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Objective: The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial is the largest open-label, pragmatic trial that has been undertaken to examine the treatment of major depressive disorder. At a cost of US$35 million over 6 years, STAR*D sought to test the effectiveness both of pharmacotherapy and of cognitive therapy, and to ascertain whether certain treatments are more optimal after one or more failed trials. Method: Patients ( n = 2876) who presented to either a psychiatry or family practice setting seeking treatment for depression were included in the STAR*D analysis. In the 4 levels of STAR*D, patients were randomized to various treatment monotherapies, combinations, or augmentation strategies. The primary outcome was remission, based on the Hamilton Depression Rating Scale. Secondary outcomes were response, as measured by clinician and patient self-report as well as various measures of patients' level of function and (or) quality of life. Results: Remission rates for treatment levels 1 to 2 and 3 to 4 were 18% to 30% and 7% to 25%, respectively. There was no difference in effectiveness between any treatments at any treatment level. Patients with longer index episodes, more concurrent psychiatric or general medical disorders, and (or) lower measures of baseline function were less likely to achieve remission. There were no major differences between outcomes in patients treated in primary, compared with specialist care, nor were there significant differences between depression rating scores obtained through clinician ratings, compared with self-report. Conclusion: Results of the STAR*D trial have shed important light on the effectiveness of current treatment strategies for patients with depression.

OBJECTIVE To determine if the inclusion of a placebo arm and/or the number of active comparators in antidepressant trials influences the response rates of the active medication and/or placebo. DATA SOURCES Searches of MEDLINE, PsycINFO, and pharmaceutical Web sites for published trials or trials conducted but unpublished between January 1996 and October 2007. STUDY SELECTION 2,275 citations were reviewed, 285 studies were retrieved, and 90 were included in the analysis. Trials reporting response and/or remission rates in adult subjects treated with an antidepressant monotherapy for unipolar major depression were included. DATA EXTRACTION The primary investigator recorded the number of responders and/or remitters in the intent-to-treat population of each study arm or computed these numbers using the quoted rates. DATA SYNTHESIS Poisson regression analyses demonstrated that mean response rate for the active medication was higher in studies comparing 2 or more active medications without a placebo arm than in studies comparing 2 or more active medications with a placebo arm (65.4% vs 57.7%, P < .0001) or in studies comparing only 1 active medication with placebo (65.4% vs 51.7%, P = .0005). Mean response rate for placebo was significantly lower in studies comparing 1 rather than 2 or more active medications (34.3% vs 44.6%, P = .003). Mean remission rates followed a similar pattern. Meta-analysis confirmed results from the pooled analysis. CONCLUSIONS These data suggest that antidepressant response rates in randomized control trials may be influenced by the presence of a placebo arm and by the number of treatment arms and that placebo response rates may be influenced by the number of active treatment arms in a study.

Purpose The aim of this study was to compare patterns of PA and its potential correlates in individuals with BD to the general population using a representative sample of Canadians. Methods We used data from the 2002 Canadian Community Health Survey 1.2, a national, cross-sectional survey focusing on mental health and addiction ( n = 36,984). We compared PA levels among individuals with BD ( n = 831) to those diagnosed with major depression ( n = 4713) and those with no identified mood disorder ( n = 31,834). Using multivariable logistic regression, we then compared independent effects of sociodemographic and clinical factors in active and inactive BD individuals stratified by relative weight status. Results There were no differences in the proportion of individuals characterized as active, moderately active or inactive among individuals with BD, major depressive disorder or the general population. No sociodemographic or clinical variables were related to PA in individuals with BD, and the relationships between these variables and PA level were not different than those observed in the general population. BD status was independently associated with being overweight (OR = 1.26, p = 0.03). An interaction between BD status and PA was also observed (OR = 1.12, p = 0.005), suggesting a reduced role for PA in reducing the risk of being overweight in person with BD. Conclusions The results suggest that levels of self-reported PA are not lower among people with BD living in the community than in the general population. Future research should assess levels of PA using objective measures and determine whether PA improves psychosocial outcomes in this population.

Objective: To add to the limited data on the prevalence, clinical characteristics, and treatment of bipolar disorder (BD) among immigrants. Method: Data were obtained from a large epidemiologic survey, the Canadian Community Health Survey—Mental Health and Well-Being (CCHS 1.2). Lifetime prevalence rates of BD were compared between immigrant and nonimmigrant respondents. Among BD subjects ( n = 831), sociodemographic, clinical, and mental health treatment use variables were compared based on immigrant status. Logistic regression was used to determine the correlates of lifetime contact with a mental health professional and 12-month psychotropic medication use. Results: Lifetime prevalence rate of CCHS 1.2–defined BD was significantly lower among immigrant, compared with nonimmigrant, participants (1.50% and 2.27%, P = 0.01). There were few sociodemographic or clinical differences, yet immigrants with BD were significantly less likely to report any lifetime contact with mental health professionals (OR = 0.25, 95% CI 0.13 to 0.50, P < 0.001). Past-year psychotropic medication use was numerically lower among immigrants with BD (24.5% and 41.0%); however, this did not reach statistical significance when controlling for other factors (OR = 0.49, 95% CI 0.24 to 1.01, P = 0.05). Conclusions: Based on the results of this study, there are in the range of 56 000 to 104 000 immigrants with BD in Canada. Further efforts are needed to better understand and address the barriers to mental health treatment use among immigrants who have BD.

Objectives: Bipolar disorder is associated with elevated risk of suicide attempts and deaths. Key aims of the International Society for Bipolar Disorders Task Force on Suicide included examining the extant literature on epidemiology, neurobiology and pharmacotherapy related to suicide attempts and deaths in bipolar disorder. Methods: Systematic review of studies from 1 January 1980 to 30 May 2014 examining suicide attempts or deaths in bipolar disorder, with a specific focus on the incidence and characterization of suicide attempts and deaths, genetic and non-genetic biological studies and pharmacotherapy studies specific to bipolar disorder. We conducted pooled, weighted analyses of suicide rates. Results: The pooled suicide rate in bipolar disorder is 164 per 100,000 person-years (95% confidence interval = [5, 324]). Sex-specific data on suicide rates identified a 1.7:1 ratio in men compared to women. People with bipolar disorder account for 3.4–14% of all suicide deaths, with self-poisoning and hanging being the most common methods. Epidemiological studies report that 23–26% of people with bipolar disorder attempt suicide, with higher rates in clinical samples. There are numerous genetic associations with suicide attempts and deaths in bipolar disorder, but few replication studies. Data on treatment with lithium or anticonvulsants are strongly suggestive for prevention of suicide attempts and deaths, but additional data are required before relative anti-suicide effects can be confirmed. There were limited data on potential anti-suicide effects of treatment with antipsychotics or antidepressants. Conclusion: This analysis identified a lower estimated suicide rate in bipolar disorder than what was previously published. Understanding the overall risk of suicide deaths and attempts, and the most common methods, are important building blocks to greater awareness and improved interventions for suicide prevention in bipolar disorder. Replication of genetic findings and stronger prospective data on treatment options are required before more decisive conclusions can be made regarding the neurobiology and specific treatment of suicide risk in bipolar disorder.

Objective: This study examined characteristics of treatment utilization in a large general population-based sample of bipolar subjects. Method: Data source was the Canadian Community Health Survey-Mental Health and Well-Being, a nationally representative, community mental health survey of over 36,000 individuals conducted from May to December 2002. Subjects who met study criteria for a current or past manic episode were classified as having bipolar disorder. Sociodemographic and illness-related factors influencing likelihood of accessing treatment, delay to contact with treatment services, and use of pharmacotherapy among bipolar subjects were determined. Results: Among the 852 bipolar subjects, 45.2% had never accessed treatment services. Male gender (p = .001), lower level of education (p = .003), and immigrant status (p < .001) were each significantly negatively correlated with use of treatment services. Mean delay from illness onset to contact with any treatment services was 3.1 years. Sixty-six percent of bipolar subjects had not taken a mood stabilizer or antidepressant medication in the past year, and 22% used antidepressants without a mood stabilizer. Female bipolar subjects were significantly more likely than male subjects to be prescribed an antidepressant medication (OR = 1.99, p = .01), even in the absence of higher frequency of recent depressions. Conclusion: Many individuals with bipolar disorder never receive any form of mental health treatment, and, among those that do, use of pharmacotherapy is not consistent with guideline-based recommendations. These findings reinforce the importance of continued efforts to better identify bipolar individuals early in their course of illness, and the need for further educational focus on bipolar disorder for all mental health treatment providers.

Objective The goal of this study was to examine the association between antidepressant use and hospitalization rate for mania or bipolar depression in a large, community-based sample of elderly bipolar patients. Method Population-based retrospective cohort design. Administrative healthcare databases were linked for all individuals aged 66 years or older in the Province of Ontario, Canada. Bipolar subjects who received a prescription for an antidepressant medication (n = 1,072) between 1 April 1997 and 31 March 2001 comprised the antidepressant cohort. The control group (n = 3,000) consisted of randomly selected subjects from the eligible bipolar population who did not receive a prescription for an antidepressant medication during the same surveillance period. Primary outcomes were admission to hospital for a manic/mixed or depressive episode. Results During a total of 5135 person-years of follow up, 113 admissions for a manic/mixed episode and 28 admissions for a depressive episode were identified. Model based estimates adjusted for a number of covariates revealed that, as compared with the control group, the antidepressant cohort had significantly lower likelihood of admissions for manic/mixed (adjusted rate ratio [aRR] = 0.5, 95% CI = 0.3–0.8) but not depressive episodes (aRR = 0.7, 95% CI = 0.2–2.2). Conclusion Antidepressant use among elderly bipolar patients was associated with decreased rates of hospitalization for manic/mixed episodes. This finding requires confirmation with further data of antidepressant use among elderly bipolars. Copyright © 2006 John Wiley & Sons, Ltd.

Objective: This study reports on the lifetime prevalence and illness characteristics of bipolar disorder (BD) in a large, representative sample of Canadians. Method: Data were obtained from the Canadian Community Health Survey: Mental Health and Well-Being. This representative, cross-sectional survey, conducted by Statistics Canada in 2002, examines the mental health of Canadians aged 15 years and over. The national response rate was 77%. We determined the prevalence rate of BD, correlates of a bipolar diagnosis, and illness characteristics. Results: The weighted lifetime prevalence rate of BD was 2.2% (95% confidence interval [CI], 1.94% to 2.37%). Younger age, low income adequacy, lifetime anxiety disorder, and presence of a substance use disorder in the past 12 months were each significantly associated with the presence of a BD diagnosis ( P < 0.001 for each). The largest effect found was for the presence of an anxiety disorder (odds ratio 7.94; 95%CI, 6.35 to 9.92). A lifetime history of anxiety disorder was reported by 51.8% (95%CI, 47.1% to 56.5%) of the respondents with BD, with both panic disorder and agoraphobia each being more frequent among women, compared with men ( P = 0.01 and P < 0.001, respectively). The mean age at onset of illness was 22.5 years, SD 12.0. Conclusions: According to the estimated lifetime prevalence of BD found in this study, over 500 000 Canadians likely suffer from this condition. Identifying those at highest risk for BD may assist in developing more effective community-based identification and intervention strategies.

Since the previous publication of Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines in 1997, there has been a substantial increase in evidence-based treatment options for bipolar disorder. The present guidelines review the new evidence and use criteria to rate strength of evidence and incorporate effectiveness, safety, and tolerability data to determine global clinical recommendations for treatment of various phases of bipolar disorder. The guidelines suggest that although pharmacotherapy forms the cornerstone of management, utilization of adjunctive psychosocial treatments and incorporation of chronic disease management model involving a healthcare team are required in providing optimal management for patients with bipolar disorder. Lithium, valproate and several atypical antipsychotics are first-line treatments for acute mania. Bipolar depression and mixed states are frequently associated with suicidal acts; therefore assessment for suicide should always be an integral part of managing any bipolar patient. Lithium, lamotrigine or various combinations of antidepressant and mood-stabilizing agents are first-line treatments for bipolar depression. First-line options in the maintenance treatment of bipolar disorder are lithium, lamotrigine, valproate and olanzapine. Historical and symptom profiles help with treatment selection. With the growing recognition of bipolar II disorders, it is anticipated that a larger body of evidence will become available to guide treatment of this common and disabling condition. These guidelines also discuss issues related to bipolar disorder in women and those with comorbidity and include a section on safety and monitoring.

Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O’Donovan C, MacQueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI. The evolution of CANMAT Bipolar Disorder Guidelines: past, present, and future. Bipolar Disord 2013: 15: 58–60. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Objective: There are few data addressing the effect of alcohol consumption on response to antidepressants among nonalcoholics with depression. Similarly, the effect of antidepressant treatment on alcohol consumption in this group is not yet understood. This study focuses on changes in depressive symptoms and alcohol consumption in response to treatment with desipramine. Method: Twenty-seven nonalcoholic outpatients with major depression (as determined by the Schedule for Affective Disorders and Schizophrenia-Lifetime Version) completed measures of depression (that is, the 17-item Hamilton Depression Rating Scale and the Beck Depression Inventory) and alcohol consumption at intake and after 5 weeks of open treatment with desipramine. Subjects were characterized as minimal or mild-to-moderate drinkers. Results: There was no significant difference between the groups with respect to effectiveness of antidepressant treatment. Analysis for repeated measures demonstrated that alcohol consumption with desipramine was significantly lower after treatment than at intake (F = 4.8, df 23:2, P Conclusions: Desipramine treatment appeared to result in decreases in alcohol consumption in nonalcoholic patients with depression. Further research is needed to elucidate the effect of alcohol consumption on the course and outcome of major depressive illness among nonalcoholics as well as the effect of antidepressant medication on alcohol consumption in this population. (Can J Psychiatry 2004;49:859-862) Information on author affiliations appears at the end of the article. Clinical Implications * Desipramine may attenuate alcohol consumption among nonalcoholics with depression. * Previous studies have suggested that nonalcoholic patients with depression would benefit by minimizing their consumption of alcohol. * Changes in alcohol and carbohydrate consumption during antidepressant treatment may be independent of changes in depressive symptoms. Limitations * The study sample was relatively small. * The length of this trial may not have been sufficient to detect the effect of alcohol on response to desipramine. * Alcohol consumption was determined by self-report and may be an underestimate of actual alcohol consumption. Key Words: depression, alcohol consumption, desipramine, carbohydrate consumption The cooccurrence of alcohol use disorders has been reported to adversely affect the course, treatment, and prognosis of major depressive disorder (1,2). What is less clearly understood is the significance of mild-to-moderate alcohol consumption on treatment response among patients with major depression. To our knowledge, Worthington and colleagues reported the only findings regarding nonabusive alcohol consumption in depression patients treated with fluoxetine (3). They found that the level of alcohol consumption at baseline predicted significantly poorer response to treatment and a nonsignificant trend toward lowered alcohol consumption in the treatment group. There are, however, no previous studies of tricyclic antidepressants (TCAs) in this respect. This study prospectively examines the effect of pretreatment alcohol consumption on response to treatment with desipramine, as well as the effect of desipramine treatment on alcohol consumption in nonalcoholic subjects with depression. We hypothesized that subjects who abstained or drank minimally would show greater depressive symptom reduction than would those with moderate alcohol consumption. Method The study sample comprised 27 consecutive outpatients (21 women and 6 men) referred to the Depression Clinic at the Clarke site of the Centre for Addiction and Mental Health, University of Toronto. At baseline, after they provided written informed consent, all patients were administered the Schedule for Affective Disorders and Schizophrenia Lifetime Version (SADS-LV, 4), the 17-item Hamilton Depression Rating Scale (HDRS, 5), the Beck Depression Inventory (BDI, 6), and the Food Pattern Questionnaire (FPQ, 7). …

Objective: To report on the prevalence of seasonal bipolar disorder (BD) and the impact of latitude in a community sample in the province of Ontario. Method: This study used the telephone-administered Depression and Seasonality Interview. Exact latitude was determined for each participant. Results: Overall, 14 of 62 (22.6%) subjects with BD had the seasonal subtype of BD. Latitude did not appear to influence the proportion of subjects with the seasonal subtype. Conclusions: We identified a seasonal pattern of illness in a proportion of subjects with BD.

Utility is a measure of undesirability for a specific health state. This study determines the utility scores for the individual symptoms of depression, and examines the impact that personal experience with depression has on these scores. Seventy-five subjects (19 with current depression, 21 with past depression, and 35 healthy controls) assigned utility scores to each of 10 individual symptoms of depression, and three depression severity profiles. Utility scores were measured using the standard gamble technique. Mean utility scores were used to list the symptoms of depression from most to least undesirable. The three diagnostic groups were compared with respect to the magnitude of undesirability of the depressive symptoms. The results of this study found that individuals assigned different utility scores to different symptoms of depression. The psychological symptoms of depression such as suicidal ideation, guilt and depressed mood were ranked as more undesirable than the somatic symptoms of depression. Each diagnostic group ranked the symptoms of depression in a similar manner. Patients with a current depression were willing to accept a greater risk of death to avoid suffering from lifelong depressive symptoms as compared to patients with a past depression or healthy controls.

Objective This research aims to determine the long-term impact of the Bloor Street Viaduct suicide barrier on rates of suicide in Toronto and whether media reporting had any impact on suicide rates. Design Natural experiment. Setting City of Toronto, Canada; records at the chief coroner’s office of Ontario 1993–2003 (11 years before the barrier) and 2004–2014 (11 years after the barrier). Participants 5403 people who died by suicide in the city of Toronto. Main outcome measure Changes in yearly rates of suicide by jumping at Bloor Street Viaduct, other bridges including nearest comparison bridge and walking distance bridges, and buildings, and by other means. Results Suicide rates at the Bloor Street Viaduct declined from 9.0 deaths/year before the barrier to 0.1 deaths/year after the barrier (incidence rate ratio (IRR) 0.005, 95% CI 0.0005 to 0.19, p=0.002). Suicide deaths from bridges in Toronto also declined significantly (IRR 0.53, 95% CI 0.40 to 0.71, p

While mental illness is a risk factor for suicidal behaviour and many suicide victims receive mental health care prior to death, there is a comparative lack of research that explores their narratives of care. Suicide notes offer unique insight into these subjective experiences. Our study explores the following questions: “How is mental health care experienced by those who die by suicide?” and “What role does this experience play in an individual's journey to suicide?” Our sample is a set of 21 purposefully selected notes that explicitly make mention of mental illness and/or mental health care, from a larger sample of 255 notes obtained through the Toronto Coroner's Office. We utilized a constructivist grounded theory framework to engage in line-by-line open coding, axial coding, memo-ing and theorizing of the data. Preliminary themes include (1) perception of recurrent utilization of mental health care as personal failure, (2) recurrent utilization of mental health care as a manifestation of accumulating hopelessness, (3) the construction of suicide as being beyond the scope of mental health care, (4) tensions between the conceptualization of mental illness as an inherent part of the self and mental illness as a disease to be fought or overcome, and (5) suicide as an exertion of self-autonomy, distinct from the influence of mental illness. An exploration of the complexity of an individual's relationship with mental illness and mental health care can foster better identification, understanding and support for those at risk for suicide.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The final decades of the 20th century may be considered the golden age of anti­ depressant medications. There was a boom in their development and clinical use as well as a sense that they might represent a major advance towards more targeted treatment for patients suffering from depression. However, recent evidence point­ ing to the failure of many antidepressant randomized controlled trials (RCTs), particularly for depression of mild­to­moderate severity [1–3], has shaken the field. Multiple factors may explain these less than promising findings. First, we now know that the antidepressant literature has been biased as a result of selective publication of positive trials [4]. There is also an increasing awareness of the het­ erogeneity of what we understand to be major depressive disorder. Culture and ethnicity, for example, have an important impact on response to psychopharma­ cology [5], to the extent that trials conducted in different places may yield different results. Indeed, there is even a question of whether our current definition of major depression represents a distinct entity or rather multiple disorders with only some responding to antidepressants [6]. However, the core issue in failed antidepres­ sant trials may not be the lack of response to active treatment, but the narrowing separation between drug and placebo, accounted for in large part by rising placebo response rates [7]. One important, yet underappreciated factor, contributing to placebo response rates is the manner in which patient expectations significantly influence study results. The reason expectations are so important for psychiatric conditions such as depression and anxiety, as well as a variety of neurological conditions such as pain syndromes, is that people with these conditions are much more likely to improve if they expect to do so. For example, one study that measured the relationship between pretreatment expectations and outcome in a group of patients treated with reboxetine for major depressive disorder, found that 90% of patients who initially expected reboxetine to be ‘very effective’ responded by the end of the trial compared with only 33% of patients who only expected it to be ‘somewhat effective’ [8]. Therefore, expectations are extremely important, and researchers and physicians are modulating them all the time, often without being aware of it. A few years ago, researchers at the California Institute of Technology studied sub­ jects tasting wine and found that both their subjective and objective experience (the latter demonstrated by functional MRI) were more positive when they were told the wine they were drinking was more expensive [9]. Subjects do a similar kind of unconscious calculation in randomized clinical trials. There is a broad literature in medicine demonstrating that research subjects generally expect drugs to be stronger and therefore respond more often to larger pills, colored rather than white pills, capsules rather than tablets and injections rather than pills [10,11].

The older population are at a high risk for suicide. This study sought to learn more about the characteristics of suicide in the oldest-old and to use a cluster analysis to determine if oldest-old suicide victims assort into clinically meaningful subgroups.Data were collected from a coroner's chart review of suicide victims in Toronto from 1998 to 2011. We compared two age groups (65-79 year olds, n = 335, and 80+ year olds, n = 191) and then conducted a hierarchical agglomerative cluster analysis using Ward's method to identify distinct clusters in the 80+ group.The younger and older age groups differed according to marital status, living circumstances and pattern of stressors. The cluster analysis identified three distinct clusters in the 80+ group. Cluster 1 was the largest (n = 124) and included people who were either married or widowed who had significantly more depression and somewhat more medical health stressors. In contrast, cluster 2 (n = 50) comprised people who were almost all single and living alone with significantly less identified depression and slightly fewer medical health stressors. All members of cluster 3 (n = 17) lived in a retirement residence or nursing home, and this group had the highest rates of depression, dementia, other mental illness and past suicide attempts.This is the first study to use the cluster analysis technique to identify meaningful subgroups among suicide victims in the oldest-old. The results reveal different patterns of suicide in the older population that may be relevant for clinical care.

Background: Little has been published on the sources of medications used in suicide by self-poisoning. Aims: To examine data on self-poisoning occurring through the use of medications returned to the next of kin after the death of a family member or friend (”returned medication”) and to examine public policies relevant to this issue. Method: A review of charts at the Office of the Chief Coroner of Ontario for deaths by self-poisoning suicide in the City of Toronto occurring between 1998 and 2010 was conducted. Information regarding the source of medication used in self-poisoning was extracted. Federal, provincial, and local policies were also examined to determine whether there are guidelines governing returning medication to next of kin. Results: Of 567 suicide deaths by self-poisoning in Toronto over 13 years, there were eight cases in which returned medication was used in suicide by self-poisoning. No policies prohibiting this type of medication return were identified. Conclusion: Suicide by self-poisoning using returned medications is an important consideration that may not yet be fully appreciated, and has relevance for suicide prevention policies.

BACKGROUND Cross-sectional studies demonstrate increased prevalence of cardiovascular disease (CVD) among adults with bipolar disorder. However, there is a paucity of prospective data regarding new-onset CVD among adults with bipolar disorder. METHOD Analyses compared the 3-year incidence of CVD (via participant-reported physician diagnoses) among participants with DSM-IV diagnoses of bipolar I disorder (n = 1,047), bipolar II disorder (n = 392), major depressive disorder (MDD; n = 4,396), or controls (n = 26,266), who completed Wave 1 (2001-2002) and Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Analyses also compared the age of participants with new-onset CVD across groups. Multivariable analyses controlled for age, sex, race, cigarette smoking, hypertension, obesity, and alcohol and drug use disorders. RESULTS The 3-year incidence of CVD among adults with bipolar I disorder, bipolar II disorder, MDD, and among controls was 6.30%, 5.74%, 3.98%, and 3.70%, respectively. The covariate-adjusted incidence of CVD was significantly greater among participants with bipolar I and II disorders versus controls and versus participants with MDD. Adjusted odds ratios (95% CI) were 2.58 (1.84-3.61; P < .0001) for bipolar I disorder vs controls; 2.76 (1.60-4.74; P = .0004) for bipolar II disorder vs controls; 2.11 (1.46-3.04; P = .0001) for bipolar I disorder vs MDD; 2.25 (1.26-4.01; P = .007) for bipolar II disorder vs MDD; and 1.22 (0.99-1.51; P = .06) for MDD vs controls. Bipolar I disorder participants with new-onset CVD were 10.70 ± 2.77 years younger than MDD participants with new-onset CVD and 16.78 ± 2.51 years younger than controls. Bipolar II disorder participants with new-onset CVD were 7.92 ± 3.27 years younger than MDD participants with new-onset CVD and 13.99 ± 2.79 years younger than controls. DISCUSSION Adults with bipolar disorder are at significantly and meaningfully increased risk to develop CVD over the course of 3 years, even as compared to adults with MDD, and despite controlling for multiple potential confounds. Combined with very early age of CVD onset, this finding underscores the need for early and assertive CVD prevention strategies for people with bipolar disorder.

Suicide is an important cause of premature mortality in people suffering from schizophrenia. This study aimed to identify demographic, personal, and suicide-specific features that distinguish suicide in people with schizophrenia from those with another severe mental illness (bipolar disorder) and those with neither illness.We conducted a coroner's chart review for 2,886 suicide victims in Toronto from 1998 to 2010. Diagnoses were made based on coroner interviews with available informants including family members, acquaintances, the deceased's physician(s) and/or review of medical records. Of the total, 258 formed what we defined as the schizophrenia group (204 schizophrenia, 34 unspecified psychotic illness, and 20 schizoaffective disorder). Of the remainder, 169 had bipolar disorder, and 2,459 had neither illness. One-way analysis of variance (ANOVA) tests and χ² tests were conducted to examine differences between the groups.The group with schizophrenia was the youngest (mean age for schizophrenia, 41.0 years; bipolar disorder, 43.3 years; and neither, 47.7 years; P.001), most likely to have never been married (schizophrenia, 75.6%; bipolar disorder, 57.4%; and neither, 52.9%; P.001), most likely to be living in temporary/assisted housing or jail (schizophrenia, 9.3%; bipolar disorder, 5.4%; and neither, 3.2%; P.001), and least likely to have experienced a recent stressor (schizophrenia, 26.7%; bipolar disorder, 37.9%; and neither, 54.1%; P.001). The schizophrenia group was the most likely to use a violent cause of death, specifically by fall from a height or by jumping in front of a vehicle (schizophrenia, 81.4%; bipolar disorder, 58.0%; and neither, 73.1%; P.001).There are important demographic and suicide-related differences between suicide victims with and without schizophrenia. Notably, suicide in schizophrenia overall appears to be more illness driven and occurs by more violent means than in the bipolar disorder group or those with neither illness.

Previous studies suggest that there is a dopamine lowering process during major depressive episodes (MDE). To investigate this, we measured the dopamine transporter binding potential (DAT BP) in the striatum of depressed and healthy subjects using [(11)C]RTI-32 PET. The DAT, a predominantly presynaptic receptor, decreases in density after chronic dopamine depletion and the BP is proportional to receptor density. In all striatal regions, subjects with MDE had significantly lower DAT BP. Low striatal DAT BP in MDE is consistent with a downregulation of DAT in response to a dopamine lowering process. There was also a strong, highly significant, inverse correlation between striatal DAT BP and neuropsychological tests of dopamine-implicated symptoms in patients (i.e. patients with lower DAT BP performed better). Lower DAT BP itself reduces extracellular clearance of dopamine. Patients who did not decrease their striatal DAT BP failed to compensate for low dopamine and showed greater impairment on dopamine related tests.

Significant progress has been made in the pharmacotherapy of alcoholism, specifically in the areas of withdrawal reaction, decreasing consumption, relapse prevention, and comorbid psychiatric illnesses. Psychosocial interventions are an important component of treatment strategies, and studies into the efficacy of medications often include psychotherapy or other nonpharmacological modalities. Increasingly, however, the evidence reveals the effectiveness of drug treatments for various components of the illness. Many different pharmacological agents and dosage regimens have been investigated for the treatment of the alcohol withdrawal syndrome. The effectiveness and simplicity of giving long-acting benzodiazepines, using a loading-dose technique, make this regimen first-line therapy. Both naltrexone (an opioid antagonist) and acamprosate (calcium acetylhomotaurinate) increase rates of abstinence and decrease relapse rates in alcohol-dependent individuals who are in abstinence-orientated programmes. If patients enter a comprehensive treatment programme, either naltrexone or acamprosate should be considered as an option in the treatment plan. The choice of medication is most likely to be determined by the availability of each, which differs considerably throughout the world. Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) seem to have short term effects, and are more effective in depressed alcoholics-dependent and in men. For all medications there is wide variability in treatment response (i.e. effect size) and compliance seems to be essential for successful treatment. Preliminary evidence suggests the usefulness of pharmacotherapy in treating alcohol dependence in the presence of other comorbid psychiatric illnesses. Antidepressants have shown efficacy in the treatment of alcoholism with comorbid depression, as has buspirone for the treatment of comorbid chronic anxiety symptoms. Further understanding of the neurobiological mechanisms of dependence in animals and humans as well as improved knowledge of predictors of treatment response will lead to improvements in the pharmacotherapy of alcohol dependence.

We evaluated individual patient data from phase II to IV clinical trials of duloxetine in major depressive disorder (MDD) (34 studies, 13,887 patients). Our goal was to identify clusters of patients with similar depressive symptom patterns at baseline, as measured by the 17-item Hamilton Depression Rating Scale (HAMD-17), and to investigate their respective predictive value of outcomes as measured by the HAMD-17 total score. Five clusters were identified at baseline: 1) "Lack of insight"; 2) "Sleep/sexual/somatic"; 3) "Typical MDD"; 4) "Gastrointestinal/weight loss"; and 5) "Mild MDD". However, it should be noted that cluster descriptors are not mutually exclusive. Analyses of the HAMD-17 total score results over time were performed using the 18 randomized placebo and/or actively controlled studies representing 6723 patients. At the end of acute treatment (ranging from 4 to 36 weeks), different levels of effect sizes for active therapy (64.5% duloxetine) vs. placebo were detected by cluster. In 3 out of 5 clusters (representing about 80% of the patients), the effect size was significantly different from 0, in favor of active therapy. The effect size was largest in those clusters with severe somatic symptoms ("Sleep/sexual/somatic" cluster [-0.4170], and "Gastrointestinal/weight loss" cluster [-0.338]). In conclusion, our cluster analysis identified 5 clinically relevant MDD patient clusters with specific mean treatment outcomes. Identification of MDD clusters may help to improve outcomes by adapting MDD treatment to particular clinical profiles.

Despite substantial cross-sectional evidence that obesity is associated with an increased medical and psychiatric burden in bipolar disorder (BD), few longitudinal studies have examined this topic.Subjects with BD (n = 1600) who completed both Wave 1 and Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were included. Analyses examined the association between obesity at Wave 1, and the subsequent course of BD, and of psychiatric and medical comorbidities, between Wave 1 and Wave 2.BD subjects with obesity (n = 506; 29.43%), compared to BD subjects without obesity (n = 1094; 70.57%) were significantly more likely to have a major depressive episode and to receive counseling for depression during follow-up, more likely to report a lifetime suicide attempt, and less likely to develop new-onset alcohol use disorders. These differences were no longer significant, however, after controlling for baseline demographic variables. No significant differences in new episodes or treatment of mania/hypomania were observed. After controlling for demographic variables, obese subjects remained significantly more likely to report any new-onset medical condition [odds ratio (OR) = 2.32, 95% confidence interval (CI): 1.63-3.30], new-onset hypertension (OR = 1.81, 95% CI: 1.16-2.82) and arthritis (OR = 1.64, 95% CI: 1.07-2.52). Obese subjects were significantly more likely to report physician-diagnosed diabetes (OR = 6.98, 95% CI: 4.27-11.40) and hyperlipidemia (OR = 2.32, 95% CI: 1.63-3.30) (assessed in Wave 2 only). The incidence of heart attacks was doubled among obese subjects, although this difference was not statistically significant.The association between obesity and increased prospective depressive burden appears to be explained by baseline demographic variables. By contrast, obesity independently predicts the accumulation of medical conditions among adults with BD. Treatment of obesity could potentially mitigate the psychiatric and medical burden of BD.

The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009. This third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunction with the previous publications.The recommendations for the management of acute mania remain largely unchanged. Lithium, valproate, and several atypical antipsychotic agents continue to be first-line treatments for acute mania. Monotherapy with asenapine, paliperidone extended release (ER), and divalproex ER, as well as adjunctive asenapine, have been added as first-line options.For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, as well as olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. Lurasidone monotherapy and the combination of lurasidone or lamotrigine plus lithium or divalproex have been added as a second-line options. Ziprasidone alone or as adjunctive therapy, and adjunctive levetiracetam have been added as not-recommended options for the treatment of bipolar depression. Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, risperidone long-acting injection, and adjunctive ziprasidone continue to be first-line options for maintenance treatment of bipolar disorder. Asenapine alone or as adjunctive therapy have been added as third-line options.

While indicated for schizophrenia and acute mania, ziprasidone’s evidence base and use in clinical practice extends beyond these regulatory approvals. We, an invited panel of experts led by a working group of 3, critically examined the evidence and our collective experience regarding the effectiveness, tolerability and safety of ziprasidone across its clinical uses. There was no opportunity for manufacturer input into the content of the review. As anticipated, ziprasidone was found to be effective for its indicated uses, although its utility in mania and mixed states lacked comparative data. Beyond these uses, the available data were either unimpressive or were lacking. An attractive characteristic is its neutral effect on weight thereby providing patients with a non-obesogenic long-term treatment option. Key challenges in practice include the need for dosing on a full stomach and managing its early onset adverse effect of restlessness. Addressing these issues are critical to its long-term success

Most individuals with mood disorders experience psychiatric and/or medical comorbidity. Available treatment guidelines for major depressive disorder (MDD) and bipolar disorder (BD) have focused on treating mood disorders in the absence of comorbidity. Treating comorbid conditions in patients with mood disorders requires sufficient decision support to inform appropriate treatment.The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force sought to prepare evidence- and consensus-based recommendations on treating comorbid conditions in patients with MDD and BD by conducting a systematic and qualitative review of extant data. The relative paucity of studies in this area often required a consensus-based approach to selecting and sequencing treatments.Several principles emerge when managing comorbidity. They include, but are not limited to: establishing the diagnosis, risk assessment, establishing the appropriate setting for treatment, chronic disease management, concurrent or sequential treatment, and measurement-based care.Efficacy, effectiveness, and comparative effectiveness research should emphasize treatment and management of conditions comorbid with mood disorders. Clinicians are encouraged to screen and systematically monitor for comorbid conditions in all individuals with mood disorders. The common comorbidity in mood disorders raises fundamental questions about overlapping and discrete pathoetiology.

Objective: To identify the substances used by people who die from suicide by overdose in Toronto and to determine the correlates of specific categories of substances used. Method: Coroner's records for all cases of suicide by overdose in Toronto, Ontario, during a 10-year period (1998 to 2007) were examined. Data collected included demographic data, all substances detected, and those determined by the coroner to have caused death. Logistic regression analyses were used to examine demographic and clinical factors associated with suicide by different drug types. Results: There were 397 documented suicides by overdose (mean age 49.1 years, 50% female). Most substances detected were psychotropic prescription medications ( n = 245), followed by other prescription medications ( n = 143) and over-the-counter (OTC) medications ( n = 83). More than one-half of all suicides by overdose were determined to have only one specifc substance as the cause of death ( n = 206). In suicides where only one class of substance was present in lethal amounts, OTC medication ( n = 48), opioid analgesics ( n = 44), and tricyclic antidepressants ( n = 44) were most common. Conclusions: Suicides by overdose involved the use of different classes of substances, including psychotropic prescription medication, other prescription medications, as well as OTC medications. Physicians and pharmacists should be aware of commonly used prescription and OTC medications in overdose and exercise increased vigilance in prescribing or dispensing them to at-risk patients.

Mood disorders, especially bipolar disorder (BD), frequently are associated with substance use disorders (SUDs). There are well-designed trials for the treatment of SUDs in the absence of a comorbid condition. However, one cannot generalize these study results to individuals with comorbid mood disorders, because therapeutic efficacy and/or safety and tolerability profiles may differ with the presence of the comorbid disorder. Therefore, a review of the available evidence is needed to provide guidance to clinicians facing the challenges of treating patients with comorbid mood disorders and SUDs.We reviewed the literature published between January 1966 and November 2010 by using the following search strategies on PubMed. Search terms were bipolar disorder or depressive disorder, major (to exclude depression, postpartum; dysthymic disorder; cyclothymic disorder; and seasonal affective disorder) cross-referenced with alcohol or drug or substance and abuse or dependence or disorder. When possible, a level of evidence was determined for each treatment using the framework of previous Canadian Network for Mood and Anxiety Treatments recommendations. The lack of evidence-based literature limited the authors' ability to generate treatment recommendations that were strictly evidence based, and as such, recommendations were often based on the authors' opinion.Even though a large number of treatments were investigated for alcohol use disorder (AUD), none have been sufficiently studied to justify the attribution of level 1 evidence in comorbid AUD with major depressive disorder (MDD) or BD. The available data allows us to generate first-choice recommendations for AUD comorbid with MDD and only third-choice recommendations for cocaine, heroin, and opiate SUD comorbid with MDD. No recommendations were possible for cannabis, amphetamines, methamphetamines, or polysubstance SUD comorbid with MDD. First-choice recommendations were possible for alcohol, cannabis, and cocaine SUD comorbid with BD and only second-choice recommendations for heroin, amphetamine, methamphetamine, and polysubstance SUD comorbid with BD. No recommendations were possible for opiate SUD comorbid with BD. Finally, psychotherapies certainly are considered an essential component of the overall treatment of SUDs comorbid with mood disorders. However, further well-designed studies are needed in order to properly assess their potential role in specific SUDs comorbid with a mood disorder.Although certain treatments show promise in the management of mood disorders comorbid with SUDs, additional well-designed studies are needed to properly assess their potential role in specific SUDs comorbid with a mood disorder.

The association between mood disorders and personality disorders (PDs) is complicated clinically, conceptually, and neurobiologically. There is a need for recommendations to assist clinicians in treating these frequently encountered patients.The literature was reviewed with the purpose of identifying clinically relevant themes. MedLine searches were supplemented with manual review of the references in relevant papers. From the extant evidence, consensus-based recommendations for clinical practice were developed.Key issues were identified with regards to the overlap of PDs and mood disorders, including whether certain personality features predispose to mood disorders, whether PDs can reliably be recognized if there is an Axis I disorder present, whether personality disturbances arise as a consequence or are a forme fruste of mood disorders, and whether personality traits or disorders modify treatment responsiveness and outcome of mood disorders.This paper describes consensus-based clinical recommendations that arise from a consideration of how signals from the literature can impact clinical practice in the treatment of patients with comorbid mood and personality pathology. Additional treatment studies of patients with the comorbid conditions are required to further inform clinical practice.

Medical comorbidity is commonly encountered in individuals with major depressive disorder (MDD) and bipolar disorder (BD). The presence of medical comorbidity has diagnostic, prognostic, treatment, and etiologic implications underscoring the importance of timely detection and treatment.A selective review of relevant articles and reviews published in English-language databases (1968 to April 2011) was conducted. Studies describing epidemiology, temporality of onset, treatment implications, and prognosis were selected for review.A growing body of evidence from epidemiologic, clinical, and biologic studies suggests that the relationship between medical illness and mood disorder is bidirectional in nature. It provides support for the multiplay of shared and specific etiologic factors interlinking these conditions.This article describes the complex interactions between medical illness and mood disorders and provides a meaningful approach to their comorbid clinical diagnosis and management.

Medical comorbidity in patients with mood disorders has become an increasingly important clinical and global public health issue. Several specific medical conditions are associated with an increased risk of mood disorders, and conversely, mood disorders are associated with increased morbidity and mortality in patients with specific medical disorders.To help understand the bidirectional relationship and to provide an evidence-based framework to guide the treatment of mood disorders that are comorbid with medical illness, we have reviewed relevant articles and reviews published in English-language databases (to April 2011) on the links between mood disorders and several common medical conditions, evaluating the efficacy and safety of pharmacologic and psychosocial treatments. The medical disorders most commonly encountered in adult populations (ie, cardiovascular disease, cerebrovascular disease, cancer, human immunodeficiency virus, hepatitis C virus, migraine, multiple sclerosis, epilepsy, and osteoporosis) were chosen as the focus of this review.Emerging evidence suggests that depression comorbid with several medical disorders is treatable and failure to treat depression in medically ill patients may have a negative effect on medical outcomes.This review summarizes the available evidence and provides treatment recommendations for the management of comorbid depression in medically ill patients.

Patients with bipolar disorder (BD) and major depressive disorder (MDD) experience adult attention-deficit/hyperactivity disorder (ADHD) at rates substantially greater than the general population. Nonetheless, ADHD frequently goes untreated in this population.We reviewed the literature regarding the management of adult ADHD in patients with mood disorders. Because a limited number of studies have been conducted in adults, our treatment recommendations also are partly informed by research in children and adolescents with BD+ADHD or MDD+ADHD, adults with ADHD, and our clinical experience.In individuals with mood disorders, ADHD is best diagnosed when typical symptoms persist during periods of sustained euthymia. Individuals with BD+ADHD, particularly those with bipolar I disorder (BD I), are at risk for mood destabilization with many ADHD treatments, and should be prescribed mood-stabilizing medications before initiating ADHD therapies. Bupropion is a reasonable first-line treatment for BD+ADHD, while mixed amphetamine salts and methylphenidate also may be considered in patients determined to be at low risk for manic switch. Modafinil and cognitive-behavioral therapy (CBT) are second-line choices. In patients with MDD+ADHD and moderate to severe depression, MDD should be the treatment priority, whereas in mildly depressed or euthymic patients the order may be reversed. First-line treatments for MDD+ADHD include bupropion, an antidepressant plus a long-acting stimulant, or an antidepressant plus CBT. Desipramine, nortriptyline, and venlafaxine are second-line options.Clinicians should be vigilant in screening for comorbid ADHD in mood disorder patients. ADHD symptoms can respond to appropriately chosen treatments.

Comorbid mood and anxiety disorders are commonly seen in clinical practice. The goal of this article is to review the available literature on the epidemiologic, etiologic, clinical, and management aspects of this comorbidity and formulate a set of evidence- and consensus-based recommendations. This article is part of a set of Canadian Network for Mood and Anxiety Treatments (CANMAT) Comorbidity Task Force papers.We conducted a PubMed search of all English-language articles published between January 1966 and November 2010. The search terms were bipolar disorder and major depressive disorder, cross-referenced with anxiety disorders/symptoms, panic disorder, agoraphobia, generalized anxiety disorder, social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder. Levels of evidence for specific interventions were assigned based on a priori determined criteria, and recommendations were developed by integrating the level of evidence and clinical opinion of the authors.Comorbid anxiety symptoms and disorders have a significant impact on the clinical presentation and treatment approach for patients with mood disorders. A set of recommendations are provided for the management of bipolar disorder (BD) with comorbid anxiety and major depressive disorder (MDD) with comorbid anxiety with a focus on comorbid posttraumatic stress disorder, use of cognitive-behavioral therapy across mood and anxiety disorders, and youth with mood and anxiety disorders.Careful attention should be given to correctly identifying anxiety comorbidities in patients with BD or MDD. Consideration of evidence- or consensus-based treatment recommendations for the management of both mood and anxiety symptoms is warranted.

One goal of the Canadian Network for Mood and Anxiety Treatments (CANMAT) is to develop evidence-based and best practice educational programs and recommendations. Our group conducted a comprehensive literature review to provide evidence-based recommendations for treating metabolic comorbidity in individuals with major depressive disorder (MDD) and bipolar disorder (BD).We searched PubMed for all English-language articles published January 1966 to November 2010 using BD and MDD cross-referenced with metabolic syndrome, obesity, diabetes mellitus, hypertension, and dyslipidemia. That search was augmented by a review of articles reporting outcomes of an intervention targeting components of metabolic syndrome in individuals with MDD or BD.Consensus exists for the recommendation that individuals with MDD and BD should be routinely screened for risk factors that increase risk for metabolic syndrome. For excess weight, the best-studied pharmacologic approaches are metformin and topiramate, with emerging evidence for liraglutide and modafinil. For binge eating disorder, the best evidence in mood disorders was for cognitive-behavioral therapy as well as topiramate, zonisamide, and in select cases selective serotonin reuptake inhibitors. For dysglycemia, dyslipidemia, and hypertension, evidence supports cognitive-behavioral interventions and anti-diabetic, antilipidemic, and antihypertensive treatments.Comprehensive care of individuals with mood disorders should include routine evaluation of the risk and presence of metabolic syndrome and its components. Systematic evaluation of preventative and targeted treatments of metabolic syndrome in mood disorder populations is insufficient.

OBJECTIVE Differences in dosing may influence results of pharmaceutical industry-sponsored medication trials. This study aims to determine the relationship between sponsorship and antidepressant dosing and efficacy in randomized controlled trials for major depressive disorder. DATA SOURCES Trials were identified through English-language searches of MEDLINE and PsycINFO (January 1996-June 2010) using specific drug names and classes and depressive disorder or major depression and double blind or double-blind method. Other limitations included human subjects and treatment study designs using the clinical queries option. Other sources were also searched following a strict set of inclusion and exclusion criteria. STUDY SELECTION Randomized controlled trials were included if they examined antidepressant treatment for major depressive disorder, reported mean final medication dosages, acknowledged an association with industry, and included study arms of medications produced by the associated manufacturer and a competitor ("sponsor" and "nonsponsor" arms) (58 trials involving 15,026 patients from 101 citations identified). DATA EXTRACTION Data on dosing, efficacy, baseline severity, and adverse events were extracted by 2 of the authors. RESULTS Meta-analyses were used to examine dosing and efficacy data. Using consensus guidelines for medication dosing, we determined that sponsor medication was dosed relatively higher than nonsponsor medication, in 37% (22/60) of comparisons as opposed to 5% (3/60) in which the nonsponsor medication was dosed higher (χ²₂ = 25.9, P < .001). Trials in which sponsor drugs were dosed higher than nonsponsor drugs demonstrated higher remission rates for the sponsor drug (OR = 1.28, 95% CI = 1.11-1.47, P < .001). These results were confirmed using regulatory dosing guidelines. There was no significant correlation between dosing or outcome with baseline severity or adverse events. CONCLUSIONS Sponsor drugs are dosed higher than nonsponsor drugs in antidepressant randomized controlled trials, and higher dosing is associated with better sponsor drug outcomes in some cases.

The aim of this study was to examine the impact of co-morbid illnesses on treatment outcomes in depressed children and adolescents aged 7-17 who were treated with fluoxetine.This data set was drawn from two large clinical trials involving children and adolescents with depression. Subjects with a diagnosis of major depressive disorder and depressive symptoms of at least moderate severity as defined by a Children's Depression Rating Score, Revised (CDRS-R) total scoreor=40 and a Clinical Global Impressions-Severity (CGI-S) ratingor=4 were included. Subjects were randomized to receive fluoxetine or placebo over an 8-week period. Predictor analyses examining two primary outcomes were conducted: (1) Response based on Clinical Global Impressions-Improvement (CGI-I) score of 1 or 2, and (2) remission based on CDRS-R score ofor=28. Logistic regression models were run to assess whether anxiety disorders were a predictor of response or remission.A total of 309 study participants were included. The only factor found to influence response was treatment with fluoxetine (p = 0.022, odds ratio [OR] = 2.08, 95% confidence interval [CI] 1.30, 3.31). Several factors were found to influence remission: Treatment with fluoxetine (p0.0001, OR = 3.17, 95% CI 1.80, 5.57), gender (p = 0.024, OR = 1.90, 95% CI 1.09, 3.30), and number of co-morbid diagnoses (p = 0.026, OR 0.73, 95% CI 0.55, 0.96).Anxiety disorders alone did not predict response or remission, but the total number of co-morbid illnesses was associated with remission in depressed children and adolescents treated with fluoxetine.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder in 2005, with a 2007 update. This second update, in conjunction with the International Society for Bipolar Disorders (ISBD), reviews new evidence and is designed to be used in conjunction with the previous publications. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate, and several atypical antipsychotics continue to be first-line treatments for acute mania. Tamoxifen is now suggested as a third-line augmentation option. The combination of olanzapine and carbamazepine is not recommended. For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. New data support the use of adjunctive modafinil as a second-line option, but also indicate that aripiprazole should not be used as monotherapy for bipolar depression. Lithium, lamotrigine, valproate, and olanzapine continue to be first-line options for maintenance treatment of bipolar disorder. New data support the use of quetiapine monotherapy and adjunctive therapy for the prevention of manic and depressive events, aripiprazole monotherapy for the prevention of manic events, and risperidone long-acting injection monotherapy and adjunctive therapy, and adjunctive ziprasidone for the prevention of mood events. Bipolar II disorder is frequently overlooked in treatment guidelines, but has an important clinical impact on patients' lives. This update provides an expanded look at bipolar II disorder.

The independent association of age and other factors with suicidality in patients with major depression with psychotic features was examined. Of the 183 study participants, 21% had a suicide attempt during the current episode. Male gender, Hispanic background, past suicide attempt, higher depression scores, and higher cognitive scores were each independently associated with greater intensity of current suicidality. Older age was independently associated with a lower risk of a lifetime suicide attempt. These findings reinforce the evidence that patients with psychotic depression are at high risk for suicide and underscore the importance of examining correlates of suicidality specific to patients with psychotic depression.

The purpose of the present study was to examine the experimental and epidemiologic evidence linking benzodiazepine use to driving impairment.We searched MEDLINE, PsycINFO, the Cochrane Collaboration, and EMBASE using the key terms ("benzodiazepines" OR "exp benzodiazepines") AND ("automobile driving" OR "accidents, traffic" OR "driving" OR "driver$") and limited the results to English citations from 1966 to August 5, 2005, with auto-updates for MEDLINE and PsycINFO to November 30, 2007.Experimental studies using driving simulators and on-road tests were sought, as were epidemiologic studies of a case-control or cohort design. Data were extracted by blinded raters and pooled using random-effects models. We excluded studies without control groups or without measures of driving or collisions. Studies with driving measures that could not be combined were also excluded.Of 405 potential articles, 11 epidemiologic and 16 experimental studies were included in the meta-analysis. Associations between motor vehicle collisions (MVCs) and benzodiazepine use were found among 6 case-control studies (OR = 1.61, 95% CI = 1.21 to 2.13, p.001), and 3 cohort studies (OR = 1.60, 95% CI = 1.29 to 1.97, p.0001). Only 10 of 97 experimental driving variables could be pooled for analysis. While no consistent findings were observed in studies using driving simulators, increased deviation of lateral position was found on on-road driving tests (standardized mean difference = 0.80, 95% CI = 0.35 to 1.25, p = .0004).Benzodiazepine users were found to be at a significantly increased risk of MVCs compared to nonusers, and these differences may be accounted for by a difficulty in maintaining road position.

Using data from a national survey, this study examined different factors and their association with mental health service use in youth aged 15-24 with depression and/or suicidality. Our sample consisted of 1,252 youth with depression and/or suicidality. In youth aged 15-18 years old, two factors influenced service use: (1) co-occurrence of depression and suicidality (OR 3.23, 95% CI 1.43, 7.32) and (2) chronic health condition (OR 2.44, 95% CI 1.22, 4.84). Several factors were associated with service use in youth aged 19-24 including gender (female) (OR 1.77, 95% CI 1.14, 2.76), and low income (OR 1.89, 95% CI 1.11, 3.23). The findings suggest differences in the factors associated with mental health service use between youth aged 15-18 and 19-24 with depression and/or suicidality.

Objective: Antidepressants are recommended for the treatment of depressive and anxiety symptoms in patients with major depressive disorder, but caution is urged when used for the treatment of these symptoms in bipolar disorder. It is not known whether these differing recommendations are reflected in clinical practice, as comparative analyses of rates of antidepressant use between bipolar disorder and major depressive disorder subjects with or without comorbid anxiety have not been reported. Method: Data source was the Canadian Community Health Survey on Mental Health and Well-Being, a large, representative mental health survey conducted from May to December 2002. Rates of antidepressant use were compared for subjects with bipolar disorder according to the World Mental Health-Composite International Diagnostic Interview or major depressive disorder according to DSM-IV criteria, with or without comorbid anxiety (DSM-IV). The independent effects of the diagnostic group and of a comorbid anxiety disorder were determined by controlling for sociodemographic and clinical variables using logistic regression. Results: Rate of antidepressant use was significantly higher among all subjects with bipolar disorder (N = 756) compared with all subjects with major depressive disorder (N = 3863) (27.2% vs. 23.1%, p = .02), but this difference was no longer significant when other factors were controlled for in the regression analysis. With the major depressive disorder without anxiety group as the reference, the likelihood of antidepressant use was significantly higher in both the bipolar disorder with anxiety group (OR = 1.83, 95% CI = 1.02 to 3.27, p = .04) and the major depressive disorder with anxiety group (OR = 1.45, 95% CI = 1.00 to 2.09, p = .05). Conclusion: After sociodemographic and clinical variables were controlled for, similar rates of antidepressant use were identified among bipolar disorder and major depressive disorder subjects. Further efforts are needed to enhance screening for bipolar disorder among depressed patients and to re-examine the risk/benefit analysis of antidepressants for bipolar disorder patients in light of emerging alternatives. Significantly increased rates of antidepressant use in subjects with a comorbid anxiety disorder suggest that anxiety symptoms may be a key reason why physicians are choosing to prescribe antidepressants for patients with bipolar disorder and major depressive disorder.

There has been an exponential increase in recent years of literature pertaining to the treatment of individuals with alcohol use disorders and co-morbid psychiatric disorders. Patients with mood and anxiety disorders in particular have a very high prevalence of alcoholism. Alcoholism confers significant morbid risks to patients with psychiatric disorders, and vice versa, including markedly increased risk of suicide. Only recently have studies examined the impact of various psychiatric medications on alcohol use among patients with these disorders. Evidence supporting the benefits of antidepressants for co-morbid alcoholism and depression continues to mount. Although these studies have demonstrated benefits in terms of quantitative decreases in the volume and frequency of consumption, the benefits in terms of remission from alcoholism have yet to be shown conclusively. The first randomised, controlled trial involving subjects with co-morbid alcoholism and bipolar disorder was recently conducted, yielding promising results for valproate in this population. The literature regarding co-morbid alcoholism and anxiety disorders has also seen recent progress, particularly in the study of post-traumatic stress disorder (PTSD). A placebo-controlled study of sertraline suggests some benefit in terms of alcohol use among individuals with early-onset PTSD and less severe alcohol dependence. Atypical antipsychotics such as olanzapine and quetipaine have been examined in several open studies of subjects with alcoholism co-morbid with a variety of psychiatric conditions including bipolar disorder, PTSD and schizophrenia. This paper selectively reviews the evidence that is currently available for the pharmacological management of alcoholism among persons with co-morbid psychiatric illness. Effectiveness, safety and tolerability are considered, and directions for future study are discussed.