Bernard Hart (1879-1966) and his influence on British psychiatry.

Bernard Hart was among the most eminent 20th-century British psychiatrists. Following medical qualification at University College Hospital, London, he trained in psychiatry, which included two years studying in Paris and Zurich. He was appointed as the first psychiatric consultant at University College Hospital, then spent some time in Liverpool, where he specialized in treating war neurosis. Early in his career, Hart was one of the first to introduce the ideas of Freud and Janet, and the importance of unconscious processes, to the British public. After the First World War, Hart returned to University College Hospital, where he remained until 1947, building up a flourishing department. Hart was appointed to numerous senior offices and directed the psychiatric section of the British Emergency Medical Services in the Second World War. Hart is believed to be the last psychiatrist to certify someone (John Amery) as being of sufficiently sound mind to die for treason.

Systematic Review and Meta-Analysis of Randomised, Other-than-Placebo Controlled, Trials of Non-Individualised Homeopathic Treatment.

INTRODUCTION: This study focuses on randomised controlled trials (RCTs) of non-individualised homeopathic treatment (NIHT) in which the control (comparator) group was other than placebo (OTP). OBJECTIVES: To determine the comparative effectiveness of NIHT on health-related outcomes in adults and children for any given condition that has been the subject of at least one OTP-controlled trial. For each study, to assess its risk of bias and to determine whether its study attitude was predominantly 'pragmatic' or 'explanatory'. METHODS: Systematic review. For each eligible trial, published in the peer-reviewed literature up to the end of 2016, we assessed its risk of bias (internal validity) using the seven-domain Cochrane tool, and its relative pragmatic or explanatory attitude (external validity) using the 10-domain PRECIS tool. We grouped RCTs by whether these examined IHT as alternative treatment (study design 1a), adjunctively with another intervention (design 1b), or compared with no intervention (design 2). RCTs were sub-categorised as superiority trials or equivalence/non-inferiority trials. For each RCT, we designated a single 'main outcome measure' to use in meta-analysis: 'effect size' was reported as odds ratio (OR; values > 1 favouring homeopathy) or standardised mean difference (SMD; values < 0 favouring homeopathy). RESULTS: Seventeen RCTs, representing 15 different medical conditions, were eligible for study. Three of the trials were more pragmatic than explanatory, two were more explanatory than pragmatic, and 12 were equally pragmatic and explanatory. Fourteen trials were rated 'high risk of bias' overall; the other three trials were rated 'uncertain risk of bias' overall. Ten trials had data that were extractable for analysis. Significant heterogeneity undermined the planned meta-analyses or their meaningful interpretation. For the three equivalence or non-inferiority trials with extractable data, the small, non-significant, pooled effect size (SMD = 0.08; p = 0.46) was consistent with a conclusion that NIHT did not differ from treatment by a comparator (Ginkgo biloba or betahistine) for vertigo or (cromolyn sodium) for seasonal allergic rhinitis. CONCLUSIONS: The current data preclude a decisive conclusion about the comparative effectiveness of NIHT. Generalisability of findings is restricted by the limited external validity identified overall. The highest intrinsic quality was observed in the equivalence and non-inferiority trials of NIHT.

Systematic Review and Meta-Analysis of Randomised, Other-than-Placebo Controlled, Trials of Individualised Homeopathic Treatment.

BACKGROUND: This study focuses on randomised controlled trials (RCTs) of individualised homeopathic treatment (IHT) in which the control (comparator) group was other than placebo (OTP). AIMS: To determine the comparative effectiveness of IHT on health-related outcomes in adults and children for any clinical condition that has been the subject of at least one OTP-controlled trial. For each study, to assess the risk of bias and to determine whether its study attitude was predominantly 'pragmatic' or 'explanatory'. METHODS: Systematic review. For each eligible trial, published in the peer-reviewed literature up to the end of 2015, we assessed its risk of bias (internal validity) using the seven-domain Cochrane tool, and its relative pragmatic or explanatory attitude (external validity) using the 10-domain PRECIS tool. We grouped RCTs by whether they examined IHT as an alternative treatment (study design Ia), adjunctively with another intervention (design Ib), or compared with a no-intervention group (design II). For each RCT, we identified a 'main outcome measure' to use in meta-analysis: 'relative effect size' was reported as odds ratio (OR; values >1 favouring homeopathy) or standardised mean difference (SMD; values < 0 favouring homeopathy). RESULTS: Eleven RCTs, representing 11 different medical conditions, were eligible for study. Five of the RCTs (four of which in design Ib) were judged to have pragmatic study attitude, two were explanatory, and four were equally pragmatic and explanatory. Ten trials were rated 'high risk of bias' overall: one of these, a pragmatic study with design Ib, had high risk of bias solely regarding participant blinding (a bias that is intrinsic to such trials); the other trial was rated 'uncertain risk of bias' overall. Eight trials had data that were extractable for analysis: for four heterogeneous trials with design Ia, the pooled OR was statistically non-significant; collectively for three clinically heterogeneous trials with design Ib, there was a statistically significant SMD favouring adjunctive IHT; in the remaining trial of design 1a, IHT was non-inferior to fluoxetine in the treatment of depression. CONCLUSIONS: Due to the low quality, the small number and the heterogeneity of studies, the current data preclude a decisive conclusion about the comparative effectiveness of IHT. Generalisability of findings is limited by the variable external validity identified overall; the most pragmatic study attitude was associated with RCTs of adjunctive IHT. Future OTP-controlled trials in homeopathy should aim, as far as possible, to promote both internal validity and external validity.

Randomised, double-blind, placebo-controlled trials of non-individualised homeopathic treatment: systematic review and meta-analysis.

BACKGROUND: A rigorous systematic review and meta-analysis focused on randomised controlled trials (RCTs) of non-individualised homeopathic treatment has not previously been reported. We tested the null hypothesis that the main outcome of treatment using a non-individualised (standardised) homeopathic medicine is indistinguishable from that of placebo. An additional aim was to quantify any condition-specific effects of non-individualised homeopathic treatment. METHODS: Literature search strategy, data extraction and statistical analysis all followed the methods described in a pre-published protocol. A trial comprised 'reliable evidence' if its risk of bias was low or it was unclear in one specified domain of assessment. 'Effect size' was reported as standardised mean difference (SMD), with arithmetic transformation for dichotomous data carried out as required; a negative SMD indicated an effect favouring homeopathy. RESULTS: Forty-eight different clinical conditions were represented in 75 eligible RCTs. Forty-nine trials were classed as 'high risk of bias' and 23 as 'uncertain risk of bias'; the remaining three, clinically heterogeneous, trials displayed sufficiently low risk of bias to be designated reliable evidence. Fifty-four trials had extractable data: pooled SMD was -0.33 (95% confidence interval (CI) -0.44, -0.21), which was attenuated to -0.16 (95% CI -0.31, -0.02) after adjustment for publication bias. The three trials with reliable evidence yielded a non-significant pooled SMD: -0.18 (95% CI -0.46, 0.09). There was no single clinical condition for which meta-analysis included reliable evidence. CONCLUSIONS: The quality of the body of evidence is low. A meta-analysis of all extractable data leads to rejection of our null hypothesis, but analysis of a small sub-group of reliable evidence does not support that rejection. Reliable evidence is lacking in condition-specific meta-analyses, precluding relevant conclusions. Better designed and more rigorous RCTs are needed in order to develop an evidence base that can decisively provide reliable effect estimates of non-individualised homeopathic treatment.

Model validity and risk of bias in randomised placebo-controlled trials of individualised homeopathic treatment.

BACKGROUND: To date, our programme of systematic reviews has assessed randomised controlled trials (RCTs) of individualised homeopathy separately for risk of bias (RoB) and for model validity of homeopathic treatment (MVHT). OBJECTIVES: The purpose of the present paper was to bring together our published RoB and MVHT findings and, using an approach based on GRADE methods, to merge the quality appraisals of these same RCTs, examining the impact on meta-analysis results. DESIGN: Systematic review with meta-analysis. METHODS: As previously, 31 papers (reporting a total of 32 RCTs) were eligible for systematic review and were the subject of study. MAIN OUTCOME MEASURES: For each trial, the separate ratings for RoB and MVHT were merged to obtain a single overall quality designation ('high', 'moderate, "low", 'very low'), based on the GRADE principle of 'downgrading'. RESULTS: Merging the assessment of MVHT and RoB identified three trials of 'high quality', eight of 'moderate quality', 18 of 'low quality' and three of 'very low quality'. There was no association between a trial's MVHT and its RoB or its direction of treatment effect (P>0.05). The three 'high quality' trials were those already labelled 'reliable evidence' based on RoB, and so no change was found in meta-analysis based on best-quality evidence: a small, statistically significant, effect favouring homeopathy. CONCLUSION: Accommodating MVHT in overall quality designation of RCTs has not modified our pre-existing conclusion that the medicines prescribed in individualised homeopathy may have small, specific, treatment effects.

A pilot randomized placebo-controlled trial of adjunctive aripiprazole for chronic PTSD in US military Veterans resistant to antidepressant treatment.

Many individuals with post-traumatic stress disorder (PTSD) experience persistent symptoms despite pharmacological treatment with antidepressants. Several open-label monotherapy and adjunctive studies have suggested that aripiprazole (a second-generation antipsychotic) may have clinical utility in PTSD. However, there have been no randomized placebo-controlled trials of aripiprazole use for PTSD. We thus conducted a pilot randomized controlled trial of adjunctive aripiprazole versus placebo among Veterans with chronic PTSD serving in the US military since 11 September 2001 to assess the feasibility, safety, tolerability, and therapeutic potential of aripiprazole. Sixteen Veterans were randomized, and 14 completed at least 4 weeks of the study; 12 completed the entire 8-week trial. Outcome measures included the Clinician-Administered PTSD Scale (CAPS), PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores. Aripiprazole was well-tolerated in this cohort, and improvements in CAPS, PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores were as hypothesized. Although CAPS change scores did not reach statistical significance, aripiprazole outperformed placebo by 9 points on the CAPS in the last observation carried forward analysis compared with the placebo group (n = 7 per group), and by 20 points in the group randomized to aripiprazole that completed the entire study (n = 5) compared with the placebo group (n = 7). Results suggest promise for aripiprazole as an adjunctive strategy for the treatment of PTSD.

Randomised placebo-controlled trials of individualised homeopathic treatment: systematic review and meta-analysis.

BACKGROUND: A rigorous and focused systematic review and meta-analysis of randomised controlled trials (RCTs) of individualised homeopathic treatment has not previously been undertaken. We tested the hypothesis that the outcome of an individualised homeopathic treatment approach using homeopathic medicines is distinguishable from that of placebos. METHODS: The review's methods, including literature search strategy, data extraction, assessment of risk of bias and statistical analysis, were strictly protocol-based. Judgment in seven assessment domains enabled a trial's risk of bias to be designated as low, unclear or high. A trial was judged to comprise 'reliable evidence' if its risk of bias was low or was unclear in one specified domain. 'Effect size' was reported as odds ratio (OR), with arithmetic transformation for continuous data carried out as required; OR > 1 signified an effect favouring homeopathy. RESULTS: Thirty-two eligible RCTs studied 24 different medical conditions in total. Twelve trials were classed 'uncertain risk of bias', three of which displayed relatively minor uncertainty and were designated reliable evidence; 20 trials were classed 'high risk of bias'. Twenty-two trials had extractable data and were subjected to meta-analysis; OR = 1.53 (95% confidence interval (CI) 1.22 to 1.91). For the three trials with reliable evidence, sensitivity analysis revealed OR = 1.98 (95% CI 1.16 to 3.38). CONCLUSIONS: Medicines prescribed in individualised homeopathy may have small, specific treatment effects. Findings are consistent with sub-group data available in a previous 'global' systematic review. The low or unclear overall quality of the evidence prompts caution in interpreting the findings. New high-quality RCT research is necessary to enable more decisive interpretation.

Examining the factor structure of the Connor-Davidson Resilience Scale (CD-RISC) in a post-9/11 U.S. military veteran sample.

The present study examined the structural validity of the 25-item Connor-Davidson Resilience Scale (CD-RISC) in a large sample of U.S. veterans with military service since September 11, 2001. Participants (N = 1,981) completed the 25-item CD-RISC, a structured clinical interview and a self-report questionnaire assessing psychiatric symptoms. The study sample was randomly divided into two subsamples: an initial sample (Sample 1: n = 990) and a replication sample (Sample 2: n = 991). Findings derived from exploratory factor analysis (EFA) did not support the five-factor analytic structure as initially suggested in Connor and Davidson's instrument validation study. Although parallel analyses indicated a two-factor structural model, we tested one to six factor solutions for best model fit using confirmatory factor analysis. Results supported a two-factor model of resilience, composed of adaptability- (8 items) and self-efficacy-themed (6 items) items; however, only the adaptability-themed factor was found to be consistent with our view of resilience-a factor of protection against the development of psychopathology following trauma exposure. The adaptability-themed factor may be a useful measure of resilience for post-9/11 U.S. military veterans.

The sleep effects of tiagabine on the first night of treatment predict post-traumatic stress disorder response at three weeks.

INTRODUCTION: We sought to test the hypothesis that improvements in sleep might mediate treatment-related improvements in daytime symptoms of post-traumatic stress disorder (PTSD). We evaluated whether changes in sleep occurring on the first night of tiagabine (a gamma-amino butyric acid (GABA) reuptake inhibitor) administration predicted subsequent PTSD response. METHODS: This was an open-label three-week polysomnographic (PSG) study of nightly treatment with tiagabine dosing from 2-12 mg including 20 adults with PTSD with ≥30 min of self-reported and PSG wake time after sleep onset (WASO). RESULTS: A treatment night 1 decrease in self-reported and PSG WASO and an increase in slow-wave sleep (SWS) accounted for 94% of the variance in week 3 Short PTSD Rating Interview (SPRINT) score, the primary outcome measure (p<0.001). Increased night 1 SWS also accounted for 91% of the variance in Work/School Impairment and 45% of the variance in Social Life Impairment as measured with the Sheehan Disability Scale (p<0.001). These relationships were much stronger correlates of three-week outcome than three-week sleep effects. CONCLUSIONS: The initial sleep response to tiagabine may mediate or be an indicator of the subsequent PTSD response. The findings highlight the importance of sleep maintenance and SWS in the treatment of PTSD and also suggest a potential relationship between SWS and daytime function.

A factor analysis of posttraumatic stress disorder symptoms using data pooled from two venlafaxine extended-release clinical trials.

BACKGROUND: Confirmatory factor analysis (CFA) of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) three-factor posttraumatic stress disorder (PTSD) diagnostic criteria was conducted to determine fit for this patient population. An exploratory factor analysis (EFA) of alternate symptom structures was planned to identify symptoms that cluster in this population. The response of symptom factors to treatment with venlafaxine extended release (ER) was explored. METHODS: Baseline 17-item Clinician-Administered PTSD Scale (CAPS-SX17) data were pooled from patients enrolled in two double-blind, randomized, placebo-controlled trials. The CFA was conducted using maximum likelihood and weighted, least-squares factor extraction methods. The EFA was performed using a polychoric correlation covariance matrix and Pearson correlation matrix. RESULTS: Data from a pooled population of 685 patients (venlafaxine ER: n = 339; placebo: n = 346) were analyzed. CFA rejected the DSM-IV three-factor structure. The EFA identified a different three-factor structure as the best fit: factor 1 included reexperiencing symptoms, factor 2 included symptoms of altered mood and cognition, whereas factor 3 comprised avoidance and arousal symptoms. All DSM-IV symptom factors and all factors in the identified three-factor model responded positively to venlafaxine ER treatment. CONCLUSIONS: Data are consistent with literature failing to confirm the three-factor structure of DSM-IV PTSD, and they support the DSM-5 inclusion of a symptom cluster addressing altered mood and cognition in PTSD. The efficacy of venlafaxine ER in reducing a range of symptom clusters in PTSD is consistent with its multiple mechanisms of action.

Fear, avoidance and physiological symptoms during cognitive-behavioral therapy for social anxiety disorder.

We examined fear, avoidance and physiological symptoms during cognitive-behavioral therapy (CBT) for social anxiety disorder (SAD). Participants were 177 individuals with generalized SAD who underwent a 14-week group CBT as part of a randomized controlled treatment trial. Participants filled out self-report measures of SAD symptoms at pre-treatment, week 4 of treatment, week 8 of treatment, and week 14 of treatment (post-treatment). Cross-lagged Structural Equation Modeling indicated that during the first 8 weeks of treatment avoidance predicted subsequent fear above and beyond previous fear, but fear did not predict subsequent avoidance beyond previous avoidance. However, during the last 6 weeks of treatment both fear and avoidance predicted changes in each other. In addition, changes in physiological symptoms occurred independently of changes in fear and avoidance. Our findings suggest that changes in avoidance spark the cycle of change in treatment of SAD, but the cycle may continue to maintain itself through reciprocal relationships between avoidance and fear. In addition, physiological symptoms may change through distinct processes that are independent from those involved in changes of fear and avoidance.

Association of anxiety and depression with all-cause mortality in individuals with coronary heart disease.

BACKGROUND: Depression has been related to mortality in coronary heart disease (CHD) patients, but few studies have evaluated the role of anxiety or the role of the co-occurrence of depression and anxiety. We examined whether anxiety is associated with increased risk of mortality after accounting for depression in individuals with established CHD. METHODS AND RESULTS: The cohort was composed of 934 men and women with confirmed CHD (mean age, 62±11 years) who completed the Hospital Anxiety and Depression scale (HADS) during hospitalization for coronary angiography. Over the 3-year follow-up period, there were 133 deaths. Elevated scores on the HADS anxiety subscale (HADS-A≥8) were associated with increased risk of mortality after accounting for established risk factors including age, congestive heart failure, left ventricular ejection fraction, 3-vessel disease, and renal disease (hazard ratio [HR], 2.27; 95% CI, 1.55 to 3.33; P<0.001). Elevated scores on the HADS depression subscale (HADS-D≥8) were also associated with increased risk of mortality (HR, 2.18; 95% CI, 1.47 to 3.22; P<0.001). When both psychosocial factors were included in the model, each maintained an association with mortality (anxiety, HR, 1.83; 95% CI, 1.18 to 2.83; P=0.006; depression, HR, 1.66; 95% CI, 1.06 to 2.58; P=0.025). Estimation of the HR for patients with both anxiety and depression versus those with neither revealed a larger HR than for patients with either factor alone (HR, 3.10; 95% CI, 1.95 to 4.94; P<0.001). CONCLUSIONS: Anxiety is associated with increased risk of mortality in CHD patients, particularly when comorbid with depression. Future studies should focus on the co-occurrence of these psychosocial factors as markers of increased mortality risk.

A pilot randomized controlled trial with paroxetine for subthreshold PTSD in Operation Enduring Freedom/Operation Iraqi Freedom era veterans.

Subthreshold posttraumatic stress disorder (PTSD) is associated with increased risk for suicidality, depression, and functional impairment. We thus conducted a small (N=12) pilot randomized controlled trial (RCT) with paroxetine for subthreshold PTSD in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) era veterans. Hospital Anxiety and Depression Scale (HADS) scores improved by 30.4% in the paroxetine group. Paroxetine may have promise for subthreshold PTSD.

Homeopathic treatments in psychiatry: a systematic review of randomized placebo-controlled studies.

OBJECTIVE: To systematically review placebo-controlled randomized trials of homeopathy for psychiatric conditions. DATA SOURCES: Eligible studies were identified using the following databases from database inception to April 2010: PubMed, CINAHL, PsycINFO, Hom-Inform, Cochrane CENTRAL, National Center for Complementary and Alternative Medicine grantee publications database, and ClinicalTrials.gov. Gray literature was also searched using Google, Google Scholar, the European Committee for Homeopathy, inquiries with homeopathic experts and manufacturers, and the bibliographic lists of included published studies and reviews. Search terms were as follows: (homeopath* or homoeopath*) and (placebo or sham) and (anxiety or panic or phobia or post-traumatic stress or PTSD or obsessive-compulsive disorder or fear or depress* or dysthym* or attention deficit hyperactivity or premenstrual syndrome or premenstrual disorder or premenstrual dysphoric disorder or traumatic brain injury or fibromyalgia or chronic fatigue syndrome or myalgic encephalitis or insomnia or sleep disturbance). Searches included only English-language literature that reported randomized controlled trials in humans. STUDY SELECTION: Trials were included if they met 7 criteria and were assessed for possible bias using the Scottish Intercollegiate Guidelines Network (SIGN) 50 guidelines. Overall assessments were made using the Grading of Recommendations Assessment, Development and Evaluation procedure. Identified studies were grouped into anxiety or stress, sleep or circadian rhythm complaints, premenstrual problems, attention-deficit/hyperactivity disorder, mild traumatic brain injury, and functional somatic syndromes. RESULTS: Twenty-five eligible studies were identified from an initial pool of 1,431. Study quality according to SIGN 50 criteria varied, with 6 assessed as good, 9 as fair, and 10 as poor. Outcome was unrelated to SIGN quality. Effect size could be calculated in 16 studies, and number needed to treat, in 10 studies. Efficacy was found for the functional somatic syndromes group (fibromyalgia and chronic fatigue syndrome), but not for anxiety or stress. For other disorders, homeopathy produced mixed effects. No placebo-controlled studies of depression were identified. Meaningful safety data were lacking in the reports, but the superficial findings suggested good tolerability of homeopathy. A funnel plot in 13 studies did not support publication bias (χ(2)(1) = 1.923, P = .166). CONCLUSIONS: The database on studies of homeopathy and placebo in psychiatry is very limited, but results do not preclude the possibility of some benefit.

Management of generalized anxiety disorder in primary care: identifying the challenges and unmet needs.

BACKGROUND: Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders in primary care, although it is often underrecognized and undertreated. GAD is chronic, disabling, and associated with other health problems. Treatment response is often unsatisfactory, but the clinical evidence base for new treatments has expanded substantially in the past decade and suggests a growing range of options for reducing the burden of GAD. The objective of this article was to review current literature on GAD and its management to provide an overview of the clinical importance of GAD in primary care and available treatments. DATA SOURCES: Recent studies (ie, over the past decade) on the epidemiology and treatment of GAD were identified by searching Medline using the term generalized anxiety disorder only and in combination with the terms epidemiology and treatment and for each drug class (benzodiazepines, azapirones, antidepressants, antihistamines, alpha-2-delta ligands, and antipsychotics) and for named drugs (buspirone, venlafaxine, duloxetine, fluoxetine, escitalopram, olanzapine, paroxetine, pregabalin, quetiapine, and risperidone in addition to psychological therapies and cognitive-behavioral therapy. The literature search was conducted in August 2008 for the period 1987-2009. STUDY SELECTION: Studies were included if judged to be relevant to a review of the epidemiology and management of GAD. Articles were excluded if they were not written in English or were published more than 10 years before the literature search was conducted. A few older studies were included for which more recent research evidence was not available. Recent national and international guidelines for the management of GAD were also reviewed. DATA EXTRACTION/SYNTHESIS: Most currently available interventions have similar overall efficacy, and treatment choices should reflect the situation of individual patients. Important unmet needs exist for treatments (1) that work rapidly, with (2) broad spectrum benefits, (3) that can improve rates of remission and well-being, (4) are devoid of risk for withdrawal symptoms, and (5) have few if any adverse interactions with other drugs. Additional needs include (6) safer drugs for the elderly, (7) safe and effective drugs for children with GAD, (8) further evaluation of psychotherapy, and (9) understanding the appropriate circumstances for, and optimal choices of, drug combination. CONCLUSION: While the development of novel treatments evolves, current management approaches can focus on improving identification and defining optimal use of available therapies for GAD.

Phobic anxiety and increased risk of mortality in coronary heart disease.

OBJECTIVES: To evaluate whether phobic anxiety is associated with increased risk of cardiac mortality in individuals with established coronary heart disease (CHD) and to examine the role of reduced heart rate variability (HRV) in mediating this risk. Previous findings suggest that phobic anxiety may pose increased risk of cardiac mortality in medically healthy cohorts. METHODS: We performed a prospective cohort study in 947 CHD patients recruited during hospitalization for coronary angiography. At baseline, supine recordings of heart rate for HRV were collected, and participants completed the Crown-Crisp phobic anxiety scale. Fatal cardiac events were identified over an average period of 3 years. RESULTS: Female CHD patients reported significantly elevated levels of phobic anxiety when compared with male patients (p < .001), and survival analysis showed an interaction between gender and phobic anxiety in the prediction of cardiac mortality (p = .058) and sudden cardiac death (p = .03). In women, phobic anxiety was associated with a 1.6-fold increased risk of cardiac mortality (hazard ratio, 1.56; 95% confidence interval, 1.15-2.11; p = .004) and a 2.0-fold increased risk of sudden cardiac death (hazard ratio, 2.02; 95% confidence interval, 1.16-3.52; p = .01) and was unassociated with increased mortality risk in men (p = .56). Phobic anxiety was weakly associated with reduced high-frequency HRV in female patients (r = -.14, p = .02), but reduced HRV did not alter the association between phobic anxiety on mortality. CONCLUSIONS: Phobic anxiety levels are high in women with CHD and may be a risk factor for cardiac-related mortality in women diagnosed with CHD. Reduced HRV measured during rest does not seem to mediate phobic anxiety-related risk.

Major depressive disorder treatment guidelines in America and Europe.

The various major American and European guidelines for the treatment of depression provide similar basic principles of treatment, which include individualizing the treatment plan, preparing the patient for potential long-term treatment, providing measurement-based care, and treating to remission. While the guidelines are all evidence-based, certain factors can influence differences in specific recommendations, such as the consensus group's composition, underlying mandates, and cultural attitudes. The similarities and differences among 6 sets of guidelines from Europe and the Americas published in the past decade are reviewed here (American Psychiatric Association, British Association for Psychopharmacology, Canadian Network for Mood and Anxiety Treatments, National Institute for Health and Clinical Excellence, Texas Medication Algorithm Project, and World Federation of Societies of Biological Psychiatry). In the guidelines, mild depression has the most variance in treatment recommendations; some, but not all, guidelines suggest that it may resolve with exercise or watchful waiting, but psychotherapy or antidepressants could be used if initial efforts fail. Moderate and severe major depression carry broadly similar recommendations among the guidelines. First-line treatment recommendations for moderate major depressive disorder include antidepressant monotherapy, psychotherapy, and the combination of both. Severe depression may require the combination of an antidepressant and an antipsychotic, electroconvulsive therapy, or the combination of an antidepressant and psychotherapy. Benzodiazepines play a very limited role in the treatment of depression; if the patient has catatonic depression, acutely suicidal depression, or depression with symptoms of anxiety, agitation, or insomnia, benzodiazepines are recommended by some guidelines for short-term treatment only.

International consensus statement on major depressive disorder.

Because considerable variability exists between countries in the management of major depressive disorder, experts in psychiatry gathered for the International Consensus Group on Depression to outline a universal treatment algorithm for this illness. The experts decided to adapt the existing treatment algorithm developed in Japan and discuss strategies for clinical issues that have been problematic in some countries. Specific recommendations were made by the consensus group for screening for, diagnosing, and treating depression, which include periodically screening all patients for depression, completing a differential diagnosis of depression, referring to a psychiatric specialist if needed, establishing a therapeutic alliance with patients and their families, choosing and optimizing the dose of appropriate antidepressants based on individual patient's needs, and incorporating nonpharmacologic treatment strategies as necessary.