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Pilot study of a lifestyle intervention for bipolar disorder: Nutrition exercise wellness treatment (NEW Tx).
Sylvia, LG, Pegg, SL, Dufour, SC, Janos, JA, Bernstein, EE, Chang, WC, Hall, NE, Ellard, KK, Nierenberg, AA, Deckersbach, T
Journal of affective disorders. 2019;:278-283
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Abstract
BACKGROUND Individuals with bipolar disorder (BD) are more likely than the general population to develop risk factors associated with cardiovascular disease, one of the leading causes of morbidity and mortality in this clinical population. To address this disproportionate medical burden, we developed Nutrition Exercise and Wellness Treatment (NEW Tx), a lifestyle intervention for individuals with BD. METHODS In this study, participants were randomized to NEW Tx (n = 19) or a treatment as usual waitlist (n = 19). We examine the intervention's efficacy to improve the physical and psychological outcomes of individuals with BD. Assessors were blind to participant condition throughout study duration. RESULTS The NEW Tx group reported increased weekly exercise duration and overall functioning, and decreased depression and illness severity over the study duration. However, only improvements in functioning were significantly greater in the NEW Tx group than in the control group. There were no group differences in weight loss or mood symptoms over the study duration. LIMITATIONS Limitations to this study include lack of objective measurement of exercise and a small and relatively homogeneous sample. CONCLUSIONS These data suggest that a manualized lifestyle intervention for BD may not be ideal to improve lifestyle changes in this clinical population. Further research is needed to pilot personalized approaches to creating a healthy lifestyle in BD.
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Serum folate levels in bipolar disorder: a systematic review and meta-analysis.
Hsieh, YC, Chou, LS, Lin, CH, Wu, HC, Li, DJ, Tseng, PT
BMC psychiatry. 2019;(1):305
Abstract
BACKGROUND Bipolar disorder (BD) is a major psychiatric illness, however its physiopathology is unclear. The role of folate in the physiopathology of BD is controversial. We conducted this systematic review and meta-analysis to investigate the effect of folate in BD patients. METHODS We performed a thorough literature study of the PubMed, Embase, ScienceDirect, ClinicalKey, Cochrane Library, ProQuest, Web of Science, and ClinicalTrials.gov databases until December 21st, 2018. Random effects meta-analysis was conducted. RESULTS Six articles involving 481 patients with BD and 760 controls were included. The meta-analysis results suggested that serum folate levels in the patients with BD were significantly lower than those in the controls (Hedges' g = - 0.211, 95% confidence interval = - 0.391 to - 0.031, p = 0.021). CONCLUSION The current meta-analysis show it might be association between lower serum folate levels and patient with BD. However, we could not distinguish the potentially confounding effects of mood states on the folate levels. Further prospective studies including subjects with different mood states and possible physiopathology are warranted to investigate the association between folate deficiency and the etiology of BD.
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Non-pharmacological interventions for preventing weight gain in patients with first episode schizophrenia or bipolar disorder: A systematic review.
Nyboe, L, Lemcke, S, Møller, AV, Stubbs, B
Psychiatry research. 2019;:112556
Abstract
Weight gain is a side effect of antipsychotic medication and highly prevalent in people with schizophrenia or bipolar disorder, increasing their overall cardio-metabolic risk. We conducted a systematic review on non-pharmacological interventions for preventing/reducing weight gain or increase in waist-circumference in young, newly diagnosed patients with schizophrenia or bipolar disorder. We searched major electronic databases from inception to 04/2019 on RCTs, pre- and post-test studies, and non-randomized controlled clinical trials. From a potential of 2963 hits, eight studies met the inclusion criteria (n = 438, mean age of 18.8 (13-45) years). The interventions comprised supervised and individually adjusted aerobic exercise activities (5 studies), individual lifestyle counselling vs. control condition (2 RCTs), and dietetic counselling and practical training of cooking and shopping (1 study). Physical activity and practical dietetic interventions seem to be more efficient than lifestyle counselling. However, the results shall be taken with caution due to the non-randomized designs and other methodologically deficits in the majority of the included studies.
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Genome-wide DNA methylomic differences between dorsolateral prefrontal and temporal pole cortices of bipolar disorder.
Ho, AM, Winham, SJ, Armasu, SM, Blacker, CJ, Millischer, V, Lavebratt, C, Overholser, JC, Jurjus, GJ, Dieter, L, Mahajan, G, et al
Journal of psychiatric research. 2019;:45-54
Abstract
Dorsolateral prefrontal cortex (DLPFC) and temporal pole (TP) are brain regions that display abnormalities in bipolar disorder (BD) patients. DNA methylation - an epigenetic mechanism both heritable and sensitive to the environment - may be involved in the pathophysiology of BD. To study BD-associated DNA methylomic differences in these brain regions, we extracted genomic DNA from the postmortem tissues of Brodmann Area (BA) 9 (DLPFC) and BA38 (TP) gray matter from 20 BD, ten major depression (MDD), and ten control age-and-sex-matched subjects. Genome-wide methylation levels were measured using the 850 K Illumina MethylationEPIC BeadChip. We detected striking differences between cortical regions, with greater numbers of between-brain-region differentially methylated positions (DMPs; i.e., CpG sites) in all groups, most pronounced in the BD group, and with substantial overlap across groups. The genes of DMPs common to both BD and MDD (hypothetically associated with their common features such as depression) and those distinct to BD (hypothetically associated with BD-specific features such as mania) were enriched in pathways involved in neurodevelopment including axon guidance. Pathways enriched only in the BD-MDD shared list pointed to GABAergic dysregulation, while those enriched in the BD-only list suggested glutamatergic dysregulation and greater impact on synaptogenesis and synaptic plasticity. We further detected group-specific between-brain-region gene expression differences in ODC1, CALY, GALNT2, and GABRD, which contained significant between-brain-region DMPs. In each brain region, no significant DMPs or differentially methylated regions (DMRs) were found between diagnostic groups. In summary, the methylation differences between DLPFC and TP may provide molecular targets for further investigations of genetic and environmental vulnerabilities associated with both unique and common features of various mood disorders and suggest directions of future development of individualized treatment strategies.
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Psychological effects of dopamine agonist treatment in patients with hyperprolactinemia and prolactin-secreting adenomas.
Ioachimescu, AG, Fleseriu, M, Hoffman, AR, Vaughan Iii, TB, Katznelson, L
European journal of endocrinology. 2019;(1):31-40
Abstract
Background Dopamine agonists (DAs) are the main treatment for patients with hyperprolactinemia and prolactinomas. Recently, an increasing number of reports emphasized DAs' psychological side effects, either de novo or as exacerbations of prior psychiatric disease. Methods Review of prospective and retrospective studies (PubMed 1976, September 2018) evaluating the psychological profile of DA-treated patients with hyperprolactinemia and prolactinomas. Case series and case reports of psychiatric complications were also reviewed. Results Most studies were cross-sectional and had a control group of healthy volunteers or patients with nonfunctioning pituitary adenomas. There were few prospective studies, with/without control group, that included small numbers of patients. Compared with controls, patients with hyperprolactinemia generally had worse quality of life, anxiety, depression and certain personality traits. Patients receiving DAs had higher impulsivity scores than normoprolactinemic controls. Impulse control disorders (ICDs) were reported in both genders, with hypersexuality mostly in men. Multiple ICDs were sometimes reported in the same patient, usually reversible after DA discontinuation. In case reports, DA therapy was temporally associated with severe depression, manic episodes or psychosis, which improved after discontinuation and administration of psychiatric medications. Gender type of DA, dose and duration of therapy did not correlate with occurrence of psychiatric pathology. Conclusion Patients with hyperprolactinemia receiving DAs may develop changes in mood and behavior regardless of prior psychiatric history. Increased awareness for ICDs, depression, mania and other types of psychosis is needed by all physicians who prescribe DAs. Larger prospective controlled clinical studies are needed to delineate prevalence, risk stratification and management.
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Quetiapine extended-release vs olanzapine for Japanese patients with bipolar depression: A Bayesian analysis.
Kishi, T, Ikuta, T, Matsuda, Y, Iwata, N
Neuropsychopharmacology reports. 2019;(3):256-259
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Abstract
OBJECTIVE It is unknown whether there are differences in efficacy and safety between quetiapine extended-release, 300 mg/d (QUEXR300), and olanzapine, 5-20 mg/d (OLA), for Japanese patients with bipolar depression. METHODS We conducted a Bayesian analysis of data from phase 3 studies in Japan of QUEXR300 and OLA. Outcomes were remission rate (primary), response rate, improvement on the Montgomery-Åsberg Depression Rating Scale and 17-item Hamilton Depression Rating Scale scores, discontinuation rate, and incidence of individual adverse events. We calculated the standardized mean difference (SMD) and the risk ratio (RR) and 95% credible interval (95% CrI) for continuous and dichotomous data, respectively. RESULTS There were no significant differences between QUEXR300 and OLA for any of the efficacy outcomes. QUEXR300 was associated with a higher incidence of somnolence than OLA (RR = 5.517; 95% CrI = 1.563, 19.787), while OLA was associated with greater increase body weight (SMD = -0.488; 95% CrI = -0.881, -0.089) and blood prolactin levels (SMD = -0.642; 95% CrI = -1.073, -0.213) than QUEXR300, and a greater decrease in high-density lipoprotein cholesterol levels (SMD = -0.408; 95% CrI = -0.785, -0.030) than QUEXR300. CONCLUSION Although the two drugs' efficacy did not differ, OLA increased the risk of metabolic syndrome and QUEXR300 the risk of somnolence. A large scale, long-term, head-to-head comparison study of QUEXR300 vs OLA for Japanese patients with bipolar depression is needed to confirm the results of the current study.
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Nutraceuticals and nutritional supplements for the treatment of bipolar disorder: protocol for a systematic review.
Ashton, MM, Berk, M, Ng, CH, Hopwood, M, Kavanagh, B, Williams, LJ, Sarris, J, Dean, OM
BMJ open. 2019;(4):e025640
Abstract
INTRODUCTION First line pharmacological treatments for bipolar disorder (BD) can leave shortfalls in recovery leading to patients seeking alternative and adjunctive treatments such as nutraceuticals. This protocol for a systematic review and proposed meta-analysis aims to answer the research question: in patients with BD, how does use of nutraceutical treatments compare with placebo in reducing depressive and mania symptoms? METHODS AND ANALYSIS Clinical trials will be identified through database searches using PubMed via PubMed, EMBASE via embase.com, Cochrane Central Register of Controlled Clinical Trials (CENTRAL) via cochranelibrary.com and CINAHL Complete via EBSCO. Search terms for BD and specific nutraceuticals (75 total search terms) will be used. Double-blind, randomised, controlled, clinical trials of adults with BD will be included in the review. Risk of bias will be assessed using the Cochrane Collaboration's tool for assessing risk of bias in randomised trials. ETHICS AND DISSEMINATION This review will only look at published data (already reviewed for ethical compliance); therefore, ethical approval is not required. We aim to publish the systematic review in a peer-reviewed journal and present at conferences. PROSPERO REGISTRATION NUMBER CRD42019100745.
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A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo.
Berk, M, Turner, A, Malhi, GS, Ng, CH, Cotton, SM, Dodd, S, Samuni, Y, Tanious, M, McAulay, C, Dowling, N, et al
BMC medicine. 2019;(1):18
Abstract
BACKGROUND A phasic dysregulation of mitochondrial bioenergetics may operate in bipolar disorder, increased in mania and decreased in depression. We aimed to examine efficacy of two add-on treatments in bipolar depression: N-acetylcysteine (NAC) and NAC with a combination of nutraceutical agents that may increase mitochondrial biogenesis. METHODS A three-arm 16-week, double-blind, randomised, placebo-controlled trial, adjunctive to usual treatment, was conducted. Participants (n = 181) with bipolar disorder and current depressive symptoms were randomised to 2000 mg/day NAC (n = 59), 2000 mg/day NAC with the combination nutraceutical treatment (CT, n = 61), or placebo (n = 61). The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 16. Young Mania Rating Scale, Clinical Global Impression (CGI)-Improvement and CGI-Severity scales, Patient Global Impression scale, Social and Occupational Functioning Assessment Scale (SOFAS), Longitudinal Interval Follow-Up Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT), and Quality of Life Enjoyment, and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) were secondary outcomes. RESULTS One hundred forty-eight participants had post-randomisation data and were analysed (NAC = 52, CT = 47, Placebo = 49). No between-group differences were found for the rate of change between baseline and 16 weeks on any of the clinical and functioning variables. Improvements in MADRS, BDRS, SOFAS, and LIFE-RIFT scores from baseline to the week 20 post-discontinuation visit were significantly greater in the CT group compared to those in the placebo. At week 20, the CGI-I was significantly lower in the CT group versus placebo. Gastrointestinal symptoms were significantly greater in the NAC than in the placebo group. CONCLUSIONS These overall negative results, with no significant differences between groups detected at the primary outcome but some positive secondary signals, suggest either delayed benefit of the combination or an improvement of symptoms on withdrawal which warrants further exploration regarding the composition, mechanisms, and application of mitochondrial agents in illnesses characterised by mitochondrial dysfunction. TRIAL REGISTRATION ANZCTR ( ACTRN12612000830897 ).
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Harms are assessed inconsistently and reported inadequately part 1: systematic adverse events.
Mayo-Wilson, E, Fusco, N, Li, T, Hong, H, Canner, JK, Dickersin, K, ,
Journal of clinical epidemiology. 2019;:20-27
Abstract
OBJECTIVES We examined systematic adverse events (AEs) in Part 1 (of 2) of a study describing the assessment and reporting of AEs in clinical trials. STUDY DESIGN AND SETTING We examined 52 public and nonpublic data sources about trials of quetiapine for bipolar depression using data from the Multiple Data Sources study. We extracted and compared information about systematic AEs (i.e., AEs assessed for all participants) in six prespecified domains: cardiovascular, cholesterol, endocrine, extrapyramidal symptoms, mania, and weight. RESULTS Eligible trials did not assess and report the same systematic AEs, and most results were not available in public sources. Overall, public sources reported 159 results, of which 92 of 159 (58%) included sufficient statistical information to calculate the treatment effect and its precision. Nonpublic sources reported 636 results; 630 of 636 (99%) reported sufficient statistical information. CONCLUSION Systematic AEs were defined and analyzed in many ways, which led to many numerical results. Most systematic AEs were not mentioned in public sources. To minimize bias, methods for defining and analyzing potential AEs should be prespecified in trial registers and protocols. All trial results should be publicly available so that stakeholders can compare benefits and AEs. Trials could report core sets of AEs to facilitate decision-making.
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Obesity in Adolescents with Psychiatric Disorders.
Chao, AM, Wadden, TA, Berkowitz, RI
Current psychiatry reports. 2019;(1):3
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Abstract
PURPOSE OF REVIEW This narrative review synthesized recent research related to obesity in adolescents with psychiatric disorders, with a focus on epidemiology, mechanisms, and weight management approaches. The paper reviews literature on depressive and anxiety disorders, bipolar disorder, and schizophrenia spectrum and other psychotic disorders. RECENT FINDINGS Depression has a bidirectional relationship with obesity. Bipolar disorder and schizophrenia spectrum disorders, and their treatments, increase the risk of developing obesity. Mechanisms underlying this weight gain include lifestyle and environmental factors and psychiatric medications, though emerging evidence has also suggested the role of genetic and neuroendocrine processes. Evidence about the most effective treatments for obesity in adolescents with psychiatric disorders remains limited. Adolescents with psychiatric disorders are at high risk for obesity. Close monitoring for increases in weight and cardiometabolic risk factors with use of antipsychotic and mood-stabilizing medications is recommended. Clinical trials are needed that test the efficacy of weight management strategies for this population.