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Background Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegenerative disorder with brain iron accumulation (NBIA). Objectives To assess PKAN diagnostic pathway, history, and burden across the spectrum of PKAN severity from patient and/or caregiver perspectives. Methods Caregivers of patients (n = 37) and patients themselves (n = 2) were interviewed in a validation study of the PKAN-Activities of Daily Living (ADL) scale. The current study used quartiles of the PKAN-ADL total score to divide patients by severity of impairment (Lowest, Second Lowest, Third Lowest, Highest). Diagnostic and treatment history, healthcare utilization, disease burden, and caregiver experience were compared between groups. Results The analyses included data from 39 patients. Mean age at PKAN symptom onset (P = 0.0007), initial MRI (P = 0.0150), and genetic testing (P = 0.0016) generally decreased across the PKAN severity spectrum. The mean duration of illness did not differ among PKAN severity groups (range, 9.7–15.2 years; P = 0.3029). First MRI led to diagnosis in 56.4% of patients (range, 30.0–90.0%). A mean (SD) of 13.0 (13.1) medical and 55.2 (78.5) therapy visits (eg, physical, speech) occurred in the past year. More patients in the higher PKAN severity groups experienced multiple current functional losses and/or earlier onset of problems (P-values

Objective Pantothenate kinase‐associated neurodegeneration (PKAN) is an autosomal‐recessive, neurodegenerative disorder with a mixed‐motor phenotype caused by a defective PanK2 enzyme, for which there are few adequate treatment options. Clinimetrically sound measures of patient‐reported outcomes are necessary to facilitate therapeutic development for this debilitating disease. This study's objective was to develop such a scale and assess its clinimetric properties. Methods A conceptually driven, iterative, content development process incorporating input from experts, caregivers, and patients was used. Scale items were initially adapted from the Unified Parkinson's Disease Rating Scale (UPDRS) Part II resulting in the 12‐item Pantothenate Kinase‐Associated Neurodegeneration Activities of Daily Living (PKAN‐ADL). The PKAN‐ADL scale was administered to caregivers (n = 37) and patients (n = 2) twice over 2 weeks, along with selected Quality of Life in Neurological Disorders (Neuro‐QoL) measures, selected attributes of the Health Utilities Index (HUI)‐2/3, and the Stroke Aphasia Depression Questionnaire (SADQ‐10) to assess construct validity. Results Internal consistency was 0.93, with excellent test‐retest reliability (intraclass correlation coefficient = 0.99). Of the 12 items, 25% (n = 3) showed a ceiling effect >30% (range, 31–54) and 42% (n = 5) showed a floor effect >30% (range, 31–46), reflecting disease heterogeneity. Convergent validity was shown with Neuro‐QoL measures (rs > 0.90) and HUI‐2/3 attributes (rs ≥ 0.48); divergent validity was demonstrated with the SADQ‐10 (r = 0.11). Participants reported a high level of comprehension (98%), and average item relevance ratings (0–10 scale) ranged from 7.0 to 9.9. Conclusion The PKAN‐ADL scale demonstrated acceptable content validity, with evidence of construct validity and excellent reliability. Overall results support the use of the PKAN‐ADL scale in clinical trials.

This chapter reexamines past estimates that 30.9% of veterans had developed PTSD during their lifetimes and that 15.2% were currently suffering from PTSD. The 1988 National Vietnam Veterans Readjustment Study (NVVRS) of a representative sample of 1,200 male veterans also found a strong dose–response relationship: as retrospective reports of combat exposure increased, PTSD occurrence increased. Skeptics have argued that these results are inflated by recall bias and other flaws. This chapter uses military records to construct a new exposure measure and to cross-check exposure reports in rigorous diagnoses of a subsample of 260 veterans. It finds little evidence of falsification, an even stronger dose–response relationship, and psychological costs that were lower than previously estimated but still substantial: 18.7% of the veterans had developed war-related PTSD during their lifetimes, and 9.1% were currently suffering from PTSD 11–12 years after the war.

This chapter presents findings that the large majority (between 61.8% and 70.9%) of U.S. male veterans in the NVVRS sample appraised the impact of Vietnam service on their personal lives as mainly positive, and that negative appraisals, especially those with high salience (i.e., importance), are strongly associated with PTSD onset and current PTSD. A substantial minority (41.7%) judged the effects to be highly salient in their present lives. It investigates the valence and salience of these appraisals in relation to PTSD and other indicators of wartime and post-war functioning. The results are consistent with the hypothesis that mainly positive appraisals are affirmations of successful wartime and post-war adaptation rather than defensive denials related to maladaptive outcomes. It discusses the possibility that mainly positive appraisals, especially those with low salience, also contribute to successful post-war adaptation.

Post-traumatic stress disorder (PTSD) is a complex and challenging condition to treat. Researchers and clinicians have developed a growing interest in the psychological and neurobiological underpinnings of PTSD. Psychosocial treatment and pharmacotherapy have been shown to be effective in all three symptom clusters of PTSD: reexperiencing, avoidance/numbing, and hyperarousal. Research on the treatment of PTSD has focused on psychosocial treatments as well as pharmacotherapy, Both have shown clinical efficacy. This chapter provides the clinician with an overview and guidance in the use of medication for patients with PTSD. Psychotropic agents might theoretically facilitate the normal recovery process that takes place after a traumatic event or might mitigate the neurobiological processes that precede the development of chronic PTSD. Although psychosocial therapies are assumed to modulate the neurobiology of PTSD, the existence of neurobiological alterations in PTSD is also a logical rationale for the use of psychotropic agents. The majority of patients with PTSD suffer from one or more comorbid psychiatric disorders.

Objective. Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder with variable onset, rate of progression, and phenotypic expression. Later-onset, more slowly progressive PKAN often presents with neuropsychiatric as well as motor manifestations that include speech difficulties, progressive dystonia, rigidity, and parkinsonism. PKAN is caused by biallelic PANK2 mutations, a gene that encodes pantothenate kinase 2, a regulatory enzyme in coenzyme A biosynthesis. Current therapeutic strategies rely on symptomatic relief. We describe the treatment of the first, later-onset PKAN patient with oral fosmetpantotenate (previously known as RE-024), a novel replacement therapy developed to bypass the enzymatic defect. Methods. This was an open-label, uncontrolled, 12-month treatment with fosmetpantotenate of a single patient with a later-onset, moderately severe, and slowly progressive form of PKAN. Results. The patient showed improvement in all clinical parameters including the Unified Parkinson’s Disease Rating Scale (UPDRS), Barry-Albright Dystonia Scale, the EuroQol five-dimensional three-level (EQ-5D-3L) scale, timed 25-foot walk test, and electroglottographic speech analysis. Fosmetpantotenate was well-tolerated with only transient liver enzyme elevation which normalized after dose reduction and did not recur after subsequent dose increases. Conclusions. Fosmetpantotenate showed promising results in a single PKAN patient and should be further studied in controlled trials.

The elevated rate of current posttraumatic stress disorder (PTSD) among Hispanic Vietnam veterans has been attributed to culturally based expressiveness that inflates symptom self-reports. To investigate this possibility, the authors conducted three hypothesis-driven analyses with National Vietnam Veterans Readjustment Study (NVVRS) data from the Structured Clinical Interview for DSM-III-R (SCID-) diagnosed subsample of male Vietnam Theater veterans (N = 260). First, persistence of the Hispanic elevation after adjusting for war-zone stress exposure initially suggested the effect of greater expressiveness. Second, symptom-based analyses isolated this effect to the self-report Mississippi Scale for Combat-Related PTSD and not to the clinician-rated SCID interview. Third, objective measures of functioning did not reveal a unique Hispanic pattern of lower impairment associated with current PTSD. These tests suggest that greater Hispanic expressiveness does not account for the Hispanic elevation in current PTSD in the NVVRS SCID-diagnosed subsample.

In 1988, the National Vietnam Veterans Readjustment Study (NVVRS) reported 30.9% lifetime and 15.2% current rates of posttraumatic stress disorder (PTSD), and a strong dose/response relationship with retrospective reports of combat exposure. Skeptics argued that recall bias and other flaws inflated the results. Using a new record-based exposure measure and diagnoses in an NVVRS subsample, the authors addressed this controversy in a recent issue of Science (B. P. Dohrenwend et al., 2006). They found little evidence of falsification, an even stronger dose/response relationship and, when fully adjusted for impairment and evidence of exposure, 18.7% onset and 9.1% current rates of war-related PTSD. The fact that these rates are lower than the original NVVRS rates has stimulated continuing controversy that has tended to obscure the more important implications of the study's results.

There are now replicated findings that posttraumatic stress disorder (PTSD) symptoms related to the September 11, 2001, attacks occurred in large numbers of persons who did not fit the traditional definition of exposure to a traumatic event. These data are not explained by traditional epidemiologic “bull’s eye” disaster models, which assume the psychological effects are narrowly, geographically circumscribed, or by existing models of PTSD onset. In this article, the authors develop a researchable model to explain these and other terrorism-related phenomena by synthesizing research and concepts from the cognitive science, risk appraisal, traumatic stress, and anxiety disorders literatures. They propose the new term relative risk appraisal to capture the psychological function that is the missing link between the event and subjective response in these and other terrorism-related studies to date. Relative risk appraisal highlights the core notion from cognitive science that human perception is an active, multidimensional process, such that for unpredictable societal threats, proximity to the event is only one of several factors that influence behavioral responses. Addressing distortions in relative risk appraisal effectively could reduce individual and societal vulnerability to a wide range of adverse economic and ethnopolitical consequences to terrorist attacks. The authors present ways in which these concepts and related techniques can be helpful in treating persons with September 11– or terrorism-related distress or psychopathology.

This study evaluated the efficacy of paroxetine for symptoms and associated features of chronic posttraumatic stress disorder (PTSD), interpersonal problems, and dissociative symptoms in an urban population of mostly minority adults. Adult outpatients with a primary DSM-IV diagnosis of chronic PTSD received 1 week of single-blind placebo (N = 70). Those not rated as significantly improved were then randomly assigned to placebo (N = 27) or paroxetine (N = 25) for 10 weeks, with a flexible dosage design (maximum 60 mg by week 7). Significantly more patients treated with paroxetine were rated as responders (14/21, 66.7%) on the Clinical Global Impression-Improvement Scale (CGI-I) compared to patients treated with placebo (6/22, 27.3%). Mixed effects models showed greater reductions on the Clinician-Administered PTSD Scale (CAPS) total score (primary plus associated features of PTSD) in the paroxetine versus placebo groups. Paroxetine was also superior to placebo on reduction of dissociative symptoms [Dissociative Experiences Scale (DES) score] and reduction in self-reported interpersonal problems [Inventory of Interpersonal Problems (IIP) score]. In a 12-week maintenance phase, paroxetine response continued to improve, but placebo response did not. Paroxetine was well tolerated and superior to placebo in ameliorating the symptoms of chronic PTSD, associated features of PTSD, dissociative symptoms, and interpersonal problems in the first trial conducted primarily in minority adults.

Exposure to trauma reminders has been considered imperative in psychotherapy for posttraumatic stress disorder (PTSD). The authors tested interpersonal psychotherapy (IPT), which has demonstrated antidepressant efficacy and shown promise in pilot PTSD research as a non-exposure-based non-cognitive-behavioral PTSD treatment.The authors conducted a randomized 14-week trial comparing IPT, prolonged exposure (an exposure-based exemplar), and relaxation therapy (an active control psychotherapy) in 110 unmedicated patients who had chronic PTSD and a score50 on the Clinician-Administered PTSD Scale (CAPS). Randomization stratified for comorbid major depression. The authors hypothesized that IPT would be no more than minimally inferior (a difference12.5 points in CAPS score) to prolonged exposure.All therapies had large within-group effect sizes (d values, 1.32-1.88). Rates of response, defined as an improvement of30% in CAPS score, were 63% for IPT, 47% for prolonged exposure, and 38% for relaxation therapy (not significantly different between groups). CAPS outcomes for IPT and prolonged exposure differed by 5.5 points (not significant), and the null hypothesis of more than minimal IPT inferiority was rejected (p=0.035). Patients with comorbid major depression were nine times more likely than nondepressed patients to drop out of prolonged exposure therapy. IPT and prolonged exposure improved quality of life and social functioning more than relaxation therapy.This study demonstrated noninferiority of individual IPT for PTSD compared with the gold-standard treatment. IPT had (nonsignificantly) lower attrition and higher response rates than prolonged exposure. Contrary to widespread clinical belief, PTSD treatment may not require cognitive-behavioral exposure to trauma reminders. Moreover, patients with comorbid major depression may fare better with IPT than with prolonged exposure.

Objectives Project Liberty was the first federally funded crisis counseling program to offer evidence-informed treatments to crisis counseling recipients in need of more intensive clinical intervention. The Adult Enhanced Services Referral Tool was developed as a screening instrument for making and monitoring referrals to enhanced services. This study aimed to examine how well the tool functioned for identifying persons who would perceive a need for professional treatment. Methods A one-page tool was created that assessed demographic characteristics, risk categories, and psychological reactions to the focal event, September 11, 2001. Psychosocial reactions were assessed by the 12-item SPRINT-E, which is an expanded version of the Short Post-Traumatic Stress Disorder Rating Interview (SPRINT). The SPRINT-E was embedded in the Adult Enhanced Services Referral Tool. Data were collected from 788 clients who received crisis counseling between June and October 2003. Results The SPRINT-E is a unidimensional measure of distress and dysfunction. Internal consistency was excellent for the total sample (alpha=.93) and subsamples. Among the 543 clients offered referral, 71 percent accepted. Among those offered referral, the number of intense reactions (score of 4, quite a bit, or 5, very much) was by far the strongest predictor of referral acceptance. Conclusions The SPRINT-E was successfully integrated into the crisis counseling program and provided an apparently successful, empirical basis for referral from counseling to professional treatment. Results of the brief psychological assessment provided a stronger basis for referral to treatment than membership in a risk category (for example, family member of deceased) alone.

The purpose of this study was to understand the impact of community-level stressors (particularly violence), coping strategies, and resources to prevent exposure to violence or to mitigate its effects in an inner-city community. Parents and children participated in focus groups, and children also completed standardized instruments. In the focus groups, parents and children identified several areas of concern related to "helpers," schools, community safety, and emotional distress. They identified protective resources including intensive monitoring and social supports. Fifty percent of the children met criteria for Posttraumatic Stress Disorder (PTSD), and another 21% met criteria for partial PTSD. The mental health issues in children living with ongoing community violence necessitate that researchers use a qualitative approach to inform future interventions.

In the wake of 9/11, the mental health community began to develop a model for recovery and preparedness. A public information campaign regarding the psychological consequences of terrorism was launched, and it succeeded in reducing the stigma of utilizing mental health services. However, as this campaign began to succeed, it became clear that most clinicians in the community had little training in evidence-based assessment and treatment procedures for the psychological sequelae of terrorism. This article describes the development, delivery, and initial assessment of one attempt to correct this problem by broadly disseminating an effective treatment for Post Traumatic Stress Disorder (PTSD). Using models of behavior change, we were able to study trainee attitudes and the training process in ways that will help improve training effectiveness beyond what traditional Continuing Professional Education (CPE) has been able to do.

A growing global concern about suicide attacks has led to attempts from various disciplines to understand the psychological profiles of persons willing to commit suicide terrorist attacks. Recent reports have suggested that more powerful explanatory models might be discovered using social psychological concepts, with a shift of focus from the individual to the group within which the individual acts and by which the individual is influenced. This paper attempts to do so by presenting an analysis of the Al Qaeda ‘final instructions’ document, which sheds light on the way members of this group were mobilised towards conducting one of the most devastating assaults in modern history. We discuss the use of religious doctrine and rhetorical devices as a psychological strategy employed by this group to inspire, control and mobilise its members before and during the September 11, 2001, attacks.

A 70.9% majority of the U.S. male veterans in a nationwide sample appraised the impact of their service in Vietnam on their present lives as mainly positive. A substantial minority, 41.7%, judged the effects to be highly salient. With controls on level of exposure to war-zone stressors measured with data from military records, the valence and salience of these appraisals are investigated in relation to posttraumatic stress disorder (PTSD) and other indicators of wartime and postwar functioning. The results are consistent with the hypothesis that mainly positive tertiary appraisals are affirmations of successful wartime and postwar adaptation rather than defensive denials related to maladaptive outcomes. The possibility that mainly positive tertiary appraisals also contribute to successful postwar adaptation is discussed.

Placebo-controlled trials have evaluated the efficacy of several medications in the treatment of social anxiety disorder but information regarding their relative efficacy is lacking. We compared the efficacy of medications systematically studied for the treatment of social anxiety disorder using meta-analytic techniques. The methodology included a database search of articles published between January 1980 and June 2001 and manual searches of bibliographies in published manuscripts. Trials were included if they reported outcome data on the Liebowitz Social Anxiety Scale (LSAS) or a categorical measure of responder status. Data were extracted independently by two authors. The Q statistic was used to assess homogeneity across trials. All analyses were conducted using intent-to-treat data. There was substantial heterogeneity across trials. The medications with largest effect sizes were phenelzine [effect size, 1.02; 95% Confidence Interval (CI), 0.52–1.52], clonazepam (effect size, .97; 95% CI, 0.49–1.45), gabapentin (effect size, .78; 95% CI, 0.29–1.27), brofaromine (effect size, .66; 95% CI, 0.38–0.94), and the selective serotonin reuptake inhibitors (SSRIs; effect size, .65; 95% CI, 0.50–0.81). There were no statistically significant differences between medications or medication groups. However, formal methods of interim monitoring adapted for meta-analyses suggested strongest evidence of efficacy for SSRIs and brofaromine. Several medications are efficacious for the treatment of social anxiety disorder. The stability of the SSRI effect size estimate in conjunction with other evidence for safety and tolerability and their ability to treat comorbid conditions supports the use of SSRIs as the first-line treatment. Direct comparisons of SSRIs vs. other promising medications deserve consideration. Depression and Anxiety 18:29–40, 2003. © 2003 Wiley-Liss, Inc.

To date, all clinical trials using a single therapeutic modality (psychotherapy or pharmacotherapy) have found that even the best validated treatments for adults with chronic Posttraumatic Stress Disorder (PTSD) leave a substantial proportion of patients with disabling residual symptoms.We reviewed the treatment course of three research patients with PTSD who received trauma-focused psychotherapy after experiencing a partial response to medication. Structured diagnostic interviews, validated symptom measures, and standardized treatment approaches were used to assess treatment response.All patients partially benefited from medication treatment, and the degree of benefit varied substantially. Also, all patients experienced an additional reduction in PTSD symptoms after a time-limited course of prolonged exposure therapy (PE). This finding differs from anecdotal observations among U.S. War veterans and has never been documented systematically among civilian adults with chronic PTSD.Maximizing treatment outcome in adults with chronic PTSD may require additional psychotherapy after a partial medication response, and further study is warranted.

Alternative therapies and therapy modalities for SAD are needed because: Established treatments (CBT and pharmacologic) do not help everyone who seeks help. Established treatments provide only partial decrease in symptoms for many patients. Patients may experience recurrence of symptoms in long-term follow-up. CBT does not reach enough patients in need. Alternative treatment approaches and modalities may also be needed to address the successful outcomes of CBT. Success in overcoming social anxiety symptoms can generate a whole new set of challenges. For example, a 31-year-old man who overcomes his fear of dating and begins his first romantic relationship may need a less symptomatically focused therapy to deal with issues that arise in this relationship. Likewise, a woman whose decreased social anxiety enables her to get a long-awaited promotion may need to deal with the stress of adjusting to her new responsibilities. An individual who overcomes phobia of public speaking and still has mild anxiety may need to graduate to a forum such as Toastmasters to provide continued exposure to further develop confidence and skills in public speaking.

Reliance on the categorical model of psychiatric disorders has led to neglected study of posttraumatic sequelae that fall short of full criteria for posttraumatic stress disorder (PTSD). Substantial disability and suicidal risk is associated with subthreshold PTSD, but this association has not been well studied. In addition, no studies have examined the role of comorbidity in explaining disability and impairment in subthreshold PTSD.On National Anxiety Disorders Screening Day 1997, 2,608 out of 9,358 individuals screened for affective and anxiety disorders at 1,521 sites across the United States reported at least one PTSD symptom of at least 1 month's duration. Impairment, comorbid anxiety disorders, major depressive disorder, and rates of suicidality were determined and compared for individuals with no, one, two, three, or four (full PTSD) symptoms on a screening questionnaire. Regression analyses examined the relative contribution of subthreshold PTSD and comorbid disorders to impairment and suicidal ideation.Impairment, number of comorbid disorders, rates of comorbid major depressive disorder, and current suicidal ideation increased linearly and significantly with each increasing number of subthreshold PTSD symptoms. Individuals with subthreshold PTSD were at greater risk for suicidal ideation even after the authors controlled for the presence of comorbid major depressive disorder.Higher numbers of subthreshold PTSD symptoms were associated with greater impairment, comorbidity, and suicidal ideation. Disability and impairment found in previous studies of subthreshold PTSD symptoms may be related in part to the presence of comorbid disorders. However, the presence of subthreshold PTSD symptoms significantly raised the risk for suicidal ideation even after the authors controlled for major depressive disorder. Given the broad public health implications of these findings, more efforts are needed to identify subthreshold PTSD symptoms in clinical populations, epidemiologic surveys, and treatment studies.

Objective: Ataque de nervios is a common, self-labeled Hispanic folk diagnosis. It typically describes episodic, dramatic outbursts of negative emotion in response to a stressor, sometimes involving destructive behavior. Dissociation and affective dysregulation during such episodes suggested a link to childhood trauma. We therefore assessed psychiatric diagnoses, history of ataque, and childhood trauma in treatment-seeking Hispanic outpatients (N = 70). Significantly more subjects with an anxiety or affective disorder plus ataque reported a history of physical abuse, sexual abuse, and/or or a substance-abusing caretaker than those with psychiatric disorder but no ataque. In some Hispanic individuals, ataque may represent a culturally sanctioned expression of extreme affect dysregulation associated with childhood trauma. Patients with ataque de nervios should receive a thorough traumatic history assessment.

Recent evidence suggests that an etiologic model of posttraumatic stress disorder (PTSD) must include both vulnerability factors (presumably related to dysregulation of stress responses and/or failure of normal restitutive mechanisms following trauma) and factors related to trauma severity. The fact that rates of PTSD increase with the severity of trauma suggests that normal adaptive mechanisms may become overwhelmed even in the absence of vulnerability factors. Consistent with this view, efforts to demarcate normative from disordered reactions to severe trauma, such as the new diagnosis of acute stress disorder, have had limited success. Debate over the moral and scientific implications of receiving a trauma-related diagnosis has further complicated the issue and perpetuated a false dichotomy concerning normative responses. The literature on clinical trials in PTSD is reviewed. The range of treatment responses, and the categorical breadth of compounds studied, requires interpretation before the literatur...

A new diagnosis can greatly influence scientific research, access to resources, and treatment selection in clinical practice. The authors review the historical evolution, rationale, empirical foundation, and clinical utility to date of the recently introduced diagnosis of acute stress disorder.The conceptual basis and relevant methods for identifying a psychiatric syndrome are reviewed with respect to acute stress disorder, including selection of criteria for core symptoms; considerations of sensitivity and specificity of a syndrome definition; longitudinal course; and distinctions between normative and pathological phenomena. Particular attention is devoted to two major issues: the implications of the core feature requirement of three of five dissociative symptoms, and the question of whether there should be two separate diagnoses (acute stress disorder and post-traumatic stress disorder [PTSD]) describing posttraumatic syndromes. The widely divergent approaches in DSM-IV and ICD-10 are also reviewed.The diagnosis of acute stress disorder does not appear to achieve the important objective of providing adequate clinical coverage for individuals with acute posttraumatic symptoms. The validity and utility of requiring peritraumatic dissociative symptoms as a core feature are questionable, as is the separation of essentially continuous clinical phenomena into two disorders with different criteria sets (acute stress disorder and PTSD) based on persistence of symptoms for 30 or more days.Longitudinal studies using acute stress disorder criteria, as well as broader considerations of the clinical and scientific functions that posttraumatic diagnoses should serve, suggest a need to reevaluate the current DSM-IV approach to posttraumatic syndromes.

She also once heard a voice say, “It’s getting bad again,” but realized she was hearing her own thoughts. She had occasionally heard a similar voice in the past that resembled her father’s. Hope also described chronic, although recently worsened, memory problems. History

To evaluate the effects of maintenance treatment and durability of gains after treatment discontinuation, responders to either phenelzine (PZ) or cognitivebehavioral group therapy (CBGT) from an acute trial comparing these two treatments as well as pill placebo and a psychotherapy control (educational supportive group therapy) were enrolled into maintenance and treatment-free follow-up phases. Experimental design: Responders to an acute trial contrasting PZ and CBGT entered a six-month maintenance phase. Patients who continued to respond through the maintenance phase entered a six-month treatment free phase. Patients receiving pill placebo or educational supportive group therapy in the acute trial did not enter the long term study. Principal observations: PZ patients entered maintenance more improved than CBGT patients, and nonrelapsing PZ patients maintained their superior gains throughout the study. Relapse during maintenance did not differ between treatments. However, PZ patients showed a trend toward greater relapse during treatment-free follow-up. There was a greater relapse among patients with generalized social phobia with phenelzine. Conclusions: PZ and cognitive-behavioral group therapy may differ in their long term effects. The superiority seen with PZ on some measures in the acute study persisted in patients who maintained their gains over the course of maintenance and treatment-free follow-up. However, CBGT may lead to a greater likelihood of maintaining response after treatment has terminated. Replication with larger samples is needed, as is a study of the acute and long-term efficacy of combined PZ and CBGT. Depression and Anxiety 10:89‐98, 1999. © 1999 Wiley-Liss, Inc.

We report the results of an 8-week open trial of imipramine in 15 patients with social phobia. Nine patients completed the trial; six dropped out early because of adverse effects. The mean reduction in the Liebowitz Social Anxiety Scale was 15% and 18% for the intent-to-treat and completer groups, respectively; the overall response rate (based on the Clinical Global Impression Scale of 1 or 2, very much or much improved) was 20% (3/15) and 22% (2/9), respectively. The results from this open trial do not support the efficacy of imipramine as a treatment for social phobia.

BackgroundMoclobemide, a reversible inhibitor of monoamine oxidase A, previously has been reported to have efficacy in the treatment of social phobia.MethodSeventy-seven non-responders to one week of single-blind placebo were randomly assigned to moclobemide or placebo for eight weeks of double-blind treatment. Outcome was assessed by independent evaluator, treating psychiatrist and self-ratings. After eight weeks, patients who were at least minimally improved continued treatment for a further eight weeks.ResultsIntention-to-treat sample response rates at week 8 were 7/40 (17.5%) for the moclobemide group and 5/37 (13.5%) for placebo (NS). Moclobemide was significantly superior to placebo on 2 of 10 primary outcome measures. Moclobemide was well tolerated.ConclusionsMoclobemide may have efficacy in the treatment of social phobia, but absence of significant differences on most primary outcome measures and small effect sizes for all outcome measures suggest that the magnitude of its clinical effect is small.

Amitifadine (EB-1010, formerly DOV 21,947) is a serotonin-preferring triple reuptake inhibitor that is a drug candidate for major depressive disorder. We investigated several relevant biopharmaceutic and drug-like characteristics of amitifadine using in vitro methodology and additionally determined the in vivo brain to plasma ratio of the drug in rats. Amitifadine was highly plasma protein bound with over 99% of drug bound to human plasma proteins. Using Caco-2 cell lines, amitifadine was bidirectionally highly permeable and showed no evidence of active secretion. Amitifadine was metabolized slowly by human hepatocytes and the major metabolite was the lactam EB-10101. In vitro studies using human liver microsomes demonstrated that EB-10101 was formed by monoamine oxidase A (MAO-A) and a NADPHdependent enzyme, possibly a cytochrome P450 (CYP) isoform. Amitifadine was a moderate inhibitor of the human isoforms of the major drug metabolizing enzymes CYP2D6, CYP3A4, CYP2C9, and CYP2C19 (IC 50 = 9 - 100 μ M), but was a potent inhibitor of human CYP2B6 (IC 50 = 1.8 μM). The brain to plasma ratio for amitifadine varied from 3.7 - 6.5 at various time points, indicating preferential partitioning into rat brain versus plasma. The low affinity for the major drug metabolizing CYP enzymes and metabolism by multiple pathways may reduce pharmacokinetic drug-drug interactions and effects of enzyme polymorphisms. Overall, these studies suggest that amitifadine has drug-like characteristics favorable for drug development.

The efficacy of psychoanalysis and long-term psychotherapy remains a fundamentally unresolved issue for lack of methodologically sound studies. This article reviews the shortcomings of prior long-term treatment research, and presents a rationale and justification of the importance of more rigorous outcome studies. An emphasis on process research is premature when efficacy remains uncertain. The modern reconceptualization of psychotherapy in terms of hermeneutic theory is discussed in relation to the empirical model. Although historically the hermeneutic perspective has served to repudiate positivism, the hermeneutic and empirical (but not positivistic) approaches to understanding information actually share common priorities. The clearest of these is that the process is ultimately evaluated and validated by the produced effect. It is argued that the recasting of psychoanalytic technique and theory according to aesthetic and pragmatic principles is not inconsistent with contemporary outcome research paradigms so long as the professed treatment objective is clearly specified in verifiable terms. The specific methodologic problems involved in extending the successful short-term psychotherapy research model to psychoanalysis are discussed. An overview of the major components of the Columbia feasibility study currently underway is presented. Finally, a number of assessment domains-for which reliable and validated instruments exist-that are thought to be relevant to outcome are reviewed.

Selective serotonin reuptake inhibitors (SSRIs) are often recommended in combination with established cognitive-behavioral therapies (CBTs) for posttraumatic stress disorder (PTSD), but combined initial treatment of PTSD has not been studied under controlled conditions. There are also few studies of either SSRIs or CBT in treating PTSD related to terrorism. The authors compared prolonged exposure therapy (a CBT) plus paroxetine (an SSRI) with prolonged exposure plus placebo in the treatment of terrorism-related PTSD.Adult survivors of the World Trade Center attack of September 11, 2001, with PTSD were randomly assigned to 10 weeks of treatment with prolonged exposure (10 sessions) plus paroxetine (N=19) or prolonged exposure plus placebo (N=18). After week 10, patients discontinued prolonged exposure and were offered 12 additional weeks of continued randomized treatment.Patients treated with prolonged exposure plus paroxetine experienced significantly greater improvement in PTSD symptoms (incidence rate ratio=0.50, 95% CI=0.30-0.85) and remission status (odds ratio=12.6, 95% CI=1.23-129) during 10 weeks of combined treatment than patients treated with prolonged exposure plus placebo. Response rate and quality of life were also significantly more improved with combined treatment. The subset of patients who continued randomized treatment for 12 additional weeks showed no group differences.Initial treatment with paroxetine plus prolonged exposure was more efficacious than prolonged exposure plus placebo for PTSD related to the World Trade Center attack. Combined treatment medication and prolonged exposure therapy deserves further study in larger samples with diverse forms of PTSD and over longer follow-up periods.

We compared personality profiles of men with sexual dysfunction (n = 51) to those of age-matched men with a primary diagnosis of paraphilia (n = 51) employing the NEO Personality Inventory (NEO-PI), a measure of the five-factor model. Preliminary analyses in a large sample of patients in a sexual behaviors consultation unit supported the reliability and factorial validity of the NEO-PI for this population. Analysis of variance showed significant differences between the dysfunctional and the paraphilic groups on two of the five NEO-PI domains, Neuroticism (N) and Agreeableness (A). The group personality profile of the sexually dysfunctional men was comparable to the normative sample of the NEO-PI, except for a slight elevation in N. By contrast, men with paraphilia had a personality profile marked by high N, low A, and low Conscientiousness (C). Treatment implications of the average personality profile of the sexual dysfunction group and the distinctive personality profile of paraphilic men are discussed.

Objective: To determine whether maternal violence-related posttraumatic stress disorder (PTSD), reflective functioning (RF), and/or quality of mental representations of her child predicts maternal behavior within a referred sample of mothers exposed to interpersonal violence and their children (aged 8–50 months). Method: A total of 41 dyads completed 2 videotaped visits including measures of maternal mental representations and behavior. Results: Negative and distorted maternal mental representations predicted atypical behavior (Cohen's d > 1.0). Although maternal PTSD and RF impacted mental representations, no significant relationships were found between PTSD, RF, and overall atypical caregiving behavior. Severity of maternal PTSD was, however, positively correlated with the avoidant caregiving behavior subscale. Conclusions: Maternal mental representations of her child are useful risk indicators that mark dysregulation of trauma-associated emotions in the caregiver.

Bipolar disorder (BD) is among the 10 most disabling medical conditions in the world (1), and has been associated with increased risk of morbidity, mortality (2) and psychiatric comorbidity (3) including post-traumatic stress disorder (PTSD) (4–8). The rate of PTSD among persons with BD has been estimated to range from 11% in patients with first-admission psychosis (7) to approximately 40% in the subgroup of respondents with BD in a nationwide community sample (8) and among ambulatory and hospitalized bipolar patients (4). Emerging evidence suggests that history of trauma may be related to both etiology and illness course of BD (5, 6). For example, early parental loss has been found to increase the risk for BD (9), and high-impact trauma, such as sexual and physical abuse, has been associated with poor illness course of BD (7, 8). Bipolar illness might be both a consequence of traumatic events (e.g., disasters, physical or sexual assaults) and a generator of additional traumatic events such as interpersonal adversities (e.g., violent events) (5, 10). The study of these trajectories can complement research on the role of family psychiatric history and genetics (11–13). It has been suggested, but not yet systematically studied, that exposure to interpersonal trauma following BD onset may result from the poor judgment and risky behaviors (e.g., substance use, reckless driving, and irritability) that partially define hypomanic and manic episodes (5). This report is based on data from a cross-sectional study of a systematic sample of 997 low-income primary care patients attending a large primary care clinic in New York City (14–16). We aimed to examine whether patients with a history of BD are at increased risk (i) to experience psychological trauma in general, physical and sexual assault in particular; and (ii) to develop PTSD following exposure to trauma. We also explored whether exposure to trauma increases the risk of BD independent from PTSD and whether comorbidity of PTSD increases the risk for impairment and functioning problems among patients with BD. We hypothesized that: (i) a history of exposure to trauma and especially assaultive trauma would be more common in patients with BD than in those without BD; (ii) the prevalence of current PTSD would be higher in patients with BD than in those without BD; (iii) exposure to trauma would increase the risk of BD independent of PTSD; and (iv) patients with BD who have comorbid PTSD would manifest greater functional impairment then those with BD but without PTSD.

Editor's note Stress reactions run from Acute Stress Reactions and Adjustment Disorders to Post-traumatic Stress Disorder (PTSD). The first two, in many instances, may be thought of as time limited in their impact and respond to many different types of psychosocial interventions. The primary purpose of intervening in these disorders is to facilitate more effecting coping with the stressor, reduce functional impairment, and return the individual to his previous level of active functioning in the community. PTSD has been shown to respond to both trauma-focused cognitive-behavioral psychotherapies and to pharmacological agents, particularly the SSRIs, though other pharmacologic interventions may impact some of the disturbed affect, anxiety, and lability, and to psychosocial interventions. As with many other disorders, there is a treatment resistant group that remain significantly impaired despite treatment, and long-term management of symptoms becomes the primary goal. Introduction: differences in classification of stress disorders The adjustment disorders, acute stress disorder, and post-traumatic stress disorder (DSM-IV) all share the common feature of occurring as a response to an adverse environmental event or cluster of events. The distinction appears clear cut; post-traumatic stress disorders follow extreme stressors that are operationally defined, whereas adjustment disorders may follow any kind of stressor of a less serious degree. Adjustment disorders are defined as “clinically significant emotional or behavioral symptoms in response to an identifiable psychosocial stressor or stressors” (DSM-IV), and must develop within 3 months of the stressor (DSM-IV).

A Web-based survey of adults who experienced loss during the September 11, 2001, terrorist attacks was conducted to examine the prevalence and correlates of complicated grief (CG) 2.5-3.5 years after the attacks. Forty-three percent of a study group of 704 bereaved adults across the United States screened positive for CG. In multivariate analyses, CG was associated with female gender, loss of a child, death of deceased at the World Trade Center, and live exposure to coverage of the attacks on television. Posttraumatic stress disorder, major depression, anxiety, suicidal ideation, and increase in post-9/11 smoking were common among participants with CG. A majority of the participants with CG reported receiving grief counseling and psychiatric medication after 9/11. Clinical and policy implications are discussed. Language: en

Background There is a continued high prevalence of benzodiazepine use by older community-residing adults and of their continued prescription by practitioners, despite well known adverse effects and the availability of safer, effective alternatives. Objectives To understand factors influencing chronic use of benzodiazepines in older adults. Design Qualitative study, semistructured interviews with physicians. Participants Thirty-three practicing primary care physicians around Philadelphia. Approach Qualitative interviews were audiotaped, transcribed, and entered into a qualitative software program. A multidisciplinary team coded transcripts and developed themes. Results Physicians generally endorsed benzodiazepines as effective treatment for anxiety, citing quick action and strong patient satisfaction. The use of benzodiazepines in older adults was not seen to be problematic because they did not show drug-seeking or escalating dose behavior suggesting addiction. Physicians minimized other risks of benzodiazepines and did not view monitoring or restricting renewal of prescriptions as an important clinical focus relative to higher-priority medical issues. Many physicians expressed skepticism about risks of continued use and considerable pessimism in the successful taper/discontinuation in older patients with long-term use and prior failed attempts. Physicians also anticipated patient resistance to any such efforts, including switching physicians. Conclusions Primary care physicians are averse to addressing the public health problem of benzodiazepine overuse in the elderly. Their attitudes generally conflict with practice guidelines and they complain of a lack of training in constructive strategies to address this problem. A 2-pronged effort should focus on increasing skill level and preventing new cases of benzodiazepine dependency through improved patient education and vigilant monitoring of prescription renewal.

Since the introduction of posttraumatic stress disorder (PTSD) into the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III; American Psychiatric Association, 1980), considerable research has demonstrated the efficacy of several cognitive-behavioral therapy (CBT) programs in the treatment of chronic PTSD. Among these efficacious treatments is exposure therapy. Despite all the evidence for the efficacy of exposure therapy and other CBT programs, few therapists are trained in these treatments and few patients receive them. In this article, the authors review extant evidence on the reasons that therapists do not use these treatments and recent research on the dissemination of efficacious treatments of PTSD.