Showing papers in "Australian and New Zealand Journal of Psychiatry in 2022"

Growth in emergency department self-harm or suicidal ideation presentations in young people: Comparing trends before and since the COVID-19 first wave in New South Wales, Australia

Abstract: Introduction: Self-harm presentations in children and young people have increased internationally over the last decade. The COVID-19 pandemic has the potential to worsen these trends. Objective: To describe trends in emergency department self-harm or suicidal ideation presentations for children and young people in New South Wales before and since the COVID-19 pandemic. Methods: We studied presentations for self-harm or suicidal ideation by 10- to 24-year-olds to New South Wales emergency departments, using interrupted time series analysis to compare annualised growth before COVID (2015 to February 2020) and since COVID (March 2020 to June 2021). Subgroup analyses compared age group, gender, triage category, rurality and disadvantage. Time series decomposition via generalised additive models identified long-term, seasonal and short-term trends. Results: Self-harm or suicidal ideation presentations by young people in New South Wales increased by 8.4% per annum pre-COVID. Growth accelerated since COVID, to 19.2% per annum, primarily due to increased presentations by females aged 13–17 years (47.1% per annum since COVID, from 290 per 10,000 in 2019 to 466 per 10,000 in 2021). Presentations in males aged 10–24 years did not increase since COVID (105.4 per 10,000 in 2019, 109.8 per 10,000 in 2021) despite growing 9.9% per annum before COVID. Presentation rates accelerated significantly in socio-economically advantaged areas. Presentations in children and adolescents were strongly linked to school semesters. Conclusion: Emergency department self-harm or suicidal ideation presentations by New South Wales young people grew steadily before COVID. Understanding the sustained increase remains a priority. Growth has increased since COVID particularly for adolescent females, but not among adolescent males. Surprisingly, the largest post-COVID increases in annual growth occurred in socio-economically advantaged and urban regions. The COVID-19 pandemic appears to have added new challenges, particularly in females in the developmentally critical early adolescent and teenage years.

Thoughts of suicide or self-harm among Australian healthcare workers during the COVID-19 pandemic

Abstract: Objective: To identify the prevalence and predictors of (a) thoughts of suicide or self-harm among healthcare workers during the COVID-19 pandemic and (b) help-seeking among those healthcare workers with thoughts of suicide or self-harm. Method: Analysis of data from the Australian COVID-19 Frontline Healthcare Workers Study, an online survey of healthcare workers conducted during the second wave of the COVID-19 pandemic in Australia. Outcomes of interest were thoughts of suicide or self-harm as measured through the Patient Health Questionnaire for depression and help-seeking behaviours. Results: Overall, 819 (10.5%) of 7795 healthcare workers reported thoughts of suicide or self-harm over a 2-week period. Healthcare workers with these thoughts experienced higher rates of depression, anxiety, post-traumatic stress disorder and burnout than their peers. In multivariable models, the odds of suicide or self-harm thoughts were higher among workers who had friends or family infected with COVID-19 (odds ratio = 1.24, 95% confidence interval = [1.06, 1.47]), were living alone (odds ratio = 1.32, 95% confidence interval = [1.06, 1.64]), younger (⩽30 years cf. >50 years; odds ratio = 1.70, 95% confidence interval = 1.36-2.13), male (odds ratio = 1.81, 95% confidence interval = [1.49, 2.20]), had increased alcohol use (odds ratio = 1.58, 95% confidence interval = [1.35, 1.86]), poor physical health (odds ratio = 1.62, 95% confidence interval = [1.36, 1.92]), increased income worries (odds ratio = 1.81, 95% confidence interval = [1.54, 2.12]) or prior mental illness (odds ratio = 3.27, 95% confidence interval = [2.80, 3.82]). Having dependent children was protective (odds ratio = 0.75, 95% confidence interval = [0.61, 0.92]). Fewer than half (388/819) of the healthcare workers who reported thoughts of suicide or self-harm sought professional support. Healthcare workers with thoughts of suicide or self-harm were more likely to seek support if they were younger (⩽30 years cf. >50 years; odds ratio = 1.78, 95% confidence interval = [1.13, 2.82]) or had prior mental health concerns (odds ratio = 4.47, 95% confidence interval = [3.25, 6.14]). Conclusion: One in 10 Australian healthcare workers reported thoughts of suicide or self-harm during the pandemic, with certain groups being more vulnerable. Most healthcare workers with thoughts of suicide or self-harm did not seek professional help. Strong and sustained action to protect the safety of healthcare workers, and provide meaningful support, is urgently needed.

Who are hikikomori? Demographic and clinical features of hikikomori (prolonged social withdrawal): A systematic review

Abstract: Objective: This review, which was registered with PROSPERO (CRD42021237988), aimed to systematically extract common elements in the hikikomori definition or criteria applied by researchers and examine cultural differences and chronological changes in the demographic characteristics of hikikomori individuals such as age, gender and hikikomori duration. Method: For inclusion in the review, the hikikomori criteria, age and gender of the hikikomori individuals had to be specified, and the article had to be peer-reviewed and written in Japanese or English, focusing on hikikomori individuals or their families. Case studies, reviews and qualitative studies were excluded. Results: The total sample size for the 52 studies included in the review was 4744. Over 80% of the studies included the elements ‘not working or attending school’, ‘not socializing outside one’s home’ and ‘duration of hikikomori’ in their hikikomori criteria, and many studies included the element ‘staying at home on most days except solitary outings’. A cross-temporal meta-analysis showed the possibility that the age of hikikomori individuals increased chronologically (β = 0.44, B = 0.50, 95% confidence interval = [0.16, 0.84]). Comparisons weighted by sample size between Japan and other countries showed the possibility that the age of hikikomori individuals was higher (d = 0.32), the percentage of males was lower (d = 0.91) and the hikikomori duration was shorter (d = 2.06) in studies conducted in countries other than Japan. However, many of the included studies had a high risk of selection bias, and this bias may have influenced the results obtained. Thus, the results of this study may represent the researcher’s perception of hikikomori rather than accurately representing the actual condition of hikikomori. Conclusion: Researchers should specifically identify similarities and differences in the clinical picture of hikikomori and compare the studies to organize the findings derived from studies focusing on hikikomori.

The challenges ahead for psychedelic ‘medicine’

Abstract: With the extensive public, commercial and scientific interest from what has been widely termed the psychedelic renaissance, it is important that the scientific practices and results obtained from its implementation into medicine are put under a critical microscope. While there are numerous works on the potential benefits and applications of psychedelics as medicines, relatively little has been written about the challenges this field will face when incorporated into modern medical practice. Indeed, as a new or at least revived area of investigation, psychedelic medicine has a particular set of challenges which need to be addressed. In this viewpoint, we identify a number of these challenges. First, challenges related to the design of individual research studies are discussed, particularly focusing on current practices surrounding blinding, expectancy, the use of therapy and sources of bias. Second, the broader context of the research environment is considered, including how medical science typically establishes evidence, funding bodies and the impact of psychedelics being scheduled at odds with their risk profile. Finally, we describe challenges relating to the implementation of psychedelic therapies into modern medicine, considering the social and economic context. Alongside, we provide suggestions for what could be included into current research protocols to mitigate these challenges.

Changes in antidepressant use in Australia: A nationwide analysis (2015–2021)

Abstract: Background: Depression and anxiety affect 4–14% of Australians every year; symptoms may have been exacerbated during the COVID-19 pandemic. We examined recent patterns of antidepressant use in Australia in the period 2015–2021, which includes the first year of the pandemic. Methods: We used national dispensing claims for people aged ⩾10 years to investigate annual trends in prevalent and new antidepressant use (no antidepressants dispensed in the year prior). We conducted stratified analyses by sex, age group and antidepressant class. We report outcomes from 2015 to 2019 and used time series analysis to quantify changes during the first year of the COVID-19 pandemic (March 2020–February 2021). Results: In 2019, the annual prevalence of antidepressant use was 170.4 per 1000 women and 101.8 per 1000 men, an increase of 7.0% and 9.2% from 2015, respectively. New antidepressant use also increased for both sexes (3.0% for women and 4.9% for men) and across most age groups, particularly among adolescents (aged 10–17 years; 46–57%). During the first year of the COVID-19 pandemic, we observed higher than expected prevalent use (+2.2%, 95% CI = [0.3%, 4.2%]) among females, corresponding to a predicted excess of 45,217 (95% CI = [5,819, 84,614]) females dispensed antidepressants. The largest increases during the first year of the pandemic occurred among female adolescents for both prevalent (+11.7%, 95% CI = [4.1%, 20.5%]) and new antidepressant use (+15.6%, 95% CI = [8.5%, 23.7%]). Conclusion: Antidepressant use continues to increase in Australia overall and especially among young people. We found a differential impact of the COVID-19 pandemic in treated depression and anxiety, greater among females than males, and greater among young females than other age groups, suggesting an increased mental health burden in populations already on a trajectory of increased use of antidepressants prior to the pandemic. Reasons for these differences require further investigation.

Clinical correlates of comorbid attention deficit hyperactivity disorder in adults suffering from bipolar disorder: A meta-analysis

Abstract: Objective: Attention deficit hyperactivity disorder is a frequent comorbid condition in adults with bipolar disorder. We performed a meta-analysis aimed at assessing sociodemographic and clinical correlates of attention deficit hyperactivity disorder in bipolar disorder. Method: We searched main electronic databases up to June 2021. Random-effects meta-analyses, with relevant meta-regression and quality-based sensitivity analyses, were carried out to estimate the association between attention deficit hyperactivity disorder and putative correlates, grading the quality of evidence. Results: We included 43 studies, based on 38 independent samples. Attention deficit hyperactivity disorder participants were more likely to be males (odds ratio = 1.46; p < 0.001) and unemployed (odds ratio = 1.45; p = 0.045), and less likely to be married (odds ratio = 0.62; p = 0.014). They had an earlier onset of bipolar disorder (standardized mean difference = −0.36; p < 0.001); more mood episodes (standardized mean difference = 0.35; p = 0.007), particularly depressive (standardized mean difference = 0.30; p = 0.011) and mixed (standardized mean difference = 0.30; p = 0.031) ones; higher odds of using antidepressants (odds ratio = 1.80; p = 0.024) and attempted suicides (odds ratio = 1.83; p < 0.001) and lower odds of psychotic features (odds ratio = 0.63; p = 0.010). Moreover, they were more likely to have generalized anxiety disorder (odds ratio = 1.50; p = 0.019), panic disorder (odds ratio = 1.89; p < 0.001), social phobia (odds ratio = 1.61; p = 0.017), eating disorders (odds ratio = 1.91; p = 0.007), antisocial personality disorder (odds ratio = 3.59; p = 0.004) and substance (odds ratio = 2.29; p < 0.001) or alcohol (odds ratio = 2.28; p < 0.001) use disorders. Quality of the evidence was generally low or very low for the majority of correlates, except for bipolar disorder onset and alcohol/substance use disorders (high), and suicide attempts (moderate). Conclusion: Comorbid bipolar disorder/attention deficit hyperactivity disorder may have some distinctive clinical features including an earlier onset of bipolar disorder and higher comorbid alcohol/substance use disorder rates. Further research is needed to identify additional clinical characteristics of this comorbidity.

Cortisol and α-amylase awakening response in children and adolescents with functional neurological (conversion) disorder

Abstract: Objective: Stress system dysregulation is considered to have an important role in the aetiology of paediatric functional neurological (conversion) disorder. This study examined salivary cortisol and α-amylase awakening responses in children with functional neurological disorder to determine activation patterns of the hypothalamic–pituitary–adrenal axis and sympathetic system. A healthy cortisol awakening response involves a robust increase in cortisol within 30 minutes of awakening. Alpha-amylase awakening response is variable in children. Methods: Cortisol and α-amylase were measured in saliva from 32 patients with functional neurological disorder (26 girls and 6 boys, aged 11.3−16.1 years) and 31 healthy controls (23 girls and 8 boys, aged 8.6–17.7 years). Saliva samples were collected using a Salivette sampling device at two time points – upon awakening and 30 minutes after awakening. Results: Patients with functional neurological disorder showed a decrease in cortisol awakening response (–4 nmol.min/L) and controls showed an increase (107 nmol.min/L), t(55) = –.4.6, p < 0.001. Within the functional neurological disorder group, 57% showed an attenuated cortisol awakening response and 43% showed an obliterated/reversed cortisol awakening response: Cortisol awakening response was negatively correlated with adverse childhood experiences, r(58) = –0.6, p = 0.002, and subjective distress (total Depression Anxiety and Stress Scales score), r(58) = –0.4, p = 0.050. In controls, cortisol awakening response showed no correlation with adverse childhood experiences and a positive correlation with subjective distress, r(56) = 0.4, p = 0.023. Total cortisol remained similar between the functional neurological disorder and control group. No significant differences were observed between the functional neurological disorder and control group in any of the α-amylase analyses. Discussion: The results suggest dysregulation of the hypothalamic–pituitary–adrenal axis in children with functional neurological disorder. Hypothalamic–pituitary–adrenal dysregulation in children with functional neurological disorder may contribute to comorbid symptoms of fatigue, sleep disturbance and subjective loss of well-being because circadian rhythms and energy metabolism are disrupted. Hypothalamic–pituitary–adrenal dysregulation – and changes in glucocorticoid (cortisol) signalling at the molecular level – may also contribute to increased vulnerability for functional neurological disorder symptoms because of epigenetically mediated changes to neural networks implicated in functional neurological disorder.

A systematic literature review and meta-analysis of the effect of psilocybin and methylenedioxymethamphetamine on mental, behavioural or developmental disorders

Abstract: Objectives: There is an increasing interest in combining psilocybin or methylenedioxymethamphetamine with psychological support in treating psychiatric disorders. Although there have been several recent systematic reviews, study and participant numbers have been limited, and the field is rapidly evolving with the publication of more studies. We therefore conducted a systematic review of PubMed, MEDLINE, PsycINFO, the Cochrane Central Register of Controlled Trials, Embase, and CINAHL for randomised controlled trials of methylenedioxymethamphetamine and psilocybin with either inactive or active controls. Methods: Outcomes were psychiatric symptoms measured by standardised, validated and internationally recognised instruments at least 2 weeks following drug administration, Quality was independently assessed using the Cochrane risk of bias assessment tool and Grading of Recommendations Assessment, Development and Evaluation framework. Results: There were eight studies on methylenedioxymethamphetamine and six on psilocybin. Diagnoses included post-traumatic stress disorder, long-standing/treatment-resistant depression, obsessive-compulsive disorder, social anxiety in adults with autism, and anxiety or depression in life-threatening disease. The most information and strongest association was for the change in methylenedioxymethamphetamine scores compared to active controls in post-traumatic stress disorder (k = 4; standardised mean difference = −0.86; 95% confidence interval = [−1.23, −0.50]; p < 0.0001). There were also small benefits for social anxiety in adults with autism. Psilocybin was superior to wait-list but not niacin (active control) in life-threatening disease anxiety or depression. It was equally as effective as escitalopram in long-standing depression for the primary study outcome and superior for most of the secondary outcomes in analyses uncorrected for multiple comparisons. Both agents were well tolerated in supervised trials. Trial quality varied with only small proportions of potential participants included in the randomised phase. Overall certainty of evidence was low or very low using the Grading of Recommendations Assessment, Development and Evaluation framework. Conclusion: Methylenedioxymethamphetamine and psilocybin may show promise in highly selected populations when administered in closely supervised settings and with intensive support.

Stigma in bipolar disorder: A current review of the literature

Abstract: Stigma has been found to have an impact on those living with bipolar disorder, with many experiencing negative consequences of stereotypes, prejudice and discrimination as a result of their condition. The aim of this review was to assess the current literature in bipolar disorder to determine the impact of stigma on people living with this condition and caregivers. Public stigma was associated with greater functional impairment, anxiety and poorer work-related outcomes, while self-stigma was also found to be associated with lower levels of functioning across a range of domains and greater depressive and anxiety symptoms. For those with bipolar disorder, public stigma was reported at similar rates to those with schizophrenia and depression in some studies, with other studies noting mixed results. Qualitative studies noted that public stigma and discrimination were experienced from family, friends and healthcare providers. Self-stigma was found to be higher for those who were younger in several studies and associated with worse medication adherence. It was generally found to be higher in bipolar disorder participants than in those with anxiety disorders and lower than those with personality disorders. Limitations of the current research include the following: few studies have used a longitudinal design, few have assessed the impact of stigma on medication adherence and few have explored these issues in younger populations. More research is needed to explore the experiences of self-stigma for those in the younger age group specifically, given the relationship between younger age and greater self-stigma noted in several studies and the relationship between this and lower treatment adherence.

Prevalence and determinants of mental health related to climate change in Australia

Abstract: Aims: The climate emergency will likely prove this century’s greatest threat to public health within which mental health effects need consideration. While studies consistently show the majority of Australians are very concerned about the impacts of climate change, there is limited evidence from nation-wide research linking climate change with mental health burden in sub-populations. This study aimed to understand the impact of climate change on mental health in the Australian population and identify populations who are most at risk of climate-related mental health burden. Methods: A nation-wide Australian survey conducted between August and November 2020 of adults was approximately representative across sex, age, location, state and area disadvantage. Two-stage recruitment involved unrestricted self-selected community sample through mainstream and social media ( N = 4428) and purposeful sampling using an online panel ( N = 1055). Results: Most Australians report having a direct experience of a climate change–related event. Young people are experiencing significant rates of eco-anxiety. One in four people with direct experience of a climate change–related event met post-traumatic stress disorder screening criteria. People who have not had a direct experience are showing symptoms of pre-trauma, particularly in younger age groups and women. There were 9.37% (503/5370) of respondents with responses indicating significant eco-anxiety, 15.68% (370/2359) with pre-traumatic stress and 25.60% (727/2840) with post-traumatic stress disorder. Multivariable regressions confirmed that younger people are more affected by eco-anxiety and post-traumatic stress disorder (pre- or post-trauma); women are more affected by post-traumatic stress disorder (pre- or post-trauma) and those from more disadvantaged regions are more affected by eco-anxiety. Conclusion: Australia is facing a potential mental health crisis. Individuals with and without direct experience of climate change are reporting significant mental health impacts, with younger age groups being disproportionately affected. There are key roles for clinicians and other health professionals in responding to and preventing climate-related mental health burden.

Palliative psychiatry in a narrow and in a broad sense: A concept clarification

Abstract: Even with optimal treatment, some persons with severe and persistent mental illness do not achieve a level of mental health, psychosocial functioning and quality of life that is acceptable to them. With each unsuccessful treatment attempt, the probability of achieving symptom reduction declines while the probability of somatic and psychological side effects increases. This worsening benefit–harm ratio of treatment aiming at symptom reduction has motivated calls for implementing palliative approaches to care into psychiatry (palliative psychiatry). Palliative psychiatry accepts that some cases of severe and persistent mental illness can be irremediable and calls for a careful evaluation of goals of care in these cases. It aims at reducing harm, relieving suffering and thus improving quality of life directly, working around irremediable psychiatric symptoms. In a narrow sense, this refers to patients likely to die of their severe and persistent mental illness soon, but palliative psychiatry in a broad sense is not limited to end-of-life care. It can – and often should – be integrated with curative and rehabilitative approaches, as is the gold standard in somatic medicine. Palliative psychiatry constitutes a valuable addition to established non-curative approaches such as rehabilitative psychiatry (which focuses on psychosocial functioning instead of quality of life) and personal recovery (a journey that persons living with severe and persistent mental illness may undertake, not necessarily accompanied by mental health care professionals). Although the implementation of palliative psychiatry is met with several challenges such as difficulties regarding decision-making capacity and prognostication in severe and persistent mental illness, it is a promising new approach in caring for persons with severe and persistent mental illness, regardless of whether they are at the end of life.

Receipt of evidence-based care for children and adolescents with anxiety in Australia

Abstract: Objective: Cognitive-behavioural therapy is recommended as the first-line treatment for children and adolescents with anxiety. Despite its efficacy, a recent United Kingdom study indicated that few children with anxiety disorders receive cognitive-behavioural therapy. The primary aim of this study was to examine the receipt of cognitive-behavioural therapy for children and adolescents with elevated anxiety symptoms in Australia. Second, this study also examined whether there was a difference in the type of treatment received based on socioeconomic status and geographical location. Method: Using self-reported questionnaires, parents of children aged 4–18 years and children aged 12–18 years (N = 784; elevated anxiety symptom sample n = 169) were recruited from four samples: community (n = 164), school (n = 177), clinic (n = 16) and online panel provider (n = 427). Participants reported on the child’s anxiety symptoms and the type of treatment (if any) the child received for their anxiety symptoms. Results: Results indicated that 19.5% of children and adolescents with elevated anxiety symptoms received evidence-based treatment (e.g. cognitive-behavioural therapy). Of those families who did seek help for anxiety in Australia, the majority (66.3%) did not receive cognitive-behavioural therapy. In addition, neither socioeconomic status (which was based on the Australian Index of Community Socio-Educational Advantage [ICSEA]) nor location (metropolitan vs regional/remote) affected whether individuals received evidence-based care or non-evidence-based care. Conclusion: Overall, children and adolescents in this study seeking support for their anxiety symptoms were not receiving adequate evidence-based care, regardless of socioeconomic status and location. These findings indicate there is a need to increase the receipt of cognitive-behavioural therapy for children and adolescents with anxiety symptoms. The findings should tentatively be interpreted, given data were collected during the COVID-19 pandemic.

Clinical wisdom, science and evidence: The neglected gifts of psychodynamic thinking

Abstract: We review five key areas of contemporary psychodynamic practice and research to highlight the contributions psychodynamic concepts can make to clinical psychiatry. These areas are as follows: (1) Contributions to understanding the development of subjectivity. (2) The psychodynamic understanding of the effects of early childhood trauma and their consequences in adult life. (3) The vital importance of the psychodynamic notion of the ‘holding environment’ based on an understanding of the dynamics of the development of subjectivity and trauma which, if applied, might improve the quality of psychiatric care in the public mental health system and enhance both the clinical competence and morale of clinicians in the system. (4) The emerging scientific disciplines of Neuropsychoanalysis and Affective Neuroscience, which illustrate the importance of seriously studying the mind as well as the brain. (5) A brief summary of some research into the clinical effectiveness and efficacy of psychoanalysis and its related psychodynamic therapies.

Patterns of attention deficit hyperactivity disorder medicine use in the era of new non-stimulant medicines: A population-based study among Australian children and adults (2013–2020)

Abstract: Background and aims: New therapeutic options such as lisdexamfetamine and guanfacine have recently become available for the treatment of attention deficit hyperactivity disorder. We described contemporary patterns of attention deficit hyperactivity disorder medicine use among children, adolescents and adults in Australia. Methods: This population-based study used dispensing data for a 10% random sample of Australian residents between July 2012 and December 2020. We estimated the annual prevalence and incidence of attention deficit hyperactivity disorder medicines, second-line guanfacine use and examined concurrent medicine use of both stimulants and non-stimulants. We followed incident users for up to 5 years and analysed treatment persistence using a novel proportion of people covered method. Analyses were stratified by attention deficit hyperactivity disorder medicine, sex and age group; young children (0–5 years), children (6–12 years), adolescents (13–17 years), young adults (18–24 years) and adults (⩾25 years). Results: We observed a twofold increase in the overall prevalence of attention deficit hyperactivity disorder medicine use between 2013 and 2020, from 4.9 to 9.7 per 1000 persons. Incident use also increased across all age groups and both sexes, with the most pronounced increases among adolescent females (from 1.4 to 5.3 per 1000 persons). Stimulant treatment persistence after 5 years was highest among those initiating treatment as young children (64%) and children (69%) and lowest among those initiating treatment in adolescence (19%). Concurrent use of stimulants and non-stimulants was more common among males and younger age groups. Most children (87%) initiating guanfacine had prior dispensings of attention deficit hyperactivity disorder medicines. Conclusion: We observed increasing attention deficit hyperactivity disorder medicine use in Australia, especially among young females. Nevertheless, treatment rates remain lower than the estimated prevalence of attention deficit hyperactivity disorder across all subpopulations. Poor long-term treatment persistence in adolescence may warrant improved clinical monitoring of attention deficit hyperactivity disorder in patients transitioning from paediatric to adult care. Reassuringly, use of newly approved guanfacine appeared to be in accordance with guidelines among children.

Telehealth use by mental health professionals during COVID-19

Abstract: Objective: To examine and describe telehealth use and attitudes among mental health professionals in Australia and New Zealand during the initial stages of the COVID-19 pandemic. Methods: Participants completed a brief online survey between May and July 2020. Participants were recruited via peak and professional organisations and through psychology-focused social media groups and networks. The survey examined frequency of telehealth use, reasons for non-use, telehealth modalities, prior use, attitudes towards use, plans for future use, and training, information or resource needs. Results: A total of 528 professionals (85.2% female) participated in the survey, of which 98.9% reported using telehealth and 32.2% reported using telehealth exclusively. Respondents were less likely to use telehealth if they worked with clients experiencing complex issues (e.g. trauma), had more hours of weekly client contact, had a choice about whether to use telehealth or felt less positive about using technology. Respondents were more likely to hold positive views towards telehealth if they were female, had used online programmes with clients previously, were frequent telehealth users and were comfortable using technology. Participants expressed mixed views on client safety and the impact of telehealth on therapeutic process and effectiveness. Conclusion: Telehealth has a clear and ongoing role within mental healthcare and there is a need for strong guidance for professionals on how to manage client risk, privacy, security and adapt therapy for delivery via telehealth. In particular, there is a need for individual-, organisational-, professional- and policy-level responses to ensure that telehealth remains a viable and effective healthcare medium into the future.

Clinical recommendations for the care of people with treatment-refractory obsessive-compulsive disorder when undergoing deep brain stimulation

Abstract: Deep brain stimulation is an emerging therapy for treatment-refractory obsessive-compulsive disorder patients. Yet, accessibility is limited, treatment protocols are heterogeneous and there is no guideline or consensus on the best practices. Here, we combine evidence from scientific investigations, expert opinions and our clinical expertise to propose several clinical recommendations from the pre-operative, surgical and post-operative phases of deep brain stimulation care for treatment-refractory obsessive-compulsive disorder patients. A person-centered and biopsychosocial approach is adopted. Briefly, we discuss clinical characteristics associated with response, the use of improved educational materials, an evaluative consent process, comprehensive programming by an expert clinician, a more global assessment of treatment efficacy, multi-disciplinary adjunct psychotherapy and the importance of peer support programs. Furthermore, where gaps are identified, future research suggestions are made, including connectome surgical targeting, scientific evaluation of hardware models and health economic data. In addition, we encourage collaborative groups of data and knowledge sharing by way of a clinical registry and a peer group of programming clinicians. We aim to commence a discussion on the determinants of deep brain stimulation efficacy for treatment-refractory obsessive-compulsive disorder patients, a rare and severe patient group, and contribute to more standardized and evidence-based practices.

Systematic review and meta-analysis of the placebo effect in panic disorder: Implications for research and clinical practice

Abstract: Objective: This review aimed to measure the degree of placebo response in panic disorder. Data Sources: We searched major databases up to 31 January 2021, for randomized pharmacotherapy trials published in English. Study Selection: A total of 43 studies met inclusion criteria to be in the analysis (with 174 separate outcome measurements). Data Extraction: Changes in outcome measures from baseline in the placebo group were used to estimate modified Cohen’s d effect size. Results: A total of 43 trials (2392 subjects, 174 outcomes using 27 rating scales) were included in the meta-analysis. Overall placebo effect size was 0.57 (95% confidence interval = [0.50, 0.64]), heterogeneity (I2: 96.3%). Higher placebo effect size was observed among clinician-rated scales compared to patient reports (0.75 vs 0.35) and among general symptom and anxiety scales compared to panic symptoms and depression scales (0.92 and 0.64 vs 0.56 and 0.54, respectively). There was an upward trend in effect size over the publication period (r = 0.02, p = 0.002) that was only significant among clinician-rated scales (r = 0.02, p = 0.011). There was no significant publication bias, Egger’s test (p = 0.08). Conclusion: We observed a substantial placebo effect size in panic disorder. This effect was more prominent for some aspects of panic disorder psychopathology than for others and was correlated with the source of the assessment and publication year. This finding has implications both for research design, to address the heterogeneity and diversity in placebo responses, and for clinical practice to ensure optimal quality of care. Systematic review registration number: PROSPERO, CRD42019125979.

Lithium plus antipsychotics or anticonvulsants for bipolar disorder: Comparing clinical response and metabolic changes

Abstract: Objective: Patients with bipolar disorder treated with lithium often require additional antipsychotics or anticonvulsants. However, the comparative effectiveness and safety of these agents as add-on to lithium has not been studied. Methods: This secondary analysis combined two similar 24-week trials on outpatients with bipolar disorder randomized to lithium (target serum level 0.4–0.6 mEq/L). Guideline-based adjunctive antipsychotics (Li+AP) and anticonvulsants (Li+AC) could be used if clinically indicated and was assessed at every study visit. Response was measured on the Clinical Global Impression scale and we performed adjusted mixed effects linear regression analyses. Analysis of variance tests compared metabolic measures including a binary diagnosis of metabolic syndrome before and after 24 weeks of treatment. Results: Among 379 outpatients (57% female, mean age 38 years, mean Clinical Global Impression 4.4), users of Li+AP (N = 50, primarily quetiapine and aripiprazole) improved to a similar degree (mean Clinical Global Impression improvement = 1.6, standard deviation = 1.5) as those using lithium-only (i.e. without adjunctive antipsychotics or anticonvulsants, N = 149, mean Clinical Global Impression improvement = 1.7, standard deviation = 1.4) (p = 0.59). Users of Li+AC (N = 107, primarily lamotrigine and valproate, mean Clinical Global Impression improvement = 1.2, standard deviation = 1.3) and users of Li+AP+AC (N = 73, mean Clinical Global Impression improvement = 1.1, standard deviation = 1.3) showed worse response compared to lithium-only users (all p < 0.01). When comparing Li+AP to Li+AC, users of Li+AP improved slightly better on general (p = 0.05) and manic symptoms (p = 0.01), but showed a worse development of glucose, triglycerides, and metabolic syndrome. Conclusion: Despite treatment-by-indication confounding, these findings are relevant for real-world treatment settings and emphasize the need for randomized trials on this clinically important topic.

Subjective cognitive complaints and subjective cognition following electroconvulsive therapy for depression: A systematic review and meta-analysis

Abstract: Background: Subjective cognitive complaints represent a leading reason for suboptimal prescription of electroconvulsive therapy, the most acutely effective treatment for depression. However, research findings regarding their presentation are conflicting. Objective: To describe, quantify and explain the variability in subjective cognitive complaints and subjective cognition following electroconvulsive therapy for depression. Methods: We searched systematically PubMed, Embase, PsycARTICLES, CINAHL and relevant reviews for research published from 1 January 1972 to 31 August 2020. We included all independent studies of patients whose subjective cognition was assessed following brief-pulse electroconvulsive therapy for depression. Three meta-analyses were conducted to quantify: (1) the prevalence of patients presenting with cognitive complaints following electroconvulsive therapy; (2) the pre–post electroconvulsive therapy change in subjective cognition and (3) the association between change in depressive symptoms and change in cognitive complaints. Effect sizes were calculated using random-effects models. Eight prespecified demographic and clinical moderators of between-study variability were assessed using sub-group analyses and meta-regressions. Results: Data from 72 studies including 5699 participants were meta-analysed. Weighted mean prevalence of patients with cognitive complaints was 48.1% (95% confidence interval = [42.3%, 53.9%]). The type of subjective measure used significantly impacted the pre–post electroconvulsive therapy change in subjective cognition, showing, respectively, large improvement (g = 0.81; 95% confidence interval = [0.59, 1.03]) after electroconvulsive therapy with the Squire Self-Rating Scale of Memory and small worsening (g = –0.48; 95% confidence interval = [–0.70, –0.26]) with 1-item memory scales. The strongest predictors of improved post-electroconvulsive therapy subjective cognition were increased age and larger post-electroconvulsive therapy decrease in depressive symptoms. The weighted mean correlation between pre–post electroconvulsive therapy decrease in depressive symptoms and pre–post electroconvulsive therapy decrease in cognitive complaints was 0.46 (95% confidence interval = [0.39, 0.53]). Conclusion: Variability in subjective cognition following electroconvulsive therapy is mostly explained by the degree of post-treatment persisting depression and by the subjective assessment used. Scales measuring exclusively subjective worsening present limited clinical utility and instruments allowing the detection of both improvement and worsening in subjective cognition should be preferred.

A systematic review of evidence-based aftercare for older adults following self-harm

Abstract: Objective: Self-harm is closely associated with suicide in older adults and may provide opportunity to intervene to prevent suicide. This study aimed to systematically review recent evidence for three components of aftercare for older adults: (1) referral pathways, (2) assessment tools and safety planning approaches and (3) engagement and intervention strategies. Methods: Databases PubMed, Medline, PsychINFO, Embase and CINAHL were searched from January 2010 to 10 July 2021 by two reviewers. Empirical studies reporting aftercare interventions for older adults (aged 60+) following self-harm (including with suicidal intent) were included. Full text of articles with abstracts meeting inclusion criteria were obtained and independently reviewed by three authors to determine final studies for review. Two reviewers extracted data and assessed level of evidence (Oxford) and quality ratings (Alberta Heritage Foundation for Medical Research Standard Quality Assessment Criteria for quantitative and Attree and Milton checklist for qualitative studies), working independently. Results: Twenty studies were reviewed (15 quantitative; 5 qualitative). Levels of evidence were low (3, 4), and quality ratings of quantitative studies variable, although qualitative studies rated highly. Most studies of referral pathways were observational and demonstrated marked variation with no clear guidelines or imperatives for community psychiatric follow-up. Of four screening tools evaluated, three were suicide-specific and one screened for depression. An evidence-informed approach to safety planning was described using cases. Strategies for aftercare engagement and intervention included two multifaceted approaches, psychotherapy and qualitative insights from older people who self-harmed, carers and clinicians. The qualitative studies identified targets for improved aftercare engagement, focused on individual context, experiences and needs. Conclusion: Dedicated older-adult aftercare interventions with a multifaceted, assertive follow-up approach accompanied by systemic change show promise but require further evaluation. Research is needed to explore the utility of needs assessment compared to screening and evaluate efficacy of safety planning and psychotherapeutic approaches.

Correlates of suicidality in young people with depressive disorders: A systematic review

Abstract: Objective: Depression is one of the most prevalent and disabling mental health conditions among young people worldwide. The health and economic burdens associated with depressive illness are substantial. Suicide and depression are closely intertwined, yet a diagnosis of depression itself lacks predictive specificity for suicidal behaviour. To better inform suicide prevention and early intervention strategies for young people, improved identification of modifiable intervention targets is needed. The objective of this review was to identify clinical, psychosocial and biological correlates of suicidality in young people diagnosed with a broad range of unipolar and bipolar depressive disorders. Method: Systematic searches were conducted across MEDLINE, Embase and PsycINFO to identify studies of young people aged 15–25 years diagnosed with unipolar or bipolar depressive disorders. An assessment of suicidality was required for inclusion. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 and Synthesis Without Meta-analysis guidelines. Results: We integrated findings from 71 studies including approximately 24,670 young people with clinically diagnosed depression. We identified 26 clinical, psychosocial and biological correlates of suicidality. Depression characteristics (type and severity), psychiatric comorbidity (particularly anxiety and substance use disorders) and neurological characteristics emerged as having the most evidence for being associated with suicidal outcomes. Our ability to pool data and conduct meaningful quantitative synthesis was hampered by substantial heterogeneity across studies and incomplete reporting; thus, meta-analysis was not possible. Conclusion: Findings of this review reinforce the notion that suicidality is a complex phenomenon arising from the interplay of multiple contributing factors. Our findings question the utility of considering a diagnosis of depression as a specific risk factor for suicidality in young people. Suicidality itself is transdiagnostic; adoption of a transdiagnostic approach to investigating its aetiology and treatment is perhaps warranted. Future research investigating specific symptoms, or symptom networks, might help to further our understanding of suicidality among young people experiencing mental illness.

Is burnout simply a stress reaction?

Abstract: Whether burnout is synonymous with stress is a question of clinical importance when considering the nosological status and management of both states. The biological changes associated with both stress and burnout suggest considerable overlap. However, we argue that the widespread acceptance by the lay community of burnout as a distinct and relatable syndrome suggests it is worthy of independent designation.

The prevalence of self-reported mental illness among those imprisoned in New South Wales across three health surveys, from 2001 to 2015

Abstract: Objective: The prevalence of mental illness among those in prison is much higher than in the community; however, very few studies have examined whether rates have changed over time, in line with increasing self-reported rates in the community. Methods: This study compares the prevalence of self-reported mental illness, self-harm and suicidal thoughts/behaviours, and drug and alcohol use across three waves (2001, 2009 and 2015) of health surveys involving men and women in New South Wales prisons and compared these rates with published community-level findings. Results: The prevalence of those reporting any mental health diagnosis increased significantly across the three surveys, even after adjustment for socio-demographic and criminal justice variables that also changed over time. Individuals surveyed in 2015 were more likely to report a mental health diagnosis than those surveyed in 2001 (adjusted odds ratio = 2.66, 95% confidence interval = [2.16, 3.27]). The prevalence of self-harm and suicidal thoughts and behaviours remained stable across the three surveys, while self-reported regular drug use decreased over the period. Women experienced a far greater burden of mental illness than men across all three surveys and experienced more growth in the prevalence of most psychiatric disorders. Conclusion: These findings have important implications for public and prison health systems given the poor social, health and criminal justice outcomes of those imprisoned with mental illness, both in custody and post-release.

Smoke and mirrors: Support from psychiatrists for nicotine e-cigarette availability in Australia

Abstract: The Royal Australian and New Zealand College of Psychiatrists’ (RANZCP) 2018 position statement supports increased, regulated availability of e-cigarettes (ECs) as a harm-reduction measure and recommends further research into their use. Aligned with this recommendation, we aimed to critically evaluate the RANZCP’s stance on this issue through a literature review focused on the areas identified in the position statement as requiring further investigation: (1) the adverse health effects attributable to ECs; (2) use of ECs for smoking cessation (particularly for people living with severe mental illness); and (3) EC-associated risks for nicotine naïve young people. We identified and summarised evidence of harm attributable to ECs that is particularly relevant to young people through direct adverse health sequelae, onset of nicotine dependence and increased risk of combustible cigarette (CC) use. A small number of studies suggest ECs can be used for harm-reduction purposes in people diagnosed with nicotine dependence and severe mental illness. However, these results must be considered alongside robust evidence supporting the effectiveness of existing pharmacological interventions for smoking cessation in people with severe mental illness. The position statement is in urgent need of review in line with the available evidence.

Rapid and unequal decline in adolescent mental health and well-being 2012–2019: Findings from New Zealand cross-sectional surveys

Abstract: Objective: To investigate prevalence and trends in key mental health and well-being indicators among New Zealand secondary school students. Methods: Representative cross-sectional youth health surveys with 2–4% of the New Zealand secondary school population were conducted in 2001, 2007, 2012 and 2019 (total n = 34,548). Results: In 2019, 69.1% reported good well-being (95% confidence interval = [67.6, 70.6]; World Health Organization 5-item), 22.8% reported clinically significant depression symptoms (95% confidence interval = [21.4, 24.1]; Reynolds Adolescent Depression Scale–Short Form) and 41.8% reported possible anxiety symptoms (95% confidence interval = [40.5, 43.2]; Generalized Anxiety Disorder 2, adapted). Past-year prevalence of periods of low mood (38.3%, 95% confidence interval = [36.6, 40.1]), deliberate self-harm (24.1%, 95% confidence interval = [22.8, 25.4]), suicide thoughts (20.8%, 95% confidence interval = [19.2, 22.4]) and suicide attempts (6.3%, 95% confidence interval = [5.5, 7.0]) were observed. After relative stability from 2001 to 2012, there were large declines in mental health to 2019. The proportion reporting good well-being decreased (odds ratio 0.71, 95% confidence interval = [0.65, 0.78], p < 0.001), depression symptoms increased (odds ratio 1.96, 95% confidence interval = [1.75, 2.20], p < 0.001) and past-year suicide thoughts and suicide attempts increased (odds ratio 1.41, 95% confidence interval = [1.25, 1.59], p < 0.001; odds ratio 1.60, 95% confidence interval = [1.32, 1.92], p < 0.001). Past-year deliberate self-harm was largely stable. Declines in mental health were unevenly spread and were generally greater among those with higher need in 2012 (females, Māori and Pacific students and those from higher deprivation neighbourhoods), increasing inequity, and among Asian students. Conclusion: Adolescent mental health needs are high in New Zealand and have increased sharply from 2012 among all demographic groups, especially females, Māori, Pacific and Asian students and those from high-deprivation neighbourhoods. Ethnic and socioeconomic disparities have widened.

The evidence for the use of long-term benzodiazepines in the setting of treatment-refractory anxiety disorders

Abstract: American Psychiatric Association (APA) (1990) Benzodiazepine Dependence, Toxicity, and Abuse: A Task Force Report of the American Psychiatric Association (APA). APA. Available at: https:// books.google.com.au/books?id=FoTursyqFP8C (accessed 2021). Calcaterra NE and Barrow JC (2014) Classics in chemical neuroscience: Diazepam (valium). ACS Chemical Neuroscience 5(4): 253–260. Committee on the Review of Medicines (CRM) (1980) Systematic review of the benzodiazepines: Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. Committee on the Review of Medicines. British Medical Journal 280(6218): 910. Greenblatt D, Shader R, Divoll M, et al. (1981) Benzodiazepines: A summary of pharmacokinetic properties. British Journal of Clinical Pharmacology 11: 11S–16S. Hollister LE (1981) Benzodiazepines: An overview. British Journal of Clinical Pharmacology 11: 117S–119S. Laughren TP, Battey Y, Greenblatt DJ, et al. (1982) A controlled trial of diazepam withdrawal in chronically anxious outpatients. Acta Psychiatrica Scandinavica 65: 171–179. Maletzky BM and Klotter J (1976) Addiction to diazepam. International Journal of the Addictions 11: 95–115. Marks J (1983) The benzodiazepines: An international perspective. Journal of Psychoactive Drugs 15: 137–149. Rickels K (1983) Benzodiazepines in emotional disorders. Journal of Psychoactive Drugs 15: 49–54. Silberman E, Balon R, Starcevic V, et al. (2020) Benzodiazepines: It’s time to return to the evidence. The British Journal of Psychiatry 218: 125–127. Sullivan W (1963) WARNING IS ISSUED ON TRANQUILIZERS; Some of most popular drugs can be addictive, expert tells science meeting BUT VALUE IS STRESSED doctor at U.S. Center cites usefulness, but declares caution is necessary six are specified increases in doses WARNING IS ISSUED ON TRANQUILIZERS. New York Times, 30 December, p. 23. Tibrewal P, Haeusler C, Kanigere MK, et al. (2021a) Are the benefits of benzodiazepines for anxiety disorders underestimated and their risks overestimated? Australian and New Zealand Journal of Psychiatry 55: 1109–1110. Vorspan F, Barré T, Pariente A, et al. (2018) Faut-il limiter la durée des traitements par benzodiazépines ? La Presse Médicale 47(10): 892–898.

Pathways to care for first-generation migrants with first episode psychosis in northwestern metropolitan Melbourne

Abstract: Objective: Understanding the pathways to care for migrants experiencing a first episode of psychosis is important, as they are more likely to experience longer delays to treatment and negative experiences, such as involuntary treatment. Despite the increased risk of developing a psychotic illness and barriers associated with pathways to care, there are limited studies exploring pathways to care in migrants in Australia. This study seeks to examine pathways to care for young people with a first episode of psychosis to a publicly funded youth mental health service. Methods: This study included all young people aged 15–24 years who presented with a first episode of psychosis to the Early Psychosis Prevention and Intervention Centre (EPPIC) between 1 February 2011 and 31 December 2016. Referral sources and place of birth were recorded at the time of presentation. The severity of psychotic symptoms was rated at baseline. Results: A total of 1220 young people presented with a first episode of psychosis during the study period, including 293 (24.5%) first-generation migrants. First-generation migrants with a first episode of psychosis were more likely to be admitted to hospital than Australian-born youth (odds ratio = 1.67, 95% confidence interval = [1.27, 2.18], p < 0.001) and this remained significant when controlled for demographic (adjusted odds ratio = 1.41, 95% confidence interval = [1.07, 1.88], p = 0.016) and clinical factors (adjusted odds ratio = 1.38,95% confidence interval = [1.01, 1.89], p = 0.044). First-generation migrants were also more likely to have an involuntary admission (odds ratio = 1.67, 95% confidence interval = [1.26, 2.21], p < 0.001) and this remained significant when controlled for demographic (adjusted odds ratio = 1.42, 95% confidence interval = [1.05, 1.91], p = 0.022) and clinical factors (adjusted odds ratio = 1.50, 95% confidence interval = [1.08, 2.09], p = 0.017). Migrants had more severe delusions (p = 0.005), bizarre behavior (p < 0.001) and positive formal thought disorder (p = 0.003) at the time of presentation. Migrants were also more likely to attend the emergency department during their presentation with first episode of psychosis (odds ratio = 1.76, 95% confidence interval = [1.31, 2.36], p < 0.001). Conclusion: First-generation migrants who develop a psychotic disorder are at greater risk of experiencing negative pathways to care than the Australian-born population. Further research is needed to identify the factors that lead to migrants being involuntarily admitted to hospital for first episode of psychosis.

Association between amyloid-beta deposition and cortical thickness in dementia with Lewy bodies

Abstract: Objective: Amyloid-beta often co-exists in dementia with Lewy bodies, but its clinical relevance in dementia with Lewy bodies remains unclear. This study aimed to investigate the clinical and imaging correlates of amyloid-beta deposition in dementia with Lewy bodies, particularly its relationship with cortical thickness in Alzheimer’s disease–prone regions and hippocampal volume. Methods: Twenty-four participants with probable dementia with Lewy bodies underwent high-resolution magnetic resonance imaging and amyloid-beta positron emission tomography imaging using the radiotracer 18F-NAV4694. Amyloid-beta deposition was quantified and reported using the Centiloid method. Results: Amyloid-beta positivity, defined as Centiloid > 50, was present in 45.8% of dementia with Lewy bodies participants. There were no statistically significant differences in clinical characteristics between Aβ+ and Aβ− dementia with Lewy bodies. Compared with the Aβ− group, Aβ+ dementia with Lewy bodies exhibited greater global cortical thinning as well as in the Alzheimer’s disease–prone region of interest, adjusted for age, sex and years of education. A mean cortical thickness of 5.12 mm across a combined meta-region of interest has a sensitivity of 88.9% and specificity of 90.0% in discriminating Aβ+ from Aβ− dementia with Lewy bodies. Hippocampal volume was not different between groups. Conclusion: Early structural changes in cortical thickness, but not hippocampal volume, were observed in dementia with Lewy bodies with significant amyloid-beta burden. This may represent an early Alzheimer’s disease–related neurodegenerative process.

Subjective cognitive decline, APOE e4 allele, and the risk of neurocognitive disorders: Age- and sex-stratified cohort study

Abstract: Objective: Subjective cognitive decline and APOE e4 allele (APOE4) are known predictors of mild cognitive impairment and dementia (mild cognitive impairment/dementia), with recent evidence showing interaction between subjective cognitive decline and APOE4 in amplifying the risk of mild cognitive impairment/dementia. However, the literature is unclear whether the interaction effect is seen across various age and sex strata. This study examined the interaction between subjective cognitive decline and APOE4—across different age and sex strata—on the risk of mild cognitive impairment/dementia. Methods: This cohort study included 16,221 participants aged ⩾50 years and had normal cognition at baseline. Participants were evaluated for subjective cognitive decline and APOE4 at baseline, and followed-up almost annually for mild cognitive impairment/dementia (median follow-up = 4.5 years). Interaction effects were examined in Cox regression using Relative Excess Risk due to Interaction, stratified by age (⩽70 vs >70 years) and sex. Results: Subjective cognitive decline and APOE4 were independently associated with mild cognitive impairment/dementia (hazard ratio: 1.4–1.8), with the highest risk when subjective cognitive decline and APOE4 co-occurred (hazard ratio: 2.6). APOE4 amplified the association between subjective cognitive decline and mild cognitive impairment/dementia in older women (Relative Excess Risk due to Interaction 1.0; 95% confidence interval = [0.3, 1.6]), but not in other age or sex strata. Among older women, half of them developed mild cognitive impairment/dementia by 12.1 years in the absence of subjective cognitive decline or APOE4. This duration shortened to 8.1–10.3 years in the presence of either subjective cognitive decline or APOE4, and to 4.4 years in the presence of both subjective cognitive decline and APOE4. Interaction effect among older women remained consistent when alternate outcomes were used (i.e. mild cognitive impairment and dementia due to Alzheimer’s disease; dementia; and Alzheimer’s dementia) (Relative Excess Risk due to Interaction 1.2–2.5). Conclusions: APOE4 amplifies the association between subjective cognitive decline and neurocognitive disorders in older women, with the findings suggesting the need for further research to delineate underlying neurobiology. APOE4 may potentially have a role in facilitating further risk stratification of older women with subjective cognitive decline in clinical practice.

Biomarkers of neuroprogression and late staging in bipolar disorder: A systematic review

Abstract: Background: Bipolar disorder may undertake a progressive course in a subset of patients, and research efforts have been made to understand the biological basis underlying this process. This systematic review examined the literature available on biological markers associated with illness progression in bipolar disorder. Methods: Peer-reviewed articles were assessed using Embase, PsycINFO and PubMed, as well as from external sources. After initial screening, a total of 871 citations from databases and other sources were identified. Participants with a diagnosis of bipolar disorder were included in our systematic review; however, studies with participants younger than 15 or older than 65 were excluded. All studies were assessed using the Newcastle-Ottawa Scale assessment tool, and data pertaining to the results were extracted into tabular form using Google Sheets and Google Documents. The systematic review was registered on PROSPERO international prospective register of systematic reviews (ID Number: CRD42020154305). Results: A total of 35 studies were included in the systematic review. Increased ventricular size and reduction of grey matter volume were the most common brain changes associated with illness progression in bipolar disorder. Among the several biomarkers evaluated in this systematic review, findings also indicate a role of peripheral inflammatory markers in this process. Discussion: The studies evaluating the biological basis of the illness progression in bipolar disorder are still scarce and heterogeneous. However, current evidence supports the notion of neuroprogression, the pathophysiological process related to progressive brain changes associated with clinical progression in patients with bipolar disorder. The increase in peripheral inflammatory biomarkers and the neuroanatomical changes in bipolar disorder suggest progressive systemic and structural brain alterations, respectively.