Martin A. Katzman

Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders.

BackgroundAnxiety and related disorders are among the most common mental disorders, with lifetime prevalence reportedly as high as 31%. Unfortunately, anxiety disorders are under-diagnosed and under-treated.MethodsThese guidelines were developed by Canadian experts in anxiety and related disorders through a consensus process. Data on the epidemiology, diagnosis, and treatment (psychological and pharmacological) were obtained through MEDLINE, PsycINFO, and manual searches (1980–2012). Treatment strategies were rated on strength of evidence, and a clinical recommendation for each intervention was made, based on global impression of efficacy, effectiveness, and side effects, using a modified version of the periodic health examination guidelines.ResultsThese guidelines are presented in 10 sections, including an introduction, principles of diagnosis and management, six sections (Sections 3 through 8) on the specific anxiety-related disorders (panic disorder, agoraphobia, specific phobia, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder), and two additional sections on special populations (children/adolescents, pregnant/lactating women, and the elderly) and clinical issues in patients with comorbid conditions.ConclusionsAnxiety and related disorders are very common in clinical practice, and frequently comorbid with other psychiatric and medical conditions. Optimal management requires a good understanding of the efficacy and side effect profiles of pharmacological and psychological treatments.

A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is complex illness of unknown etiology. Among the broad range of symptoms, many patients report disturbances in the emotional realm, the most frequent of which is anxiety. Research shows that patients with CFS and other so-called functional somatic disorders have alterations in the intestinal microbial flora. Emerging studies have suggested that pathogenic and non-pathogenic gut bacteria might influence mood-related symptoms and even behavior in animals and humans. In this pilot study, 39 CFS patients were randomized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) or a placebo daily for two months. Patients provided stool samples and completed the Beck Depression and Beck Anxiety Inventories before and after the intervention. We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS, and there was also a significant decrease in anxiety symptoms among those taking the probiotic vs controls (p = 0.01). These results lend further support to the presence of a gut-brain interface, one that may be mediated by microbes that reside or pass through the intestinal tract.

Adult ADHD and its comorbidities, with a focus on bipolar disorder

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.

Examining the role of neuroinflammation in major depression

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.

Neuroinflammatory pathways in anxiety, posttraumatic stress, and obsessive compulsive disorders

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.

Multi-component yoga breath program for Vietnam veteran post-traumatic stress disorder: randomized controlled trial

Multi-Component Yoga Breath Program for Vietnam Veteran Post Traumatic Stress Disorder: Randomized Controlled Trial It is appropriate to acknowledge that despite treatment, Post Traumatic Stress Disorder (PTSD) continually debilitates many Vietnam veterans. Although therapies have been developed, remission is hard to obtain with either pharmacotherapy or psychotherapy. Evidence has suggested that some forms of yoga may reduce sympathetic overactivity and increase parasympathetic activity, thereby improving stress resilience.

Acute and Chronic Role of 5-HT3 Neuronal System on Behavioral and Neuroendocrine Changes Induced by Intravenous Cholecystokinin Tetrapeptide Administration in Humans

The influence of single and multiple oral doses of ondansetron, a selective 5-HT3 receptor antagonist, was evaluated against placebo on cholecystokinin tetrapeptide (CCK-4)-induced behavioral and neuroendocrine changes in humans. As compared to placebo, subjects receiving acute ondansetron treatment showed a significant decrease in the sum intensity of CCK-4-induced-panic symptoms (iPSS). Pre-CCK-4 neuropeptide Y (NPY) plasma levels were significantly higher and maximal changes in cortisol, growth hormone, and prolactin secretion from baseline (Δmax) were significantly lower in the ondansetron group. After ondansetron and placebo chronic administration, there were no statistical differences in the iPSS between groups. Pre-CCK-4 NPY plasma levels were significantly higher; whereas, Δmax for NPY significantly lower in the ondansetron group as compared to placebo. These results suggest a role for the 5-HT3 receptor in the neurobiology of panic disorder through a possible interaction with CCK and NPY systems. Ondansetron chronic effect on CCK-4-induced behavioral changes needs further exploration.

Aripiprazole: A clinical review of its use for the treatment of anxiety disorders and anxiety as a comorbidity in mental illness

BACKGROUND Although anxiety disorders are common, optimal treatment is elusive. More than half of anxiety patients treated with an adequate course of antidepressants fail to fully improve: treatment resistance, residual symptoms, and recurrence/relapse remain a challenge. Recently, atypical antipsychotics have been considered for treatment-resistant anxiety disorders. This review will explore the available data for the role of aripiprazole in the treatment of anxiety. METHODS PubMed and conference abstracts were searched for randomized, double-blind studies that investigated the efficacy of aripiprazole in anxiety; its efficacy in bipolar disorder and depression was also explored for comparison. RESULTS A number of studies have shown atypical antipsychotics to be effective in anxiety, and currently available data suggest that aripiprazole augmentation in patients with anxiety disorders is likely as effective as other atypical antipsychotic drugs. Although there have been no randomized, controlled trials, aripiprazole has been found to be effective in treating anxiety disorders in two open-label trials. This combined with the larger data base demonstrating its utility in bipolar disorder and depression, its safety profile and its unique mechanism of action, make aripiprazole for anxiety an intriguing avenue of exploration. LIMITATIONS Data from large randomized, controlled trials on the use of atypical antipsychotics for anxiety in general, and aripiprazole in particular, are currently lacking. CONCLUSION The results of open-label trials of aripiprazole in anxiety provide enough support to warrant its further study. This, combined with a larger data base demonstrating its utility in bipolar disorder and depression, its safety profile and its unique mechanism of action, make aripiprazole for anxiety an intriguing avenue of exploration.

Comorbid Attention Deficit/Hyperactivity Disorder and Substance Use Disorder: Treatment Considerations

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.

Central and peripheral chemoreflexes in panic disorder

Klein (Arch Gen Psychiatry, 50, 1993, 306-317) has suggested that panic disorder patients have a false suffocation alarm that may be associated with a lowered threshold for carbon dioxide detection. We compared the thresholds and sensitivities of the central and peripheral chemoreflexes between panic disorder patients and age- and sex-matched healthy volunteers to test this aspect of the hypothesis. We used a modified version of Reads rebreathing technique in 11 panic disorder patients and 10 healthy volunteers to examine the peripheral and central chemoreflex characteristics in these two populations. Subjects were examined during three rebreathing tests: training, hyperoxic (central chemoreflex alone) and hypoxic (combined central and peripheral chemoreflex). Panic symptoms were retrospectively assessed between groups using a DSM-IV derived Panic Symptom Scale. Comparisons of panic disorder patients with agoraphobia and healthy volunteers showed no significant differences in sensitivities or thresholds. Kleins hypothesis is not supported by these data. If a false suffocation alarm exists, its triggering may not be implemented within the respiratory chemoreflexes.