Bipolar Disorder: O'Donovan C

Yatham LN, Kennedy SH, O'Donovan C, Parikh SV, MacQueen G, McIntyre RS, Sharma V, Beaulieu S, Anonymous00162. · Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada. · Bipolar Disord. · Pubmed #17156158 No free full text.

Abstract: In 2005, the Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder. This update reviews new evidence since the previous publication and incorporates recommendations based on the most current evidence for treatment of various phases of bipolar disorder. It is designed to be used in conjunction with the 2005 CANMAT Guidelines. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate and several atypical antipsychotics continue to be recommended as first-line treatments for acute mania. For the management of bipolar depression, new data support quetiapine monotherapy as a first-line option. Lithium and lamotrigine monotherapy, olanzapine plus selective serotonin reuptake inhibitors (SSRI), and lithium or divalproex plus SSRI/bupropion continue to remain the other first-line options. First-line options in the maintenance treatment of bipolar disorder continue to be lithium, lamotrigine, valproate and olanzapine. There is recent evidence to support the combination of olanzapine and fluoxetine as a second-line maintenance therapy for bipolar depression. New data also support quetiapine monotherapy as a second-line option for the management of acute bipolar II depression. The importance of comorbid psychiatric and medical conditions cannot be understated, and this update provides an expanded look at the prevalence, impact and management of comorbid conditions in patients with bipolar disorder.

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.

Alda M, Hajek T, Calkin C, O'Donovan C. · Department of Psychiatry, Dalhousie University, 5909 Veterans Memorial Lane, Halifax, Nova Scotia, Canada. · Ann Med. · Pubmed #18821183 No free full text.

Abstract: Treatment of bipolar disorder (BD) has traditionally focused on alleviation of acute symptoms and prevention of future recurrences. Current treatment guide-lines advocate more or less similar treatment algorithms for all patients. Such approach largely ignores the clinical, genetic, and pathophysiological heterogeneity of BD, which makes certain patients more (or less) likely to respond to specific treatments. Variables such as family history, comorbidity, course of illness, quality and duration of previous remissions, physical and medical comorbidity, and side-effects may help in selecting the most effective treatment for an individual patient, yet their value is not recognized by current algorithms. As well, polymorphisms of specific genes may prove useful in predicting treatment outcome and/or understanding the pharmacological mechanisms of mood stabilization. Novel molecular targets have recently emerged from studies of mechanisms of action of available mood stabilizers. They include inhibitors of protein kinase C, inhibitors of glycogen synthase kinase, or medications modulating glutamatergic neurotransmission. As well, treatment targets are moving beyond acute symptoms and prevention of mood episodes. Cognitive deficits, persistence of residual symptoms, and increased mortality of BD are recognized as important for outcome of BD, yet are not always adequately addressed by traditional treatments.

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.

O'Donovan C, Garnham JS, Hajek T, Alda M. · Queen Elizabeth II Health Sciences Centre, Mood Disorders Program, Department of Psychiatry, Abbie J. Ln. Memorial Bldg., 3rd floor, Veterans Memorial Lane, Dalhousie University, Halifax, Nova Scotia, Canada. · J Affect Disord. · Pubmed #17850879 No free full text.

Abstract: OBJECTIVE: To identify specific treatment-emergent symptoms in response to antidepressant therapy in depression preceding bipolar disorder. METHODS: Retrospective chart review of response to antidepressants in "pre-bipolar" depression, compared to a matched unipolar sample. RESULTS: Family history of completed suicide (p=0.0003) and bipolar disorder (p=0.004) were more common in the pre-bipolar subgroup. Earlier age of onset of diagnosed depression (p=0.005) as well as even earlier episodes of untreated retrospectively diagnosed major depression (p<0.0001) were associated with a future bipolar course. The pre-bipolar group was less likely to respond to antidepressant treatment (p=0.009). Treatment-emergent "mixed" symptoms (two or more symptoms of DSM IV mania, mood lability, irritability/rage with co-existing depression) and in particular, "serious symptoms" (treatment emergent or increased agitation, rage or suicidality) occurred more commonly in the bipolar group. The two variables that best accounted for the between-group differences in logistic regression, were early age at first symptoms of depression and treatment-emergent agitation. CONCLUSIONS: Family history of completed suicide and/or bipolar disorder, early onset of depressive symptoms as well as treatment-emergent "mixed" symptoms are common in depression preceding the diagnosis of bipolar disorder.

Garnham J, Munro A, Slaney C, Macdougall M, Passmore M, Duffy A, O'Donovan C, Teehan A, Alda M. · Department of Psychiatry, Capital District Health Authority, Halifax, Canada. · J Affect Disord. · Pubmed #17442400 No free full text.

Abstract: BACKGROUND: The objective of this study was to evaluate effectiveness of commonly used prophylactic treatments for bipolar disorder in a naturalistic setting and to explore factors associated with treatment response. METHODS: We reviewed charts of 120 patients with a confirmed diagnosis of bipolar I or bipolar II disorder. The sample consisted of 37 males and 83 females, in the age range of 20 to 81 years (mean age 45+/-14 years), treated at an outpatient psychiatry program in a teaching hospital. In contrast to controlled clinical trials, we did not exclude subjects with co-morbid conditions and/or substance abuse. Treatment outcome was evaluated using a scale for retrospective assessment of prophylactic treatment response. The scale rates the degree of improvement in the course of treatment weighted by the likelihood of response being attributable to the treatment. The inter-reliability of the assessments was good with concordance of ratings of 90% and weighted kappa of 0.8. RESULTS: Rates of full response to individual mood stabilizers were: lithium 30%, carbamazepine 0%, valproate 13%, lamotrigine 11%, and olanzapine 25%. Lithium responders were more likely to be bipolar II, and had a typically episodic course of illness with earlier onset in comparison with non-responders. Responders to valproate had higher rates of psychosis. LIMITATIONS: Data were obtained by chart reviews. CONCLUSIONS: Less than one-third of patients treated with lithium achieved remission; the effectiveness of other treatments in this naturalistic sample was even lower.

Grof P, Duffy A, Cavazzoni P, Grof E, Garnham J, MacDougall M, O'Donovan C, Alda M. · Department of Psychiatry, University of Ottawa, Ontario, Canada. · J Clin Psychiatry. · Pubmed #12416605 No free full text.

Abstract: BACKGROUND: Selecting a drug according to the treatment response in a relative has been widely accepted advice in the management of mood disorders. However, this recommendation has not been adequately substantiated in the literature. We tested the hypothesis that response to long-term lithium treatment is a familial trait. METHOD: We compared response to long-term lithium treatment in bipolar relatives of bipolar lithium responders and bipolar controls. Twenty-four relatives with bipolar disorder (as determined using the Schedule for Affective Disorders and Schizophrenia-Lifetime version [SADS-L] and Research Diagnostic Criteria [RDC]) were identified in families of 106 patients with lithium-responsive bipolar disorder. A consecutive series of 40 lithium-treated patients in a bipolar clinic (meeting RDC and DSM-IV criteria for bipolar disorder) served as a comparison group. Lithium response was evaluated on a rating scale reflecting the quality and quantity of available data. RESULTS: The prevalence of unequivocal response among the relatives was 67%, as compared with the response rate of 35% in the comparison group (chi2 = 6.04, df = 1, p = .014). CONCLUSION: This highly significant difference in response between relatives and the control group supports the view that the response to lithium prophylaxis clusters in families.

O'Donovan C, Kusumakar V, Graves GR, Bird DC. · Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. · J Clin Psychiatry. · Pubmed #12000206 No free full text.

Abstract: BACKGROUND: Valproate treatment has been associated with high rates of menstrual abnormalities, hyperandrogenism, and polycystic ovaries in women with epilepsy. This pilot study investigated whether valproate treatment had the same associations in women with bipolar disorder. METHOD: One hundred forty outpatient women with a DSM-IV diagnosis of bipolar disorder (aged 15-45 years) were surveyed on their medical, psychiatric, and reproductive health history. Thirty-two women met entry criteria for the study and were divided into 2 groups: (1) those currently receiving valproate (valproate, N = 17) and (2) those who were not currently taking valproate (nonvalproate, N = 15). These 2 groups were compared with a normal (never diagnosed with a psychiatric disorder) control group of 22 women. Women in the valproate group with current menstrual problems (N = 7) underwent further assessment for the presence of polycystic ovaries and hyperandrogenism. RESULTS: The age at onset of menses, mean length of menstrual cycle, and mean length of menses were not significantly different between the groups. Significantly more women reported menstrual abnormalities in the valproate group (47%) than women not receiving valproate (13%) and controls (0%). Forty-one percent of women with bipolar disorder taking valproate had polycystic ovary syndrome. CONCLUSION: These results suggest high rates of menstrual disturbances and polycystic ovary syndrome in women with bipolar disorder currently receiving valproate.