Venkat Bhat

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder Section 3. Pharmacological Treatments

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Pharmacological Treatments” is the third of six sections of the 2016 guidelines. With little new information on older medications, treatment recommendations focus on second-generation antidepressants. Results: Evidence-informed responses are given for 21 questions under 4 broad categories: 1) principles of pharmacological management, including individualized assessment of patient and medication factors for antidepressant selection, regular and frequent monitoring, and assessing clinical and functional outcomes with measurement-based care; 2) comparative aspects of antidepressant medications based on efficacy, tolerability, and safety, including summaries of newly approved drugs since 2009; 3) practical approaches to pharmacological management, including drug-drug interactions and maintenance recommendations; and 4) managing inadequate response and treatment resistance, with a focus on switching antidepressants, applying adjunctive treatments, and new and emerging agents. Conclusions: Evidence-based pharmacological treatments are available for first-line treatment of MDD and for management of inadequate response. However, given the limitations of the evidence base, pharmacological management of MDD still depends on tailoring treatments to the patient.

Is Adult Attention-Deficit Hyperactivity Disorder Being Overdiagnosed?:

This review offers a perspective on the question as to whether attention-deficit hyperactivity disorder (ADHD) is being overdiagnosed in adults. Considering underlying causes as well as consequences, we conclude that the diagnosis of adult ADHD should be made cautiously, making use of multiple sources of information, including self-report, clinical interviews, collateral information, childhood documentation, and neuropsychological testing. Routine screening with symptom checklists is insufficient, and stimulant response is diagnostically uninformative. The causes of overdiagnosis may include changes in diagnostic thresholds, poor diagnostic practices, and advertising by the pharmaceutical industry. Overdiagnosis leads to overtreatment, and dramatic increases in prescriptions for adult ADHD during the last decade should arouse concern.

In vivo tracking of tau pathology using positron emission tomography (PET) molecular imaging in small animals.

Hyperphosphorylation of the tau protein leading to the formation of neurofibrillary tangles (NFTs) is a common feature in a wide range of neurodegenerative diseases known as tauopathies, which include Alzheimer’s disease (AD) and the frontotemporal dementias (FTDs). Although heavily investigated, the mechanisms underlying the pathogenesis and progression of tauopathies have yet to be fully understood. In this context, several rodent models have been developed that successfully recapitulate the behavioral and neurochemical features of tau pathology, aiming to achieve a better understanding of the link between tau and neurodegeneration. To date, behavioral and biochemical parameters assessed using these models have been conducted using a combination of memory tasks and invasive methods such as cerebrospinal fluid (CSF) sampling or post-mortem analysis. Recently, several novel positron emission tomography (PET) radiopharmaceuticals targeting tau tangles have been developed, allowing for non-invasive in vivo quantification of tau pathology. Combined with tau transgenic models and microPET, these tracers hold the promise of advancing the development of theoretical models and advancing our understanding of the natural history of AD and non-AD tauopathies. In this review, we briefly describe some of the most important insights for understanding the biological basis of tau pathology, and shed light on the opportunity for improved modeling of tau pathology using a combination of tau-radiopharmaceuticals and animal models.

Parental psychopathology in families of children with attention-deficit/hyperactivity disorder and exposed to maternal smoking during pregnancy.

BACKGROUND Both genetic and environmental factors have been implicated in the etiology of attention-deficit/hyperactivity disorder (ADHD). We had previously suggested that exposure to maternal smoking during pregnancy (MSDP) may be a valid basis for delineating a distinct subtype of ADHD, where children exposed to MSDP present with a more severe clinical picture. Here, we examine the psychopathology of parents in this group, to better understand the etiology of ADHD. METHODS Using the Family Interview for Genetic Studies in a sample of 514 families of children with ADHD, we collected data pertaining to lifetime parental psychopathology. Families were stratified based on maternal smoking during the complete gestational period. The frequency of different disorders was compared using the χ2 statistic. RESULTS In the group where mothers smoked during pregnancy, both parents were significantly more likely to have antisocial personality disorder, and problems with alcohol and drug abuse. Mothers had a significantly higher frequency of major depressive disorder (MDD), while fathers showed a trend for both MDD and bipolar disorder. CONCLUSIONS Based on the pattern of psychopathology in parents of children exposed to MSDP, as well as earlier reports of the severe clinical, behavioral, and cognitive phenotype in these children, combined with the large body of epidemiological evidence, we propose that these children present a distinct subtype of ADHD with comorbid conduct disorder. Furthermore, we propose that MSDP may be a proxy measure to help delineate this subtype.

Adult Attention-Deficit Hyperactivity Disorder is Being Overdiagnosed

Dear Editor: In commenting on our paper, Dr Jerome’s letter addresses the problem of making more careful diagnoses, but not the questions we raised about the validity of adult attention-deficit hyperactivity disorder (ADHD) as currently defined. A recent paper by Moffitt et al using longitudinal data suggests that childhood ADHD and adult ADHD could be entirely different syndromes. In the absence of an etiology or biomarkers, ADHD in adults is a rough approximation that defines a heterogeneous syndrome. In this context, the rapid increase that we have seen in the prescription of stimulant medications for adult ADHD raises concerns about overdiagnosis and overtreatment. The letter by Katzman et al raises the question as to whether greater caution in diagnosing adult ADHD could deny patients the benefits of effective therapy. But there is no evidence that treatment with stimulants benefits patients whose diagnosis is doubtful. Another point raised by Katzman et al is that other diagnoses (bipolar II, autism spectrum disorders, and social anxiety disorder) have also dramatically increased in prevalence in recent years. There is reason for concern that these disorders are also being overdiagnosed. These changes in diagnostic habits derive in part from the overinclusiveness of current criteria, as well as the wish to reduce complex psychopathology to a single diagnostic construct. There is no clear evidence that these increased diagnoses have benefited patients. Yours truly,

Research-Track Programs for Residents in Psychiatry: A Review of Literature and a Report of 3 Canadian Experiences

Objectives: Clinician-scientists occupy an interesting position at the interface between science and care, and have a role to play in bridging the 2 valleys between fundamental and clinical research, and between clinical research and clinical practice. However, research training during medical residency for future clinician scientists is an important but challenging process. Our article, written by residents and directors of research-track (RT) programs, aimed at reviewing literature on RT programs for residents, and describing the organization of RT programs at 3 Canadian universities (the University of British Columbia, the University of Toronto, and McGill University). Methods: A systematic MEDLINE search was conducted for the review section. Psychiatry program directors in Canada were also contacted to provide information about potential RT programs. Results: Twenty articles were related to resident RT programs in medicine, including 6 in psychiatry. Moreover, 5 out of 16 Canadian programs were found to offer a formal RT program, of which 3 are described here. Most reviewed articles described the program organization, while only one provided an outcome assessment with evidence of increased scholarly activity following RT implementation. Conclusions: Our article sheds light on postgraduate programs aiming at facilitating the dual training of future clinician-scientists, and developed during the last 10 years. It also highlights the lack of outcome assessment, and the paucity of guidelines to organize these programs in relation to the national requirements.

Imaging biomarkers for amyloid: a new generation of probes and what lies ahead.

Since the original 1984 criteria for Alzheimers disease (AD), put forth by a work group jointly established by the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimers Disease and Related Disorders Association (ADRDA) (McKhann et al ., 1984), important advances have occurred in our ability to detect AD pathophysiology, with the incorporation of biomarkers – defined as anatomic, biochemical, or physiologic parameters that provide in vivo evidence of AD neuropathology (Cummings, 2011) – that can improve the certainty of AD diagnosis. Use of imaging biomarkers such as positron emission tomography (PET) with amyloid ligands, particularly in asymptomatic and pre-dementia stages of AD, however, has been the subject of debate (Dubois et al ., 2013), with arguments both for and against the biomarker driven diagnosis of AD.

Transatlantic variation in the attributed etiology of psychosis

Background: Differences in transatlantic perception of psychosis have been reported in the historical psychiatric literature. Aims: This study aims to determine if articles in the American Journal of Psychiatry (AJP) are more likely to attribute biological factors to the etiology of psychosis than those of the British Journal of Psychiatry (BJP). Methods: A systematic MEDLINE search for articles in the AJP and BJP from 2005 to 2007 identified 360 abstracts with psychosis and etiology-related words. Chi-square analyses were used to test differences in the proportion of attributed biological or psychosocial etiology of psychosis in each journal. Results: A greater proportion of abstracts (83/87) in the AJP attributed biological etiology of psychosis (χ2 = 12.33, df = 1, p < 0.001), while a greater proportion in the BJP (16/44 abstracts) attributed psychosocial etiology (χ2 = 19.76, df = 1, p < 0.001). Conclusions: The AJP tends to publish biomedical explanations of psychosis, while the BJP shows a relative preference for psychosocial theories.