How can we improve antidepressant adherence in the management of depression? A targeted review and 10 clinical recommendations

Adherence to antidepressants is crucial for optimal treatment outcomes when treating depressive disorders. However, poor adherence is common among patients prescribed antidepressants. This targeted review summarizes the main factors associated with poor adherence, interventions that promote antidepressant adherence, pharmacological aspects related to antidepressant adherence, and formulates 10 clinical recommendations to optimize antidepressant adherence. Patient-related factors associated with antidepressant non-adherence include younger age, psychiatric and medical comorbidities, cognitive impairment, and substance use disorders. Prescriber behavior-related factors include neglecting medical and family histories, selecting poorly tolerated antidepressants, or complex antidepressant regimens. Multi-disciplinary interventions targeting both patient and prescriber, aimed at improving antidepressant adherence, include psychoeducation and providing the patient with clear behavioral interventions to prevent/minimize poor adherence. Regarding antidepressant choice, agents with individually tailored tolerability profile should be chosen. Ten clinical recommendations include four points focusing on the patient (therapeutic alliance, adequate history taking, measurement of depressive symptoms, and adverse effects improved access to clinical care), three focusing on prescribing practice (psychoeducation, individually tailored antidepressant choice, simplified regimen), two focusing on mental health services (improved access to mental health care, incentivized adherence promotion and monitoring), and one relating to adherence measurement (adherence measurement with scales and/or therapeutic drug monitoring).

Personality disorder and functioning in major depressive disorder: a nested study within a randomized controlled trial

Objective: This study aimed to determine if personality disorder (PD) predicted functional outcomes in patients with major depressive disorder (MDD). Methods: Data (n=71) from a double-blind, randomized, placebo-controlled 12-week trial assessing the efficacy of 200 mg/day adjunctive minocycline for MDD were examined. PD was measured using the Standardized Assessment of Personality Abbreviated Scale. Outcome measures included Clinical Global Impression - Improvement (CGI-I), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Social and Occupational Functioning Scale (SOFAS), and Range of Impaired Functioning (RIFT). Analysis of covariance was used to examine the impact of PD (dichotomized factor [≥ 3] or continuous measure) on the outcome measures-treatment group correlation. Results: PD was identified in 69% of the sample. After adjusting for age, sex, and baseline scores for each of the outcome measures, there was no significant difference between participants with and without PD on week 12 scores for any of the outcome measures (all p > 0.14). Conclusion: In this secondary analysis of a primary efficacy study, PD was a common comorbidity among those with MDD, but was not a significant predictor of functional outcomes. This study adds to the limited literature on PD in randomized controlled trials for MDD. Clinical trial registration: ACTRN12612000283875.

Efficacy of adjunctive Garcinia mangostana Linn (mangosteen) pericarp for bipolar depression: study protocol for a proof-of-concept trial

Objective: Bipolar depression is characterized by neurobiological features including perturbed oxidative biology, reduction in antioxidant levels, and a concomitant rise in oxidative stress markers. Bipolar depression manifests systemic inflammation, mitochondrial dysfunction, and changes in brain growth factors. The depressive phase of the disorder is the most common and responds the least to conventional treatments. Garcinia mangostana Linn, commonly known as mangosteen, is a tropical fruit. The pericarp's properties may reduce oxidative stress and inflammation and improve neurogenesis, making mangosteen pericarp a promising add-on therapy for bipolar depression. Methods: Participants will receive 24 weeks of either 1,000 mg mangosteen pericarp or placebo per day, in addition to their usual treatment. The primary outcome is change in severity of mood symptoms, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), over the treatment phase. Secondary outcomes include global psychopathology, quality of life, functioning, substance use, cognition, safety, biological data, and cost-effectiveness. A follow-up interview will be conducted 4 weeks post-treatment. Conclusion: The findings of this study may have implications for improving treatment outcomes for those with bipolar disorder and may contribute to our understanding of the pathophysiology of bipolar depression. Clinical trial registration: Australian and New Zealand Clinical Trial Registry, ACTRN12616000028404.

Mental health information online: what we have learned from social media metrics in BuzzFeed's Mental Health Week / Informações de saúde mental on-line: o que aprendemos com as métricas de mídias sociais na Semana de Saúde Mental do BuzzFeed

Abstract Introduction The Internet has seen rapid growth in the number of websites focusing on mental health content. Considering the increased need for access to accurate information about mental health treatment, it is important to understand the promotion of this information online. Objective To analyze BuzzFeed's Mental Health Week (BFMHW) interactions on its own website and in related social media platforms (Facebook, Twitter and YouTube) using metrics of information delivery in mental health topics. Methods We extracted social media metrics from the 20 posts with the highest number of BuzzFeed interactions on the BFMHW website and from 41 videos available on the BFMHW playlist created by the BuzzFeed Video profile on YouTube. We analyzed the format and content used in BuzzFeed's publishing methods as well as the following social media metrics: exposure (presence online, views and time online), influence (likes) and engagement (comments, shares, replies and BuzzFeed interactions). Results Analysis of the variables revealed that audience engagement is associated with the number of medias in which the content is published: views on YouTube and shares on Facebook (0.71, p<0.001), total interactions on Facebook (0.66, p<0.001) and BuzzFeed number of total interactions (0.56, p<0.001). Conclusions Our results suggest that videos on YouTube may be an important information channel, including activity and engagement on other medias such as Facebook. Information may be more effective in reaching the audience if it is delivered in more than one media and includes personal experiences, some humor in content and detailed information about treatment.

Resumo Introdução O número de sites com foco em conteúdo de saúde mental vem crescendo rapidamente. Considerando a necessidade crescente de acesso a informações precisas sobre tratamento em saúde mental, é importante entender a promoção dessas informações on-line. Objetivo Analisar as interações da Semana de Saúde Mental do BuzzFeed (BuzzFeed's Mental Health Week - BFMHW) em seu próprio site e em plataformas de mídia social relacionadas (Facebook, Twitter e YouTube) usando métricas de entrega de informações em tópicos de saúde mental. Métodos Extraímos métricas de mídias sociais das 20 postagens com o maior número de interações no site da BFMHW e de 41 vídeos disponíveis na playlist da BFMHW criada pelo perfil BuzzFeed Video no YouTube. Analisamos o formato e o conteúdo usados nos métodos de publicação do BuzzFeed, bem como as seguintes métricas de mídias sociais: exposição (presença on-line, visualizações e tempo on-line), influência (curtidas) e engajamento (comentários, compartilhamentos, respostas e interações do BuzzFeed). Resultados A análise das variáveis revelou que o envolvimento do público está associado ao número de mídias em que o conteúdo é publicado: visualizações no YouTube e compartilhamentos no Facebook (0,71, p <0,001), interações totais no Facebook (0,66, p <0,001) e número de interações totais no BuzzFeed (0,56, p <0,001). Conclusões Nossos resultados sugerem que o YouTube pode ser um importante canal de informações, incluindo atividades e envolvimento em outras mídias, como o Facebook. As informações podem alcançar o público de forma mais eficaz se forem exibidas em mais de uma mídia e incluírem experiências pessoais, algum humor no conteúdo e informações detalhadas sobre o tratamento.

Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

Objective: Bipolar disorder (BD) has been associated with increased rates of age-related diseases, such as type II diabetes, metabolic syndrome, osteoporosis, and cardiovascular disorders. Several biological findings have been associated with age-related disorders, including increased oxidative stress, inflammation, and telomere shortening. The objective of this study was to compare telomere length among participants with BD at early and late stages and age- and gender-matched healthy controls. Methods: Twenty-six euthymic subjects with BD and 34 healthy controls were recruited. Genomic DNA was extracted from peripheral blood and mean telomere length was measured using real-time quantitative polymerase chain reaction. Results: Telomere length was significantly shorter in both the early and late subgroups of BD subjects when compared to the respective controls (p = 0.002 and p = 0.005, respectively). The sample size prevented additional subgroup analyses, including potential effects of medication, smoking status, and lifestyle. Conclusion: This study is concordant with previous evidence of telomere shortening in BD, in both early and late stages of the disorder, and supports the notion of accelerated aging in BD.

Design and rationale of a 16-week adjunctive randomized placebo-controlled trial of mitochondrial agents for the treatment of bipolar depression

Objective: Bipolar disorder places a significant burden on individuals, caregivers and family, and the broader community. Current treatments are believed to be more effective against manic symptoms, leaving a shortfall in recovery during the depressive phase of the illness. The current study draws on recent evidence suggesting that, in addition to increased oxidative load, alterations in mitochondrial function occur in bipolar disorder. Methods: This 16-week study aims to explore the potential benefits of N-acetylcysteine (NAC) alone or in combination (CT) with selected nutraceuticals believed to enhance mitochondrial function. The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression. Participants are asked to take NAC, CT, or placebo in addition to any usual treatments. A post-discontinuation visit is conducted 4 weeks following the treatment phase. Results: The primary outcome of the study will be mean change on the Montgomery-Asberg Depression Rating Scale. Secondary outcomes include functioning, substance use, mania ratings, and quality of life. Blood samples will be collected at baseline and week 16 to explore biochemical alterations following treatment. Conclusion: This study may provide a novel adjunctive treatment for bipolar depression. Analysis of biological samples may assist in understanding the therapeutic benefits and the underlying etiology of bipolar depression. Trial registration: Australian and New Zealand Clinical Trial Registry ACTRN12612000830897. .

Oxidative stress markers, cognitive functions, and psychosocial functioning in bipolar disorder: an empirical cross-sectional study

Objective: This study aimed to evaluate the relationship between oxidative stress markers and cognitive functions and domains of psychosocial functioning in bipolar disorder. Methods: Oxidative stress markers, cognitive functions, and domains of psychosocial functioning were evaluated in 51 patients with bipolar disorder who were in remission. Correlation analyses between these parameters were calculated with data controlled for duration of illness and number of episodes. Results: There was no statistically significant correlation between oxidative stress markers and cognitive functions. In terms of psychosocial functioning, significant correlations were found between malondialdehyde and sense of stigmatization (r = -0.502); household activities and superoxide dismutase (r = 0.501); participation in social activities and nitric oxide (r = 0.414); hobbies and leisure time activities and total glutathione (r = -0.567), superoxide dismutase (r = 0.667), and neurotrophin 4 (r = 0.450); and taking initiative and self-sufficiency and superoxide dismutase (r = 0.597). There was no correlation between other domains of psychosocial functioning and oxidative stress markers. Conclusion: These results imply that oxidative stress markers do not appear to correlate clearly with cognitive impairment and reduced psychosocial functioning. However, there were some associations between selected oxidative markers and activity-oriented functional markers. This may represent a true negative association, or may be an artifact of oxidative stress being a state rather than a trait marker. .

Systematic review of N-acetylcysteine in the treatment of addictions

Objective: To conduct the first systematic literature review of clinical trials of N-acetylcysteine (NAC) for the treatment of substance abuse disorders and addictive behaviors. Methods: A search of the MEDLINE, Embase and PsycINFO databases was conducted. The inclusion criteria for the review were clinical trials that used NAC in the treatment of a disorder related to substance use and/or addictive behaviors, limited to texts in English, Spanish, or French. The selected studies were evaluated with respect to type of trial, sample size, diagnostic input, intervention, length of follow-up, outcome variables, and results. Results: Nine studies analyzing a total of 165 patients met the eligibility criteria and were included in qualitative analysis. These studies evaluated the role of NAC in cocaine dependence (three studies), cannabis dependence (two studies), nicotine dependence (two studies), methamphetamine addiction (one study), and pathological gambling (one study). Five of these trials were double-blind, randomized, and placebo-controlled. Conclusions: The studies analyzed suggest a potential role for NAC in the treatment of addiction, especially of cocaine and cannabis dependence. These results are concordant with the hypothesis of the involvement of glutamatergic pathways in the pathophysiology of addiction. .

N-acetylcysteine for major depressive episodes in bipolar disorder / N-acetilcisteína para o tratamento de episódios de depressão maior no transtorno bipolar

OBJECTIVE: In this report, we aimed to evaluate the effect of add-on N-acetylcysteine (NAC) on depressive symptoms and functional outcomes in bipolar disorder. To that end, we conducted a secondary analysis of all patients meeting full criteria for a depressive episode in a placebo controlled trial of adjunctive NAC for bipolar disorder. METHOD: Twenty-four week randomised clinical trial comparing adjunctive NAC and placebo in individuals with bipolar disorder experiencing major depressive episodes. Symptomatic and functional outcome data were collected over the study period. RESULTS: Seventeen participants were available for this report. Very large effect sizes in favor of NAC were found for depressive symptoms and functional outcomes at endpoint. Eight of the ten participants on NAC had a treatment response at endpoint; the same was true for only one of the seven participants allocated to placebo. DISCUSSION: These results indicate that adjunctive NAC may be useful for major depressive episodes in bipolar disorder. Further studies designed to confirm this hypothesis are necessary.

OBJETIVO: Neste relato, avaliamos o efeito da N-acetilcisteína (NAC) adjuvante em sintomas depressivos e desfechos funcionais no transtorno bipolar. Para isso, conduzimos uma análise secundária de todos os pacientes com critérios diagnósticos para um episódio depressivo em um ensaio clínico randomizado comparando NAC adjuvante com placebo no transtorno bipolar. MÉTODO: Ensaio clínico randomizado comparando NAC adjuvante com placebo para episódios depressivos no transtorno bipolar durante 24 semanas. Desfechos funcionais e sintomáticos foram coletados no período. RESULTADOS: Dezessete participantes estavam disponíveis para esta análise. Tamanhos de efeito grandes foram encontrados para sintomas depressivos e desfechos funcionais. Oito dos dez participantes no grupo da NAC tiveram resposta clínica ao fim do tratamento. O mesmo ocorreu em apenas um dos sete que receberam placebo. DISCUSSÃO: Esses resultados indicam que a NAC adjuvante pode ser útil para episódios de depressão maior no transtorno bipolar. Estudos desenhados para confirmar esta hipótese são necessários.

Serum levels of brain-derived neurotrophic factor and thiobarbituric acid reactive substances in chronically medicated schizophrenic patients: a positive correlation / Níveis séricos do fator neurotrófico derivado do cérebro e dos produtos de reação com o ácido tiobarbitúrico em pacientes com esquizofrenia cronicamente medicados: correlação positiva

OBJECTIVE: The neurotrophins, antioxidant enzymes and oxidative markers have reciprocal interactions. This report verified in chronically stable medicated schizophrenic patients whether there are correlations between the serum levels of superoxide dismutase, a key enzyme in the antioxidant defense, thiobarbituric acid reactive substances, a direct index of lipid peroxidation, and brain-derived neurotrophic factor, the most widely distributed neurotrophin. METHOD: Sixty DSM-IV schizophrenic patients were included (43 males, 17 females). Mean age was 34.7 ± 10.8 years, mean age at first episode was 19.8 ± 7.9 years, and mean illness duration was 14.9 ± 8.5 years. Each subject had a blood sample collected for the determination of serum levels of brain-derived neurotrophic factor, thiobarbituric acid reactive substances and superoxide dismutase. RESULTS: Brain-derived neurotrophic factor levels showed a positive correlation with thiobarbituric acid reactive substances levels (r = 0.333, p = 0.009). Brain-derived neurotrophic factor levels were not correlated with superoxide dismutase levels (r = - 0.181, p = 0.166), and superoxide dismutase levels were not correlated with thiobarbituric acid reactive substances levels (r = 0.141, p = 0.284). CONCLUSIONS: The positive correlation between brain-derived neurotrophic factor and thiobarbituric acid reactive substances suggests the need of further investigation on intracellular interactions of neurotrophins, antioxidant enzymes and oxidative markers. In addition, this opens a venue for investigation on treatments for the prevention of neurotoxicity along the course of schizophrenia.

OBJETIVO: As neurotrofinas, enzimas antioxidantes e marcadores de oxidação têm interações. Este estudo verificou se existem correlações entre os níveis séricos de superóxido-dismutase, uma enzima chave na defesa antioxidante, os produtos de reação com o ácido tiobarbitúrico, um indicador direto de peroxidação lipídica, e o fator neurotrófico derivado do cérebro, a neurotrofina mais amplamente distribuída. MÉTODO: Sessenta pacientes portadores de Esquizofrenia pelo DSM-IV foram incluídos (43 homens, 17 mulheres), com idade média de 34,7 ± 10,8 anos, idade média no primeiro episódio de 19,8 ± 7,9 anos, e tempo médio de duração da doença de 14,9 ± 8,5 anos. Foi coletado sangue de cada sujeito para a determinação dos níveis séricos de fator neurotrófico derivado do cérebro, superóxido-dismutase e ácido tiobarbitúrico. RESULTADOS: Os níveis de fator neurotrófico derivado do cérebro se correlacionaram positivamente aos de ácido tiobarbitúrico (r = 0,333, p = 0,009) e não mostraram correlação com os de superóxido-dismutase (r = - 0,181, p = 0,166). Este último também não se correlacionou aos níveis de ácido tiobarbitúrico (r = 0,141, p = 0,284). CONCLUSÕES: A correlação positiva entre fator neurotrófico derivado do cérebro e ácido tiobarbitúrico direciona para investigações na interação intracelular entre neurotrofinas, enzimas antioxidantes e marcadores de oxidação, além de abrir perspectives para pesquisa em tratamentos para a prevenção da neurotoxicidade ao longo do curso da esquizofrenia.