Ayal Schaffer

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2009

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.

Lower dopamine transporter binding potential in striatum during depression.

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 [11C]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.

Does inclusion of a placebo arm influence response to active antidepressant treatment in randomized controlled trials? Results from pooled and meta-analyses.

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.

Community Survey of Bipolar Disorder in Canada: Lifetime Prevalence and Illness Characteristics

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.

International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder.

Bipolar disorder is associated with a high risk of suicide attempts and suicide death. The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder.

The burden of obesity among adults with bipolar disorder in the United States

Goldstein BI, Liu S‐M, Zivkovic N, Schaffer A, Chien L‐C, Blanco C. The burden of obesity among adults with bipolar disorder in the United States.
Bipolar Disord 2011: 13: 387–395.

Suicidal ideation in major depression: sex differences and impact of comorbid anxiety.

Background: Being female and having comorbid anxiety are both thought to increase suicidality in patients with major depression. Whether these effects are independent or related to severity of depression is not known. Method We conducted a retrospective review of 533 patients (190 men, 343 women) with major depression at the time of assessment. Results Suicidal ideation was present in 57.8% of all patients, and 43.2% of all patients had a lifetime anxiety disorder. Significantly more women than men experienced suicidal ideation, and both men and women with a lifetime anxiety disorder were more likely to be suicidal. Age and severity of depression did not account for these results. Conclusions In patients with a current major depression, being female and having a lifetime anxiety disorder increase suicidality independently of one another and independently of severity of depression.

Obesity and the three-year longitudinal course of bipolar disorder

Goldstein BI, Liu S‐Min, Schaffer A, Sala R, Blanco C. Obesity and the three‐year longitudinal course of bipolar disorder. 
Bipolar Disord 2013: 00: 000–000.

Bipolar disorder among adolescents and young adults: Results from an epidemiological sample

BACKGROUND Over the past decade, the clinical recognition and treatment of bipolar disorder (BD) in youth have increased significantly; however, little is known about prevalence of and service use for this disorder at a population level. The objective of this study was to measure the lifetime prevalence of BD, and to describe the socio-demographics, comorbidities, and use of mental health services among 15-24-year-olds with BD. METHODS Data were extracted from the Canadian Community Health Survey: Mental Health and Well-being (CCHS 1.2), a representative population-based survey of 36,984 people age 15 and older. Among subjects age 15-18 and 19-24 (N=5673), we calculated lifetime prevalence rates of BD and report the demographic and clinical characteristics and rates of service use of this sample. RESULTS The weighted lifetime prevalence of BD was 3.0% among 15-24-year-olds (N=191): 2.1% among 15-18-year-olds, and 3.8% among 19-24-year-olds. Rates of psychiatric comorbidity were high, with anxiety disorders, problematic substance use, and suicidality present among nearly half of the sample. Mental health services were accessed in the previous 12 months by 56.1% of youth with BD. LIMITATIONS The questionnaire used in CCHS 1.2 relied on self-report, limiting its applicability to this younger sample. CONCLUSIONS BD is particularly common among young adults and there are specific factors associated with BD in youth. Nearly half of all youth with BD have never used mental health services, suggesting that clinicians should be more vigilant about the signs and symptoms of BD in young people.

Excessive and premature new-onset cardiovascular disease among adults with bipolar disorder in the US NESARC cohort.

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.