Making meaning of multimorbidity and severe mental illness: A viewpoint.

People living with severe mental illness, such as schizophrenia and bipolar affective disorder, frequently experience poorer physical health compared to those without mental illness. This issue has hitherto been approached through the disease-centred construct of comorbidity, where subsequent conditions are viewed as secondary to an 'index condition'. In contrast, this Viewpoint sets out to explain why multimorbidity, a patient-centred concept that instead refers to the coexistence of multiple chronic illnesses, is a more versatile and robust framework for tackling the issue of poor physical health in people with severe mental illness. In establishing this argument, this Viewpoint has sought to address three key areas. First, this article will discuss the epidemiology of both physical and psychiatric multimorbidity, with respect to how they manifest at greater frequency and at younger ages in people with severe mental illness. Second, the profound consequences of this multimorbidity burden will be explored, with respect to the 'three D's' of death (premature mortality), disability (functional impacts) and deficit (health-economic impacts). Finally, the utility of multimorbidity as a framework will be illustrated through a proposal for a three-dimensional multimorbidity construct composed of (1) quantity, (2) severity and (3) duration of an individual's chronic illnesses. Consequently, this Viewpoint aims to capture why it is necessary for modern psychiatry to grasp the concept of multimorbidity to facilitate holistic healthcare for people living with severe mental illness.

Preliminary results from the Australian Genetics of Bipolar Disorder Study: A nation-wide cohort.

OBJECTIVE: The Australian Genetics of Bipolar Disorder Study is a nation-wide cohort of adults living with bipolar disorder. The study aims to detect the relationships between genetic risk, symptom severity, and the lifetime prevalence of bipolar disorder, treatment response and medication side effects, and patterns and costs of health care usage. METHODS: A total of 6682 participants (68.3% female; aged 44.8 ± 13.6 years [range = 18-90]) were recruited in three waves: a nation-wide media campaign, a mail-out based on prescriptions for lithium carbonate and through the Australian Genetics of Depression Study. Participants completed a self-report questionnaire. A total of 4706 (70%) participants provided a saliva sample and were genotyped and 5506 (82%) consented to record linkage of their Pharmaceutical and Medicare Benefits Schedule data. RESULTS: Most participants were living with bipolar I disorder (n = 4068) while 1622 participants were living with bipolar II disorder and 992 with sub-threshold bipolar disorder. The mean age of bipolar disorder diagnosis was 32.7 ± 11.6 years but was younger in bipolar I (p = 2.0E-26) and females (p = 5.7E-23). Excluding depression with onset prior to bipolar disorder diagnosis, 64.5% of participants reported one or more co-occurring psychiatric disorders: most commonly generalised anxiety disorder (43.5%) and posttraumatic stress disorder (20.7%). Adverse drug reactions were common and resulted in discontinuation rates ranging from 33.4% for lithium to 63.0% for carbamazepine. CONCLUSION: Our findings highlight the high rate of comorbidities and adverse drug reactions among adults living with bipolar disorder in the general Australian population. Future genomic analyses focus on identifying genetic variants influencing pharmacotherapy treatment response and side effects.

The effect of exercise on global, social, daily living and occupational functioning in people living with schizophrenia: A systematic review and meta-analysis.

BACKGROUND: Schizophrenia is associated with high rates of global, social and occupational functional impairments. While prior meta-analyses have extensively examined the impact of exercise on physical and mental health, the impact on functioning in schizophrenia have yet to be fully established. This review aimed to update the evidence base regarding the impact of exercise on functioning in schizophrenia, and explore moderators of effect. METHODS: A systematic search was conducted to identify randomized controlled trials (RCTs) of exercise evaluating global functioning versus any comparator in people with schizophrenia; between group meta-analyses of global functioning (and secondary - social, living skills, occupational, adverse events) were computed using a random effects model. Subgroup analyses based on diagnosis and aspects of the intervention were conducted. RESULTS: 18 full text articles were included, involving 734 participants. A moderate impact of exercise on global functioning was found (g = 0.40, 95 % C·I. = 0.12 to 0.69, p = 0.006), with a moderate impact of exercise on social (N = 5, g = 0.54 95 % C.I = 0.16 to 0.9 p = 0.005), and daily living functioning (N = 3, g = 0.65, 95 % C.I. = 0.07 to 1.22, p = 0.005). CONCLUSIONS: There is good evidence that exercise can improve the global functioning of people with schizophrenia, with preliminary evidence for social and daily living skills; exercise should be considered an important adjunct to usual care. Higher impacts on global functioning were seen in aerobic interventions and of at least moderate to vigorous intensity. More research is required into resistance training, in early psychosis cohorts and to evaluate the comparison of exercise with other established psychosocial therapies.

Increase in telemental health services on the Medicare Benefits Schedule after the start of the coronavirus pandemic: data from 2019 to 2021.

Objective To describe the change in telemental health service volume that resulted from the introduction of the Medicare Benefits Schedule (MBS) item numbers in 2020 for services provided by psychologists and psychiatrists in Australia for a 3-year period, from January 2019 to December 2021. Methods Quarterly MBS activity and cost data for mental health services provided by consultant psychiatrists, clinical psychologists, and psychologists between January 2019 and December 2021 were extracted from the MBS statistics website. Data were grouped by profession and delivery mode (in-person, telephone or videoconference) and reported using activity counts. Descriptive analysis and interrupted time-series regression analysis were conducted. Specific descriptive explorations were also conducted for psychiatrists, including: new client consultations, review or general consultations, and group consultations. Results The delivery of mental health services by telehealth (telemental health) during the pandemic has increased (P < 0.0001). When the pandemic started in March 2020, telemental health services provided by psychiatrists and psychologists increased from a combined 1-2% per quarter to 29% videoconference and 20% telephone in quarter two 2020. After the onset of the pandemic, videoconference remained the primary form of telehealth for these professions. However, the telephone accounted for approximately a third of the telehealth activity after the new item numbers were introduced. Conclusion Telemental health services are more likely to be conducted by videoconference than by telephone. The observed increase in telehealth service activity confirms how crucial appropriate funding models are to the sustainability of telehealth services in Australia. The growth in telehealth was used to support people with mental health conditions in Australia.

Colorectal cancer Outcomes in people with Severe Mental Illness Cohort (COSMIC): a protocol for an Australian retrospective cohort using linked administrative data.

INTRODUCTION: Colorectal cancer (CRC) mortality is significantly higher in those with severe mental illness (SMI) compared with the general population, despite similar incidence rates, suggesting that barriers to optimal screening and cancer care may contribute to disparities in CRC mortality in those with SMI. This study aims to compare participation in Australia's National Bowel Cancer Screening Programme (NBCSP) in those with SMI and those in the general population. We will also investigate treatment pathways after diagnosis to determine whether treatment variations could explain differences in CRC mortality. METHODS AND ANALYSIS: We will undertake a retrospective cohort study of Australians using linked administrative data to assess differences in screening and cancer care between those with and without SMI, aged 50-74 years on or after 1 January 2006. People with SMI will be defined using antipsychotic medication prescription data. The comparison group will be people enrolled in Medicare (Australia's universal healthcare system) who have not been prescribed antipsychotic medication. Data on outcomes (NBCSP participation, follow-up colonoscopy, CRC incidence and CRC-cause and all-cause mortality) and confounders will be obtained from national-based and state-based administrative health datasets. All people in New South Wales, aged 50-74 with a new diagnosis of CRC on or after 1 January 2006, will be ascertained to examine stage at diagnosis and cancer treatment in those with and without SMI. Poisson regression will be used to calculate incidence rates and rate ratios for each outcome. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the University of Queensland Human Research Ethics Committee, the Australian Institute of Health and Welfare Ethics Committee and data custodians from every Australian State/Territory. Findings will be disseminated via publications in peer-reviewed journals and presented at appropriate conferences. TRIAL REGISTRATION NUMBER: ACTRN12620000781943.

Medicinal psychedelics for mental health and addiction: Advancing research of an emerging paradigm.

The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the 'Clinical Memorandum on Psychedelics' recently released by the Royal Australian and New Zealand College of Psychiatrists and note subsequent developments including the application for down-scheduling of psilocybin and 3,4-methylenedioxymethamphetamine presently being considered by the Therapeutic Goods Administration and approvals for access via the Special Access Scheme. We suggest that this field is worthy of rigorous research to assess potential benefits, address safety parameters and clarify therapeutic mechanisms. To this end, we outline recent research findings, provide an overview of current knowledge relating to mechanisms of action and discuss salient aspects of the psychedelic-assisted psychotherapy treatment model. The sum of this research points towards medicinal psychedelics as a potential new class of psychiatric treatments when used within a medically supervised framework with integrated psychotherapeutic support. However, before widespread translation into clinical use can occur, appropriately designed and sufficiently powered trials are required to detect both potential positive and negative outcomes. Unique safety and regulatory challenges also need to be addressed. As for any new medical therapy, psychedelic research needs to be conducted in a rigorous manner, through the dispassionate lens of scientific enquiry. Carte blanche availability to practitioners, without specific protocols and appropriate training, would be potentially harmful to individuals and detrimental to the field.

Meta-analysis of randomised controlled trials with N-acetylcysteine in the treatment of schizophrenia.

OBJECTIVE: There is accumulating evidence that adjunctive treatment with N-acetylcysteine may be effective for schizophrenia. This study aimed to conduct a comprehensive meta-analysis examining the efficacy of randomised control trials investigating N-acetylcysteine as an adjunct treatment for schizophrenia and the first to investigate cognition as an outcome. METHODS: We systematically reviewed Medline, EmCare, PsycINFO, Embase, CINAHL Complete, China Knowledge Resource Integrated Database and the Cochrane Clinical Trials online registry for randomised control trials of N-acetylcysteine for schizophrenia. We undertook pairwise meta-analyses of N-acetylcysteine vs placebo for psychosis symptoms and cognition. RESULTS: Seven studies, including n = 220 receiving N-acetylcysteine and n = 220 receiving placebo, met inclusion criteria for the pairwise meta-analyses. Positive and Negative Syndrome Scale negative and total scores were significantly improved in the N-acetylcysteine group after 24 weeks of treatment. The cognitive domain of working memory improved with N-acetylcysteine supplementation. CONCLUSION: Evidence supports the notion that N-acetylcysteine may be a useful adjunct to standard treatment for the improvement of schizophrenia symptoms, as well as the cognitive domain of working memory. Treatment effects were observed at the later time point (⩾24 weeks), suggesting that longer interventions are required for the success of N-acetylcysteine treatment.

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials.

The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from "nutrient supplements", such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta-analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta-review of this top-tier evidence, we identified, synthesized and appraised all meta-analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta-analyses of placebo-controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention-deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate-based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high-dose methylfolate in major depressive disorder. There was emergent evidence for N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence-based supplements, to further elucidate the underlying mechanisms.

Treatment Strategies for Clozapine-Induced Sialorrhea: A Systematic Review and Meta-analysis.

BACKGROUND: Clozapine is the most effective medication for treatment-refractory schizophrenia. However, it has a high burden of adverse events, including common adverse events such as sialorrhea. Sialorrhea can lead to severe physical complications such as aspiration pneumonia, as well as psychological complications including embarrassment and low self-esteem. Compromised adherence and treatment discontinuation can occur due to intolerability. There have been no meta-analyses examining strategies to mitigate clozapine-induced sialorrhea. METHODS: We systematically searched Chinese and Western research databases for randomised controlled trials examining agents for clozapine-induced sialorrhea. No limit to language or date were applied to the search. Where sufficient data for individual agents was available, pairwise meta-analyses were conducted. Results were provided as risk ratios and number needed to treat. Sensitivity analysis was conducted by study quality. Adverse events were provided as number needed to harm. RESULTS: 19 studies provided data for use in the meta-analysis. Improvement in clozapine-induced sialorrhea was seen in meta-analyses of propantheline (studies = 6, risk ratio [RR] 2.38, 95% confidence interval [CI] 1.52-3.73; number needed to treat [NNT] 3, 95% CI 1.9-2.7), diphenhydramine (studies = 5, RR 3.09, 95% CI 2.36-4.03; NNT 2, 95% CI 1.5-2.0), chlorpheniramine (studies = 2, RR 2.37, 95% CI 1.59-3.55; NNT 3, 95% CI 1.6-3.5), and benzamide derivatives (odds ratio [OR] 6.93, 95% CI 3.03-15.86). When meta-analyses were limited to high-quality studies, all these results remained significant. Single studies of benzhexol, cyproheptadine, doxepin and Kongyan Tang showed promise. Propantheline increased rates of constipation with a number needed to harm (NNH) of 9 (95% CI 4.2-204.1). CONCLUSION: Clozapine-induced sialorrhea is a potentially serious adverse event. Included studies in this meta-analysis were limited by poor study quality. Diphenhydramine, chlorpheniramine and benzamide derivatives appear to have the best supporting evidence and lowest reported adverse events. Caution should be exercised when using propantheline given its increased risk of constipation.

Mania associated with self-prescribed acetyl-l-carnitine in a man with bipolar I disorder.

OBJECTIVE: Complementary medicines are readily available and becoming increasingly popular. Acetyl-l-carnitine (ALC) is widely recognised as a safe dietary supplement to aid weight loss. We present the case of a patient who had a relapse of mania in the context of ALC use for weight loss over a two week period, on the background of bipolar I disorder previously in remission. The patient's symptoms resolved a few days after ALC was ceased. CONCLUSIONS: Given the high rates of obesity among people with mental illness, it is possible ALC may be utilised in the hope of aiding weight loss. This case highlights the importance of psychiatrists maintaining open communication with their patients about use of complementary medicines, and the risks and benefits of their use.

An evidence-based scale for the antecedents of depressive symptoms in Australian adults.

OBJECTIVE: To develop and test a self-reported scale designed to measure the antecedents of depression. METHODS: Participants of the Sustainable Mastery of Innovative Lifelong Exercise (SMILE) Tai Chi program were invited to complete the scale for antecedents of depressive symptoms. The scale included questions regarding events/factors the participants have experienced over the past three months and preceded their depressive symptoms. The reliability of the questions was assessed using the Cronbach's alpha. Principal components analysis was used to examine if there were domains of interest across the scale questions. RESULTS: A total of 126 participants completed the scale. The scale had a good internal consistency (Cronbach's α = 0.82). Principal components analysis identified three components (life events, psychosocial problems, and physical/health problems) in the scale and the components detected the root categories of depression in more than 56% of the cases. CONCLUSIONS: This simple self-administered scale has proven to provide a reliable measure for the antecedent factors of depression in the SMILE Tai Chi cohort; further validation of the scale in different settings is encouraged.

A systematic review and meta-analysis of the effects of Qigong and Tai Chi for depressive symptoms.

BACKGROUND: Qigong and Tai Chi are the two most popular traditional Chinese exercises, known as mind-body movement therapies. Previous studies suggest that Qigong and Tai Chi may be beneficial in reducing depressive symptoms. This was the first study to systematically review and compare the effects of Qigong and Tai Chi on depressive symptoms. METHODS: A systematic search of six electronic databases was undertaken through to February 2014, for randomized controlled trials (RCTs) which reported depressive symptoms measured by a depressive symptom rating scale. The standardized mean difference in depressive symptoms score between Qigong or Tai Chi and a control group (at the end of follow-up) was extracted as a primary outcome. The secondary outcome was the standardized mean gain in symptom score (SMG) relative to the baseline from individual arms of the RCTs for various forms of care including Qigong, Tai Chi, usual care, other exercise, education and miscellaneous interventions. RESULTS: Thirty studies with a total of 2328 participants (823 males and 1505 females) were included. A significant effect was found for the Qigong interventions (Cohen's d -0.48 95% CI -0.48 to -0.12; SMG -0.52, 95% CI -0.79 to -0.26). There was no significant effect seen for Tai Chi for the primary endpoint. No mean change in symptom scores were seen for Tai Chi, usual care, other exercises, education and the 'miscellaneous' group in pre-post assessment in single arms. The Qigong results were found to be robust in sensitivity analyses. CONCLUSIONS: Qigong appears to be beneficial for reducing depressive symptom severity. However, given the low quality of the included studies and the documented evidence of publication bias, these results should be viewed cautiously.