Adjunctive Docosahexaenoic Acid in Residual Symptoms of Depression and Anxiety.

OBJECTIVE: The aim of the study is to examine the efficacy of omega-3 fatty acid as an adjunct to ongoing pharmacological treatments in patients with residual symptoms of depression and anxiety. METHODS/PROCEDURES: This randomized, double-blind, placebo-controlled, cross-over trial was conducted at a single private practice site. Participants were drawn from patients attending the practice.Patients meeting criteria had a 4-week run-in period where they continued to receive their prescribed medications and omega-3 supplements. Depression and anxiety ratings were assessed at recruitment and completion of the run-in phase. Patients were randomized to receive an omega-3 supplement (Neurospark) or placebo once daily for 8 weeks then crossed over to the alternative treatment. At the end of the double-blind, cross-over phase, patients received the supplement and were assessed after a 4-week run-out phase.Depression and anxiety symptoms were assessed using the Hamilton scales. Efficacy of treatment was assessed using a linear mixed model analysis with time, order of treatment, diagnosis, and their interaction as factors. Depression and anxiety scales were analyzed as independent measures. RESULTS: The study enrolled 47 patients (mean [SD] age, 46.1 [11.2] years; [59.6%] male). Depression scores did not significantly change across assessments ( P > 0.1); there was no effect of order of treatment ( P > 0.1) or an interaction between time, order of treatment, and psychiatric diagnosis ( P > 0.1). Anxiety scores were similarly unchanged across treatment visits and order of treatment, and there was no interaction between time, order of treatment, and psychiatric diagnosis. CONCLUSIONS: Omega-3 fatty acid supplementation did not significantly alter residual symptoms in this group of patients.

Black cohosh extracts in women with menopausal symptoms: an updated pairwise meta-analysis.

OBJECTIVE: Menopausal symptoms are common in midlife women and have broad impacts on their daily functioning and quality of life. Black cohosh extracts have been widely used to relieve menopausal symptoms. However, the comparative benefits of different combined black cohosh regimens remain inconclusive. The aim of the current updated meta-analysis is to address the comparative efficacies of different black cohosh regimens in improving menopausal symptoms. METHODS: Random-effect model pairwise meta-analysis of randomized controlled trials was conducted to investigate the treatment effect on menopausal symptoms by the black cohosh extract both alone or combined with other related active ingredients. The outcomes studied were changes in menopausal symptoms after treatment with black cohosh extracts in menopausal women. RESULTS: Twenty-two articles including information on 2,310 menopausal women were included in the analyses. Black cohosh extracts were associated with significant improvements in overall menopausal symptoms (Hedges' g = 0.575, 95% CI = 0.283 to 0.867, P < 0.001), as well as in hot flashes (Hedges' g = 0.315, 95% CIs = 0.107 to 0.524, P = 0.003), and somatic symptoms (Hedges' g = 0.418, 95% CI = 0.165 to 0.670, P = 0.001), compared with placebo. However, black cohosh did not significantly improve anxiety (Hedges' g = 0.194, 95% CI = -0.296 to 0.684, P = 0.438) or depressive symptoms (Hedges' g = 0.406, 95% CI = -0.121 to 0.932, P = 0.131). The dropout rate for black cohosh products was similar to that for placebo (odds ratio = 0.911, 95% CI = 0.660 to 1.256, P = 0.568). CONCLUSIONS: This study provides updated evidence regarding the potentially beneficial effects of black cohosh extracts for relieving menopausal symptoms in menopausal women.

Changes in private psychiatric practice in Australia: An analysis of trends in claims for outpatient Medicare item numbers over 14 years.

OBJECTIVE: The Better Health Access Initiative added 32 Medicare Benefits Schedule (MBS) item numbers in 2006 to increase the number of people with access to mental health care. We investigated trends in the provision of outpatient Medicare-subsidised psychiatric services since the introduction of these item numbers in 2006 through 2019. METHODS: Medicare Benefits Schedule aggregated item-number claims data were obtained from the Services Australia Medicare website, between January 2006 and December 2019 inclusive, for face-to-face psychiatrist consultations. Item number rates were collated and graphed per 100,000 population according to year and item number. RESULTS: There has been an increase in the number of claims for new patient assessments (291-296) and a reduction in most ongoing care Medicare item numbers, especially longer appointments that are often associated with psychotherapy provision (306-308). CONCLUSION: There have been changes in private psychiatric practice in Australia over the past 14 years. There are several possible causes for these changes and further research is required to determine the impact on patient care.

A Systematic Review of Nutraceuticals for the Treatment of Bipolar Disorder.

BACKGROUND: Certain nutrient supplements (nutraceuticals) may target neurobiological pathways perturbed in bipolar disorder (BD) such as inflammation, oxidative stress, and mitochondrial dysfunction. Nutraceuticals thus may have a potential role as adjunctive treatments for BD. METHODS: A search of Embase via embase.com, PubMed via PubMed, Cumulated index to nursing and allied health literature (CINAHL) Complete via EBSCO, and Cochrane Central Register of Controlled Clinical Trials via cochranelibrary.com was conducted to identify published randomized controlled trials assessing the efficacy of nutraceuticals on mood symptomatology in adults with BD. Search terms for BD, nutraceuticals, and clinical trials (total search terms = 75) were used to search from inception to February 20, 2020. The Cochrane Collaboration's tool for assessing the risk of bias in randomized trials was used to assess the risk of bias. RESULTS: A total of 1,712 studies were identified through the search. After rigorous screening, 22 studies were included in the review. There was large variability across the studies with 15 different nutraceutical agents assessed and as such insufficient homogeneity for a meta-analysis to be conducted (I2 > 50%). Studies revealed promising, albeit conflicting, evidence for omega-3 fatty acids and N-acetylcysteine. Isolated positive results were reported for coenzyme Q10. CONCLUSION: Given nutraceuticals are tolerable and accessible, they may be useful as potential adjunctive treatments for BD. Nutraceuticals targeting neuroinflammation or mitochondrial activity may have the most potential for the depressive phase. However, further studies are required to determine efficacy.

Physical Activity as a Predictor of Clinical Trial Outcomes in Bipolar Depression: A Subanalysis of a Mitochondrial-Enhancing Nutraceutical Randomized Controlled Trial.

OBJECTIVES: Individuals with bipolar disorder (BD) generally engage in low levels of physical activity (PA), and yet few studies have investigated the relationship between PA and change in BD symptom severity. The aim of this subanalysis of an adjunctive nutraceutical randomized controlled trial for the treatment of bipolar depression was to explore the relationship between PA, the active adjunctive treatments (a nutraceutical "mitochondrial cocktail"), and clinical outcomes. METHODS: Participants with bipolar depression were randomized to receive N-acetylcysteine alone, N-acetylcysteine with a combination of nutraceuticals (chosen for the potential to increase mitochondrial activity), or placebo for 16 weeks. Participants (n = 145) who completed the International Physical Activity Questionnaire-Short Form (IPAQ-SF; measured at Week 4) were included in this exploratory subanalysis. Assessments of BD symptoms, functioning, and quality of life were completed at monthly visits up until Week 20. Generalised Estimating Equations were used to explore whether IPAQ-SF scores were a moderator of treatment received on outcomes of the study. RESULTS: Week-4 PA was not related to changes in Montgomery Åsberg Depression Rating Scale scores across the study until Week 20. However, participants who engaged in more PA and who received the combination treatment were more likely to have a reduction in scores on the Bipolar Depression Rating Scale (P = 0.03). However, this was not consistent in all domains explored using the IPAQ-SF. Participants who engaged in higher levels of PA also experienced greater improvement in social and occupational functioning and less impairment in functioning due to their psychopathology and improvement in quality of life at Week 20, irrespective of treatment. CONCLUSIONS: This study provides novel evidence of the association between PA and reduction in BD symptoms in a nutraceutical clinical trial. However, further research assessing the potential synergistic effects of PA in BD is required.

Diet quality, dietary inflammatory index and body mass index as predictors of response to adjunctive N-acetylcysteine and mitochondrial agents in adults with bipolar disorder: A sub-study of a randomised placebo-controlled trial.

AIMS: We aimed to explore the relationships between diet quality, dietary inflammatory potential or body mass index and outcomes of a clinical trial of nutraceutical treatment for bipolar depression. METHODS: This is a sub-study of a randomised controlled trial of participants with bipolar depression who provided dietary intake data (n = 133). Participants received 16 weeks adjunctive treatment of either placebo or N-acetylcysteine-alone or a combination of mitochondrial-enhancing nutraceuticals including N-acetylcysteine (combination treatment). Participants were followed up 4 weeks post-treatment discontinuation (Week 20). Diet was assessed by the Cancer Council Victoria Dietary Questionnaire for Epidemiological Studies, Version 2, converted into an Australian Recommended Food Score to measure diet quality, and energy-adjusted dietary inflammatory index score to measure inflammatory potential of diet. Body mass index was also measured. Generalised estimating equation models were used to assess whether diet quality, energy-adjusted dietary inflammatory index score and/or body mass index were predictors of response to significant outcomes of the primary trial: depression symptoms, clinician-rated improvement and functioning measures. RESULTS: In participants taking combination treatment compared to placebo, change in depression scores was not predicted by Australian Recommended Food Score, dietary inflammatory index or body mass index scores. However, participants with better diet quality (Australian Recommended Food Score) reported reduced general depression and bipolar depression symptoms (p = 0.01 and p = 0.03, respectively) and greater clinician-rated improvement (p = 0.02) irrespective of treatment and time. Participants who had a more anti-inflammatory dietary inflammatory index had less impairment in functioning (p = 0.01). Combination treatment may attenuate the adverse effects of pro-inflammatory diet (p = 0.03) on functioning. Participants with lower body mass index who received combination treatment (p = 0.02) or N-acetylcysteine (p = 0.02) showed greater clinician-rated improvement. CONCLUSION: These data support a possible association between diet (quality and inflammatory potential), body mass index and response to treatment for bipolar depression in the context of a nutraceutical trial. The results should be interpreted cautiously because of limitations, including numerous null findings, modest sample size and being secondary analyses.

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.

Nutraceuticals and nutritional supplements for the treatment of bipolar disorder: protocol for a systematic review.

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.

The Therapeutic Potential of Mangosteen Pericarp as an Adjunctive Therapy for Bipolar Disorder and Schizophrenia.

New treatments are urgently needed for serious mental illnesses including bipolar disorder and schizophrenia. This review proposes that Garcinia mangostana Linn. (mangosteen) pericarp is a possible adjunctive therapeutic agent for these disorders. Research to date demonstrates that neurobiological properties of the mangosteen pericarp are well aligned with the current understanding of the pathophysiology of bipolar disorder and schizophrenia. Mangosteen pericarp has antioxidant, putative neuroprotective, anti-inflammatory, and putative mitochondrial enhancing properties, with animal studies demonstrating favorable pharmacotherapeutic benefits with respect to these disorders. This review summarizes evidence of its properties and supports the case for future studies to assess the utility of mangosteen pericarp as an adjunctive treatment option for mood and psychotic disorders.

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.

Pharmacotherapy for the pseudobulbar affect in individuals who have sustained a traumatic brain injury: a systematic review protocol.

REVIEW OBJECTIVE/QUESTION: The objective of this systematic review is to synthesize current evidence on the effectiveness of pharmacotherapy as compared to all comparators for the management of pseudobulbar affect in adults 16 years and over who have sustained a traumatic brain injury. The specific review question is: What is the effectiveness of pharmacotherapy for the management of pseudobulbar affect in adults 16 years and over who have sustained a traumatic brain injury?

Anger in PTSD: is there a need for a concept of PTSD-related posttraumatic anger?

Despite extensive research on posttraumatic stress disorder (PTSD), anger in PTSD has received little attention. This is surprising, given anger is a key predictor of treatment outcome in PTSD. This paper seeks to build an argument for investigating anger in PTSD as a discrete entity. A key argument is that the capacity to image visual mental phenomena is crucial to the aetiology and maintenance of anger in PTSD. Evidence is reviewed for the influence of visual imagery in anger in PTSD from the perspectives of neuropsychology, psychopathology, anger and PTSD. An argument is advanced for including visual imagery in an integrated (visual-linguistic) cognitive model of anger in PTSD. Directions for research on visual imagery in anger in PTSD and its treatment implications are discussed.

Imagery rehearsal in the treatment of posttraumatic nightmares in Australian veterans with chronic combat-related PTSD: 12-month follow-up data.

Nightmares are often a distressing symptom for veterans with chronic combat-related posttraumatic stress disorder (PTSD). A psychological treatment that has recently shown considerable promise is Imagery Rehearsal Therapy (IRT). In a pilot study by the current authors, IRT was demonstrated to be effective in the treatment of posttraumatic nightmares in a group of combat veterans up to 3-month posttreatment. This study reports the 12-month follow-up data of the pilot study, examining the longer term outcome of the IRT treatment. Twelve Australian Vietnam veterans with chronic combat-related PTSD were treated with 6 once weekly sessions of imagery rehearsal and assessed using standardised measures of nightmare frequency and intensity, PTSD, depression, anxiety and broader symptomatology at intake, posttreatment, and 3-and 12-month follow-up. Significant improvements in targeted nightmare frequency and intensity were evident to 12-month posttreatment. Similarly, improvements in overall PTSD, depression, anxiety, and broader based symptomatology were also maintained to 12 months. This study provides preliminary evidence that the positive treatment effects of IRT on posttraumatic nightmares, PTSD, and broader symptomatology in males with chronic combat-related PTSD are maintained in the longer term.