Anxiety Disorders: Yatham LN

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.

Cassidy F, Yatham LN, Berk M, Grof P. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. · Bipolar Disord. · Pubmed #18199232 No free full text.

Abstract: OBJECTIVE: To review issues surrounding the diagnosis and validity of bipolar manic states. METHODS: Studies of the manic syndrome and its diagnostic subtypes were reviewed emphasizing historical development, conceptualizations, formal diagnostic proposals, and validation. RESULTS: Definitions delineating mixed and pure manic states derive some validity from external measures. DSM-IV and ICD-10 diagnosis of bipolar mixed states are too rigid and less restrictive definitions can be validated. Anxiety is a symptom often overlooked in diagnosis of manic subtypes and may be relevant to the mixed manic state. The boundary for separation of mixed mania and depression remains unclear. A 'pure' non-psychotic manic state similar to Kraepelin's 'hypomania' has been observed in several independent studies. CONCLUSIONS: Issues surrounding diagnostic subtyping of manic states remain complex and the debates surrounding categorical versus dimensional approaches continue. To the extent that categorical approaches for mixed mania diagnosis are adopted, both DSM-IV and ICD-10 are too rigid. Inclusion of non-specific symptoms in definitions of mixed mania, such as psychomotor agitation, does not facilitate and may hinder the diagnostic separation of pure and mixed mania. The inclusion of a diagnostic seasonal specifier for DSM-IV, which is currently based on seasonal patterns for depression might be expanded to include seasonal patterns for mania. Boundaries between subtypes may be 'fuzzy' rather than crisp, and graded approaches could be considered. With the continued development of new tools, such as imaging and genetics, alternative approaches to diagnosis other than the purely symptom-centric paradigms might be considered.

Yatham LN. · Division of Mood Disorders, University of British Columbia, Vancouver, British Columbia, Canada. · J Clin Psychiatry. · Pubmed #15242330 No free full text.

Abstract: The anticonvulsants valproate and carbamazepine have efficacy in treating acute mania, but their efficacy in treating acute bipolar depression and preventing mood episodes remains uncertain. Despite this, and given their utility and widespread use, both are widely accepted as standard treatments for bipolar disorder. All the newer anticonvulsants that have become available during the last decade have been or are being assessed to determine their efficacy in the treatment of various phases of bipolar disorder. Among the newer anticonvulsants, some appear to have efficacy in treating core bipolar symptoms, while others have efficacy in treating psychiatric comorbidity such as substance abuse or an anxiety disorder. Lamotrigine is the most widely studied and is effective in treating and preventing bipolar depression, and it is the only anticonvulsant approved by the U.S. Food and Drug Administration as a maintenance treatment for bipolar disorder. Other newer anticonvulsants, levetiracetam, oxcarbazepine, phenytoin, and zonisamide offer promise, but further studies are required before they can be recommended for routine use to treat bipolar disorder. Gabapentin and topiramate do not appear to have efficacy in treating acute mania, but their utility in bipolar depression and prevention of mood episodes has not been studied in double-blind trials. Pregabalin has utility in treating generalized anxiety disorder, but it has not been studied in bipolar disorder. Given the success of lamotrigine in treating bipolar disorder, further double-blind controlled trials of the newer anticonvulsants in treating bipolar disorder are warranted. This article summarizes current evidence from trials of anticonvulsants in bipolar disorder and makes recommendations for their clinical use.

Yatham LN. · Mood Disorders Clinical Research Unit, The University of British Columbia, Vancouver, BC, V6T 2A1, Canada. · Bipolar Disord. · Pubmed #14700009 No free full text.

Abstract: Bipolar disorder is a complex condition including depression, mania, and in many cases associated with comorbid anxiety symptoms and substance abuse. Mood stabilizers including lithium and divalproex have been considered standard therapy for the treatment of patients with bipolar disorder, but remission rates remain inadequate. Conventional antipsychotics have demonstrated efficacy for acute mania, but they appear to have little role in the maintenance treatment of bipolar disorder. Despite substantial evidence of efficacy and recent guideline recommendations, atypical antipsychotics remain underused for the treatment of bipolar disorder. Data from double-blind, controlled trials are available for a number of clinically meaningful efficacy measures, including improvement in manic symptoms, onset of action, response rates, remission rates, improvement in comorbid depressive symptoms, and induction/worsening of mania or depression. Atypical antipsychotics are effective both as alternatives to lithium or divalproex as monotherapy, or in combination with these mood stabilizers, in the acute and likely the maintenance treatment of mania. The atypical antipsychotics represent an effective and relatively safe addition to our armamentarium for the treatment of bipolar disorder.

Piver A, Yatham LN, Lam RW. · Nelson Mental Health Centre, Kootenay Lake Regional Hospital, Nelson, BC. · Can Fam Physician. · Pubmed #12053634 links to  free full text

Abstract: OBJECTIVE: To review new perspectives on diagnosis, clinical features, epidemiology, and treatment of bipolar II and related disorders. QUALITY OF EVIDENCE: Articles were identified by searching MEDLINE and ClinPSYCH from January 1994 to August 2001 using the key words bipolar disorder, type II or 2; hypomania; spectrum; or variants. Reference lists from articles were reviewed. Overall, the quality of evidence was not high; we found no randomized controlled trials that specifically addressed bipolar II or bipolar spectrum disorders (BSDs). MAIN MESSAGE: Characterized by elevated mood cycling with depression, BSDs appear to be much more common than previously thought, affecting up to 30% of primary care patients presenting with anxiety or depressive symptoms. Hypomania, the defining feature of bipolar II disorder, is often not detected. Collateral information, semistructured interviews, and brief screening instruments could improve diagnosis. Antidepressants should be used with caution. The newer mood stabilizers or combinations of mood stabilizers might be the treatments of choice in the future. CONCLUSION: Family physicians, as primary providers of mental health care, should try to recognize and treat BSDs more frequently. These disorders are becoming increasingly common in primary care populations.

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.

Malempati RN, Bond DJ, Yatham LN. · Mood and Anxiety Disorders Program, Hotel-Dieu Grace Hospital, Windsor, Ontario, Canada. · Int Clin Psychopharmacol. · Pubmed #18301123 No free full text.

Abstract: Nonadherence with pharmacotherapy occurs frequently in bipolar patients, and is a common cause of relapse. Depot formulations of first-generation antipsychotic medications have been shown to reduce manic relapses during maintenance therapy in bipolar patients, but appear to increase liability for depressive episodes. A depot formulation of risperidone has recently become commercially available, but to date there is little evidence regarding its efficacy or safety in bipolar patients. Ten outpatients with bipolar I or II disorder, with a predominantly depressive course of illness, were prescribed risperidone Consta as an adjunct to mood stabilizing and other medications in routine clinical practice, and were followed during 2 years of maintenance therapy. The number of mood episodes, including depressive episodes, decreased in all patients compared with an equivalent pretreatment period. No patient required hospitalization for a mood episode. The number and doses of concomitant medications was reduced in most patients risperidone Consta was well tolerated, with minimal to modest weight gain, absent or reduced extrapyramidal symptoms, and few other side effects. Clinicians may consider risperidone Consta as an option in patients with refractory bipolar illness, including those with a predominantly depressive course, and particularly in patients' nonadherence with prescribed medications.

Lam RW, Tam EM, Yatham LN, Shiah IS, Zis AP. · Division of Mood Disorders, Department of Psychiatry, University of British Columbia Hospital, Vancouver Hospital and Health Sciences Centre, 2255 Wesbrook Mall, BC, Canada V6T 2A1. · J Affect Disord. · Pubmed #11246088 No free full text.

Abstract: OBJECTIVE: In DSM-IV, winter seasonal affective disorder (SAD) is classified as a seasonal pattern of recurrent major depressive episodes in winter with full remission of symptoms in summer. However, other groups with "winter depression" have been identified, including patients with incomplete summer remission (ISR) and subsyndromal SAD (sub-SAD, winter depressive symptoms that do not meet criteria for major depression). In this study, we compare the clinical characteristics of these three seasonal groups and their response to light therapy. METHOD: 558 patients assessed at a specialized SAD Clinic were diagnosed using DSM-III-R or DSM-IV criteria. Clinical information was recorded using a checklist at index assessment. A subset of patients (N=192) were treated with an open, 2 week trial of light therapy using a 10000 lux fluorescent light box for 30 min per day in the early morning. Patients were assessed before and after treatment with the 29 item modified Hamilton Depression Rating Scale and clinical response was defined as greater than 50% improvement in scores. RESULTS: The rates of some melancholic symptoms, anxiety, panic, suicidal ideation, and family history of mood disorder were lowest in the sub-SAD group. The clinical response rates to light therapy were highest in the sub-SAD group (N=32, 78%), intermediate in the SAD group (N=113, 66%), and lowest in the ISR group (N=47, 51%). LIMITATIONS: This was a retrospective study of patients seen in a specialty clinic, although information was obtained in a standardized format. The light therapy trial had an open design so that placebo response could not be determined. CONCLUSIONS: There are differences in both the patterns of clinical symptoms and the response to light therapy in these three groups with winter depression. These results are consistent with a dual vulnerability hypothesis that considers these groups to result from interaction of separate factors for seasonality and depression.

Tohen M, Frank E, Bowden CL, Colom F, Ghaemi SN, Yatham LN, Malhi GS, Calabrese JR, Nolen WA, Vieta E, Kapczinski F, Goodwin GM, Suppes T, Sachs GS, Chengappa KR, Grunze H, Mitchell PB, Kanba S, Berk M. · Department of Psychiatry, Division of Mood and Anxiety Disorders, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7792, San Antonio, TX 78229, USA. · Bipolar Disord. · Pubmed #19624385 No free full text.

Abstract: OBJECTIVES: Via an international panel of experts, this paper attempts to document, review, interpret, and propose operational definitions used to describe the course of bipolar disorders for worldwide use, and to disseminate consensus opinion, supported by the existing literature, in order to better predict course and treatment outcomes. METHODS: Under the auspices of the International Society for Bipolar Disorders, a task force was convened to examine, report, discuss, and integrate findings from the scientific literature related to observational and clinical trial studies in order to reach consensus and propose terminology describing course and outcome in bipolar disorders. RESULTS: Consensus opinion was reached regarding the definition of nine terms (response, remission, recovery, relapse, recurrence, subsyndromal states, predominant polarity, switch, and functional outcome) commonly used to describe course and outcomes in bipolar disorders. Further studies are needed to validate the proposed definitions. CONCLUSION: Determination and dissemination of a consensus nomenclature serve as the first step toward producing a validated and standardized system to define course and outcome in bipolar disorders in order to identify predictors of outcome and effects of treatment. The task force acknowledges that there is limited validity to the proposed terms, as for the most part they represent a consensus opinion. These definitions need to be validated in existing databases and in future studies, and the primary goals of the task force are to stimulate research on the validity of proposed concepts and further standardize the technical nomenclature.

Yatham LN, Fallu A, Binder CE. · Mood Disorders Program, The University of British Columbia, UBC Hospital, Vancouver, BC, Canada. · Acta Psychiatr Scand Suppl. · Pubmed #17688463 No free full text.

Abstract: OBJECTIVE: To determine the safety and effectiveness of long-acting injectable risperidone (LAI-ris) add-on in bipolar patients. METHOD: A 6-month, open-label, randomized, pilot trial enrolled 49 bipolar out-patients who were taking a mood stabilizer and an atypical antipsychotic (AAP). Patients were maintained on a mood stabilizer and were randomized to continuation of their current AAP or switched to LAI-ris treatment. Safety outcomes included adverse events and changes in vital signs, laboratory tests and extrapyramidal symptoms (EPS). Effectiveness measures included Clinical Global Impression-Severity, scales assessing mania, depression, anxiety, resource utilization, quality of life, subject satisfaction with treatment, and time to intervention. RESULTS: Twenty-three subjects were randomized to LAI-ris and 26 to oral AAP. There were no significant differences between the groups in adverse events, EPS change scores, weight or other safety measures. LAI-ris group had significant reductions in symptoms as measured by changes in Clinical Global Impression-Severity scores and Young Mania Rating Scale at endpoint relative to baseline and oral AAP group had reductions in Hamilton Anxiety Rating Scale scores relative to baseline but no significant differences were noted between the groups on any of the efficacy measures. CONCLUSION: LAI-ris demonstrated similar effectiveness, safety and tolerability compared to oral AAP in this 6 month pilot trial.

Kauer-Sant'Anna M, Tramontina J, Andreazza AC, Cereser K, da Costa S, Santin A, Yatham LN, Kapczinski F. · Post-Graduate Biochemistry Program, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. · Bipolar Disord. · Pubmed #17543031 No free full text.

Abstract: BACKGROUND: There is evidence that vulnerability to depression and anxiety disorders is markedly increased by traumatic life events. While childhood abuse has been reported to be associated with poorer outcomes in bipolar disorder, little is known about the neurobiological basis underlying this association. The aim of this study was to ascertain whether bipolar patients who were exposed to a traumatic event or events (TE) have lower brain-derived neurotrophic factor (BDNF) levels and more severe psychopathology as indicated by increased comorbidity and other clinical features when compared to those who were not exposed to TE. METHODS: One-hundred and sixty-three consecutively recruited bipolar outpatients were assessed by Structured Clinical Interview for DSM-IV (SCID) and standard protocol in order to evaluation psychopathology and clinical features. The reported TE was assessed using DSM-IV stem criteria for trauma (as defined by A1 and A2 criteria for trauma for post-traumatic stress disorder). Subjects were divided into 2 groups according to presence or absence of lifetime TE. The levels of BDNF, comorbidity and other clinical features were compared between groups. RESULTS: After adjusting for confounders, results indicated that bipolar patients with a history of TE have alcohol abuse/dependence (p < 0.001), anxiety comorbidity, and lower levels of serum BDNF (p < 0.01) compared to those without a history of TE. There was no difference between the 2 groups in age of onset, presence of psychosis, other substance abuse and dependence, rapid cycling or suicide attempts. CONCLUSIONS: Our findings suggest that TE are associated with significantly increased prevalence of alcohol and anxiety comorbidity as well as lower BDNF levels in bipolar patients. It is possible that a decrease in BDNF levels may account for increased comorbidity, but further prospective studies are required to confirm this.

Yatham LN, Kennedy SH, Lam RW. · University of British Columbia, Vancouver, BC. · Bipolar Disord. · Pubmed #14687068 No free full text.

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