Nicholas Myles

Tobacco use before, at, and after first-episode psychosis: a systematic meta-analysis.

OBJECTIVE Patients with first-episode psychosis have a high prevalence of tobacco use. We aimed to examine the prevalence and course of tobacco use during early psychosis using meta-analysis. DATA SOURCES Systematic search of MEDLINE (1948-2011), Embase (1947-2011), CINAHL (1984-2011), PsycINFO (1967-2011), and ISI Web of Science (1900-2011) using the search terms [psychosis OR schizophrenia] AND [tobacco OR smoking OR nicotine]. STUDY SELECTION We located 10 studies reporting the age at initiation of daily tobacco use and the age at onset of psychosis, 31 studies reporting prevalence of tobacco use in patients with first-episode psychosis, 10 studies comparing smoking to age-/gender-matched controls, and 7 studies reporting prevalence of tobacco use at intervals after treatment. DATA EXTRACTION The following data were extracted: age at initiation of daily tobacco use and at onset of psychosis, the proportion of patients with first-episode psychosis who used tobacco, the proportion of the general population who used tobacco, and the proportion of patients with psychosis who used tobacco at various intervals after initiation of antipsychotic treatment. RESULTS The pooled estimate for the interval between initiation of tobacco use and the onset of psychosis was 5.3 years (standardized mean difference = 0.85). The estimated prevalence of tobacco users in first episode of psychosis is 58.9% (95% CI, 54.3%-63.4%). There is a strong association between first-episode psychosis and tobacco use (OR = 6.04; 95% CI, 3.03-12.02) compared with healthy controls. The prevalence of tobacco use at intervals between 6 and 120 months after treatment remained unchanged (OR = 0.996; 95% CI, 0.907-1.094). CONCLUSIONS Patients with first-episode psychosis tend to have smoked for some years prior to the onset of psychosis, have high prevalence of tobacco use at the time of presenting for treatment, and are much more likely to smoke than aged-matched controls. Their apparent difficulty in quitting has implications for tobacco cessation programs and efforts to reduce cardiovascular disease among people with mental illness.

Systematic meta-analysis of individual selective serotonin reuptake inhibitor medications and congenital malformations

Context: It has been suggested that the commonly prescribed class of antidepressants selective serotonin reuptake inhibitors (SSRIs) are associated with birth defects. However, the teratogenic effect of individual SSRIs has not been previously compared using meta-analysis. Objective: To determine the strength of the association between individual SSRIs and major, minor, and cardiac malformation among infants born to women taking these medications. Data sources: Electronic search of CINAHL, EMBASE, Medline, PsycINFO, and ISI Web of Science using the search terms (SSRI OR antidepressant) AND (obstetric outcome OR malformation OR birth outcome OR teratogen), supplemented by manual searching of published references and requests of primary researchers for unpublished data. Study selection: There were 115 studies identified by electronic search and reviewed in full text, which yielded 16 papers reporting 36 data samples for major malformations, nine papers reporting 26 data samples for cardiac malformations, and four papers reporting seven data samples for minor malformations. Data synthesis: Fluoxetine (OR 1.14, 95% CI 1.01–1.30) and paroxetine (OR 1.29, 95% CI 1.11–1.49) were associated with increased risk of major malformations. Paroxetine was associated with increased risk of cardiac malformations (OR 1.44, 95% CI 1.12–1.86). Sertraline and citalopram were not significantly associated with congenital malformation. Between-sample heterogeneity was low and a range of methodological considerations had no significant impact on effect size. There was little evidence of publication bias. Conclusions: Fluoxetine and paroxetine should be avoided in the first trimester and among those at risk of an unplanned pregnancy.

Meta-Analysis of Longitudinal Cohort Studies of Suicide Risk Assessment among Psychiatric Patients: Heterogeneity in Results and Lack of Improvement over Time.

Objective It is widely assumed that the clinical care of psychiatric patients can be guided by estimates of suicide risk and by using patient characteristics to define a group of high-risk patients. However, the statistical strength and reliability of suicide risk categorization is unknown. Our objective was to investigate the odds of suicide in high-risk compared to lower-risk categories and the suicide rates in high-risk and lower-risk groups. Method We located longitudinal cohort studies where psychiatric patients or people who had made suicide attempts were stratified into high-risk and lower-risk groups for suicide with suicide mortality as the outcome by searching for peer reviewed publications indexed in PubMed or PsychINFO. Electronic searches were supplemented by hand searching of included studies and relevant review articles. Two authors independently extracted data regarding effect size, study population and study design from 53 samples of risk-assessed patients reported in 37 studies. Results The pooled odds of suicide among high-risk patients compared to lower-risk patients calculated by random effects meta-analysis was of 4.84 (95% Confidence Interval (CI) 3.79–6.20). Between-study heterogeneity was very high (I2 = 93.3). There was no evidence that more recent studies had greater statistical strength than older studies. Over an average follow up period of 63 months the proportion of suicides among the high-risk patients was 5.5% and was 0.9% among lower-risk patients. The meta-analytically derived sensitivity and specificity of a high-risk categorization were 56% and 79% respectively. There was evidence of publication bias in favour of studies that inflated the pooled odds of suicide in high-risk patients. Conclusions The strength of suicide risk categorizations based on the presence of multiple risk factors does not greatly exceed the association between individual suicide risk factors and suicide. A statistically strong and reliable method to usefully distinguish patients with a high-risk of suicide remains elusive.

Efficacy of metformin for prevention of weight gain in psychiatric populations: a review

There is uncertainty with regard to the appropriate use of metformin for the prevention and management of second-generation antipsychotic-induced weight gain and metabolic abnormalities. We aim to systematically review the primary literature and to provide recommendations with regard to the use of metformin in psychiatric populations prescribed second-generation antipsychotics. The authors undertook a literature search of Medline, EMBASE, and PsycINFO using the search terms; antipsychotic OR atypical antipsychotic AND weight AND metformin. Narrative review was undertaken without additional statistical analysis. The search provided 198 results from which 10 original research papers were identified: six randomized controlled trials and one open-label study for adults and two randomized controlled trials and one open-label study for children and adolescents. Four meta-analyses were also identified. We concluded that if weight gain occurs after second-generation antipsychotic initiation, despite lifestyle intervention, metformin should be considered. Further studies with adequate statistical power are required to determine the efficacy of metformin in those with chronic psychotic illness.

The Association between Cannabis Use and Earlier Age at Onset of Schizophrenia and other Psychoses: Meta-analysis of Possible Confounding Factors

A recent meta-analysis showed that the mean age of onset of psychosis among cannabis users was almost three years earlier than that of non-cannabis users. However, because cannabis users usually smoke tobacco, the use of tobacco might independently contribute to the earlier onset of psychosis. We aimed to use meta-analysis to compare the extent to which cannabis and tobacco use are each associated with an earlier age at onset of schizophrenia and other psychoses. We also examined other factors that might have contributed to the finding of an earlier age of onset among cannabis users, including the proportion of males in the samples, the diagnostic inclusion criteria and aspects of study quality. The electronic databases MEDLINE, EMBASE, PsycINFO and ISI Web of Science, were searched for English-language peer-reviewed publications that reported age at onset of schizophrenia and other psychoses separately for cannabis users and non-users, or for tobaccosmokers and non-smokers. Meta-analysis showed that the age at onset of psychosis for cannabis users was 32 months earlier than for cannabis non-users (SMD=- 0.399, 95%CI -0.493 - -0.306, z=-8.34, p < 0.001), and was two weeks later in tobacco smokers compared with non-smokers (SMD=0.002, 95%CI -0.094 - 0.097, z=0.03, p=0.974). The main results were not affected by subgroup analyses examining studies of a single sex, the methods for making psychiatric diagnoses and measures of study quality. The results suggest that the association between cannabis use and earlier onset of psychosis is robust and is not the result either of tobacco smoking by cannabis using patients or the other potentially confounding factors we examined. This supports the hypothesis that, in some patients, cannabis use plays a causal role in the development of schizophrenia and raises the possibility of treating schizophrenia with new pharmacological treatments that have an affinity for endo-cannabinoid receptors.

Cannabis use in first episode psychosis: Meta-analysis of prevalence, and the time course of initiation and continued use:

Objectives: Cannabis use is prevalent among people with first episode psychosis and the epidemiology of its use in early psychosis is unclear. We performed a meta-analysis of observational studies to determine; (1) the interval between age at initiation of cannabis use and age at onset of first episode psychosis, (2) the prevalence of cannabis use at time of first episode psychosis, and (3) the odds of continuing cannabis following treatment for first episode psychosis. Data sources: Search of electronic databases MEDLINE, EMBASE, PsycINFO, Web of Science and CINAHL for English-language papers using search terms (psychosis OR schizophrenia) AND (cannabis OR marijuana) IN (title OR keyword OR abstract), current to October 2014. Study selection: Studies were included if they reported on prevalence of current cannabis use in first episode psychosis cohorts. A total of 37 samples were included for meta-analysis. Data extraction: Rates of cannabis use in each sample were extracted to determine prevalence estimates. The age at initiation of regular cannabis and age at onset of psychosis were used to determine the length of cannabis use preceding psychosis. Prevalence estimates at first episode psychosis and various time points of follow-up following first episode psychosis were analysed to determine odds ratio of continuing cannabis use. Data synthesis was performed using random-effects meta-analyses. Results: The pooled estimate for the interval between initiation of regular cannabis use and age at onset of psychosis was 6.3 years (10 samples, standardised mean difference = 1.56, 95% confidence interval = [1.40, 1.72]). The estimated prevalence of cannabis use at first episode psychosis was 33.7% (35 samples, 95% confidence interval = [31%, 39%]). Odds of continued cannabis use between 6 months and 10 years following first episode psychosis was 0.56 (19 samples, 95% confidence interval = [0.40, 0.79]).

Considering metformin in cardiometabolic protection in psychosis.

A 20% reduction in life expectancy is testament to the disproportionate burden of cardiovascular morbidity and mortality in psychiatric populations. Cardiovascular disease largely explains the mortality gap between those with schizophrenia and the general population, a gap that continues to widen (1). Lifestyle factors such as poor nutrition, obesity, cigarette smoking, substance abuse and sedentariness contribute to a complex set of cardiovascular risks. However, cardiometabolic disturbances and weight gain occur within weeks of first exposure to antipsychotic medications (2), a particular concern as psychotic disorders typically commence in youth at a vulnerable developmental phase and with a lifetime ahead. By the time this population reach their late 30s, rates of diabetes (10.2%) and prediabetes (37%) indicate that early weight gain and its attendant insulin resistance effect a biological path from normal glucose metabolism to disease (3). For young people with early psychosis, this means that not only can early weight gain influence a path towards obesity-related medical disorders, but it may limit ability to engage in healthy physical activities as basic as walking, as well as damaging self-worth and confidence to participate in active physical pursuits (4). In tackling or preventing cardiometabolic risk, a lifestyle programme to prevent weight gain at initiation of antipsychotic treatment is primary and fundamental. A multipronged approach is required, including healthy eating strategies, supervised caloric restriction for those gaining weight and sedentariness-reducing strategies. Another potential tool in our armamentarium is metformin, first line in treating type 2 diabetes mellitus and with established efficacy in euglycaemic disorders such as polycystic ovary syndrome. Twelve RCTs and three meta-analyses demonstrate that metformin alone or with lifestyle intervention can attenuate weight gain in normoglycaemic patients with psychosis commencing or receiving antipsychotic medications (5). The weight benefit translated to clinically meaningful improvements in cardiometabolic risk factors. The utility of these studies to influence practice is limited by low statistical power and relatively short study length. Nevertheless, in four adequately powered studies, metformin consistently improved weight and metabolic parameters for a variety of antipsychotics applicable to general psychiatric practice (5). These benefits were evident in the critical early phase following antipsychotic initiation in drugnaı̈ve, first-episode psychosis patients, regardless of the antipsychotic used. The review also observed that metformin plus lifestyle intervention was significantly more effective than metformin or lifestyle intervention alone: compared with placebo, metformin plus lifestyle gave a net weight reduction of 7.8 kg in as short a period as 12 weeks. The utility of metformin as a safe and cheap treatment for preventing diabetes in at-risk obese populations without psychiatric disease is established. In our view, patients with psychosis constitute another important at-risk group, similar to those with prediabetes: in particular, those on antipsychotic medications with significant weight gain and acquisition of cardiometabolic risk factors. Just as in the non-psychiatric atrisk population, metformin is not a solitary panacea. Early lifestyle intervention is an opportunity to modify the long-term health trajectory of a generation of at-risk psychiatric patients and should be primary. However, metformin addition increases the effectiveness of lifestyle intervention, at least in the short term. We suggest that metformin in concert with a structured, supervised lifestyle programme could be considered in the severely mentally ill when antipsychotic agents are initiated or in antipsychotic recipients who are overweight, obese or have elevated cardiometabolic risk factors. A precipitous rise in body weight, waist circumference or fasting glucose can be viewed similarly to an obese non-psychiatric patient with impaired glucose tolerance, where lifestyle and metformin intervention are considered acceptable. Furthermore, obesity has a disproportionately greater impact on the psychiatric patient s ability to exercise and their self-confidence to participate in physical activities (4). Taken alongside their greater likelihood of co-occurring hyperlipidaemia and tobacco smoking, then perhaps this psychiatric population should be considered at even greater cardiovascular risk and hence with a stronger justification for early intervention, than their equivalent obese non-psychiatric population. We believe the opportunity exists for medical practitioners to actively engage in cardiometabolic protection of people with schizophrenia, perhaps some of our most vulnerable patients. Early, pro-active intervention with lifestyle strategies and, where necessary, metformin may offer a primary preventative strategy in antipsychotic recipients. Actively protecting cardiometabolic health could be an efficient way to reduce clinical, social and economic burden in the psychiatric population. Is it time to extend the early intervention paradigm for treating first-episode psychosis to encompass the body as well as the mind?

Known unknowns and unknown unknowns in suicide risk assessment: evidence from meta-analyses of aleatory and epistemic uncertainty

Suicide risk assessment aims to reduce uncertainty in order to focus treatment and supervision on those who are judged to be more likely to die by suicide. In this article we consider recent meta-analytic research that highlights the difference between uncertainty about suicide due to chance factors (aleatory uncertainty) and uncertainty that results from lack of knowledge (epistemic uncertainty). We conclude that much of the uncertainty about suicide is aleatory rather than epistemic, and discuss the implications for clinicians.

Obstructive sleep apnea and schizophrenia: A systematic review to inform clinical practice.

BACKGROUND Risk factors for obstructive sleep apnea (OSA) are common in people with schizophrenia. Identification and treatment of OSA may improve physical health in this population; however there are no guidelines to inform screening and management. OBJECTIVES Systematic review to determine, in people with schizophrenia and related disorders: the prevalence of OSA; the prevalence of OSA compared to general population controls; the physical and psychiatric correlates of OSA, associations between antipsychotic medications and OSA; the impact of treatment of OSA on psychiatric and physical health; and the diagnostic validity of OSA screening tools. DATA SOURCES Medline, EMBASE, ISI Web of Science and PsycINFO electronic databases. Cohort, case-control and cross-sectional studies and RCTs reporting on prevalence of OSA in subjects with schizophrenia and related disorders were reviewed. RESULTS The prevalence of OSA varied between 1.6% and 52%. The prevalence of OSA was similar between people with schizophrenia and population controls in two studies. Diagnosis of OSA was associated with larger neck circumference, BMI>25, male sex and age>50years. There were no data on physical or psychiatric outcomes following treatment of OSA. The diagnostic utility of OSA screening tools had not been investigated. CONCLUSION OSA may be prevalent and potentially under-recognized in people with schizophrenia. Further research is required to determine utility of OSA screening tools, the relationships between antipsychotic medications and OSA and any benefits of treating OSA. We propose a strategy for the identification of OSA in people with schizophrenia and related disorders.

Australia’s economic transition, unemployment, suicide and mental health needs:

Objective: There have been substantial changes in workforce and employment patterns in Australia over the past 50 years as a result of economic globalisation. This has resulted in substantial reduction in employment in the manufacturing industry often with large-scale job losses in concentrated sectors and communities. Large-scale job loss events receive significant community attention. To what extent these mass unemployment events contribute to increased psychological distress, mental illness and suicide in affected individuals warrants further consideration. Methods: Here we undertake a narrative review of published job loss literature. We discuss the impact that large-scale job loss events in the manufacturing sector may have on population mental health, with particular reference to contemporary trends in the Australian economy. We also provide a commentary on the expected outcomes of future job loss events in this context and the implications for Australian public mental health care services. Results and conclusion: Job loss due to plant closure results in a doubling of psychological distress that peaks 9 months following the unemployment event. The link between job loss and increased rates of mental illness and suicide is less clear. The threat of impending job loss and the social context in which job loss occurs has a significant bearing on psychological outcomes. The implications for Australian public mental health services are discussed.