Anxiety Disorders: Pollack MH

Allgulander C, Bandelow B, Hollander E, Montgomery SA, Nutt DJ, Okasha A, Pollack MH, Stein DJ, Swinson RP, Anonymous00175. · Department of Psychiatry, Harvard University School of Medicine, Boston, Massachusetts, USA. · CNS Spectr. · Pubmed #14767398 No free full text.

Abstract: What are the current recommendations for the long-term treatment of generalized anxiety disorder (GAD)? GAD is a common disorder with a lifetime prevalence of 4% to 7% in the general population. GAD is characterized by excessive, uncontrollable worry or anxiety about a number of events or activities that the individual experiences on more days than not over a 6-month period. Onset of GAD symptoms usually occurs during an individual's early twenties; however, high rates of GAD have also been seen in children and adolescents. The clinical course of GAD is often chronic, with 40% of patients reporting illness lasting >5 years. GAD is associated with pronounced functional impairment, resulting in decreased vocational function and reduced quality of life. Patients with GAD tend to be high users of outpatient medical care, which contributes significantly to healthcare costs. Currently, benzodiazepines and buspirone are prescribed frequently to treat GAD. Although both show efficacy in acute treatment trials, few long-term studies have been performed. Benzodiazepines are not recommended for long-term treatment of GAD, due to associated development of tolerance, psychomotor impairment, cognitive and memory changes, physical dependence, and a withdrawal reaction on discontinuation. The antidepressant venlafaxine extended-release (XR) has received approval for the treatment of GAD in the United States and many other countries. Venlafaxine XR has demonstrated efficacy over placebo in two randomized treatment trials of 6 months' duration as well as in other acute trials. Paroxetine is the first of the selective serotonin reuptake inhibitors (SSRIs) to receive US approval for the treatment of GAD. Paroxetine demonstrated superiority to placebo in short-term trials, and investigations into the use of other SSRIs are ongoing. This suggests that other SSRIs, and serotonin and noradrenaline reuptake inhibitors, are likely to be effective in the treatment of GAD. Of the psychological therapies, cognitive-behavioral therapy (CBT) shows the greatest benefit in treating GAD patients. Treatment gains after a 12-week course of CBT may be maintained for up to 1 year. Currently, no guidelines exist for the long-term treatment of GAD.

Van Ameringen M, Allgulander C, Bandelow B, Greist JH, Hollander E, Montgomery SA, Nutt DJ, Okasha A, Pollack MH, Stein DJ, Swinson RP, Anonymous00174. · Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada. · CNS Spectr. · Pubmed #14767397 No free full text.

Abstract: What is the best approach for treating patients with social phobia (social anxiety disorder) over the long term? Social phobia is the most common anxiety disorder, with reported prevalence rates of up to 18.7%. Social phobia is characterized by a marked and persistent fear of being observed or evaluated by others in social performance or interaction situations and is associated with physical, cognitive, and behavioral (ie, avoidance) symptoms. The onset of social phobia typically occurs in childhood or adolescence and the clinical course, if left untreated, is usually chronic, unremitting, and associated with significant functional impairment. Social phobia exhibits a high degree of comorbidity with other psychiatric disorders, including mood disorders, anxiety disorders, and substance abuse/dependence. Few people with social phobia seek professional help despite the existence of beneficial treatment approaches. The efficacy, tolerability, and safety of the selective serotonin reuptake inhibitors (SSRIs), evidenced in randomized clinical trials, support these agents as first-line treatment. The benzodiazepine clonazepam and certain monoamine oxidase inhibitors (representing both reversible and nonreversible inhibitors) may also be of benefit. Treatment of social phobia may need to be continued for several months to consolidate response and achieve full remission. The SSRIs have shown benefit in long-term treatment trials, while long-term treatment data from clinical studies of clonazepam are limited but support the drug's efficacy. There is also evidence for the effectiveness of exposure-based strategies of cognitive-behavioral therapy, and controlled studies suggest that the effects of treatment are generally maintained at long-term follow-up. In light of the chronicity and disability associated with social phobia, as well as the high relapse rate after short-term therapy, it is recommended that effective treatment be continued for at least 12 months.

Stein DJ, Bandelow B, Hollander E, Nutt DJ, Okasha A, Pollack MH, Swinson RP, Zohar J, Anonymous00173. · Medical Research Council Research Unit on Anxiety Disorder, University of Stellenbosch, Cape Town, Tygerberg, South Africa. · CNS Spectr. · Pubmed #14767396 No free full text.

Abstract: Posttraumatic stress disorder (PTSD) is a common and disabling condition. In addition to combat-related PTSD, the disorder occurs in civilians exposed to severe traumatic events, with the community prevalence rate for the combined populations reaching as high as 12%. If left untreated, PTSD may continue for years after the stressor event, resulting in severe functional and emotional impairment and a dramatic reduction in quality of life, with negative economic consequences for both the sufferer and society as a whole. Although PTSD is often overlooked, diagnosis is relatively straightforward once a triggering stressor event and the triad of persistent symptoms-reexperiencing the traumatic event, avoiding stimuli associated with the trauma, and hyperarousal have been identified. However, comorbid conditions of anxiety and depression frequently hamper accurate diagnosis. Treatment for PTSD includes psychotherapy and pharmacotherapy. The latter includes selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and monoamine oxidase inhibitors. Only SSRIs have been proven effective and safe in long-term randomized controlled trials. Current guidelines from the Expert Consensus Panel for PTSD recommend treatment of chronic PTSD for a minimum of 12-24 months.

Pollack MH, Allgulander C, Bandelow B, Cassano GB, Greist JH, Hollander E, Nutt DJ, Okasha A, Swinson RP, Anonymous00172. · Division of Psychiatry, Huddinge University Hospital, Stockholm, Sweden. · CNS Spectr. · Pubmed #14767395 No free full text.

Abstract: What are the symptoms of panic disorder and how is the disorder most effectively treated? One of the most commonly encountered anxiety disorders in the primary care setting, panic disorder is a chronic and debilitating illness. The core symptoms are recurrent panic attacks coupled with anticipatory anxiety and phobic avoidance, which together impair the patient's professional, social, and familial functioning. Patients with panic disorder have medically unexplained symptoms that lead to overutilization of healthcare services. Panic disorder is often comorbid with agoraphobia and major depression, and patients may be at increased risk of cardiovascular disease and, possibly, suicide. Research into the optimal treatment of this disorder has been undertaken in the past 2 decades, and numerous randomized, controlled trials have been published. Selective serotonin reuptake inhibitors have emerged as the most favorable treatment, as they have a beneficial side-effect profile, are relatively safe (even if taken in overdose), and do not produce physical dependency. High-potency benzodiazepines, reversible monoamine oxidase inhibitors, and tricyclic antidepressants have also shown antipanic efficacy. In addition, cognitive-behavioral therapy has demonstrated efficacy in the acute and long-term treatment of panic disorder. An integrated treatment approach that combines pharmacotherapy with cognitive-behavioral therapy may provide the best treatment. Long-term efficacy and ease of use are important considerations in treatment selection, as maintenance treatment is recommended for at least 12-24 months, and in some cases, indefinitely.

Pollack MH. · Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. · J Clin Psychiatry. · Pubmed #19371505 No free full text.

Abstract: Generalized anxiety disorder (GAD) has a lifetime prevalence in the US population of about 5.7%. Typically, GAD begins in early adulthood and tends to have a chronic and persistent course. The disorder frequently presents comorbidly with other conditions, and about 90% of patients with GAD have at least 1 comorbid lifetime psychiatric disorder. Patients with GAD tend to be high users of medical services; the disorder is associated with significant physical as well as psychological symptomatology and impacts health, family relationships, and employment. Pharmacologic and psychosocial treatments are available for GAD. Different side effect profiles, speed of onset of action, and discontinuation requirements of individual drugs need to be taken into account when selecting treatment. Treatment selection should include consideration of comorbidity, psychological function, social impairment, and refractoriness, as well as the need for ongoing intervention for many individuals. Innovative treatments, including anticonvulsants, atypical antipsychotics, and others, as well as treatment targeting concomitant insomnia, may help improve outcomes for affected individuals.

Hofmann SG, Pollack MH, Otto MW. · Department of Psychology, Center for Anxiety and Related Disorders, Boston University, Boston, Massachusetts 02215, USA. · CNS Drug Rev. · Pubmed #17227287 links to  free full text

Abstract: Anxiety disorders are among the most common mental disorders. One of the most effective strategies to treat anxiety disorders is exposure therapy with or without cognitive intervention. Fear reduction in exposure therapy is similar to extinction learning. Preclinical studies suggest that extinction learning can be blocked by antagonists at the glutamatergic N-methyl-D-aspartate (NMDA) receptor, and facilitated with D-cycloserine (DCS), a partial agonist at the glycine recognition site of the NMDA receptor in the amygdala. DCS is an established antibiotic drug for the chronic treatment of tuberculosis in humans, but has only recently been investigated as an augmentation therapy for psychological treatment procedures. The review of the literature provides preliminary support for the use of acute dosing of DCS as an adjunctive intervention to exposure therapy for anxiety disorders, including specific phobia and social anxiety disorder. Negative results have recently been reported in the treatment of subclinical fears of animals. These studies suggest that DCS needs to be administered on an acute rather than a chronic dosing schedule, include sufficient time for memory consolidation, and be administered together with psychological treatment that leaves sufficient room for further improvement. It remains to be seen whether these highly promising findings represent reliable pharmacological strategies to enhance exposure therapy of anxiety disorders.

Hoge EA, Austin ED, Pollack MH. · Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. · Depress Anxiety. · Pubmed #16892420 No free full text.

Abstract: The growing recognition and occurrence of traumatic exposure in the general population has given increased salience to the need to understand the concept of resilience. More than just the "flip side" of a risk factor, the notion of resilience encompasses psychological and biological characteristics, intrinsic to an individual, that might be modifiable and that confer protection against the development of psychopathology in the face of stress. In this review, we provide some perspective on the concept of "resilience" by examining early use of the term in research on "children at risk" and discuss the relationship between risk and resilience factors. We then review psychological and biological factors that may confer resilience to the development of posttraumatic stress disorder (PTSD) following trauma, examine how resilience has been assessed and measured, and discuss issues to be addressed in furthering our understanding of this critical concept going forward.

Evans KC, Dougherty DD, Pollack MH, Rauch SL. · Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Ann Clin Psychiatry. · Pubmed #16517451 No free full text.

Abstract: BACKGROUND: Functional neuroimaging has begun to show promise as a clinical tool in the prediction of treatment response in mood and anxiety disorders. Given the variance in patient responses to psychiatric treatments, the use of such predictive tools could be tremendously valuable, especially in situations where treatments carry substantial risks or costs. METHODS: A literature search was conducted in December 2004 to identify published neuroimaging treatment prediction papers. "Neuroimaging," "treatment," and "depression or anxiety" were used as keywords. Studies of treatment prediction were complemented by studies of treatment effects to provide context. RESULTS: Fifteen original published papers were identified as investigations of treatment prediction in mood and anxiety disorders. These studies have predominantly been conducted in patients with major depression (MDD) and obsessive-compulsive disorder (OCD). We review this literature and provide a discussion of design considerations in psychiatric neuroimaging studies of treatment response prediction. CONCLUSIONS: The neuroimaging literature pertaining to treatment response prediction is largely limited to studies of MDD and OCD. While these initial reports are preliminary, the findings reviewed suggest that treatment outcome may be predicted by patterns of pre-treatment brain activity in psychiatric patients. However, the actual clinical utility of such tests remains to be shown.

Pollack MH. · Center for Anxiety and Traumatic Stress Related Disorders, Massachusetts General Hospital, Harvard Medical School, Boston, Mass 02114, USA. · J Clin Psychiatry. · Pubmed #16336033 No free full text.

Abstract: Anxiety and depressive disorders often occur as comorbid illnesses and share many common symptoms. Risk factors for these disorders most likely include interactions of environmental and genetic factors. The presence of comorbid anxiety and depression adversely affects clinical and treatment outcomes. Selective serotonin reuptake inhibitors are usually considered first-line treatment for patients with these disorders, although alternative antidepressants or additional therapies are often necessary. Studies suggest that benzodiazepines, anticonvulsants, and atypical antipsychotics may be effective as augmentation therapy to optimize outcome, with buspirone and beta-blockers useful in some patients as well. Cognitive-behavioral therapy is also an effective therapeutic alternative for affected patients.

Stevens JC, Pollack MH. · Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital, Boston, MA 02114, USA. · J Clin Psychiatry. · Pubmed #15762816 No free full text.

Abstract: Despite increasing focus on the use of antidepressants and other agents for the treatment of anxiety, benzodiazepines have remained a mainstay of anxiolytic pharmacotherapy due to their robust efficacy, rapid onset of therapeutic effect, and generally favorable side effect profile. In this article, we examine issues related to the long-term use of benzodiazepines, including concerns about the development of therapeutic tolerance, dose escalation, and adverse cognitive effects. We also consider currently available alternatives to benzodiazepines and novel mechanisms of action that may prove fruitful in the development of future generations of anxiolytics.

Otto MW, Perlman CA, Wernicke R, Reese HE, Bauer MS, Pollack MH. · Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Bipolar Disord. · Pubmed #15541062 No free full text.

Abstract: OBJECTIVES: In this article, we review the evidence for, and implications of, a high rate of comorbid posttraumatic stress disorder (PTSD) in individuals with bipolar disorder. METHODS: We reviewed studies providing comorbidity data on patients with bipolar disorder, and also examined the PTSD literature for risk factors and empirically supported treatment options for PTSD. RESULTS: Studies of bipolar patients have documented elevated rates of PTSD. Based on our review, representing 1214 bipolar patients, the mean prevalence of PTSD in bipolar patients is 16.0% (95% CI: 14-18%), a rate that is roughly double the lifetime prevalence for PTSD in the general population. Risk factors for PTSD that are also characteristic of bipolar samples include the presence of multiple axis I disorders, greater trauma exposure, elevated neuroticism and lower extraversion, and lower social support and socio-economic status. CONCLUSIONS: These findings are discussed in relation to the cost of PTSD symptoms to the course of bipolar disorder. Pharmacological and cognitive-behavioral treatment options are reviewed, with discussion of modifications to current cognitive-behavioral protocols for addressing PTSD in individuals at risk for mood episodes.

Doyle A, Pollack MH. · Center for Anxiety and Traumatic Stress Related Disorders, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA. · J Clin Psychiatry. · Pubmed #15078115 No free full text.

Abstract: Panic disorder is a chronic, disabling condition that is often associated with a need for long-term clinical treatment. While a variety of pharmacotherapy options, including tricyclic antidepressants, selective serotonin reuptake inhibitors, and benzodiazepines, are effective in reducing symptoms in the acute phase, a significant number of patients do not fully respond to initial treatment, and a large majority of patients experience relapse after medication discontinuation. Optimal long-term treatment of panic disorder involves attention to adequate medication dosing and adequate duration of treatment to achieve maximum improvement before discontinuing. Recent reports suggest the efficacy of adjunctive pharmacotherapies and combining pharmacotherapy with behavioral therapy to improve treatment response. Further research is necessary to determine the long-term effectiveness of these multifaceted treatment strategies among patients suffering from refractory panic disorder.

Otto MW, Safren SA, Pollack MH. · Massachusetts General Hospital and Harvard Medical School, WACC-812, 15 Parkman St, Boston, MA 02114, USA. · J Anxiety Disord. · Pubmed #14725869 No free full text.

Abstract: Despite early recognition of the importance of internal cues (craving sensations and emotional states) for relapse in substance use disorders, relatively little attention has been devoted to exposure-based treatments targeting these cues. Drawing upon research on the conceptualization and treatment of panic disorder, we discuss the application of internal (largely emotional) cue exposure for substance use disorders. Our model for this discussion was based on the role of exposure to feared sensations of anxiety in the treatment of panic disorder and benzodiazepine (BZ) discontinuation. Shared research strategies between panic disorder and substance use--studies of biological provocation and anxiety sensitivity--were discussed, as were gender differences in drug-use motives. In accordance with research on anxiety sensitivity, provocation effects, and the treatment of benzodiazepine withdrawal, we discussed the potential value of internal cue-exposure strategies for individuals who use substances as a way to cope with negative affect.

Doyle AC, Pollack MH. · Center for Anxiety and Traumatic Stress Related Disorders, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. · J Clin Psychiatry. · Pubmed #14658990 No free full text.

Abstract: Anxiety disorders such as generalized anxiety disorder, social anxiety disorder, panic disorder, and posttraumatic stress disorder are typically chronic conditions associated with high health care costs and are often accompanied by psychiatric comorbidity, including major depressive disorder, substance abuse, and other anxiety disorders. Anxiety disorders are associated with significant functional impairment in social, vocational, and familial spheres and with diminished overall quality of life. The following clinical overview provides informal guidelines for identifying remission in patients with an anxiety disorder. A systematic approach to treatment that includes patient education, encouragement of exposure, attention to relevant comorbidities, use of empirically proven pharmacotherapies, and psychosocial interventions of adequate intensity and duration will improve outcomes and move patients toward marked improvement and remission.

Pollack MH, Doyle AC. · Center for Anxiety and Traumatic Stress-Related Disorders, Massachusetts General Hospital, Boston, MA 02114, USA. · Psychopharmacol Bull. · Pubmed #14566201 links to  free full text

Abstract: Panic disorder is a chronic and disabling condition associated with significant morbidity. Treatment of panic disorder has evolved significantly in the past 20 years with the availability of serotonergic antidepressants, including the selective serotonin reuptake inhibitors (SSRIs). Of these, paroxetine was the first to receive an indication for treatment of panic disorder and has been extensively studied in this area. A series of randomized, double-blind, placebo-controlled studies have demonstrated the efficacy and safety of paroxetine treatment of panic disorder, with a majority of patients achieving panic-free status during 12-week studies. Continued treatment with paroxetine results in sustained rates of remission compared with placebo. The combination of paroxetine and cognitive behavioral therapy appears to offer benefits of efficacy and sustained therapeutic response.

Huffman JC, Pollack MH. · Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. · Psychosomatics. · Pubmed #12724504 links to  free full text

Abstract: As many as 25% of patients with chest pain who come to hospital emergency departments have panic disorder. Rates of panic disorder are even higher among those who present for outpatient evaluation of their chest pain. Unfortunately, panic disorder remains largely undiagnosed and untreated in these settings. The authors reviewed studies published between 1970 and 2001 that addressed the prevalence of panic disorder among persons who seek treatment for chest pain in an emergency department or outpatient cardiology clinic. A meta-analysis of the findings revealed five variables that appear to correlate with higher rates of panic disorder among persons who present with chest pain: 1). absence of coronary artery disease, 2). atypical quality of chest pain, 3). female sex, 4). younger age, and 5). a high level of self-reported anxiety. Further studies of these and other variables associated with panic disorder should aid in the detection of this disabling but treatable cause of chest pain.

Simon NM, Blacker D, Korbly NB, Sharma SG, Worthington JJ, Otto MW, Pollack MH. · Anxiety Disorders Program, Massachusetts General Hospital and Harvard Medical School, 15 Parkman Street, WAC 815, Boston, MA 02114, USA. · J Affect Disord. · Pubmed #12103468 No free full text.

Abstract: BACKGROUND: The need for thyroid screening of patients presenting with panic disorder (PD), social phobia (SP) or generalized anxiety disorder (GAD) remains uncertain. METHODS: We examined thyroid histories and serum testing in 169 patients, 92 with PD, 48 with SP, and 29 with GAD. Combined prevalence rates of hyperthyroidism and hypothyroidism were compared with expected rates (2.7%) derived from the population based Whickham Survey. Data from previously published studies were also compared with these expected rates. RESULTS: In our sample, only 2/169 patients had thyroid dysfunction detected by serum testing, but 5/169 [1/92 (1%) with PD, 1/48 (2%) with SP, and 3/29 (10%) with GAD], all currently euthyroid, reported a history of thyroid disease. The rates were statistically significant only for GAD (10.4%; z = 2.56, p = 0.01). However, combining prior PD studies that examined both thyroid history and test results with our data also suggests significantly elevated rates of thyroid dysfunction (6.5%; z = 4.69, p < 0.0001). LIMITATIONS: As with previous data, the 95% confidence interval for our findings is broad, reflecting the instability of low rates of illness in relatively small samples. Further, methods for obtaining thyroid histories and tests were not uniform. CONCLUSIONS: Despite relatively low yields on serum testing, lifetime prevalence of thyroid dysfunction does appear elevated for GAD and PD, with minimal data addressing this issue for SP. The data support the need to query GAD and PD patients regarding thyroid history and perform serum testing in those without prior testing.

Pollack MH. · Anxiety Disorders Program, Massachusetts General Hospital, Boston 02114, USA. · J Clin Psychiatry. · Pubmed #11577787 No free full text.

Abstract: More than half of patients with generalized anxiety disorder (GAD) have chronic and persistent symptomatology that may warrant ongoing pharmacotherapy. Many of these patients also have significant comorbid mood and anxiety disorders. There is growing consensus among clinicians that the treatment goal for anxiety disorders should be remission, including the minimization of anxiety and depression and resolution of functional impairment. Clinical management strategies for optimizing pharmacotherapy aimed at achieving remission in GAD include attention to drug selection, dosing levels, and duration of treatment. To optimize treatment for GAD with the goal of achieving remission, it is reasonable to select an agent with demonstrated effectiveness for GAD and associated comorbidities as well as a favorable side effect profile. Dosing and duration of treatment should be adequate, and consideration of adjunctive strategies for refractory patients may be warranted. This article discusses the optimization of pharmacotherapy with the goal of promoting remission in patients with GAD.

Pollack MH. · Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA. · J Clin Psychiatry. · Pubmed #11430615 No free full text.

Abstract: Social anxiety disorder is a common psychiatric illness that imposes persistent functional impairment and disability on persons who have the disorder. The disorder is characterized by a marked and persistent fear of social or performance situations in which embarrassment may occur. It is the most prevalent of any anxiety disorder and is the third most common psychiatric disorder after depression and alcohol abuse. Social anxiety disorder typically begins during childhood with a mean age at onset between 14 and 16 years and is sometimes preceded by a history of social inhibition or shyness. Persons who have social anxiety disorder either endure or avoid social situations altogether because the fear of embarrassment causes such intense anxiety; such avoidance may ultimately interfere with occupational and/or social functioning and lead to significant disability. The duration of social anxiety disorder is frequently lifelong, and there is a high degree of comorbidity with other psychiatric disorders. Social anxiety disorder is a serious illness that frequently runs a chronic course and is associated with significant morbidity. Patients should be treated aggressively using pharmacotherapeutic agents that can be tolerated over the long term. Cognitive-behavioral therapy should also be considered in treatment planning. Efforts to increase the recognition of social anxiety disorder as a common, distressing, and disabling condition are critical. This article discusses the comorbidity, neurobiology, and pharmacotherapy of social anxiety disorder.

Marzol PC, Pollack MH. · Massachusetts General Hospital, 15 Parkman Street, WACC 815, Boston, MA 02114, USA. · Curr Psychiatry Rep. · Pubmed #11122981 No free full text.

Abstract: Panic disorder is a distressing and disabling disorder characterized by recurring panic attacks; anticipatory anxiety about having additional attacks; and agoraphobic fear and avoidance of situations in which attacks have occurred, ready escape is difficult, or help is unavailable in the event of an attack. It is typically associated with impairment in social, emotional, and vocational functioning, as well as excessive utilization of the medical care system. A number of pharmacologic agents and cognitive-behavioral treatments have proven effective for the treatment of panic disorder. Selective serotonin reuptake inhibitors are becoming first-line pharmacotherapy because of their favorable side effect profile and greater spectrum of efficacy in comparison with older classes of agents. In this article, we provide an overview of the prevalence, associated health care utilization, impairment in quality of life, and treatment of panic disorder.

Pollack MH, Marzol PC. · Clinical Psychopharmacology/Behavior Therapy Unit, Massachusetts General Hospital, Boston 02114, USA. · J Psychopharmacol. · Pubmed #10888028 No free full text.

Abstract: Panic disorder is a chronic condition typically associated with significant distress and disability. In addition to the acute distress associated with the panic attack itself, the disorder often leads to distressing anticipatory anxiety and phobic avoidance. Affected individuals experience significant impairment in social and vocational functioning, high utilization of medical resources, constriction of function, premature mortality and diminution in overall quality of life. Panic disorder is frequently comorbid with other conditions, particularly depression, as well as alcohol and other substance abuse, and other anxiety disorders including social phobia, generalized anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. A number of pharmacological agents and cognitive-behavioural treatments have been shown to be effective in the treatment of panic disorder, with the selective serotonin reuptake inhibitors (SSRIs) becoming first-line pharmacotherapy for this condition. Among these, the SSRI sertraline appears effective not only in improving symptoms of panic, but also in reducing anticipatory anxiety and improving multiple aspects of quality of life. For patients who remain partly or fully symptomatic despite adequate first-line treatment, a variety of strategies are emerging for the management of refractory conditions. We provide an overview of the prevalence, presentation and associated complications of panic disorder, review the therapeutic options and discuss the management of refractory patients.

Smoller JW, Simon NM, Pollack MH, Kradin R, Stern T. · Departments of Psychiatry and Pulmonary Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. · Semin Clin Neuropsychiatry. · Pubmed #10378952 No free full text.

Abstract: Anxiety is a common and sometimes disabling symptom among patients with respiratory disease. Anxiety disorders appear to be the most prevalent psychiatric disorders in clinical samples of patients with pulmonary disease. Recognition that the differential diagnosis of dyspnea and anxiety includes both pulmonary and psychiatric conditions can be crucial to appropriate medical management and minimizing iatrogenic harm. This article reviews the epidemiology, comorbidity, diagnosis, and treatment of anxiety syndromes in patients with pulmonary disease. Successful treatment of anxiety disorders can substantially improve quality of life and a variety of treatment options are available. Safe and effective pharmacotherapy requires attention to potential adverse drug effects on pulmonary function and drug-to-drug interactions. Nonpharmacological treatments such as cognitive/behavioral therapies offer effective treatment without the risk of medication side effects.

Evans KC, Simon NM, Dougherty DD, Hoge EA, Worthington JJ, Chow C, Kaufman RE, Gold AL, Fischman AJ, Pollack MH, Rauch SL. · Department of Psychiatry, Psychiatric Neuroscience Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA. · Neuropsychopharmacology. · Pubmed #18536708 No free full text.

Abstract: Corticolimbic circuitry has been implicated in generalized social anxiety disorder (gSAD) by several neuroimaging symptom provocation studies. However, there are limited data regarding resting state or treatment effects on regional cerebral metabolic rate of glucose uptake (rCMRglu). Given evidence for anxiolytic effects conferred by tiagabine, a gamma-aminobutyric acid (GABA) reuptake inhibitor, the present [(18)F] fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) study sought to (1) compare resting rCMRglu between healthy control (HC) and pretreatment gSAD cohorts, (2) examine pre- to post-tiagabine treatment rCMRglu changes in gSAD, and (3) determine rCMRglu predictors of tiagabine treatment response. Fifteen unmedicated individuals with gSAD and ten HCs underwent a baseline (pretreatment) resting-state (18)FDG-PET scan. Twelve of the gSAD individuals completed an open, 6-week, flexible dose trial of tiagabine, and underwent a second (posttreatment) resting-state (18)FDG-PET scan. Compared to the HC subjects, individuals with gSAD demonstrated less pretreatment rCMRglu within the anterior cingulate cortex and ventral medial prefrontal cortex (vmPFC) at baseline. Following tiagabine treatment, vmPFC rCMRglu increased significantly in the gSAD group. Further, the magnitude of treatment response was inversely correlated with pretreatment rCMRglu within vmPFC. Taken together the present findings converge with neuroimaging findings from studies of social cognition in healthy individuals and symptom provocation in gSAD to support a role for the vmPFC in the pathophysiology of gSAD. Given the pharmacological profile of tiagabine, these findings suggest that its therapeutic effects in gSAD may be mediated by GABAergic modulation within the vmPFC.

Simon NM, Connor KM, Lang AJ, Rauch S, Krulewicz S, LeBeau RT, Davidson JR, Stein MB, Otto MW, Foa EB, Pollack MH. · Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital, Boston, MA 02114, USA. · J Clin Psychiatry. · Pubmed #18348595 No free full text.

Abstract: OBJECTIVE: Little is known about the efficacy of "next step" strategies for patients with post-traumatic stress disorder (PTSD) who remain symptomatic despite treatment. This study prospectively examines the relative efficacy of augmentation of continued prolonged exposure therapy (PE) with paroxetine CR versus placebo for individuals remaining symptomatic despite a course of PE. METHOD: Adult outpatients meeting DSM-IV criteria for PTSD were recruited from February 2003 to September 2005 at 4 academic centers. Phase I consisted of 8 sessions of individual PE over a 4- to 6-week period. Participants who remained symptomatic, defined as a score of >or= 6 on the Short PTSD Rating Interview (SPRINT) and a Clinical Global Impressions-Severity of Illness scale (CGI-S) score >or= 3, were randomly assigned to the addition of paroxetine CR or matched placebo to an additional 5 sessions of PE (Phase II). RESULTS: Consistent with prior studies, the 44 Phase I completers improved significantly with initial PE (SPRINT: paired t = 7.6, df = 41, p < .0001; CGI-S: paired t = 6.37, df = 41, p < .0001). Counter to our hypothesis, however, we found no additive benefit of augmentation of continued PE with paroxetine CR compared to pill placebo for the 23 randomly assigned patients, with relatively minimal further gains overall in Phase II. CONCLUSION: Although replication with larger samples is needed before definitive conclusions can be drawn, our data do not support the addition of paroxetine CR compared with placebo to continued PE for individuals with PTSD who remain symptomatic after initial PE, suggesting that the development of novel treatment approaches for PTSD refractory to PE is needed. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00215163.

Pollack MH, Jensen JE, Simon NM, Kaufman RE, Renshaw PF. · Psychiatry Department, Massachusetts General Hospital, Boston, MA 02114, United States. · Prog Neuropsychopharmacol Biol Psychiatry. · Pubmed #18206286 No free full text.

Abstract: OBJECTIVE: Abnormalities in brain gamma-aminobutyric acid (GABA) and glutamate may be relevant to the underlying pathophysiology of anxiety disorders including social anxiety disorder (SAD). METHODS: We used proton magnetic resonance spectroscopy (pMRS) to examine whole brain and regional GABA, glutamate and glutamine in patients (N=10) with SAD at baseline compared to a matched group of healthy controls (HC), and changes following 8 weeks of pharmacotherapy with levetiracetam. RESULTS: For SAD subjects, there were significantly higher whole brain levels of glutamate and glutamine, though no significant differences in GABA. In the thalamus, glutamine was higher and GABA lower for SAD subjects. There was a significant reduction in thalamic glutamine with levetiracetam treatment. CONCLUSION: Our findings provide preliminary support for impaired GABAergic and overactive glutamatergic function in social anxiety disorder and the potential relevance of changes in these systems for the anxiolytic response to levetiracetam.