care providers on the domains we probed. The domains pertaining to knowledge and professional identity were perceived as facilitators to implementation, while domains related to beliefs about consequences, emotion, and environmental context acted as barriers and/or facilitators to healthcare providers implementing mood management interventions. Conclusion: Both strategies served as reminders and reinforced providers' knowledge regarding the connection between smoking and depressed mood. The TDF can help researchers better understand the influence of specific knowledge translation strategies on healthcare provider behavior change, as well as potential barriers and facilitators to implementation of evidence-informed interventions. Environmental context should be considered to address challenges and facilitate the movement of knowledge into clinical practice.
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BACKGROUND: Antidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has not been well studied. METHODS: We conducted a multisite, double-blind, randomized, placebo-controlled trial of maintenance of treatment with adjunctive escitalopram or bupropion XL as compared with discontinuation of antidepressant therapy in patients with bipolar I disorder who had recently had remission of a depressive episode. Patients were randomly assigned in a 1:1 ratio to continue treatment with antidepressants for 52 weeks after remission or to switch to placebo at 8 weeks. The primary outcome, assessed in a time-to-event analysis, was any mood episode, as defined by scores on scales measuring symptoms of hypomania or mania, depression, suicidality, and mood-episode severity; additional treatment or hospitalization for mood symptoms; or attempted or completed suicide. Key secondary outcomes included the time to an episode of mania or hypomania or depression. RESULTS: Of 209 patients with bipolar I disorder who participated in an open-label treatment phase, 150 who had remission of depression were enrolled in the double-blind phase in addition to 27 patients who were enrolled directly. A total of 90 patients were assigned to continue treatment with the prescribed antidepressant for 52 weeks (52-week group) and 87 were assigned to switch to placebo at 8 weeks (8-week group). The trial was stopped before full recruitment was reached owing to slow recruitment and funding limitations. At 52 weeks, 28 of the patients in the 52-week group (31%) and 40 in the 8-week group (46%) had a primary-outcome event. The hazard ratio for time to any mood episode in the 52-week group relative to the 8-week group was 0.68 (95% confidence interval [CI], 0.43 to 1.10; P = 0.12 by log-rank test). A total of 11 patients in the 52-week group (12%) as compared with 5 patients in the 8-week group (6%) had mania or hypomania (hazard ratio, 2.28; 95% CI, 0.86 to 6.08), and 15 patients (17%) as compared with 35 patients (40%) had recurrence of depression (hazard ratio, 0.43; 95% CI, 0.25 to 0.75). The incidence of adverse events was similar in the two groups. CONCLUSIONS: In a trial involving patients with bipolar I disorder and a recently remitted depressive episode, adjunctive treatment with escitalopram or bupropion XL that continued for 52 weeks did not show a significant benefit as compared with treatment for 8 weeks in preventing relapse of any mood episode. The trial was stopped early owing to slow recruitment and funding limitations. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00958633.).
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Trastorno Bipolar , Humanos , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/diagnóstico , Manía , Bupropión/efectos adversos , Depresión , Escitalopram , Canadá , Recurrencia Local de Neoplasia/tratamiento farmacológico , Antidepresivos/efectos adversos , Método Doble Ciego , Resultado del TratamientoRESUMEN
Yoga is an integrated holistic system originating in India that provides a path to alleviate physical, mental, and emotional suffering. Interest in the application of yoga in health care to manage and treat psychiatric conditions has grown. While research and clinical interventions using yoga show promising results for improving mental and emotional well-being, more data are needed. This perspective article summarizes the current evidence on yoga as a treatment for mental health conditions, potential mechanisms of action, future directions, and a call to action for proactive clinical and research agendas for yoga-based interventions in mental health care.
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The increasing number of coronavirus disease 2019 (COVID-19) infections have highlighted the long-term consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection called long COVID. Although the concept and definition of long COVID are described differently across countries and institutions, there is general agreement that it affects multiple systems, including the immune, respiratory, cardiovascular, gastrointestinal, neuropsychological, musculoskeletal, and other systems. This review aims to provide a synthesis of published epidemiology, symptoms, and risk factors of long COVID. We also summarize potential pathophysiological mechanisms and biomarkers for precise prevention, early diagnosis, and accurate treatment of long COVID. Furthermore, we suggest evidence-based guidelines for the comprehensive evaluation and management of long COVID, involving treatment, health systems, health finance, public attitudes, and international cooperation, which is proposed to improve the treatment strategies, preventive measures, and public health policy making of long COVID.
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COVID-19 , Humanos , SARS-CoV-2 , Síndrome Post Agudo de COVID-19 , Factores de RiesgoRESUMEN
Despite considerable efforts to study the relationship between insomnia and depression, there is minimal research investigating whether insomnia symptoms change over time during a course of antidepressant pharmacotherapy. This study investigated the course of insomnia symptoms during the acute treatment of major depressive disorder (MDD) using a secondary analysis of data from MDD patients (N = 180) who were treated with open-label escitalopram (10-20 mg/day) for 8-weeks. Montgomery-Asberg Depression Rating Scale without sleep item (modified-MADRS) assessed depression and Self-reported Quick Inventory Depressive Scale (QIDS-SR) measured subjective sleep-onset, mid-nocturnal, and early-morning insomnia throughout 8-weeks of treatment. Pittsburgh Sleep Quality Index (PSQI) was used to assess subjective sleep quality, duration, onset latency, and efficiency throughout 8-weeks of treatment. Remission of depression was defined as modified-MADRS ≤10 at week-8. Mixed model repeated measures (MMRMs) were conducted with remission status as an independent variable and each sleep variable as a dependent variable. MMRMs demonstrated that remitters had significantly lower QIDS-SR sleep-onset and mid-nocturnal insomnia scores as well as a significantly lower PSQI sleep quality score than non-remitters throughout 8-weeks of treatment. Monitoring subjective sleep-onset and mid-nocturnal insomnia during the course of treatment with serotonergic antidepressants may be useful for predicting acute remission of depression.
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Trastorno Depresivo Mayor , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/diagnóstico , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Antidepresivos/uso terapéutico , Sueño , Escitalopram , Resultado del TratamientoRESUMEN
OBJECTIVE: Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder. METHODS: A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria. RESULTS: Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient. CONCLUSIONS: There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.
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Trastorno Depresivo Mayor , Alucinógenos , Neoplasias , Humanos , Alucinógenos/efectos adversos , Psilocibina/farmacología , Psilocibina/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Canadá , Ansiedad , Neoplasias/inducido químicamente , Neoplasias/tratamiento farmacológicoRESUMEN
BACKGROUND: Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on mood disorders. OBJECTIVE: The purpose of this task force report is to examine the association between cannabis use and incidence, presentation, course and treatment of bipolar disorder and major depressive disorder, and the treatment of comorbid cannabis use disorder. METHODS: We conducted a systematic literature review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Embase, PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials from inception to October 2020 focusing on cannabis use and bipolar disorder or major depressive disorder, and treatment of comorbid cannabis use disorder. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of evidence and clinical considerations were integrated to generate Canadian Network for Mood and Anxiety Treatments recommendations. RESULTS: Of 12,691 publications, 56 met the criteria: 23 on bipolar disorder, 21 on major depressive disorder, 11 on both diagnoses and 1 on treatment of comorbid cannabis use disorder and major depressive disorder. Of 2,479,640 participants, 12,502 were comparison participants, 73,891 had bipolar disorder and 408,223 major depressive disorder without cannabis use. Of those with cannabis use, 2,761 had bipolar disorder and 5,044 major depressive disorder. The lifetime prevalence of cannabis use was 52%-71% and 6%-50% in bipolar disorder and major depressive disorder, respectively. Cannabis use was associated with worsening course and symptoms of both mood disorders, with more consistent associations in bipolar disorder than major depressive disorder: increased severity of depressive, manic and psychotic symptoms in bipolar disorder and depressive symptoms in major depressive disorder. Cannabis use was associated with increased suicidality and decreased functioning in both bipolar disorder and major depressive disorder. Treatment of comorbid cannabis use disorder and major depressive disorder did not show significant results. CONCLUSION: The data indicate that cannabis use is associated with worsened course and functioning of bipolar disorder and major depressive disorder. Future studies should include more accurate determinations of type, amount and frequency of cannabis use and select comparison groups which allow to control for underlying common factors.
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Trastorno Bipolar , Cannabis , Trastorno Depresivo Mayor , Abuso de Marihuana , Trastornos Relacionados con Sustancias , Humanos , Trastorno Bipolar/epidemiología , Trastorno Bipolar/terapia , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/terapia , Abuso de Marihuana/epidemiología , Abuso de Marihuana/terapia , Canadá/epidemiología , Ansiedad , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
OBJECTIVES: The primary objectives of these international guidelines were to provide a global audience of clinicians with (a) a series of evidence-based recommendations for the provision of lifestyle-based mental health care in clinical practice for adults with Major Depressive Disorder (MDD) and (b) a series of implementation considerations that may be applicable across a range of settings. METHODS: Recommendations and associated evidence-based gradings were based on a series of systematic literature searches of published research as well as the clinical expertise of taskforce members. The focus of the guidelines was eight lifestyle domains: physical activity and exercise, smoking cessation, work-directed interventions, mindfulness-based and stress management therapies, diet, sleep, loneliness and social support, and green space interaction. The following electronic bibliographic databases were searched for articles published prior to June 2020: PubMed, EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register), CINAHL, PsycINFO. Evidence grading was based on the level of evidence specific to MDD and risk of bias, in accordance with the World Federation of Societies for Biological Psychiatry criteria. RESULTS: Nine recommendations were formed. The recommendations with the highest ratings to improve MDD were the use of physical activity and exercise, relaxation techniques, work-directed interventions, sleep, and mindfulness-based therapies (Grade 2). Interventions related to diet and green space were recommended, but with a lower strength of evidence (Grade 3). Recommendations regarding smoking cessation and loneliness and social support were based on expert opinion. Key implementation considerations included the need for input from allied health professionals and support networks to implement this type of approach, the importance of partnering such recommendations with behaviour change support, and the need to deliver interventions using a biopsychosocial-cultural framework. CONCLUSIONS: Lifestyle-based interventions are recommended as a foundational component of mental health care in clinical practice for adults with Major Depressive Disorder, where other evidence-based therapies can be added or used in combination. The findings and recommendations of these guidelines support the need for further research to address existing gaps in efficacy and implementation research, especially for emerging lifestyle-based approaches (e.g. green space, loneliness and social support interventions) where data are limited. Further work is also needed to develop innovative approaches for delivery and models of care, and to support the training of health professionals regarding lifestyle-based mental health care.
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Psiquiatría Biológica , Trastorno Depresivo Mayor , Adulto , Humanos , Trastorno Depresivo Mayor/terapia , Salud Mental , Revisiones Sistemáticas como Asunto , Estilo de VidaRESUMEN
INTRODUCTION: Brolucizumab, a low-molecular weight anti-vascular endothelial growth factor, was approved in the USA in October 2019 for the treatment of neovascular age-related macular degeneration. Following post-marketing reports of vasculitis, including retinal occlusive vasculitis, a safety signal of retinal vasculitis (RV) and/or retinal vascular occlusion (RO) that may result in severe vision loss was confirmed. This brief communication reviews the trends in the cumulative reporting rates of RV and/or RO and associated vision loss from May 2020 to September 2022. METHODS: This is a descriptive analysis of the cumulative post-marketing reporting rates of RV and/or RO cases, and associated vision loss included in the Novartis safety database between May 2020 and September 2022, utilizing an enhanced pharmacovigilance program. RESULTS: The RV-alone rates demonstrated an upward trend, rising to 5.1 events per 10,000 injections by October 2020 and subsequently remained stable until July 2021. Thereafter, the rate for RV-alone events increased modestly until October 2021 and then remained stable until September 2022. The RO-alone rates increased to 3.4 events per 10,000 injections by January 2021 and subsequently remained stable until September 2022. The combined reports of RV and RO showed an upward trend until December 2020 (7.5 events per 10,000 injections), followed by a plateau until September 2021 and then a downward trend until September 2022. Vision loss associated with RV and/or RO progressively increased until December 2020 (5.9 events per 10,000 injections) followed by a declining trend until September 2022 to the most recent reporting rate of 4.1 events per 10,000 injections. CONCLUSION: The cumulative post-marketing reporting rates of vision loss associated with RV and/or RO, following brolucizumab treatment, have shown a declining trend after an initial rise in the reporting rates immediately after identification of the safety signal.
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BACKGROUND AND OBJECTIVES: Diabetes mellitus, a global health problem, is associated with metabolic complications such as hyperglycemia, hyperlipidemia, hypertension, cardiovascular diseases, and loss of vision. The present study evaluated the antidiabetic and antihyperlipidemic effects of ethanol extract of Garcinia cambogia (L.) N. Robson (G. cambogia) fruit rind in a streptozotocin-nicotinamide induced diabetic Wistar Rat model. MATERIALS AND METHODS: Streptozotocin-nicotinamide was injected intraperitoneally to induce diabetes in Wistar rats. Five groups of rats (n=6) - normal control, diabetic, diabetic treated with G. cambogia at 400 mg/kg and 800 mg/kg body weight, and diabetic treated with metformin at 500 mg/kg body weight, were studied. Blood samples were collected after three weeks of treatment. Random blood glucose (RBG), Serum total cholesterol levels (TCL), serum total triglyceride levels (TGL), high-density lipoprotein levels, and body weight were measured. RESULTS: Although G. cambogia treatment did not have any antidiabetic activity (p>0.05) rind in the streptozotocin-nicotinamide induced diabetic Wistar Rat model, it decreased the serum TCL, and body weight significantly (P<0.05). CONCLUSIONS: Ethanolic extract of G. cambogia fruit rind possesses anti-obesity activity and significantly reduces total cholesterol but does not have antidiabetic activity.
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BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that affects approximately 2-7 % of children globally and is associated with a myriad of difficulties that have long-term consequences. Most children and adolescents live in low- and middle-income countries (LMICs), but there are few reports and no consolidation of findings on ADHD treatment outcomes in this population. We conducted a review of ADHD treatment literature for children and adolescents living in LMICs. METHODS: Studies were identified using databases (PsychoINFO, Pubmed, MEDLINER, EMBASE, Global Health, Academic Search Complete, Google Scholar). The initial search produced 139 articles. These were filtered for language, title, abstract, and full-text keyword identification to yield a final 20 articles to be included in this review. RESULTS: Reports on outcomes of both psychological and pharmacological treatment were relatively sparse, particularly the former, which mostly referred to parent training and multimodal programs in pre-school children. Most evidence exists for the benefit of methylphenidate-IR with a few reports on other agents, including clonidine, atomoxetine, and lisdexamfetamine. Methylphenidate is the most common agent to treat ADHD in youth in LMICs. Younger age, combined subtype, and comorbid oppositional defiant disorder were associated with poorer treatment outcome. CONCLUSION: Access to treatment for ADHD is overall limited in LMICs and varied among individual countries. Pharmacological treatments were generally more available than psychological interventions. Several barriers including stigma, cost, and lack of resources were reported to impact treatment acceptance. More research in LMICs is needed to improve and expand mental health services in these regions.
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Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Metilfenidato , Adolescente , Clorhidrato de Atomoxetina , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Niño , Preescolar , Clonidina/uso terapéutico , Países en Desarrollo , Humanos , Metilfenidato/uso terapéuticoRESUMEN
BACKGROUND: Antidepressant use for major depressive disorder (MDD) is frequently associated with sexual dysfunction. AIMS: Cross-sectional and longitudinal relationships between antidepressant treatment outcomes and sexual functioning (SF) were evaluated separately for males and females receiving escitalopram. We further assessed the association between pre- and posttreatment SF. METHODS: In all, 208 of the 211 CAN-BIND-1 trial participants (77 males and 131 females) with MDD and detectable drug blood levels were eligible for the analyses. All received escitalopram (10-20 mg) for 8 weeks. At baseline and Week 8, participants completed the Montgomery-Åsberg Depression Rating Scale (MADRS) and the SexFx scale, which measures sexual satisfaction and SF frequency. Mixed-model repeated measures assessed baseline to Week 8 SF changes among participants with different response/remission statuses. Multiple linear regression analyses examined SF differences between treatment outcomes at Week 8 as well as associations between pretreatment and eventual SF. RESULTS: For both sexes, overall sexual satisfaction improved among responders but not among nonresponders (p < 0.05). For females, overall SF frequency did not change significantly over time regardless of response status. For males, overall SF decreased significantly among nonresponders; orgasm decreased significantly among nonresponders and, to a lesser extent, among responders (p < 0.05). For both sexes, pretreatment SF was significantly associated with SF at Week 8 across all domains (p < 0.05). CONCLUSION: For both sexes, sexual satisfaction improves with response to escitalopram. For females, the response does not correspond to improvements in SF frequency. For males, SF frequency, particularly that of orgasm, declines regardless of response/nonresponse.ClinicalTrials.gov identifier: NCT01655706.
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Trastorno Depresivo Mayor , Antidepresivos/uso terapéutico , Citalopram/uso terapéutico , Estudios Transversales , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/tratamiento farmacológico , Método Doble Ciego , Escitalopram , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
Escitalopram may have pain-alleviating effects for patients with comorbid pain and depression. This study aimed to quantify improvements in pain for patients on escitalopram and adjunctive aripiprazole. A secondary analysis of the CAN-BIND-1 trial was conducted which only included participants with a current depressive episode and pain. Participants received escitalopram (10-20mg) for eight weeks and treatment response was defined as a reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) of at least 50% from baseline. Non-responders at week 8 received adjunctive aripiprazole (2-10mg) for another eight weeks. The Brief Pain Inventory's pain severity (PSC) and pain interference (PIC) composite scores were measured at baseline, week 8, and week 16. Linear regression was used to determine how PSC and PIC differed between treatment responders and non-responders. Eighty-two participants with pain and depression received escitalopram. PSC and PIC decreased significantly regardless of treatment response at week 8, although responders had significantly lower PSC and PIC than non-responders. For the group receiving aripiprazole after week 8, neither PSC nor PIC improved further. Further research is needed to identify interventions that might treat both pain and depression symptoms.