Anxiety Disorders: McIntyre RS

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.

Enns MW, Swenson JR, McIntyre RS, Swinson RP, Kennedy SH, Anonymous00077. · Department of Psychiatry, University of Manitoba, Winnipeg, Manitoba. · Can J Psychiatry. · Pubmed #11441774 No free full text.

Abstract: BACKGROUND: The Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments partnered to produce clinical guidelines for psychiatrists for the treatment of depressive disorders. METHODS: A standard guidelines development process was followed. Relevant literature was identified using a computerized Medline search supplemented by review of bibliographies. Operational criteria were used to rate the quality of scientific evidence, and the line of treatment recommendations included consensus clinical opinion. This section, on Axis I, Axis II, and Axis III comorbidity, is 1 of 7 articles that were drafted and reviewed by clinicians. Revised drafts underwent national and international expert peer review. RESULTS: Comorbid depression on Axis I is particularly prevalent in patients with anxiety disorders, substance use disorders, and eating disorders, but it also occurs in patients with schizophrenia, attention-deficit hyperactivity disorder (ADHD), and dementia. Depressive comorbidity has implications for assessment, management, and outcome. The relation between depression and personality disorders is complex. Patient with this comorbidity often require longer, more intense, and multimodal therapies. Depression is also prevalent in medical illnesses, requires careful diagnosis, and responds to standard antidepressant treatments. CONCLUSIONS: Comorbidity can influence the course and outcome of both associated conditions. Depression-specific psychotherapy and/or pharmacotherapy should be considered when comorbid depression is diagnosed.

McIntyre RS, Keck PE. · No affiliation provided · Bipolar Disord. · Pubmed #17156151 No free full text.

This publication has no abstract.

McIntyre RS, Fallu A, Konarski JZ. · Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, Ontario, Canada. · Clin Ther. · Pubmed #17213009 No free full text.

Abstract: BACKGROUND: Mental disorders are highly prevalent, heterogeneous, and of multifactorial etiology. Collectively, they are associated with significant morbidity, mortality, and economic cost. Wellness is the optimal outcome in the management of chronic medical and psychiatric disorders. OBJECTIVES: This review provides a synopsis of definitions and operational criteria for remission in major depressive disorder, bipolar disorder, schizophrenia, anxiety disorders, and attention-deficit/hyperactivity disorder (ADHD). The overall goals were to propose a treatment framework that gives primacy to therapeutic outcomes and to provide a rationale for psychiatry to quantify and measure patient outcome. METHODS: Articles proposing definitions for remission were identified using a MEDLINE search (1966-April 2005) of the English-language literature (key terms: remission, anxiety disorders, bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder, and schizophrenia). RESULTS: Operationalizing and quantifying critical end points in psychiatric disorders may help sharpen the focus of therapeutic activity and benefit patient outcome. In the absence of a validated biomarker of psychiatric illness activity, symptomatic remission and functional restoration are the only available markers of wellness in psychiatry. There is an emerging consensus regarding a definition for remission in major depressive disorder; several working definitions for bipolar disorder, schizophrenia, and anxiety disorders have been proposed. Developments in adult mood disorders-albeit incomplete-have been informative; managing psychiatric disorders that first appear in childhood (eg, ADHD) may also benefit by objectifying patient outcome. CONCLUSIONS: Research is needed to determine the impact of applying a remission-focused model of illness management--emphasizing quantifiable, objective, and measurable end points--on overall patient outcomes.

McIntyre RS, Soczynska JK, Bottas A, Bordbar K, Konarski JZ, Kennedy SH. · Department of Psychiatry and Pharmacology, University Health Network, University of Toronto, 399 Bathurst Street, Toronto, Ontario, Canada. · Bipolar Disord. · Pubmed #17156153 No free full text.

Abstract: CONTEXT: Epidemiological, clinical and familial studies indicate that anxiety disorders (ADs) are highly comorbid in persons with bipolar disorder (BPD). The phenomenological overlap between ADs and BPD is reported more frequently in individuals with female predominant bipolar presentations (e.g., bipolar II disorder). Anxiety comorbidity in the BPD population poses a serious hazard. For example, it is associated with an intensification of symptoms, non-recovery, substance use comorbidity and harmful dysfunction (e.g., suicidality). OBJECTIVE: The evidentiary base informing treatment decisions for the anxious bipolar patient is woefully inadequate. Several expert consensus and evidence-based treatment guidelines for BPD suggest various treatment avenues, although these have been insufficiently studied. The encompassing aim of this paper is to synthesize extant studies reporting on the co-occurrence of AD and BPD. Taken together, a compelling basis emerges for prioritizing the identification and management of anxiety symptomatology in the BPD population.

McIntyre RS, Konarski JZ. · University Health Network, Edith Cavell Wing 3D-003, 399 Bathurst St, M5T 2S8, Ontario, Canada. · CNS Spectr. · Pubmed #15529087 links to  free full text

Abstract: Bipolar disorders are prevalent, disabling, and costly diseases that often pursue an inexorable course. Underdetection, misdiagnosis, and diagnostic delay frequently and unnecessarily interfere with appropriate treatment of the disorder. Mortality studies in bipolar disorder underscore the relevance of both unnatural and natural causes of death, inviting the need for improved preventative and primary health care for bipolar patients. The treatment framework for bipolar disorder must recognize and anticipate the multidimensionality and comorbidity of this illness. Pharmacotherapy is necessary, with multiple concomitant medications required for most patients. In addition, adjunctive psychosocial interventions offer enhanced compliance and may beneficially influence psychopathological and functional outcomes. This article emphasizes the public health concern of bipolar disorder, and provides tactics to enhance detection of cryptic bipolar states, underscore the clinical and pathophysiological relevance of comorbidity in bipolar disorder, and provide a framework for multimodality therapy for this condition.

Khullar A, McIntyre RS. · Department of Psychiatry, University of Alberta, Edmonton. · Can Fam Physician. · Pubmed #15526874 links to  free full text

Abstract: OBJECTIVE: To provide family physicians with a contemporary approach to formulating a treatment model for major depressive disorder that integrates definitions of new therapeutic end points, familiarizes them with tools for assessing these end points, and describes newer methods for enhancing outcome. SOURCES OF INFORMATION: Canadian Psychiatric Association Guidelines for the Treatment of Depressive Disorders, relevant articles from a MEDLINE search using the MeSH headings"full remission" and "depression," and the authors' clinical experience. MAIN MESSAGE: Major depressive disorder is an episodic, relapsing, and sometimes chronic illness. Depressive symptoms in primary care settings are often vague reports of anhedonia, anxiety, and nonspecific somatic complaints. Therapeutic objectives in depression are full remission of depressive symptoms, prevention of recurrence, and restoration of function. Depression rating scales can be useful for monitoring and treating depression. CONCLUSION: The proposed therapeutic model anticipates the chronic course of illness, defines treatment end points, encourages longer duration of treatment, and includes both pharmacologic and lifestyle therapies. The 7-item Hamilton Depression Rating Scale can assist clinicians in determining when full remission has occurred.

McIntyre RS, McCann SM, Kennedy SH. · Centre for Addiction and Mental Health, Clarke Site, Mood and Anxiety Disorders Program, 250 College Street, Toronto, ON M5T 1R8. · Can J Psychiatry. · Pubmed #11320682 No free full text.

Abstract: OBJECTIVE: To review published and nonpublished literature describing changes in weight, glucose homeostasis, and lipid milieu with antipsychotics. METHODS: A Medline search was completed using the words weight gain, diabetes mellitus, cholesterol, triglycerides, risperidone, clozapine, olanzapine, quetiapine, ziprasidone, predictors, prolactin, obesity, and conventional antipsychotics. Publications, including original articles, review articles, letters to the editor, abstracts or posters presented at professional meetings in the last 4 years, and references from published articles, were collected. Manufacturers, including Eli Lilly Canada Inc, JanssenOrtho Inc, Pfizer Canada Inc, AstraZeneca Inc, and Novartis Pharmaceuticals, were contacted to retrieve additional medical information. RESULTS: The topic of antipsychotic-induced weight gain is understudied, and there are relatively few well-controlled studies. Weight gain as a side effect has been described with both conventional and atypical antipsychotics. Moreover, some atypical antipsychotics are associated with de novo diabetes mellitus and increased serum triglyceride levels. Predictors of weight gain may be age, baseline body mass index, appetite stimulation, previous antipsychotic exposure, and antipsychotic treatment duration. CONCLUSION: Significant weight gain is reported with the existing atypical antipsychotics. The weight gain described is highly distressing to patients, may reduce treatment adherence, and may increase the relative risk for diabetes mellitus and hypertriglyceridemia. Physicians employing these agents should routinely monitor weight, fasting blood glucose, and lipid profiles.

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.

McIntyre RS, Mancini DA, McCann S, Srinivasan J, Sagman D, Kennedy SH. · Department of Psychiatry, University of Toronto, Mood and Anxiety Disorders Program, Center for Addiction and Mental Health, Clarke Site, Ontario, Canada. · Bipolar Disord. · Pubmed #12180276 No free full text.

Abstract: OBJECTIVE: Antiepileptic drugs (AEDs) are commonly employed in the treatment of bipolar disorder. The efficacy and tolerability of topiramate, a novel anticonvulsant, and bupropion SR when added to mood stabilizer therapy were compared under single-blind conditions (rater-blinded) in patients meeting DSM-IV criteria for bipolar I/II depression. METHODS: A total of 36 out-patients with Hamilton Depression Rating Scale (HDRS-17) scores > or = 16 were randomized to receive escalating doses of either topiramate (50-300 mg/day) or bupropion SR (100-400 mg/day) for 8 weeks. Data were analyzed on an intent-to-treat basis using the last observation carried forward method. RESULTS: The percentage of patients meeting a priori response criteria (> or = 50% decrease from baseline in mean HDRS-17 total score) was significant for both topiramate (56%) and bupropion SR (59%) [t(17) = 2.542, p = 0.04 and t(17) = 2.661, p = 0.03, respectively]. Baseline demographic and clinical parameters were comparable between the two treatment groups. The mean doses of study medication were 176 mg/day (SD = 102 mg/day) for the topiramate-treated group and 250 mg/day (SD = 133 mg/day) for the bupropion SR-treated group. A significant and comparable reduction in depressive symptoms was observed from baseline to endpoint following topiramate and bupropion SR treatment, according to a > or = 50% reduction in the HDRS-17. Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups (p = 0.001), however, differences between the topiramate-treated group and the bupropion SR-treated group were not significant [t(36) = 1.754, p = 0.097]. Both topiramate and bupropion SR were generally well tolerated. Thirteen patients discontinued the study: 2 because of lack of efficacy, 1 due to withdrawal of consent and 10 following side-effects (six in the topiramate and four in the bupropion SR-treated group). There were no cases of affective switch in either arm. Weight loss was experienced by patients in both groups (mean weight loss at endpoint was 1.2 kg in bupropion SR and 5.8 kg in topiramate) [t(17) = 2.325, p = 0.061 and t(17) = 2.481, p = 0.043, respectively]. CONCLUSIONS: These preliminary data suggest that adjunctive topiramate may reduce depressive symptom severity in acute bipolar depression. The antidepressant efficacy of this compound requires confirmation via double-blind placebo controlled investigation.

Giacobbe P, McIntyre RS, Goldstein BI, Kennedy SH, Flint AJ. · Department of Psychiatry, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada. · Psychiatr Serv. · Pubmed #18832492 No free full text.

This publication has no abstract.

McIntyre RS, Konarski JZ, Soczynska JK, Kennedy SH. · University of Toronto, Toronto, Ontario, Canada. · J Psychiatr Pract. · Pubmed #17414691 No free full text.

Abstract: BACKGROUND: The goal of this study was to characterize the burden of anxiety among residual depressive symptoms in naturalistic primary care settings. METHODS: A post-hoc analysis of a database comprised of naturalistically treated depressed patients across Canada was done. This bilingual (English and French), multi-center, randomized validation study was conducted in 47 primary care settings in four provinces of Canada. Patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text-Revision (DSM-IV-TR) criteria for a major depressive episode, in the context of a major depressive disorder (N=454) were enrolled. Eligible patients received open-label, flexible-dose antidepressant treatment. The analysis reported here was limited to patients whose depression severity was evaluated using the Hamilton Depression Rating Scale (HAMD-17) (n=205). Patients completing 8 weeks of open-label antidepressant treatment (n=157) were considered evaluable. As a proxy for anxiety symptoms, scores on 6 items from the HAMD-17 (psychological anxiety, somatic anxiety, gastrointestinal distress, fatigue, hypochondriasis, and insight into illness) were summed to arrive at a composite anxiety score, which was then used to calculate an anxiety ratio (with the composite anxiety score as the numerator and the total HAMD-17 score as the denominator). RESULTS: The composite anxiety ratio at baseline did not correlate with the probability of remitting at endpoint (p=0.534). After 8 weeks of antidepressant therapy, remitting patients evinced a statistically significant decrease in anxiety ratio (p=0.041). Moreover, an inverse correlation was noted between severity of anxious symptoms at endpoint and probability of remission (p=0.026). The burden of anxiety, presented as the anxiety ratio, was higher in non-remitting patients at endpoint (p=0.828). CONCLUSION: Residual depressive symptoms represent ongoing illness activity in depression. Sharpening the focus of therapeutic interventions in the clinical environment calls for tracking and managing residual anxiety symptoms.

McIntyre RS, Soczynska JK, Lewis GF, MacQueen GM, Konarski JZ, Kennedy SH. · Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street-Toronto, ON, M5T 2S8, Canada. · Expert Opin Pharmacother. · Pubmed #16805717 No free full text.

Abstract: The objective of this paper is to synthesise extant studies describing the neurotherapeutic effects of antidiabetic agents in neuropsychiatric disorders. The authors conducted a MedLine search of all English-language articles published between 1966 and March 2006. The search terms were the nonproprietary names of established and putative antidiabetic agents (e.g., insulin, insulin secretagogues and sensitisers) cross-referenced with the individual names of Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R/IV/-TR-defined mood, psychotic, anxiety and dementing disorders. The search was augmented with a manual review of article reference lists. Contemporary models of disease pathophysiology in major depressive disorder, bipolar disorder and several dementing disorders (e.g., Alzheimer's disease) emphasise alterations in cellular plasticity and cytoarchitecture, with associated regional abnormalities in neuronal and glial density and morphology. Antidiabetic treatments (e.g., thiazolidinediones) may be capable of attenuating this pathological process via disparate mechanisms (e.g., neuroprotective, neurotrophic, anti-inflammatory). Enhanced insulin signalling with antidiabetic treatments may preserve and/or augment cognitive function in several neuropsychiatric disorders. Antidiabetic treatments, which maintain euglycaemia, hold promise as potent and clinically significant therapeutic interventions for several neuropsychiatric disorders.

McIntyre RS, Konarski JZ, Wilkins K, Bouffard B, Soczynska JK, Kennedy SH. · Department of Psychiatry, University of Toronto, Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street, Toronto, ON, Canada M5T 2S8. · Headache. · Pubmed #16732843 No free full text.

Abstract: OBJECTIVE: To report on the prevalence of comorbid migraine in bipolar disorder and the implications for bipolar age of onset, psychiatric comorbidity, illness course, functional outcome, and medical service utilization. BACKGROUND: Migraine comorbidity is differentially reported in bipolar versus unipolar depressed clinical samples. The bipolar disorder-migraine association and its consequences have been infrequently reported in epidemiological studies. METHODS: Data for this analysis were derived from respondents (n = 36 984) to the Canadian Community Health Survey - Mental Health and Well-Being (CCHS). Respondents reporting a lifetime WHO-CIDI-defined manic episode and physician-diagnosed migraine (lifetime) were compared to respondents without migraine on sociodemography, course of illness, and medical service utilization indices. RESULTS: An estimated 2.4% of the sample met criteria for bipolar disorder. Persons with bipolar disorder had a relatively higher prevalence of migraine versus the general population (24.8% vs. 10.3%; P < .05). The sex-specific prevalence of comorbid migraine in bipolar disorder was 14.9% for males and 34.7% for females. Bipolar males with comorbid migraine were more likely to live in a low income household (P < .05); receive welfare and social assistance (P < .05); report an earlier age of onset of bipolar disorder (P < .05); and have a higher lifetime prevalence of comorbid anxiety disorders (P < .05). Bipolar males with comorbid migraine were also more likely to utilize primary (P < .05) and mental health care services (P < .05) . Bipolar females with comorbid migraine had more comorbid medical disorders (P < .05) and were more likely to require help with personal or instrumental activities of daily living when compared to bipolar females without migraine. CONCLUSION: Bipolar disorder with comorbid migraine is prevalent and associated with greater dysfunction and medical service utilization, notable in males. Opportunistic screening and surveillance for bipolar and comorbid migraine is warranted.

Kennedy SH, Lam RW, Cohen NL, Rosenbluth M, Sokolov ST, McIntyre RS, Chue P, Craigen G, Anonymous00053. · University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ont. · J Psychiatry Neurosci. · Pubmed #12491574 links to  free full text

Abstract: OBJECTIVE: To describe the effectiveness and tolerability of reboxetine under Special Access Program conditions in Canada in a group of patients with refractory depressive disorders. DESIGN: Retrospective open-label study. SETTING: Six clinical academic settings in Canada, primarily tertiary institutional settings. PATIENTS: Twenty-six female and 19 male outpatients with depressive disorders, primarily unipolar depression. Most of the patients were treatment resistant. INTERVENTION: Reboxetine through the Special Access Program. OUTCOME MEASURE: Severity of depression before treatment with reboxetine was retrospectively assessed with the Clinical Global Impression (CGI) Global Severity Scale; change with treatment was evaluated with the CGI Global Improvement Scale. RESULTS: Before reboxetine treatment, 20 (44%) patients scored in the moderate CGI severity category, 11 (24%) in the marked category and 12 (27%) in the severe category. The dose range for reboxetine was 2-16 mg, with 40 (89%) patients in the 4-10 mg range. With reboxetine treatment, 25 (56%) patients were considered "very much improved" or "much improved"; 8 (18%) patients were "minimally improved"; 7 (16%) received ratings that reflected "no change" or minimal worsening, and 5 (11%) were rated as "much worse" or "very much worse." CONCLUSIONS: Reboxetine was effective at a clinically meaningful level in decreasing severity of depression in 56% of patients. Given the high rate of prior resistance to other antidepressant therapies, there is a definite role for this agent in the treatment of depressive disorders.