Anxiety Disorders: Young LT

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.

MacQueen GM, Young LT. · McMaster University, McMaster University Medical Center, Hamilton, Ontario, Canada. · Psychiatr Serv. · Pubmed #11239105 links to  free full text

Abstract: The authors provide an overview of the diagnosis, course, and treatment of bipolar II disorder, a distinct subtype that is often misdiagnosed as unipolar depression or bipolar I disorder. They discuss research suggesting that underdiagnosis of bipolar II disorder reflects a failure to identify subthreshold expression of mania (hypomania). The course of bipolar II disorder is different from that of bipolar I disorder or unipolar depression, with distinct differences in rates of recovery, clinical features, and number of episodes. The risk of suicide appears to be particularly elevated. High rates of comorbid disorders have been reported, including substance abuse or dependence, anxiety disorders, and personality disorders. Few definitive studies exist on which to base conclusions about the differential efficacy of various treatment strategies in bipolar II disorder and bipolar I disorder. Preliminary studies suggest that the newer anticonvulsants may be of benefit for patients with bipolar II disorder, while other data suggest that there may be a greater role for antidepressant medications.

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.

Boylan KR, Bieling PJ, Marriott M, Begin H, Young LT, MacQueen GM. · Mood Disorders Program, Center for Mountain Health Services, St. Joseph's Hospital, Hamilton, Ontario, Canada. · J Clin Psychiatry. · Pubmed #15323597 No free full text.

Abstract: BACKGROUND: High rates of comorbid anxiety disorders have been described in individuals with bipolar disorder. Although it is well recognized that anxiety disorders often co-occur with bipolar disorder, few studies have examined the impact of more than 1 anxiety disorder on long-term outcome in patients with bipolar disorder. METHOD: The rates of DSM-IV generalized anxiety disorder, panic disorder, social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder were determined using structured clinical interviews in 138 patients with bipolar disorder who presented consecutively between 1994 and 1999. Patients were then followed for up to 3 years with longitudinal clinical surveillance. The impact of 1 or more comorbid anxiety disorders on mood symptoms and general function was evaluated. RESULTS: In our sample, 55.8% of the patients had at least 1 comorbid anxiety disorder, and 31.8% had 2 or more anxiety disorder diagnoses. The most common anxiety disorder was generalized anxiety disorder, followed by panic disorder. The presence of an anxiety disorder led to significantly (p <.05) worse outcome on global as well as specific illness measures, including illness severity, proportion of patients characterized as euthymic, and proportion of the year spent ill. Number of anxiety disorders was less important than type, with generalized anxiety disorder and social phobia having the most negative impact on outcome. CONCLUSION: Our data suggested that multiple anxiety disorder comorbidities were not infrequent in bipolar disorder and that generalized anxiety disorder and social phobia were more likely to be associated with poor outcome. We discuss some potential mechanisms and implications in our findings.

MacQueen GM, Marriott M, Begin H, Robb J, Joffe RT, Young LT. · Mood Disorders Program, McMaster University, Hamilton, ON, Canada. · Bipolar Disord. · Pubmed #14525555 No free full text.

Abstract: BACKGROUND: Many patients with bipolar disorder (BD) do not regain full function following an acute illness episode, but the extent to which this impairment is the result of persistent symptoms has not been well established. This study examined factors associated with persistent subsyndromal symptoms in a well characterized group of BD patients who were prospectively followed for an average of 3 years. METHODS: Detailed life charting data from 138 patients with BD were reviewed. Patients were categorized into euthymic, subsyndromal or syndromal groups according to the clinical state during their most recent year of follow-up. The three groups were then examined with respect to comorbidity, function and treatment received. RESULTS: Patients with subsyndromal symptoms had high rates of comorbid anxiety disorders, and were more likely to have increased rates of eating disorders as well. Patients with subsyndromal symptoms had lower global assessment of function (GAF) scores than euthymic patients, and had as many clinic contacts and medication trials as patients with full episodes of illness. CONCLUSIONS: Persistent subsyndromal symptoms in BD patients are associated with high rates of comorbidity that is important to recognize and treat in order to optimize mood and functioning.

MacQueen GM, Ramakrishnan K, Croll SD, Siuciak JA, Yu G, Young LT, Fahnestock M. · Department of Psychiatry and Behavioral Neurosciences, McMaster University Medical Centre, Hamilton, Ontario, Canada. · Behav Neurosci. · Pubmed #11584927 No free full text.

Abstract: Evidence suggests that brain-derived neurotrophic factor (BDNF) may be important in the pathophysiology of depression, in addition to its role as a neurotrophic factor for sensory neurons. The authors conducted a series of experiments examining the behavioral profile of BDNF heterozygous knockout and wild-type mice. The heterozygous and wild-type mice did not differ on measures of activity, exploration, or hedonic sensitivity, or in the forced swim test. When assessed in the learned helplessness paradigm, heterozygous mice were slower to escape after training than were wild-type mice (p = .02). This effect may be accounted for by the fact that these mice demonstrate a reduced sensitivity to centrally mediated pain, apparent on the hot plate and Formalin injection tests of nociception. Overall, heterozygous mice were not more likely to display anxious or depressive-like behaviors and, consequently, may not constitute a murine model of genetic vulnerability to mood and anxiety disorders.

Furukawa TA, Streiner DL, Young LT. · Department of Psychiatry, Nagoya City University Medical School, Mizuho-cho Mizuho-ku, Nagoya 467-8601, Japan. · J Affect Disord. · Pubmed #11356241 No free full text.

Abstract: BACKGROUND: Anxiety frequently coexists with depression, and benzodiazepines are often prescribed together with antidepressants. However, benzodiazepines themselves have little or no antidepressive effects and we lack firm evidence for or against this combination therapy. We therefore conducted a meta-analysis of relevant randomized controlled trials to date. METHODS: All randomized controlled trials that compared antidepressant-benzodiazepine treatment with antidepressant alone for adult patients with major depression were sought by electronic searches of Medline and several other databases (January 1972 to December 1998), combined with hand searching, reference searching and SciSearch. Two reviewers independently assessed the eligibility and quality of the studies. Relative risks were estimated with random effects model. RESULTS: Aggregating nine studies with a total of 679 patients, the combination therapy group was 37% (95%CI: 19-51%) less likely to drop out than the antidepressant alone group. The intention-to-treat analysis showed that the former were 63% (18-127%) to 38% (15-66%) more likely to show response (defined as 50% or greater reduction in the depression scale from baseline) up to 4 weeks. Limitations: None of the included RCTs followed the patients beyond 8 weeks. CONCLUSIONS: The potential benefits of adding a benzodiazepine to an antidepressant must be balanced judiciously against possible harm, including development of dependence and accident proneness, on the one hand, and against continued suffering following no response and drop-out, on the other.