The Murray Springs Clovis site, Pleistocene extinction, and the question of extraterrestrial impact.

Some of the evidence for the recent hypothesis of an extraterrestrial impact that caused late Pleistocene megafaunal extinctions [Firestone et al. (2007) Proc Natl Acad Sci USA 104:16016-16021] was based upon samples collected at Murray Springs, a Clovis archaeological site in southeastern Arizona. Here we describe sampling and analyses of magnetic separates from within, above, and below the lower Younger Dryas boundary (LYDB) black mat at Murray Springs, as well as radiation measurements from the LYDB at Murray Springs and two other well-stratified Clovis sites. The main magnetic fraction at Murray Springs is maghemite. Magnetic microspherules have terrestrial origins but also occur as cosmic dust particles. We failed to find iridium or radiation anomalies. The evidence for massive biomass burning at Murray Springs is addressed and found to be lacking. We could not substantiate some of the claims by Firestone and others, but our findings do not preclude a terminal Pleistocene cosmic event.

Personality and symptom sensitivity predictors of alprazolam withdrawal in panic disorder.

BACKGROUND: Discontinuation of benzodiazepine (BZ) treatment results in a well-characterized withdrawal syndrome in 40-50% of anxious patients. While numerous studies have established the role of BZ dose, treatment duration, half-life, potency, rate of withdrawal and severity of underling anxiety disorder in predicting severity of withdrawal symptoms, fewer studies have examined the role of psychological and personality factors. METHOD: In 123 panic disorder patients undergoing gradual tapered discontinuation of alprazolam in conjunction with pre-treatment with carbamazepine or placebo, the relationship between measures of 'symptom sensitivity' and 'harm avoidance', and severity of withdrawal symptoms measured as peak severity of symptoms, time before taper needed to be slowed due to symptoms, and ability to complete taper, was examined. RESULTS: After controlling for the less substantial effects of dose, treatment duration, pre-taper anxiety and panic attack frequency, measures of symptom sensitivity and harm avoidance accounted for an additional 3-6% of withdrawal variance. CONCLUSIONS: These results show an effect of symptom sensitivity and harm avoidance on BZ withdrawal symptoms, comparable to prior findings linking dependent personality characteristics to withdrawal severity. Failure to show the expected effect on ability to complete taper may be due to either the more symptomatic nature of the patients in this study.

The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial.

OBJECTIVE: Benzodiazepines are the mainstay of treatment for mild-to-moderate alcohol withdrawal in outpatient settings, but they can interact with alcohol, cause motor incoordination, or be abused. This study compared the therapeutic responses of the benzodiazepine lorazepam and the anticonvulsant carbamazepine for the outpatient treatment of acute alcohol withdrawal in terms of patients' previous detoxification histories, and compared the effects of these 2 medications on drinking behaviors in the immediate postdetoxification period. DESIGN: This was a randomized double-blind trial comparing patient responses to carbamazepine and lorazepam across 2 levels of detoxification histories (0-1 or >or=2 previous medicated detoxifications). SETTING: A university medical center substance abuse clinic in Charleston, SC. PATIENTS: One hundred thirty-six patients in moderate alcohol withdrawal were randomized. Major exclusions were significant hepatic or hematologic abnormalities and use of medications that could alter withdrawal symptoms. INTERVENTIONS: Patients received 600-800 mg of carbamazepine or 6-8 mg of lorazepam in divided doses on day 1 tapering to 200 mg of carbamazepine or 2 mg of lorazepam. MAIN OUTCOME MEASURES: The Clinical Institute Withdrawal Assessment for Alcohol-Revised was used to assess alcohol withdrawal symptoms on days 1 through 5 and postmedication at days 7 and 12. Daily drinking was measured by patient report using a daily drinking log and a breath alcohol level with each visit. Side effects were recorded daily. RESULTS: Carbamazepine and lorazepam were equally effective at decreasing the symptoms of alcohol withdrawal. In the post-treatment period, 89 patients drank on at least 1 day; on average, carbamazepine patients drank less than 1 drink per drinking day and lorazepam patients drank almost 3 drinks per drinking day (P =.003). Among those with multiple past detoxifications, the carbamazepine group drank less than 1 drink per day on average and the lorazepam group drank about 5 drinks per day on average (P =.033). Lorazepam-treated patients had a significant rebound of alcohol withdrawal symptoms post-treatment (P =.007) and the risk of having a first drink was 3 times greater (P =.04) than for carbamazepine-treated patients. Twenty percent of lorazepam-treated patients had dizziness, motor incoordination, or ataxia and did not recognize their impairment. Twenty percent of carbamazepine-treated patients reported pruritus but no rash. CONCLUSIONS: Carbamazepine and lorazepam were both effective in decreasing the symptoms of alcohol withdrawal in relatively healthy, middle-aged outpatients. Carbamazepine, however, was superior to lorazepam in preventing rebound withdrawal symptoms and reducing post-treatment drinking, especially for those with a history of multiple treated withdrawals.

Overview of different pharmacotherapies for attaining remission in generalized anxiety disorder.

gamma-Aminobutyric acid (GABA), serotonin (5-HT), and norepinephrine (NE) have each been implicated in the putative pathophysiology of anxiety, and patients with generalized anxiety disorder (GAD) demonstrate dysregulation of these neurotransmitters. In addition, neurobiological studies have demonstrated that these neurotransmitter systems are extensively interrelated. As a result, drugs that affect serotonergic systems may also, directly or indirectly, affect other neurotransmitter systems including GABA and NE. In recent years, clinical pharmacology studies have demonstrated that pharmacotherapeutic agents that target more than one neurotransmitter system are more effective than agents that target a single system, presumably due to synergistic mechanisms. Agents that modulate more than one neurochemical have a broader spectrum of action and may facilitate the attainment of remission among patients with moderate to severe GAD, who are likely to have comorbid psychiatric illnesses such as depression. Preclinical and clinical data supporting the role of GABA, 5-HT, and NE in the pathophysiology of GAD are reviewed here. The pharmacotherapeutic agents that modulate these neurotransmitter systems and have been proved efficacious in reducing the symptoms associated with GAD are also summarized.

Consensus statement on transcultural issues in depression and anxiety from the International Consensus Group on Depression and Anxiety.

OBJECTIVE: To provide primary care physicians with a better understanding of transcultural issues in depression and anxiety. PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Five faculty invited by the chair also participated: Laurence J. Kirmayer, Jean-Pierre Lepine, Keh-Ming Lin, Osamu Tajima, and Yutaka Ono. EVIDENCE: The consensus statement is based on the 5 review articles that are published in this supplement and the scientific literature relevant to the issues reviewed in these articles. CONSENSUS PROCESS: Group meetings were held over a 2-day period. On day 1, the group discussed the review articles, and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. CONCLUSION: The consensus statement underlines the prevalence of depression and anxiety disorders across all cultures and nations while recognizing that cultural differences exist in symptom presentation and prevalence estimates. In all countries, the recognition of depression by clinicians in the primary care setting is low (generally less than 50%), and the consensus group recommends a 2-step process to aid the recognition and diagnosis of depression. In line with the low recognition of depression and anxiety disorders is the finding that only a small proportion of patients with depression or anxiety are receiving appropriate treatments for their condition. Biological diversity across ethnic groups may account for the differential sensitivity of some groups to psychotropic medication, but this area requires further investigation.

Effects of positive impression management on the NEO Personality Inventory--Revised in a clinical population.

Sixty adults in outpatient psychotherapy completed the NEO Personality Inventory--Revised (NEO PI-R, P. T. Costa & R. R. McCrae, 1992a). Half were instructed to fake good and half were given standard instructions. All completed the Interpersonal Adjective Scale--Revised, Big Five (J. S. Wiggins & P. D. Trapnell, 1997) under standard instructions, and their therapists completed the observer rating form of the NEO Five-Factor Inventory. A comparison group of 30 students completed the NEO PI-R under standard instructions. Standard and fake-good participants obtained significantly different NEO PI-R domain scores. Correlations between the NEO PI-R and criterion measures were significantly lower for faking than for standard patients. Validity scales for the NEO PI-R (J. A. Schinka, B. N. Kinder, & T. Kremer, 1997) were moderately accurate in discriminating faking from standard patients, but were only marginally accurate in discriminating faking patients from students.

Consensus statement on generalized anxiety disorder from the International Consensus Group on Depression and Anxiety.

OBJECTIVE: To provide primary care clinicians with a better understanding of management issues in generalized anxiety disorder (GAD) and guide clinical practice with recommendations on the appropriate treatment strategy. PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R.T. Davidson, Yves Lecrubier, and David J. Nutt. Four additional faculty members invited by the chair were Karl Rickels, Hans-Ulrich Wittchen, Dan J. Stein, and Thomas D. Borkovec. EVIDENCE: The consensus statement is based on the 6 review articles that are published in this supplement and the scientific literature relevant to the issues reviewed in these articles. CONSENSUS PROCESS: Group meetings were held over a 2-day period. On day 1, the group discussed the review articles and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. CONCLUSIONS: GAD is the most common anxiety disorder in primary care and is highly debilitating. Furthermore, it is frequently comorbid with depression and other anxiety disorders, which exacerbates functional impairment. Antidepressants (serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and nonsedating tricyclic antidepressants) are generally the most appropriate first-line pharmacotherapy for GAD, since they are also effective against comorbid psychiatric disorders and are suitable for long-term use. Cognitive-behavioral therapy is the preferred form of psychotherapy for GAD, although when GAD is comorbid with depression, pharmacotherapy is increasingly indicated.

Treatment of anxiety disorders to remission.

Treating anxiety disorders to remission should be the goal of all practitioners. A remitted patient should be well, both in symptoms and function, and be indistinguishable from a never-ill counterpart. The definition of remission in patients with anxiety disorders should also be clear, practical, and easy to use. It is useful to measure response in an objective way, such as with standardized instruments appropriate for the disorder, and to develop remission criteria specific to each disorder. This article proposes remission criteria, using standardized measures, for 5 common anxiety disorders: panic disorder, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder.

A brief scale for assessing patients' satisfaction with care in outpatient psychiatric services.

OBJECTIVE: The authors evaluated the reliability and preliminary validity of the Charleston Psychiatric Outpatient Satisfaction Scale, a 15-item measure of patients' satisfaction designed for use in outpatient settings. The instrument uses a 5-point Likert-type response format that minimizes positive response bias and optimizes variability and predictive validity. METHODS: The Charleston Psychiatric Outpatient Satisfaction Scale was administered to 282 patients seen in psychiatric outpatient clinics affiliated with a public-academic psychiatric institution over a one-week period in 1995. RESULTS: The internal reliability of the instrument was high (alpha=.87), and its convergent validity was supported by the significant correlation of all items with anchor items that measured overall satisfaction with care and likelihood of recommending the clinic to others. The best predictors of overall ratings of care were the items measuring patients' satisfaction with helpfulness of the services and with the respect shown for patients' opinions about treatment. The best predictors of recommendation of the program to others were the items measuring satisfaction with matching of the treatment plan to patients' individual needs and with the respect shown for patients' opinions about treatment. Mean scores for all items ranged from 3.6 (satisfaction with parking) to 4.5 (satisfaction with helpfulness of the secretary and with the overall quality of care), indicating that overall satisfaction in this sample was high. CONCLUSIONS: The results provide preliminary support for the reliability and validity of the Charleston Psychiatric Outpatient Satisfaction Scale:

Update on anticonvulsants for the treatment of alcohol withdrawal.

Some anticonvulsants have been shown to be as effective as some benzodiazepines for the treatment of alcohol withdrawal. Anticonvulsants may offer advantages over benzodiazepines in the outpatient treatment of alcohol withdrawal: they lack abuse potential, have minimal interactions with alcohol, and may be more effective in ameliorating psychiatric symptoms of alcohol withdrawal. Carbamazepine appears to be as effective as lorazepam and oxazepam in ameliorating the symptoms of alcohol withdrawal. In addition, a recent study indicates that carbamazepine may suppress post-withdrawal alcohol use. Divalproex may also reduce symptoms of alcohol withdrawal, based on several open-label studies. However, both carbamazepine and divalproex have limited usefulness in alcoholics with severe hepatic or hematologic complications. Newer anticonvulsants, such as gabapentin and vigabatrin, also appear to reduce alcohol withdrawal symptoms in preclinical and open-label clinical trials while lacking the toxicities of carbamazepine and divalproex. Controlled trials are underway exploring the efficacy and safety of newer anticonvulsants for the treatment of alcohol withdrawal.

Structural issues and policy in the management of depressive illness. Overview and expert panel commentary.

Opening with an overview of the current state of knowledge regarding management of depression and anxiety spectrum disorders, this paper then reports commentary from the expert panel on the question: When there are effective treatments, why are optimal outcomes not achieved in clinical practice?

Procedural and methodological issues in telepsychiatry research and program development.

OBJECTIVE: The authors reviewed the literature related to telepsychiatry-applications of videoconferencing technology for mental health care-which offers hope for an affordable means of solving long-standing workforce problems, particularly in geographical areas where specialist providers are not readily available. METHODS: To conduct a comprehensive review of the telepsychiatry literature, the authors searched the MEDLINE database (1970 to February 2000), using the keywords telepsychiatry, telemedicine, and videoconferencing. Studies were selected that included the use of videoconferencing technology for the provision of any form of mental health care services. RESULTS AND CONCLUSIONS: Psychiatric interviews conducted by telepsychiatry appear to be generally reliable, and patients and clinicians generally report high levels of satisfaction with telepsychiatry. A significant limitation of the literature is the lack of empirical research on telepsychiatry, especially cost analyses and clinical outcome studies. The authors outline a research agenda addressing the procedural and methodological issues that should shape future research: study design, outcome measurement, consideration of patient characteristics, and program design.

Bupropion-SR in treatment of social phobia.

A 12-week, open label flexible dosing study was conducted to evaluate the efficacy of bupropion-SR in the treatment of generalized social phobia. The primary outcome measures include the Clinical Global Impression of Improvement (CGI-I) and the Brief Social Phobia Rating Scale (BSPS). A total of 18 subjects were enrolled. Five of the ten subjects who completed all 12 weeks were considered as responders. Response to treatment was defined as a CGI-I score of 1 or 2, ("much improved" or "very much improved," respectively) and a > 50% decrease in BSPS score. The final doses for the completers ranged between 200 and 400 mg/day (mean 366 +/- 68 mg/day). The medication was generally well tolerated. Findings from this open-label trial suggest that bupropion-SR may be useful in treating generalized social phobia.

A controlled trial of daily left prefrontal cortex TMS for treating depression.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a new technology for noninvasively stimulating the brain. Several studies have suggested that daily stimulation of the left prefrontal cortex with TMS for 2 weeks has probable antidepressant effects. We conducted a parallel-design, double-masked, sham-controlled study to address whether 2 weeks of daily TMS over the left prefrontal cortex has antidepressant activity greater than sham. METHODS: Thirty medication-free adult outpatients with nonpsychotic, major depressive (n = 21) or bipolar (n = 9) (depressed phase) disorder who were in a current major depression (Hamilton Rating Scale for Depression [HRSD] 21-item score of >18) were treated each weekday for 2 weeks. Subjects were randomly assigned to receive either daily active (20 subjects) or sham (10 subjects) stimulation. Additionally, the 20 active subjects were equally divided between slower (5 Hz) and faster (20 Hz) frequency treatment. Antidepressant response was defined as greater than a 50% improvement in the baseline HRSD. RESULTS: Active TMS resulted in significantly more responders (9/20) than did sham (0/10) (chi(2) = 6.42, p <.01). The number of responders did not differ significantly between the two active cells (3/10 faster and 6/10 slower). Expressed as a percent change from baseline, active TMS subjects had significantly greater improvement on the Beck Depression Inventory as well as the Hamilton Anxiety Rating Scale than did those who received sham. CONCLUSIONS: Daily left prefrontal TMS for 2 weeks significantly reduced depression symptoms greater than did sham. The two forms of active TMS treatment did not differ significantly.

Recognizing the patient with social anxiety disorder.

Social anxiety disorder is a prevalent and highly disabling condition, affecting 7-13% of the population at some point in their lives. Most sufferers are not diagnosed however, even after visiting a healthcare professional. Social anxiety disorder need not be a difficult condition to diagnose. Characteristic features of the disorder include blushing as the principal symptom and an early age of onset. Social anxiety disorder is also easily distinguished from other anxiety disorders by the situations in which patients experience fear and avoidance; for the patient with social anxiety disorder, these situations always involve social interaction or scrutiny by other people. The consequences of untreated social anxiety disorder include social isolation, impaired educational attainment and career progression, depression, and alcohol abuse. Rating scales such as the Liebowitz Social Anxiety Scale (LSAS) give a consistent measure of severity of social anxiety disorder and so help physicians assess their patients' need for treatment and their improvement. Social anxiety disorder is an eminently treatable condition, as demonstrated by treatment-induced reduction in LSAS scores in clinical trials and by individual case histories. Appropriate therapy can give patients relief from their distressing and disabling symptoms and allows them to make substantial improvements to their quality of life.

Consensus statement on posttraumatic stress disorder from the International Consensus Group on Depression and Anxiety.

OBJECTIVE: To provide primary care clinicians with a better understanding of management issues in posttraumatic stress disorder (PTSD) and guide clinical practice with recommendations on the appropriate management strategy. PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Other faculty invited by the chair were Edna B. Foa, Ronald C. Kessler, Alexander C. McFarlane, and Arieh Y. Shalev. EVIDENCE: The consensus statement is based on the 6 review articles that are published in this supplement and the scientific literature relevant to the issues reviewed in these articles. CONSENSUS PROCESS: Group meetings were held over a 2-day period. On day 1, the group discussed the review articles and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. CONCLUSION: PTSD is often a chronic and recurring condition associated with an increased risk of developing secondary comorbid disorders, such as depression. Selective serotonin reuptake inhibitors are generally the most appropriate choice of first-line medication for PTSD, and effective therapy should be continued for 12 months or longer. The most appropriate psychotherapy is exposure therapy, and it should be continued for 6 months, with follow-up therapy as needed.

Vagus nerve stimulation: a new tool for brain research and therapy.

Biological psychiatry has a long history of using somatic therapies to treat neuropsychiatric illnesses and to understand brain function. These methods have included neurosurgery, electroconvulsive therapy, and, most recently, transcranial magnetic stimulation. Fourteen years ago researchers discovered that intermittent electrical stimulation of the vagus nerve produces inhibition of neural processes, which can alter brain electrical activity and terminate seizures in dogs. Since then, approximately 6000 people worldwide have received vagus nerve stimulation for treatment-resistant epilepsy. We review the neurobiology and anatomy of the vagus nerve and provide an overview of the vagus nerve stimulation technique. We also describe the safety and potential utility of vagus nerve stimulation as a neuroscience research tool and as a putative treatment for psychiatric conditions. Vagus nerve stimulation appears to be a promising new somatic intervention that may improve our understanding of brain function and has promise in the treatment of neuropsychiatric disorders.