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Background. There are a large number of factors mediating suicide. Many studies have searched for a direct causal relationship between economic hardship and suicide, however, findings have been varied.Method. Suicide data was obtained from the Australian Bureau of Statistics for the period between January 1968 and August 2002. These were correlated with a suite of macroeconomic data including housing loan interest rates, unemployment rates, days lost to industrial disputes, Consumer Price Index, gross domestic product, and the Consumer Sentiment Index.Results. A total of 51845 males and 16327 females committed suicide between these dates. There were significant associations between suicide rates and eleven macroeconomic indicators for both genders in at least one age range. Data was divided into male and female and five age ranges and pooled ages. Analyses were conducted on these 132 datasets resulting in 80 significant findings. The data was generally stronger for indices measuring economic performance than indices measuring consumers' perceptions of the state of the economy. A striking difference between male and female trends was seen. Generally, male suicide rates increased with markers of economic adversity, while the opposite pattern was seen in females. There were significantly different patterns in age-stratified data, with for example higher housing loan interest rates having a positive association with suicide in younger people and a negative association in older age groups.Conclusion. Macroeconomic trends are significantly associated with suicide. The patterns in males and females are very different, and there are further substantial age-related differences.

Objective Treatment resistant depression is a common clinical problem and a major public health concern. The use of antidepressant combinations to overcome treatment resistance, while somewhat controversial, is a popular strategy in practice. This paper reviews published trials on combination antidepressants with a view to inform clinical practice. Method A systematic but selective review of the published literature was conducted using EMBASE, PSYCHLIT and MEDLINE with relevant search terms. Results A number of trials suggesting efficacy of combination antidepressants were found. These are incorporated into a number of treatment guidelines for the management of treatment refractory depression. Clinicians should be cautious regarding pharmacokinetic and pharmacodynamic interactions, including the serotonin syndrome, however combination strategies are an effective option. Conclusions Many antidepressants can be usefully combined especially if they engage separate mechanisms of action. Clinically, antidepressant combinations provide a useful resort in otherwise treatment resistant individuals. However, much further research is needed to determine relative efficacy and determine long term outcome.

Objective: Reduced bone mineral density (BMD) in women with a history of depressive disorders has been shown in some, but not all studies. This study investigated the association between self-reported depression and BMD in an age-stratified community sample of perimenopausal women residing in the South-Eastern region of Australia. Design: Symptoms of depression in the year between July 2000 and July 2001 were ascertained by a self-report questionnaire based on Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. Women in the perimenopausal group who had undergone a BMD total hip and spine assessment within the 12-month period after the depression assessment were included in the analysis, resulting in a sample of 78 women aged 45 to 60 years. Results: In this sample, 14 women were identified as depressed. There was no difference in age, hormone therapy (HT) use, or unadjusted BMD at the total hip or spine between the depressed and nondepressed women (P = 0.14, 0.89, 0.57, and 0.70, respectively), but the depressed women tended to be heavier [depressed (median weight, interquartile range = 80 kg, 66-94) vs nondepressed (72 kg, 61-80) P = 0.06]. Whereas there was no significant difference in age-, HT-, and weight-adjusted BMD at the spine [depressed (mean ± SE = 1.21 ± 0.05) vs nondepressed (1.28 ± 0.03 g/cm2) P = 0.18], adjusted BMD at the total hip for the depressed women was 7.8% lower than for the nondepressed [depressed (mean ± SE = 0.957 ± 0.038) vs nondepressed (1.038 ± 0.023 g/cm2) P = 0.04]. Conclusions: These results suggest that in perimenopausal women, self-reported depression is associated with lower BMD at the hip.

Objectives: To review the current knowledge of bipolar II disorder. Methods: Literature was reviewed after conducting a Medline search and a hand search of relevant literature. Results: Bipolar II disorder is a common disorder, with a prevalence of approximately 3–5%. Distinct clinical features of bipolar II disorder have been described. The key to diagnosis is the recognition of past hypomania, while depression is the typical presenting feature of the illness. This is responsible for a significant rate of missed diagnosis, and consequent management according to unipolar guidelines. It is unclear if bipolar II disorder is over-represented amongst resistant depression populations and if abrupt offset of antidepressant action is a phenomenon over represented in bipolar II disorder, reflecting induction of predominantly depressive cycling. A few mood-stabilizer studies available provide provisional suggestion of utility. A supportive role for psychosocial therapies is suggested, however, there is a sparsity of published studies specific to bipolar II disorder cohorts. A small number of short-term antidepressant trials have suggested efficacy, however, compelling long-term maintenance data is absent. Conclusions: An emerging literature on the specific clinical signature and management of the disorder exists, however, this is disproportionately small relative to the epidemiology and clinical significance of the disorder.

Bipolar disorder is a severe and recurrent disorder. Atypical antipsychotics have emerged as both an alternative and adjunct to conventional mood stabilisers. The manic phase of the illness is the best studied, and it appears that a class effect with regards to efficacy is present in both monotherapy and augmentation studies. Evidence for efficacy of atypical antipsychotics in depression is emerging. At this stage controlled data are available for both olanzapine and quetiapine. Maintenance data demonstrating efficacy are available for olanzapine. Atypical antipsychotics have utility in treating acute agitation and aggression in manic episodes of bipolar disorder. Subgroup analyses from trials treating manic phase bipolar disorder, and an open-label study of rapid cycling, have suggested that atypical antipsychotics may be useful for the treatment of mixed states and rapid cycling. Several studies have suggested that atypical antipsychotics may be useful in treatment-refractory episodes of bipolar disorder. The current available data suggest greater efficacy of the atypical antipsychotics in mania than in depression, although the data are fairly clear that induction of depression is not an issue with the atypical antipsychotics. A number of trials are underway that will hopefully address many of the questions still pending.

Objective To evaluate outcome and client and referrer satisfaction with the service provided by a Mood and Anxiety Disorders Unit (MADU). Method MADU was a specialized clinical service for the assessment and management of individuals suffering with affective and anxiety disorders. Clients were referred to MADU from a variety of health service providers. A telephone survey of 30 clients and 20 referrers who have used the services of MADU was conducted, investigating outcome satisfaction with the service provided by MADU. Results Clients and referrers reported a high level of satisfaction with the service provided by MADU. There was a high degree of adherence to treatment recommendations. The mean Patient Global Impression of Improvement (PGI) rating by the clients before the MADU assessment was 2.74 (SD = 1.27). In comparison the mean PGI rat-ing at the time of follow-up was 6.64 (SD = 1.91). Conclusions Specialist mood disorders units are a useful and potentially cost-effective additional service included as a part of a mental health service.

Treating bipolar disorder in women during reproduction presents a significant challenge to the physician. The pharmaceutical agents most commonly used for treating bipolar disorder have been associated with adverse effects when used during pregnancy and breastfeeding. Of particular concern has been the association of lithium with cardiac malformations, and the association of carbamazepine and valproate with neural tube defects including spina bifida. Toxicity in neonates has also been reported for the most commonly used mood-stabilising agents. Treatment options for mood stabilisation are either associated with risks of adverse events, have been used less frequently and their associated risks are unknown, or may not provide effective prophylaxis against recurrences of bipolar episodes. However, strategies are available that minimise the risk to the fetus and infant whilst still providing effective prophylaxis against bipolar disorder in the mother. Ideally, a treatment regimen tailored to suit the individual should consider both mother and baby and should be planned prior to conception.

Quinine is a bitter alkaloid that is used as a flavoring agent in tonic water. Studies suggest that quinine can inhibit cytochrome P450 2D6 (CYP2D6) which could have implications for the metabolism of co-ingested drugs. We conducted a study with 11 healthy volunteers (7 men, 4 women; aged 26–54). After urinary void, each subject consumed either 1000 ml of carbonated water or 1000 ml of tonic water containing 80 mg quinine in a crossover design. Following each beverage subjects ingested an oral dose of 30 mg dextromethorphan (DM). Urine was collected for 8 h and analyzed for DM and dextrophran, its CYP2D6 mediated metabolite. The ratio of DM and its metabolite is an established measure of CYP2D6 activity. All subjects metabolized the vast majority of DM to its metabolite after both the carbonated water and the tonic water. The ratio (mean±S.D.) of DM to its metabolite was 0.013±0.028 after the carbonated water and 0.032±0.067 after the quinine containing water. No significant difference in the ratios was observed between the two beverages (P>0.05). We conclude that quinine as consumed in tonic water does not inhibit CYP2D6 activity in vivo. Thus, quinine should not alter the metabolism of CYP2D6 substrates taken concomitantly with tonic water.

Antidepressants are amongst the most commonly prescribed classes of drugs and their use continues to grow. The World Health Organisation estimates that depression effects approximately 121 million people worldwide, with 26 million people receiving some form of medical care for depression [1]. A large number of these people will be treated with antidepressants. Moreover, antidepressants are commonly administered to special populations, such as the elderly, children and women during reproductive life stages. Depression is also commonly associated with comorbid physical illnesses [2], being overweight [3], tobacco smoking [4], poor diet [5] and lack of physical activity [6]. Large numbers of people being treated, often with vulnerabilities, increases the likelihood of adverse drug reactions to antidepressant treatment.

Alpha(1)-acid glycoprotein is a plasma protein that exhibits both microheterogeneity and polymorphism. Its purification from human plasma is usually performed using a sequence of different fractionation steps. Here we report a one-step isolation technique of this protein based upon pseudo-ligand affinity chromatography on immobilized Cibacron Blue F3GA at acidic pH. In addition, the use of two narrow pH elution buffers allows us to separate the two genetic products of this protein, which differ from each other by 21 amino acid substitutions. This technique will facilitate the study of the structural, biological and pharmacokinetic properties of each individual allele product.

Paired blood and breast-milk samples were collected from 10 nursing mothers receiving sertraline. Samples were collected at steady state when the patients had been taking stable doses of 50-150 mg/day over several weeks. Sertraline concentrations in both fluids were determined using a specific, validated HPLC method. Plasma and milk concentrations showed a wide inter-individual variability for the same dose. Mean plasma concentrations were linearly related to dose, but this was not the case for breast-milk concentrations. An overall milk to plasma ratio of 1.76+/-1.72 was recorded. The average dose to the infants ranged from 1.1 to 31.1mgr;g/kg, which is less than 2 per cent of the maternal dose per day. Further studies are necessary to determine if these doses are detrimental to the development of the infant. Copyright 2000 John WileySons, Ltd.

This editorial discusses past studies which have looked at whether oral contraceptives containing drospirenone had an increased risk of venous thromboembolism (VTE) compared to earlier generation oral contraceptives. It discusses the conclusions of those studies and possible arguments for both sides of the fence.

Objectives: Persistent environmental pollutants, including heavy metals and persistent organic pollutants (POPs), have a ubiquitous presence. Many of these pollutants affect neurobiological processes, either accidentally or by design. The aim of this study was to explore the associations between assayed measures of POPs and heavy metals and depressive symptoms. We hypothesised that higher levels of pollutants and metals would be associated with depressive symptoms. Setting: National Health and Nutrition Examination Survey (NHANES). Participants: A total of 15 140 eligible people were included across the three examined waves of NHANES. Primary and secondary outcome measures: Depressive symptoms were assessed using the nineitem version of the Patient Health Questionnaire (PHQ9), using a cut-off point of 9/10 as likely depression cases. Organic pollutants and heavy metals, including cadmium, lead and mercury, as well as polyfluorinated compounds (PFCs), pesticides, phenols and phthalates, were measured in blood or urine. Results: Higher cadmium was positively associated with depression (adjusted Prevalence Ratios (PR) =1.48, 95% CI 1.16 to 1.90). Higher levels of mercury were negatively associated with depression (adjusted PR=0.62, 95% CI 0.50 to 0.78), and mercury was associated with increased fish consumption (n=5500, r=0.366, p

A method is described for the determination of the two enantiomers of mirtazapine in human blood plasma by high-performance liquid chromatography. Measurements were performed on drug free plasma spiked with mirtazapine and used to prepare and validate standard curves. Levels of enantiomers of mirtazapine were also measured in patients being treated for depression with racemic mirtazapine. Mirtazapine was separated from plasma by solid-phase extraction using CERTIFY columns. Chromatographic separation was achieved using a Chiralpak AD column and pre-column and compounds were detected by their absorption at 290 nm. Imipramine was used as an internal standard. The assay was validated for each analyte in the concentration range 10-100 ng/ml. The coefficient of variance was 16% and 5.5% for(+)-mirtazapine for 10 and 100 ng/ml control specimens respectively and 15% and 7.3% for mirtazapine for 10 and 100 ng/ml control specimens respectively. This assay is appropriate for use in the clinical range. The range of plasma mirtazapine concentrations from eleven patients taking daily doses of 30-45 mg of racemate was

For every antidepressant so far investigated in the breast milk of mothers prescribed these medications, findings indicate that some amount of drug will be excreted into the breast milk. Nursing infants will be exposed to some, usually a very low, amount of drug and drug metabolites. Levels of drug exposure to infants for the many antidepressants available are examined, discussing milk to plasma drug concentration ratios and the infant dose as a percentage of the maternal dose. Drug concentrations in infant plasma and adverse effects of drug exposures to infants are reviewed. Factors influencing the decision on whether to breast or bottle feed an infant nursed by a mother taking antidepressants are discussed, concluding that the decision needs to be made on an individual basis. The lactating mother, in consultation with her doctor, should be in a position to make an informed decision on whether or not to breast feed. Under certain circumstances the decision to bottle feed may be wise, but more commonly the advantages of breast-feeding will outweigh the very low risk of an adverse event from drug exposure to the infant.

A method is described for the determination of nefazodone and its active metabolites hydroxynefazodone, the dione BMS-180492 and m-chlorophenylpiperazine in blood plasma and expressed human milk based on reversed-phase high-performance liquid chromatography. Measurements were performed on drug-free plasma and expressed human milk spiked with nefazodone and metabolites to prepare and validate standard curves and specimens collected from nursing mothers. Parent drug and metabolites were separated from the biological matrices by solid-phase extraction using CERTIFY columns. Chromatographic separation was achieved with a C18 column and compounds were detected by their absorbance at 205 nm. Trazodone was used as an internal standard. The assay was validated for each analyte in the concentration range 200 to 1200 ng/ml.

Background In cross-sectional and longitudinal community studies, regular exercise has been shown to be protective against the development of depression and has a therapeutic role in depression, while physical inactivity is a demonstrated risk factor for the development of depressive symptoms. Emerging evidence indicates that early life exposures influence adult health outcomes and there is cause to hypothesise a role for physical activity (PA) in childhood as a protective factor in adult depression. This investigation focused on the association between self-reported levels of PA in childhood and self-reported depressive illness in adulthood in a community sample of adult men and women from South-eastern Australia. Methods This study assessed 1404 men (20–96 yr) and 748 women (20–97 yr) participating in an ongoing Australian epidemiological study involving subjects randomly selected from the community (Geelong Osteoporosis Study). A self-report questionnaire based on DSM-IV criteria was utilised to determine lifetime prevalence rates of depression, and another ascertained levels of physical activity (Low PA vs High PA) in childhood, defined as < 15 yr of age. Results In this sample, 141 women (18.9%) and 169 men (12.0%) reported ever having a depressive episode (p < 0.001). Moreover, women were more likely than men to report Low PA in childhood (45.7% vs 23.2%, p < 0.001). Results of logistic regression analyses showed that Low PA in childhood was associated with an increased risk of reporting depression in adulthood (OR = 1.70, 95%CI = 1.32–2.17, p < 0.001). Adjustment for gender attenuated the relationship somewhat (OR = 1.53, 95%CI = 1.19–1.97, p = 0.001), however further adjustment for age and/or country of birth did not affect this relationship. Discussion In this community-based study, lower levels of self-reported PA in childhood increased the risk for self-reported depression in adulthood by more than 50%. These results indicate that lower levels of PA in childhood may be a risk factor for adult depression.

Introduction There is data to suggest that the prevalence of low bone mineral density (BMD) is disproportionately higher among those with depression, although findings are equivocal. The aim of this study was to investigate the association between depression and BMD in 448 premenopausal women (20–58 yr) drawn from a randomly-selected community based sample of women participating in the Geelong Osteoporosis Study. Methods Lifetime history of depressive and anxiety disorders were diagnosed utilising a clinical interview (SCID-I/NP). BMD was measured at the PA-spine, hip, total body and forearm using dual energy absorptiometry (Lunar DPX-L) and anthropometric measurements were recorded. Medication use, menopause status, activity levels, dietary intake and smoking status were self-reported. Results There were no differences in age, weight, height, BMI, alcohol consumption, calcium intake, smoking or unadjusted BMD between the groups, although women with a lifetime history of depression were less physically active than those with no previous history (81.9% vs 90.8%, p = 0.009). Weight, height and anxiety-adjusted BMD was 2.4% lower at the PA-spine (1.263 (95% CI 1.238–1.289) vs 1.294 (1.270–1.318) g/cm2, p = 0.04) and age, weight and anxiety-adjusted BMD was 2.8% lower at the total hip (1.034 (1.014–1.055) vs 1.064 (1.044–1.083) g/cm2, p = 0.02) in those with a lifetime history of depression compared to those non-depressed. There was a trend towards BMD being lower at the total body (p = 0.12) but no relationship was detected at the forearm sites. These patterns persisted after further adjustment for smoking, physical activity, alcohol consumption, calcium intake and medications known to affect BMD. Conclusions BMD was reduced among those with a lifetime history of depression independent of age, weight, height, anxiety, smoking, physical activity, alcohol consumption, calcium intake and medications known to affect BMD. These data are consistent with previous findings and suggest that depression is a risk factor for reduced BMD among younger women.

Introduction Antidepressants are amongst the most commonly prescribed classes of drugs and their use continues to grow. Adverse outcomes are part of the landscape in prescribing medications and therefore management of safety issues need to be an integral part of practice. Objectives We have developed consensus guidelines for safety monitoring with antidepressant treatments. Aims To present an overview of screening and safety considerations for pharmacotherapy of clinical depressive disorders and make recommendations for safety monitoring. Methods Data were sourced by a literature search using Medline and a manual search of scientific journals to identify relevant articles. Draft guidelines were prepared and serially revised in an iterative manner until all co-authors gave final approval of content. Results A guidelines document was produced after approval by all 19 co-authors. The final document gives guidance on; the decision to treat, baseline screening prior to commencement of treatment, and ongoing monitoring during antidepressant treatment. The guidelines state or reference screening protocols that may detect medical causes of depression as well as screening and monitoring protocols to investigate specific adverse effects associated with antidepressant treatments that may be reduced or identified earlier by baseline screening and agent-specific monitoring after commencing treatment. Conclusions The implementation of safety monitoring guidelines for treatment of clinical depression may significantly improve outcome, by improving a patient's overall physical health status.

The association of antidepressants with suicidal thought in people aged up to 25 year is a thorny issue. Balancing risk with benefit must always be at the core of any decision to treat and when the risk is an increased risk of suicide then a balanced decision can be difficult to make. Some clinicians who have been successfully treating patients using antidepressants have felt skepticism with these studies, finding them to be not reflective of their personal clinical experience. It may be wondered by some whether highlighting the link between suicidal thoughts and antidepressants may paradoxically lead to an increase in suicide by reducing the number of cases treated, however there is no evidence that this has occurred. The association between antidepressants and suicidal thought may be unpalatable, but as with all new research the only way it can be judged is by the evidence to support it. The weight of evidence to demonstrate the association between antidepressants and suicidal thought in young people is convincing although the risk is low, estimated at one case of emerging suicidal ideation or suicide attempt for every 143 pediatric patients treated [1]. This risk is too low to displace antidepressants as the first line of treatment for depression but is too high a risk to be ignored. The risk is also too low to be recognized based on clinical experience alone as it is low enough to be imperceptible amongst suicides which occur due to depressive illness independent of antidepressant treatment. Only large studies are sufficiently powered to detect suicidal thought associated with antidepressant treatment. Clearly further studies would be helpful, especially if they can help characterize those at greatest risk. This is why the study by Lucy Goldsmith and Joanna Moncrieff in this issue of Current Drug Safety is an important step towards improving our understanding of antidepressant safety. These researchers find a link between increased suicidal impulses and emotional blunting and emotional instability. Treating clinicians are urged to monitor for risk of suicide after initiation of antidepressant treatment, typically more frequently for the first four weeks of treatment and as indicated thereafter. However, if there is no history of suicidal thought or attempt and the patient does not admit to suicidal thought, suicidality may be missed by the treating clinician, ending in tragedy. Studies that provide new insights into this serious problem may lead to improvements in the effectiveness of monitoring patients for suicide risk, ultimately leading to better outcomes for patients.

To determine if oxidative stress and inflammation are linked with major depressive disorder, nicotine dependence and both disorders combined. This study comprised 150 smokers and 191 never smokers. The instruments were: a socio-demographic questionnaire, diagnoses of mood disorder and nicotine dependence according to DSM-IV, (SCID-IV), and the Alcohol, Smoking and Substance Involvement Screening Test. Laboratory assessments included: nitric oxide metabolites (NOx), lipid hydroperoxides, malondialdehyde (MDA), total reactive antioxidant potential (TRAP), advanced oxidation protein products (AOPP), fibrinogen concentrations, homocysteine, erythrocytes sedimentation rate (ESR) and high-sensitivity C-reactive protein (hs-CRP) were assayed from blood specimens. Statistically significant differences were found among depressed smokers who had more severe depressive symptoms, a higher risk of alcohol consumption, more suicide attempts, and more disability for work than non-depressed never smokers. Depressed smokers had significantly higher levels of NOx, fibrinogen, hs-CRP, AOPP, ESR and lower levels of TRAP compared to non-depressed never smokers. Depressed smokers had significant levels of oxidative stress and inflammatory biomarkers after adjusting for gender, age, years of education, disability for work, and laboratory measures. The levels of NOx, lipid hydroperoxides, AOPP, and fibrinogen were substantially higher, whereas levels of TRAP were lower in depressed smokers compared to non-depressed never smokers. (1) Depressed smokers exhibited altered concentrations of NOx, lipid hydroperoxides, AOPP, TRAP, and fibrinogen. (2) Depressed smokers were more unable to work, showed more severe depressive symptoms and attempted suicide more frequently.

SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents. (DOCX 18 kb)

Personalized treatment is defined as choosing the "right treatment for the right person at the right time." Although psychiatry has not yet reached this level of precision, we are on the way thanks to recent technological developments that may aid to detect plausible molecular and genetic markers. At the moment there are some models that are contributing to precision psychiatry through the concept of staging. While staging was initially presented as a way to categorize patients according to clinical presentation, course, and illness severity, current staging models integrate multiple levels of information that can help to define each patient's characteristics, severity, and prognosis in a more precise and individualized way. Moreover, staging might serve as the foundation to create a clinical decision-making algorithm on the basis of the patient's stage. In this review we will summarize the evolution of the bipolar disorder staging model in relation to the new discoveries on the neurobiology of bipolar disorder. Furthermore, we will discuss how the latest and future progress in psychiatry might transform current staging models into precision staging models.

Accurate diagnosis of bipolar disorder is essential for effective treatment. The diagnosis of bipolar disorder is particularly complex, resulting in lengthy delays between first presentation and initiation of appropriate therapy. Inappropriate therapy destabilises the course and outcome of the disease. Although the defining features of bipolar disorder are manic or hypomanic episodes, patients typically present for treatment of depression and commonly deny symptoms of mood elevation. A correct diagnosis can easily be masked by comorbidities, personality issues and complex phenomenology. A diagnosis of bipolar disorder can be assisted by: asking about symptoms of mania or hypomania in every patient presenting with symptoms of depression. recognising mixed states in which manic and depressive symptoms occur simultaneously. identifying the features of bipolar depression that distinguish it from unipolar depression. There is a risk of over-diagnosis of bipolar disorder among patients who are histrionic, show abnormal illness behaviour and/or have issues of secondary gain.

Additional file 1: Table S1. Adverse event data: comparing Rosuvastatin and Aspirin to placebo. Table S2. Most frequent adverse events. Table S3. Secondary outcome measures comparing Rosuvastatin and Aspirin to placebo; with 12 weeks follow-up as the primary comparison. Table S4. Subgroup analyses: comparing Rosuvastatin and Aspirin to placebo; with 12 weeks follow-up as the primary comparison. Table S5. History and ongoing psychological therapy: comparing Rosuvastatin and Aspirin to placebo. Table S6. History and ongoing antidepressants therapy: comparing Rosuvastatin and Aspirin to placebo.

Bipolar disorder is a common, debilitating, chronic illness that emerges early in life and has serious consequences such as long-term unemployment and suicide. It confers considerable functional disability to the individual, their family and society as a whole and yet it is often undetected, misdiagnosed and treated poorly. In the past decade, many new treatment strategies have been trialled in the management of bipolar disorder with variable success. The emerging evidence, for pharmacological agents in particular, is promising but when considered alone does not directly translate to real-world clinical populations of bipolar disorder. Data from drug trials are largely based on findings that identify differences between groups determined in a time-limited manner, whereas clinical management concerns the treatment of individuals over the life-long course of the illness. Considering the findings in the context of the individual and their particular needs perhaps best bridges the gap between the evidence from research studies and their application in clinical practice. Specifically, only lithium and valproate have moderate or strong evidence for use across all three phases of bipolar disorder. Anticonvulsants, such as lamotrigine, have strong evidence in maintenance; whereas antipsychotics largely have strong evidence in acute mania, with the exception of quetiapine, which has strong evidence in bipolar depression. Maintenance data for antipsychotics is emerging but at present remains weak. Combinations have strong evidence in acute phases of illness but maintenance data is urgently needed. Conventional antidepressants only have weak evidence in bipolar depression and do not have a role in maintenance therapy. Therefore, this paper summarizes the efficacy data for treating bipolar disorder and also applies clinical considerations to these data when formulating recommendations for the management of bipolar disorder.

Background There are obstacles to early identification of bipolar disorder. Identifying and treating illness early in its time course may be associated with a better prognosis. Methods A questionnaire was administered at interview, when the participant was euthymic, to participants (n = 240) enrolled in the Bipolar Comprehensive Outcomes Study (BCOS). Information was collected about the sequential timeline of specific symptoms of mental illness up to when they first received a diagnosis of Bipolar Disorder or Schizoaffective Disorder. Results Any symptoms of mental illness were first experienced at 17.5 years (median; Inter Quartile Range (IQR) 13.8–24.3; n = 216) and mood swings at 18.0 years (IQR 14–25; n = 197). Symptoms of depression were experienced at 18.0 years (IQR 14–25; n = 197), a full episode of depression at 21.2 years (IQR 17–28.5; n = 200), symptoms of mania at 21.0 years (IQR 16.8–29.5; n = 212) and a full episode of mania at 24.1 years (IQR 19–30.5; n = 205). Medical treatment was sought at 24.0 years (IQR 19–31.5; n = 217). Participants received a diagnosis of Bipolar Disorder or Schizoaffective Disorder at 30.0 years (IQR 23–37.3; n = 215). Having had a previous diagnosis other than Bipolar Disorder or Schizoaffective Disorder was reported by 120 of 216 participants who answered this question, most commonly unipolar depression (26.6%). Diagnostic delay was greater in individuals with early onset disorder. Conclusions Participants typically experience a long sequential course of symptoms, episodes, treatments and diagnosis. The polarity of onset is most commonly depressive, and subthreshold symptoms tend to precede threshold symptoms of both polarities. Limitations Data were collected retrospectively.

Bipolar disorder is associated with extreme mood symptoms, disability and suicide risk. Close family or friends often have a primary role in supporting an adult with bipolar disorder. However, not all support is helpful and there is little publicly accessible evidence-based information to guide caregivers. Caregiver burden increases the risk of caregiver depression and health problems. To help fill the information gap, expert clinicians, caregivers and consumers contributed to the development of guidelines for caregivers of adults with bipolar disorder using the Delphi consensus method. This paper reports on an evaluation of the acceptability and usefulness of the online version of the guidelines, http://www.bipolarcaregivers.org . Visitors to the website responded to an initial online survey about the usefulness of the information (N = 536). A more detailed follow-up feedback survey was emailed to web users who were adult caregivers of adults with bipolar disorder a month later (N = 121). The feedback was analyzed quantitatively and qualitatively to establish user appraisals of the online information, whether and how caregivers applied the information and ways it could be improved. The majority of users (86.4% to 97.4%) found the various sections of the website useful. At follow-up, nearly 93% of caregivers reported that the information was relevant to them and 96% thought it would help others. Most respondents said that the information was supportive and encouraged adaptive control appraisals. However, a few respondents who were experiencing complex family problems, or who cared for a person with severe chronic bipolar disorder did not appraise it as positively. Nevertheless, over two-thirds of the caregivers reported using the information. Optional interactive features were recommended to maximize benefits. Overall, http://www.bipolarcaregivers.org was appraised positively and used. It appears useful to close family and friends seeking basic information and reassurance, and may be an inexpensive way to disseminate guidelines for caregivers. Those who care for people with more severe and chronic bipolar disorder, or who have complex family problems might benefit from more specialized interventions, suggesting the importance of a stepped-care approach to supporting caregivers. The potential of evidence-based, collaboratively developed information websites to enhance caregiver and consumer outcomes merits further investigation.