Bipolar Disorder: Schaffer A

Yatham LN, Kennedy SH, O'Donovan C, Parikh S, MacQueen G, McIntyre R, Sharma V, Silverstone P, Alda M, Baruch P, Beaulieu S, Daigneault A, Milev R, Young LT, Ravindran A, Schaffer A, Connolly M, Gorman CP, Anonymous00076. · Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. · Bipolar Disord. · Pubmed #15952957 No free full text.

Abstract: 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.

Goldstein BI, Diamantouros A, Schaffer A, Naranjo CA. · Department of Psychiatry, Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Toronto, Canada. · Drugs. · Pubmed #16827599 No free full text.

Abstract: 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.

Yatham LN, Kennedy SH, Schaffer A, Parikh SV, Beaulieu S, O'Donovan C, MacQueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Young AH, Alda M, Milev R, Vieta E, Calabrese JR, Berk M, Ha K, Kapczinski F. · Department of Psychiatry, University of British Columbia,2255 Wesbrook Mall, Vancouver, BC V6T 2A1, , Canada. · Bipolar Disord. · Pubmed #19419382 No free full text.

Abstract: 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.

Schaffer A, Levitt AJ. · No affiliation provided · J Clin Psychopharmacol. · Pubmed #16160638 No free full text.

This publication has no abstract.

Schaffer A, Levitt AJ, Joffe RT. · Department of Psychiatry, Sunnybrook Health Science Center, 2075 Bayview Avenue, Room FG46, University of Toronto, Toronto, Canada. · J Affect Disord. · Pubmed #10708839 No free full text.

Abstract: BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of mexiletine, a medication with antiarrhythmic, anticonvulsant and analgesic properties, in treatment-resistant bipolar disorder patients. METHODS: Twenty subjects with rapid-cycling bipolar disorder who had failed to respond or were intolerant to lithium, valproic acid and carbamazepine were entered into the 6-week, open label study. Subjects were followed on a weekly basis for dosing of mexiletine, blood levels, and completion of the Hamilton Depression Rating Scale (HAM-D) and the Manic State Rating Scale (MSRS). "Burden of Mood Symptoms" (BMS) was calculated by combining scores for the HAM-D and MSRS. RESULTS: Thirteen subjects (10 female, 3 male), mean age 41 years (S.D.=7.6), and mean duration of illness 20 years (S.D.=7.7) completed the study. The dose range of mexiletine was 200-1200 mg/day. Full response (>/=50% reduction in BMS) was seen in 46% of the subjects, and a partial response (25-49% reduction in BMS) in 15%. Of note, 5/5 subjects with a mixed or manic state demonstrated a full or partial response. LIMITATIONS: This study has an open label design, and a small number of subjects. CONCLUSIONS: Mexiletine may be effective and safe in patients with highly treatment-resistant, chronic bipolar disorder. Randomized, controlled trials are required to confirm the current results.

Schaffer A, Cairney J, Veldhuizen S, Cheung A, Levitt A. · Mood Disorders Program, Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. · J Clin Psychiatry. · Pubmed #18052573 No free full text.

Abstract: 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.

Schaffer A, Zuker P, Levitt A. · Mood Disorders Program, Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. · J Affect Disord. · Pubmed #16820213 No free full text.

Abstract: BACKGROUND: Uncertainty exists regarding the best approach for treating bipolar depression among patients already receiving a first-line mood stabilizer. The aim of this pilot study was to compare adding a second mood stabilizer or an antidepressant at this treatment decision point. METHODS: Twelve-week, randomized, double-blind pilot trial comparing the addition of lamotrigine or citalopram for bipolar depressed patients on mood stabilizer medication. Change in depressive symptoms and risk of switch were examined. RESULTS: Twenty subjects were randomized. Each treatment group experienced a significant mean reduction in total MADRS scores (citalopram Delta - 14.2, p=0.002; lamotrigine Delta - 13.3, p= 0.001), and there was no significant difference between treatment groups (p=0.78). Total response rates increased from 31.6% at week 6 to 52.6% at week 12. One out of ten patients in each group experienced a switch to hypomania. LIMITATIONS: Small sample size. Lack of a placebo arm. CONCLUSIONS: Results of this small trial suggest that both lamotrigine and citalopram appear to be reasonable choices as add-on acute treatment for bipolar depression, with response rates continuing to rise considerably past 6 weeks of treatment.

Schaffer A, Cairney J, Cheung AH, Veldhuizen S, Levitt AJ. · Department of Psychiatry, Sunnybrook & Women's College Health Sciences Centre, University of Toronto, Canada. · J Clin Psychiatry. · Pubmed #16649824 No free full text.

Abstract: 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.

Schaffer A, Cairney J, Cheung A, Veldhuizen S, Levitt A. · Sunnybrook and Women's College Health Sciences Center, University of Toronto, Toronto, Ontatrio. · Can J Psychiatry. · Pubmed #16491979 No free full text.

Abstract: 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% (955% 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.

Schaffer A, Mamdani M, Levitt A, Herrmann N. · Department of Psychiatry, Sunnybrook & Women's College Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. · Int J Geriatr Psychiatry. · Pubmed #16477586 No free full text.

Abstract: 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.

Shin K, Schaffer A, Levitt AJ, Boyle MH. · Department of Psychiatry, University of Toronto, Canada. · J Affect Disord. · Pubmed #15820267 No free full text.

Abstract: BACKGROUND: This study examined seasonality in a community sample of five diagnostic groups: normal subjects, those with non-seasonal depression (NSD), seasonal depression (SD), non-seasonal bipolar disorder (NSBD) and seasonal bipolar disorder (SBD). METHODS: Telephone interviews were conducted across the Province of Ontario. Seasonal changes in mood and behaviour were determined using the Seasonal Pattern Assessment Questionnaire (SPAQ). Five additional seasonality items consisting of depressive symptoms were included in the interview. The mean global severity of seasonality (GSS) scores were obtained and the entire inventory of 11 seasonality items were compared across the identified groups. RESULTS: The mean GSS score for the controls was 5.2 (S.D. = 4.0), 8.0 (S.D. = 4.9) for NSD, 10.5 (S.D. = 3.9) for SD, 10.5 (S.D. = 5.4) for NSBD and 13.4 (S.D. = 5.4) for SBD. These scores differed significantly (F = 61.68, df = 4, p < 0.001). For the majority of the individual items, the SBD group rated the highest degree of seasonal fluctuation, while the NSBD and SD groups had nearly identical item scores. LIMITATIONS: Limitations in this study include the relatively small number of subjects in the NSBD and SBD groups, and the inherent limitations in a telephone interview. CONCLUSIONS: Individuals with bipolar disorder experience greater seasonality than those with depression or healthy controls. Even the non-seasonal bipolar group had as much seasonal fluctuation as the seasonal depression group, which has important implications for the management of bipolar illness.

Schaffer A, Levitt AJ, Boyle M. · Department of Psychiatry, University of Toronto, Mood Disorders Program, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario. · Can J Psychiatry. · Pubmed #12776396 No free full text.

Abstract: 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.