High expectancy and early response produce optimal effects in sertraline treatment for post-traumatic stress disorder.

BACKGROUND: Better indicators of prognosis are needed to personalise post-traumatic stress disorder (PTSD) treatments.AimsWe aimed to evaluate early symptom reduction as a predictor of better outcome and examine predictors of early response. METHOD: Patients with PTSD (N = 134) received sertraline or prolonged exposure in a randomised trial. Early response was defined as 20% PTSD symptom reduction by session two and good end-state functioning defined as non-clinical levels of PTSD, depression and anxiety. RESULTS: Early response rates were similar in prolonged exposure and sertraline (40 and 42%), but in sertraline only, early responders were four times more likely to achieve good end-state functioning at post-treatment (Number Needed to Treat = 1.8, 95% CI 1.28-3.00) and final follow-up (Number Needed to Treat = 3.1, 95% CI 1.68-16.71). Better outcome expectations of sertraline also predicted higher likelihood of early response. CONCLUSIONS: Higher expectancy of sertraline coupled with early response may produce a cascade-like effect for optimal conditions for long-term symptom reduction. Therefore, assessing expectations and providing clear treatment rationales may optimise sertraline effects. DECLARATION OF INTEREST: None.

Study Design and Rationale for the Mood and Methylation Study: A Platform for Multi-Omics Investigation of Depression in Twins.

Major depression is a complex disorder with no single, direct causal mechanism. Morbidity has been linked to genetic processes, developmental history, and unique environmental exposures. Epigenetic mechanisms, especially DNA methylation, are also likely important factors in the pathogenesis of major depressive disorder (MDD). A community-based twin sample has many advantages for epigenetic studies, given the shared genetic and developmental histories of same-sex twin pairs. This article describes the rationale and study design for the Mood and Methylation Study in which 133 twin pairs (101 monozygotic and 32 dizygotic), both discordant and concordant for lifetime history of MDD, were evaluated on a large number of variables related to MDD. The twins also provided blood samples for an epigenome-wide association study of differentially methylated regions (DMR) relevant to MDD. Although MDD is typically considered a disorder of the central nervous system, it is unfeasible to obtain a large sample of brain tissues. However, epigenetic variation is not limited to the affected tissue but can also be detected in peripheral blood leukocytes. Thus, this study focused on monocytes for the major analyses. Additional plans for the study include gene expression analysis from the same set of twins using RNA-seq and validation of significant DMRs in postmortem brain tissues from a separate sample. Moreover, sufficient samples have been collected to perform future 'multi-omic' analyses, including metabolome, microbiome, and transcriptome. Our long-term goal is to understand how epigenomic and other 'omic' factors can be manipulated for diagnostic, preventive, and therapeutic purposes for MDD and its related conditions.

Improving outcomes for patients with medication-resistant anxiety: effects of collaborative care with cognitive behavioral therapy.

BACKGROUND: Many patients with anxiety disorders remain symptomatic after receiving evidence-based treatment, yet research on treatment-resistant anxiety is limited. We evaluated effects of cognitive behavioral therapy (CBT) on outcomes of patients with medication-resistant anxiety disorders using data from the Coordinated Anxiety Learning and Management (CALM) trial. METHODS: Primary care patients who met study entry criteria (including DSM-IV diagnosis of generalized anxiety disorder, panic disorder, posttraumatic stress disorder, or social anxiety disorder) despite ongoing pharmacotherapy of appropriate type, dose, and duration were classified as medication resistant (n = 227). Logistic regression was used to estimate effects of CALM's CBT program (CALM-CBT; chosen by 104 of 117 medication-resistant patients randomized to CALM) versus usual care (UC; n = 110) on response [≥ 50% reduction of 12-item Brief Symptom Inventory (BSI-12) anxiety and somatic symptom score] and remission (BSI-12 < 6) at 6, 12, and 18 months. Within-group analyses examined outcomes by treatment choice (CBT vs. CBT plus medication management) and CBT dose. RESULTS: Approximately 58% of medication-resistant CALM-CBT patients responded and 46% remitted during the study. Relative to UC, CALM-CBT was associated with greater response at 6 months (AOR = 3.78, 95% CI 2.02-7.07) and 12 months (AOR = 2.49, 95% CI 1.36-4.58) and remission at 6, 12, and 18 months (AORs = 2.44 to 3.18). Patients in CBT plus medication management fared no better than those in CBT only. Some evidence suggested higher CBT dose produced better outcomes. CONCLUSIONS: CBT can improve outcomes for patients whose anxiety symptoms are resistant to standard pharmacotherapy.

Trajectories of change in anxiety severity and impairment during and after treatment with evidence-based treatment for multiple anxiety disorders in primary care.

BACKGROUND: Coordinated Anxiety Learning and Management (CALM) is a model for delivering evidence-based treatment for anxiety disorders in primary care. Compared to usual care, CALM produced greater improvement in anxiety symptoms. However, mean estimates can obscure heterogeneity in treatment response. This study aimed to identify (1) clusters of participants with similar patterns of change in anxiety severity and impairment (trajectory groups); and (2) characteristics that predict trajectory group membership. METHODS: The CALM randomized controlled effectiveness trial was conducted in 17 primary care clinics in four US cities in 2006-2009. 1,004 English- or Spanish-speaking patients age 18-75 with panic, generalized anxiety, social anxiety, and/or posttraumatic stress disorder participated. The Overall Anxiety Severity and Impairment Scale was administered repeatedly to 482 participants randomized to CALM treatment. Group-based trajectory modeling was applied to identify trajectory groups and multinomial logit to predict trajectory group membership. RESULTS: Two predicted trajectories, representing about two-thirds of participants, were below the cut-off for clinically significant anxiety a couple of months after treatment initiation. The predicted trajectory for the majority of remaining participants was below the cut-off by 9 months. A small group of participants did not show consistent improvement. Being sicker at baseline, not working, and reporting less social support were associated with less favorable trajectories. CONCLUSIONS: There is heterogeneity in patient response to anxiety treatment. Adverse circumstances appear to hamper treatment response. To what extent anxiety symptoms improve insufficiently because adverse patient circumstances contribute to suboptimal treatment delivery, suboptimal treatment adherence, or suboptimal treatment response requires further investigation.

Race and beliefs about mental health treatment among anxious primary care patients.

Large racial disparities in the use of mental health care persist. Differences in treatment preferences could partially explain the differences in care between minority and nonminority populations. We compared beliefs about mental illness and treatment preferences between adult African-Americans, Hispanics, Asian Americans, Native Americans, and White Americans with diagnosed anxiety disorders. Measures of beliefs about mental illness and treatment were drawn from the National Comorbidity Survey Replication and from our previous work. There were no significant differences in beliefs between the African-Americans and the White Americans. The beliefs of the Hispanics and the Native Americans were most distinctive, but the differences were small in magnitude. Across race/ethnicity, the associations between beliefs and service use were generally weak and statistically insignificant. The differences in illness beliefs and treatment preferences do not fully explain the large, persistent racial disparities in mental health care. Other crucial barriers to quality care exist in our health care system and our society as a whole.

Diagnostic overlap of generalized anxiety disorder and major depressive disorder in a primary care sample.

BACKGROUND: Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are highly comorbid. A possible explanation is that they share four symptoms according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR). The present study addressed the symptom overlap of people meeting DSM-IV-TR diagnostic criteria for GAD, MDD, or both to investigate whether comorbidity might be explained by overlapping diagnostic criteria. METHODS: Participants (N = 1,218) were enrolled in the Coordinated Anxiety Learning and Management study (a randomized effectiveness clinical trial in primary care). Hypotheses were (1) the comorbid GAD/MDD group endorses the overlapping symptoms more than the nonoverlapping symptoms, and (2) the comorbid GAD/MDD group endorses the overlapping symptoms more than GAD only or MDD only groups, whereas differences would not occur for nonoverlapping symptoms. RESULTS: The overlapping GAD/MDD symptoms were endorsed more by the comorbid group than the MDD group but not the GAD group when covarying for total symptom endorsement. Similarly, the comorbid group endorsed the overlapping symptoms more than the nonoverlapping symptoms and did not endorse the nonoverlapping symptoms more than the GAD or MDD groups when covarying for total symptom endorsement. CONCLUSIONS: The results suggest that comorbidity of GAD and MDD is strongly influenced by diagnostic overlap. Results are discussed in terms of errors of diagnostic criteria, as well as models of shared psychopathology that account for diagnostic criteria overlap.

Use of complementary and alternative medicine in a large sample of anxiety patients.

OBJECTIVE: To examine a large sample of patients with anxiety and the association between types of complementary and alternative treatments that were used, demographic variables, diagnostic categories, and treatment outcomes. METHOD: Cross-sectional and longitudinal survey during the Coordinated Anxiety Learning and Management (CALM) study that assessed this intervention against the Usual Care in a sample of patients with anxiety recruited from primary care. Interviewer-administered questionnaires via a centralized telephone survey by blinded assessment raters. The interviews were done at baseline, 6, 12, and 18 months of the study. A total of 1004 adults ages 18-75 who met DSM-IV criteria for Generalized Anxiety Disorder (GAD), Panic Disorder, Social Anxiety Disorder, or Post-Traumatic Stress Disorder. We assessed medication/herbal use, the use of any alternative therapies, and combined Complementary and Alternative Medicine (CAM) use. RESULTS: We found an extensive (43%) use of a variety of CAM treatments that is consistent with previous study results in populations with anxiety. Only a few significant demographic or interventional characteristics of CAM users were found. Users most often had a diagnosis of GAD, were older, more educated, and had two or more chronic medical conditions. CAM users who had a 50% or more drop in anxiety scores over 18 months were less likely to report continued use of alternative therapies. CONCLUSIONS: The study confirms the importance of awareness of CAM use in this population for possible interference with traditional first-line treatments of these disorders, but also for finding the best integrative use for patients who require multiple treatment modalities.

Effectiveness of therapeutic massage for generalized anxiety disorder: a randomized controlled trial.

BACKGROUND: Although massage is one of the most popular complementary and alternative medical (CAM) treatments for anxiety, its effectiveness has never been rigorously evaluated for a diagnosed anxiety disorder. This study evaluates the effectiveness of therapeutic massage for persons with generalized anxiety disorder (GAD). METHODS: Sixty-eight persons with GAD were randomized to therapeutic massage (n=23), thermotherapy (n=22), or relaxing room therapy (n=23) for a total of 10 sessions over 12 weeks. Mean reduction in anxiety was measured by the Hamilton Anxiety Rating Scale (HARS). Secondary outcomes included 50% reduction in HARS and symptom resolution of GAD, changes in depressive symptoms (Patient Health Questionnaire (PHQ-8)), worry and GAD-related disability. We compared changes in these outcomes in the massage and control groups posttreatment and at 6 months using generalized estimating equation (GEE) regression. RESULTS: All groups had improved by the end of treatment (adjusted mean change scores for the HARS ranged from -10.0 to -13.0; P<.001) and maintained their gains at the 26-week followup. No differences were seen between groups (P=.39). Symptom reduction and resolution of GAD, depressive symptoms, worry and disability showed similar patterns. CONCLUSIONS: Massage was not superior to the control treatments, and all showed some clinically important improvements, likely due to some beneficial but generalized relaxation response. Because the relaxing room treatment is substantially less expensive than the other treatments, a similar treatment packaged in a clinically credible manner might be the most cost effective option for persons with GAD who want to try relaxation-oriented CAM therapies.

What would you choose? Sertraline or prolonged exposure in community and PTSD treatment seeking women.

BACKGROUND: Both sertraline (SER) and prolonged exposure (PE) are empirically supported treatments for chronic posttraumatic stress disorder (PTSD). While efficacious, these treatments are quite different in approach, and such differences may influence both treatment choice and treatment outcome. To date, we know very little about the relative efficacy of pharmacological and psychological treatments for chronic PTSD. METHOD: In Study 1, we compared rates of treatment choice (SER or PE) in 74 trauma-exposed women. In Study 2, we extended this work to an open-choice treatment trial, in which 31 female assault survivors with chronic PTSD received their choice of SER or PE for ten weeks and were followed over time. RESULTS: In Study 1 (82%) and Study 2 (74.2%), the majority of women chose PE. In Study 2, both SER and PE evidenced moderate to large unadjusted effect sizes, with evidence of an advantage for PE in propensity adjusted analyses at posttreatment. Women with co-occurring major depressive disorder (MDD) were more likely to choose SER than those without MDD. However, among those with MDD, the advantage of PE was particularly evident. CONCLUSIONS: Our results highlight the presence of clear treatment preferences for PTSD and their potential impact on outcome. This study underscores the importance of systematic study of patient preferences and encourages a rethinking of one-size fits all approaches to treatment for mental disorders.

Computer-assisted delivery of cognitive behavioral therapy for anxiety disorders in primary-care settings.

OBJECTIVES: This article describes a computer-assisted cognitive behavioral therapy (CBT) program designed to support the delivery of evidenced-based CBT for the four most commonly occurring anxiety disorders (panic disorder, posttraumatic stress disorder, generalized anxiety disorder, and social anxiety disorder) in primary-care settings. The purpose of the current report is to (1) present the structure and format of the computer-assisted CBT program, and (2) to present evidence for acceptance of the program by clinicians and the effectiveness of the program for patients. METHODS: Thirteen clinicians using the computer-assisted CBT program with patients in our ongoing Coordinated Anxiety Learning and Management study provided Likert-scale ratings and open-ended responses about the program. Rating scale data from 261 patients who completed at least one CBT session were also collected. RESULTS: Overall, the program was highly rated and modally described as very helpful. Results indicate that the patients fully participated (i.e., attendance and homework compliance), understood the program material, and acquired CBT skills. In addition, significant and substantial improvements occurred to the same degree in randomly audited subsets of each of the four primary anxiety disorders (N=74), in terms of self ratings of anxiety, depression, and expectations for improvement. CONCLUSIONS: Computer-assisted CBT programs provide a practice-based system for disseminating evidence-based mental health treatment in primary-care settings while maintaining treatment fidelity, even in the hands of novice clinicians.

Addiction and suicidal behavior in acute psychiatric inpatients.

OBJECTIVE: This study aims to evaluate the relationship of alcohol/drug use and effect severities to the degree of suicidality in acutely admitted psychiatric patients. Both degree of substance dependency and degree of substance-induced syndrome were analyzed. In addition, length of stay, involuntary status, and against medical advice discharge status were determined as they related to these variables. METHODS: Structured clinical admissions and discharge ratings were gathered from 10,667 consecutive, single-case individual records, from an urban acute care county psychiatric hospital. RESULTS: Data indicate that of the most severely suicidal group, 56% had substance abuse or dependence, 40% were rated as having half or more of their admission syndrome substance induced, and most had nonpsychotic diagnoses. There was an inverse relationship between degree of substance problem and length of stay. Although these patients more commonly left against medical advice, and were readmitted more frequently, they were less likely to be involuntarily committed. CONCLUSIONS: A large, potentially lethal, and highly expensive subgroup of patients has been characterized, which might be called the "New Revolving Door acute psychiatric inpatient." This group, which uses the most expensive level of care in the mental health system but is substantially addiction related, poses special challenges for inpatient psychiatric units, addiction treatment providers, and health care planners.

Predictors of clinical improvement in a randomized effectiveness trial for primary care patients with panic disorder.

This study's aim was to prospectively examine and identify a model of demographic, clinical, and attitudinal variables that impact improvement among patients with panic disorder. Subjects were 232 primary care patients meeting criteria for DSM-IV panic disorder. Eligible patients were randomly assigned to a collaborative care intervention or to treatment as usual. Assessments occurred at 3-month intervals during the course of 1 year. In final multivariate logistic regression models, patients with higher anxiety sensitivity and higher neuroticism scores at baseline were less likely to show clinical improvement (using a criterion of 20 or less on the Anxiety Sensitivity Index) at 3 months. Those who were non-white, had higher anxiety sensitivity, and higher overall phobic avoidance at baseline were less likely to show clinical improvement at 12 months. A greater understanding of these predictors may help clinicians identify who is at greatest risk for persistent panic-related symptoms and to plan the intensity of interventions accordingly.

Doubly Randomized Preference Trial of Prolonged Exposure Versus Sertraline for Treatment of PTSD.

OBJECTIVE: The authors examined the effect of patient treatment preference on the differential effectiveness of prolonged exposure and sertraline for the treatment of posttraumatic stress disorder (PTSD). METHOD: In a doubly randomized preference trial, 200 patients with PTSD viewed standardized treatment rationales prior to randomization. Patients were first randomized to choice of treatment or no choice. Those assigned to no choice were then randomized to prolonged exposure or sertraline. Acute treatment was 10 weeks, with 24-month follow-up. Interviewer-rated PTSD symptom severity was the main outcome measure, and depression, anxiety, and functioning were assessed as additional outcomes. RESULTS: Patients preferred prolonged exposure over sertraline (number needed to benefit [NNTB]=4.5). Using intent-to-treat analyses (N=200), both prolonged exposure and sertraline showed large gains that were maintained over 24 months. Although no differential effect was observed on interviewer-rated PTSD severity, there was a significant benefit of prolonged exposure over sertraline on interview-rated loss of PTSD diagnosis (NNTB=7.0), responder status (NNTB=5.7), and self-reported PTSD, depression, and anxiety symptoms and functioning (effect sizes, 0.35-0.44). Patients who received their preferred treatment were more likely to be adherent, lose their PTSD diagnosis (NNTB=3.4), achieve responder status (NNTB=3.4), and have lower self-reported PTSD, depression, and anxiety symptoms (effect sizes, 0.40-0.72). CONCLUSIONS: Prolonged exposure and sertraline confer significant benefits for PTSD, with some evidence of an advantage for prolonged exposure. Giving patients with PTSD their preferred treatment also confers important benefits, including enhancing adherence.

Relationships among pain, anxiety, and depression in primary care.

Pain, anxiety, and depression are commonly seen in primary care patients and there is considerable evidence that these experiences are related. This study examined associations between symptoms of pain and symptoms and diagnoses of anxiety and depression in primary care patients. Results indicate that primary care patients who endorse symptoms of muscle pain, headache, or stomach pain are approximately 2.5-10 times more likely to screen positively for panic disorder, generalized anxiety disorder, or major depressive disorder. Endorsement of pain symptoms was also significantly associated with confirmed diagnoses of several of the anxiety disorders and/or major depression, with odds ratios ranging from approximately 3 to 9 for the diagnoses. Patients with an anxiety or depressive disorder also reported greater interference from pain. Similarly, patients endorsing pain symptoms reported lower mental health functioning and higher scores on severity measures of depression, social anxiety, and posttraumatic stress disorder. Mediation analyses indicated that depression mediated some, but not all of the relationships between anxiety and pain. Overall, these results reveal an association between reports of pain symptoms and not only depression, but also anxiety. An awareness of these relationships may be particularly important in primary care settings where a patient who presents with reports of pain may have an undiagnosed anxiety or depressive disorder.

Novel treatment approaches for refractory anxiety disorders.

The Anxiety Disorders Association of America convened a conference of experts to address treatment-resistant anxiety disorders and review promising novel approaches to the treatment of refractory anxiety disorders. Workgroup leaders and other participants reviewed the literature and considered the presentations and discussions from the conference. Authors placed the emerging literature on new therapeutic approaches into clinical perspective and identified unmet needs and priority areas for future research. There is a relative paucity of efforts addressing inadequate response to anxiety disorder treatment. Systematic efforts to exhaust all therapeutic options and overcome barriers to effective treatment delivery are needed before patients can be considered treatment refractory. Cognitive behavioral therapy, especially in combination with pharmacotherapy, must be tailored to accommodate the effects of clinical context on treatment response. The literature on pharmacologic treatment of refractory anxiety disorders is small but growing and includes studies of augmentation strategies and non-traditional anxiolytics. Research efforts to discover new pharmacologic targets are focusing on neuronal systems that mediate responses to stress and fear. A number of clinical and basic science studies were proposed that would advance the research agenda and improve treatment of patients with anxiety disorders. Significant advances have been made in the development of psychotherapeutic and pharmacologic treatments for anxiety disorders. Unfortunately, many patients remain symptomatic and functionally impaired. Progress in the development of new treatments has great promise, but will only succeed through a concerted research effort that systematically evaluates potential areas of importance and properly uses scarce resources.

Anxiety disorders and comorbid medical illness.

OBJECTIVE: To provide an overview of the role of anxiety disorders in medical illness. METHOD: The Anxiety Disorders Association of America held a multidisciplinary conference from which conference leaders and speakers reviewed presentations and discussions, considered literature on prevalence, comorbidity, etiology and treatment, and made recommendations for research. Irritable bowel syndrome (IBS), asthma, cardiovascular disease (CVD), cancer and chronic pain were reviewed. RESULTS: A substantial literature supports clinically important associations between psychiatric illness and chronic medical conditions. Most research focuses on depression, finding that depression can adversely affect self-care and increase the risk of incident medical illness, complications and mortality. Anxiety disorders are less well studied, but robust epidemiological and clinical evidence shows that anxiety disorders play an equally important role. Biological theories of the interactions between anxiety and IBS, CVD and chronic pain are presented. Available data suggest that anxiety disorders in medically ill patients should not be ignored and could be considered conjointly with depression when developing strategies for screening and intervention, particularly in primary care. CONCLUSIONS: Emerging data offer a strong argument for the role of anxiety in medical illness and suggest that anxiety disorders rival depression in terms of risk, comorbidity and outcome. Research programs designed to advance our understanding of the impact of anxiety disorders on medical illness are needed to develop evidence-based approaches to improving patient care.

Substance-induced suicidal admissions to an acute psychiatric service: characteristics and outcomes.

The degree of substance-induced syndrome (SIS) was evaluated in 5,116 acutely hospitalized suicidal psychiatric inpatients. Admission and discharge severity ratings were made by academic attendings using structured forms. Outcome variables analyzed include ratings of psychiatric symptom severity on admission and discharge, length of stay, severity of SIS, and severity of alcohol/drug problems. Suicidal inpatients rated with a high degree of SIS were more likely to be homeless, to be unemployed, to be uncooperative, to have shorter lengths of stay, and to show a more rapid improvement in symptoms. These patients represent a subgroup of the co-occurring disorders population having a high degree of addiction severity with temporary substance-induced suicidal syndromes and are subjected to the most expensive level of care in the mental health system. Implications of these findings include the fact that psychiatric inpatient services need to provide intensive addiction intervention treatment and that outpatient addiction services need improved capability and capacity to care for suicidal patients.

Panic disorder.

Panic disorder is a common mental disorder that affects up to 5% of the population at some point in life. It is often disabling, especially when complicated by agoraphobia, and is associated with substantial functional morbidity and reduced quality of life. The disorder is also costly for individuals and society, as shown by increased use of health care, absenteeism, and reduced workplace productivity. Some physical illnesses (eg, asthma) commonly occur with panic disorder, and certain lifestyle factors (eg, smoking) increase the risk for the disorder, but causal pathways are still unclear. Genetic and early experiential susceptibility factors also exist, but their exact nature and pathophysiological mechanisms remain unknown. Despite an imprecise, although increased, understanding of cause, strong evidence supports the use of several effective treatments (eg, pharmacological, cognitive-behavioural). The adaptation and dissemination of these treatments to the frontlines of medical-care delivery should be urgent goals for the public-health community.