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Velehorschi C.,Windsor Regional Hospital | Velehorschi C.,University of Western Ontario | Bleau P.,McGill University | Vermani M.,START Clinic for Mood and Anxiety Disorders | And 3 more authors.
Psychiatry Research | Year: 2014

Major depressive disorder (MDD) is a common disorder with a lifetime prevalence of 16.2% and the fourth highest cause of disability globally. It is hypothesized to be a syndromatic manifestation of multiple pathological processes leading to similar clinical manifestation. MDD is associated with at least three categories of peripheral hormone-type factors including neurotrophic factors, proinflammatory cytokines, and processes that impair regulation of the hypothalamic-pituitary-adrenocortical axis. Neuroimaging studies have identified functional abnormalities including subcortical systems associated with reward and emotion processing, medial prefrontal and anterior cingulate cortical regions and the lateral prefrontal cortical systems involved in cognitive control and voluntary emotion regulation. Studies investigating the effects of psychotherapy and pharmacotherapy on functional brain measures show normalization of brain function with return to euthymia. Nevertheless, approximately 50% of patients with MDD will not respond sufficiently and 60 to 70% will not achieve full remission with first-line pharmacotherapy, therefore clinicians strive to improve patient responses through the use of adjunct therapies. This review discusses recent research in the various biological processes associated with MDD as well as recent data in support of the use of adjunctive non-pharmacological therapies including psychotherapy, bibliotherapy, Internet therapy, "natural" or herbal approaches, exercise therapy, and somatic therapies. © 2014 Elsevier Ireland Ltd.

Vermani M.,START Clinic for Mood and Anxiety Disorders | Vermani M.,Lakehead University | Marcus M.,York University | Katzman M.A.,START Clinic for Mood and Anxiety Disorders | And 2 more authors.
Primary Care Companion to the Journal of Clinical Psychiatry | Year: 2011

Objective: To determine the incidence of major depressive disorder, bipolar disorder, panic disorder, social anxiety disorder, and generalized anxiety disorder and to assess their detection rates in the Canadian primary care setting. Method: The descriptive, cross-sectional study was conducted in 7 primary care clinics in 3 Canadian provinces, Ontario, British Columbia, and Nova Scotia, from December 6, 2005, to May 5, 2006. Patients in clinic waiting rooms who consented to participate in the study were administered the Mini International Neuropsychiatric Interview (MINI) (N = 840). These patients' medical charts were then reviewed for evidence of previous diagnosis of a mood or anxiety disorder. Misdiagnosis was defined as cases for which a diagnosis was reached on the MINI but not in the patient's chart. Results: Of the 840 primary care patients assessed, 27.2%, 11.4%, 12.6%, 31.2%, and 16.5% of patients met criteria for major depressive disorder, bipolar disorder, panic disorder, generalized anxiety disorder, and social anxiety disorder, respectively. Misdiagnosis rates reached 65.9% for major depressive disorder, 92.7% for bipolar disorder, 85.8% for panic disorder, 71.0% for generalized anxiety disorder, and 97.8% for social anxiety disorder. Conclusions: With high prevalence rates and poor detection, there is an obvious need to enhance diagnostic screening in the primary care setting. © 2011 Physicians Postgraduate Press, Inc.

Logan A.C.,CAMNR | Katzman M.A.,START Clinic for Mood and Anxiety Disorders | Balanza-Martinez V.,University of Valencia
Journal of Physiological Anthropology | Year: 2015

Famed microbiologist René J. Dubos (1901-1982) was an early pioneer in the developmental origins of health and disease (DOHaD) construct. In the 1960s, he conducted groundbreaking experimental research concerning the ways in which early-life experience with nutrition, microbiota, stress, and other environmental variables could influence later-life health outcomes. He also wrote extensively on potential health consequences of a progressive loss of contact with natural environments (now referred to as green or blue space), arguing that Paleolithic experiences have created needs, particularly in the mental realm, that might not be met in the context of rapid global urbanization. He posited that humans would certainly adapt to modern urban landscapes and high technology, but there might be a toll to be paid in the form of higher psychological distress (symptoms of anxiety and depression) and diminished quality of life. In particular, there might be an erosion of humanness, exemplified by declines in altruism/empathy. Here in the first of a two-part review, we examine contemporary research related to natural environments and question to what extent Dubos might have been correct in some of his 50-year-old assertions. © 2015 Logan et al.; licensee BioMed Central.

Katzman M.A.,START Clinic for Mood and Anxiety Disorders | Katzman M.A.,Lakehead University | Katzman M.A.,University of Toronto | Katzman M.A.,Adler Graduate School | And 3 more authors.
CNS Drugs | Year: 2014

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioural disorder with onset during childhood. It affects a child's development, both at home and at school, and impacts on social, emotional and cognitive functioning, in both the home and the school environment. Untreated ADHD is very often associated with poor academic achievement, low occupational status, increased risk of substance abuse and delinquency. Current practice guidelines recommend a multimodal approach in the treatment of ADHD, which includes educational, behavioural and mental health interventions, and pharmacological management. Stimulant medications, including methylphenidate (MPH) and amphetamine products, are recommended as first-line pharmacotherapy in the treatment of ADHD. The choice of stimulant is influenced by several factors; the most influential factor is the duration of action. Long-acting medication provides benefits long after school and work. It also increases the likelihood of once-daily dosing, thereby eliminating the need for mid-day dosing, making the treatment more private, avoiding stigma and improving adherence to medication. MPH is the most widely used psychotropic medication in child psychiatry. It was first developed for use in children as an oral, immediate-release formulation and more recently as various extended-release formulations. These latter formulations include the 12 h preparation Concerta® (osmotic-release oral system [OROS] MPH), which utilizes an osmotic pump system, designed to overcome the difficulties of multiple daily dosing. Since it received approval from the US Food and Drug Administration in August 2000, OROS MPH has been quickly and widely accepted as one of the preferred treatments for ADHD because of its once-daily dosing. This paper reviews the data in support of long-acting OROS MPH in children, adolescents and adults, both in ADHD and in association with its comorbidities. © 2014 Springer International Publishing Switzerland.

Katzman M.A.,START Clinic for Mood and Anxiety Disorders | Katzman M.A.,University of Toronto | Katzman M.A.,Lakehead University | Brawman-Mintzer O.,Medical University of South Carolina | And 4 more authors.
International Clinical Psychopharmacology | Year: 2011

The objective of this study was to evaluate the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) as maintenance monotherapy for patients with generalized anxiety disorder (GAD). Time-to-event (anxiety symptom recurrence; maximum 52 weeks) multicenter, randomized- withdrawal, parallel-group, double-blind, placebo-controlled study of quetiapine XR (50-300 mg/day) following open-label run-in (4-8 weeks) and open-label stabilization (12 weeks). Primary variable: time from randomization to anxiety event. Secondary variables included: Hamilton Anxiety Rating Scale (HAM-A) total, HAM-A psychic/somatic anxiety factors, Clinical Global Impression-Severity of Illness (CGI-S), and Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scores; adverse events (AE) reporting. Four hundred and thirty-two patients, stabilized on quetiapine XR, were randomized to continue quetiapine XR (N=216) or switch to placebo (N=216). Risk of anxiety symptom recurrence was significantly reduced by 81% for quetiapine XR versus placebo: hazard ratio=0.19 (95% confidence interval 0.12-0.31; P<0.001). Fewer patients receiving quetiapine XR (N=22, 10.2%) than placebo (N=84, 38.9%) experienced anxiety symptom recurrence. Significant differences were observed between quetiapine XR and placebo in: HAM-A total, psychic/somatic, CGI-S (all P<0.001) and Q-LES-Q (P<0.05) scores. AEs (>10%) during open-label treatment were dry mouth, sedation, somnolence, dizziness, fatigue, and constipation. During randomized treatment, the most common AEs for quetiapine XR were headache and nasopharyngitis. Quetiapine XR monotherapy reduced the risk of anxiety symptom recurrence in patients with GAD stabilized on quetiapine XR, with tolerability results consistent with the known profile of quetiapine. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Klassen L.J.,University of Manitoba | Klassen L.J.,Eden Mental Health Center | Katzman M.A.,START Clinic for Mood and Anxiety Disorders | Katzman M.A.,University of Toronto | And 2 more authors.
Journal of Affective Disorders | Year: 2010

Attention deficit hyperactivity disorder (ADHD) is a syndrome that most often presents in childhood. However, the condition is also relatively common in adults, with prevalence rates reaching 5% in the general population, with more than half the children affected by ADHD retaining the condition during their adult years. While the disorder in children is most often described as a disorder involving hyperactivity and impulsiveness, ADHD presents with very different characteristics in adulthood, notably with less externalizing symptoms and with a higher rate of psychiatric comorbidities, including major depressive disorder, bipolar disorder (BD), anxiety disorders and substance abuse. This review will focus on the evidence relating to bipolar disorder BD and its potential link with ADHD, looking at epidemiological, familial and neuroimaging studies. The comorbid presentation of people suffering with ADHD and BD (ADHD/BD) is associated with a more severe disease course, more severe mood disorder symptoms, and lower functional scores. Importantly, the co-segregation of these two conditions makes ADHD diagnosis challenging because its symptoms are often mistakenly assumed to be part of BD. As a result, patients with comorbid ADHD/BD are under-diagnosed and under-treated. Optimal diagnosis, understanding and treatment of the comorbid condition are important, as ADHD/BD has been associated with significant functional impairment and suboptimal treatment responses when compared to ADHD or BD populations alone. © 2009 Elsevier B.V. All rights reserved.

Klassen L.J.,Eden Mental Health Center | Klassen L.J.,University of Manitoba | Bilkey T.S.,Ontario Bilkey ADHD Clinics | Katzman M.A.,START Clinic for Mood and Anxiety Disorders | And 3 more authors.
Current Drug Abuse Reviews | Year: 2012

Background: Attention-deficit hyperactivity disorder (ADHD) is predominantly a diagnosis of childhood and adolescence but has also been recognized in adults. It is associated with high rates of comorbid psychiatric conditions, particularly substance use disorders (SUD). Methods: A review of the literature was conducted with a focus on ADHD, SUD, their comorbidity, and treatment considerations. Results: Literature suggests that the use of methylphenidate (MPH) in children does not increase SUD later in life, and may in fact reduce substance use and abuse in adolescence and adulthood. Concurrent treatment of ADHD-SUD, which may be supported theoretically, has yielded inconsistent data on clinical trials. While MPH use in adults with ADHDSUD may be effective in alleviating ADHD symptoms, the benefits on SUD are not clear and remain controversial. Studies suggest that adults with comorbid ADHD-SUD do not misuse or divert their medication, but MPH does not consistently improve substance use. However, data are lacking for substances other than cocaine and stimulants other than MPH. While the risk of stimulant abuse should not be ignored, it may be minimized by selecting medications that are not readily crushed and solubilized for parenteral administration, or by utilizing non-stimulant medications and/or psychotherapy. Conclusion: While there are a lack of evidence-based guidelines for the concurrent treatment of ADHD and SUD, evidence to date suggests that stimulant medications should not necessarily be avoided for patients with comorbid ADHDSUD and that concurrent treatment may be a successful approach to improve ADHD outcomes without worsening SUD symptoms. © 2012 Bentham Science Publishers.

Furtado M.,START Clinic for Mood and Anxiety Disorders | Katzman M.A.,START Clinic for Mood and Anxiety Disorders | Katzman M.A.,University of Toronto | Katzman M.A.,Lakehead University | Katzman M.A.,Adler Graduate School
Psychiatry Research | Year: 2015

Recent findings have established a connection between inflammation and major depression and specifically the role of the hypothalamic-pituitary-adrenal (HPA) axis in depression. This article reviews clinical and experimental studies examining the role of the HPA axis, HPA hyperactivity (resulting in increased cortisol levels), as well as the proinflammatory cytokines tumor necrosis factor, C-reactive protein, and the interleukins, in depressed patients. Similarly this paper will review data supporting increased cytokine levels in depression and specifically differential effects in treatment-resistant patients, as well as potentially distinguishing in particular depression subtypes. Understanding the role of the immune system and inflammation in patients with major depression is essential in order to develop efficacious treatments potentially targeting inflammation in relation to the depression in order to reduce patient symptomatology and comorbidities. © 2015 .

Furtado M.,START Clinic for Mood and Anxiety Disorders | Katzman M.A.,START Clinic for Mood and Anxiety Disorders | Katzman M.A.,University of Toronto | Katzman M.A.,Lakehead University | Katzman M.A.,Adler Graduate School
Psychiatry Research | Year: 2015

As prevalence of anxiety, posttraumatic stress, and obsessive compulsive disorders continue to rise worldwide, increasing focus has been placed on immune mediated theories in understanding the underlying mechanisms of these disorders. Associations between the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and these disorders have been recognized in the scientific literature, specifically in regard to cortisol levels, as well as changes in pro- and anti-inflammatory cytokines. The present commentary will systematically assess the scientific literature within the past decade in regard to the psychoneuroimmunology of anxiety, posttraumatic stress, and obsessive compulsive disorders. Understanding the mechanisms of these disorders is essential in order to determine efficacious and targeted treatment strategies, which may lead to substantial improvements in overall functioning, as well as significant decreases in societal and economic burden. © 2015 Elsevier Ireland Ltd.

Cameron C.,START Clinic for Mood and Anxiety Disorders | Habert J.,University of Toronto | Anand L.,START Clinic for Mood and Anxiety Disorders | Furtado M.,START Clinic for Mood and Anxiety Disorders
Psychiatry Research | Year: 2014

This article is intended to identify some of the most important challenges faced by family physicians when treating MDD and to provide practical solutions. Key issues, reviewed from a primary care view point will include: treating to remission (and not just response), identification of high-risk groups, diagnosis, acute treatment approaches (including pharmacotherapy and the management of related side effects), the use of psychotherapy and somatic therapies, assessment of the adequacy of treatment including the assessment of remission, response measurement, optimal follow-up care throughout the phase of treatment, the key components of patient education and strategies for partial/limited response to the first-line antidepressant (switching, augmentation and combination strategies), how to provide support for improved treatment adherence, and approaches to prevent the recurrence of depressive episodes. © 2014 Elsevier Ireland Ltd.

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