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BACKGROUND: Tourette syndrome is a neurodevelopmental movement disorder involving basal ganglia dysfunction. PDE10A inhibitors modulate signaling in the striatal basal ganglia nuclei and are thus of interest as potential therapeutics in treating Tourette syndrome and other movement disorders. METHODS: The preclinical pharmacology and toxicology, human safety and tolerability, and human PET striatal enzyme occupancy data for the PDE10A inhibitor EM-221 are presented. RESULTS: EM-221 inhibited PDE10A with an in vitro IC50 of 9 pM and was >100,000 selective vs. other PDEs and other CNS receptors and enzymes. In rats, at doses of 0.05-0.50 mg/kg, EM-221 reduced hyperlocomotion and the disruption of prepulse inhibition induced by MK-801, attenuated conditioned avoidance, and facilitated novel object recognition, consistent with PDE10A's inhibition. EM-221 displayed no genotoxicity and was well tolerated up to 300 mg/kg in rats and 100 mg/kg in dogs. In single- and multiple-day ascending dose studies in healthy human volunteers, EM-221 was well tolerated up to 10 mg, with a maximum tolerated dose of 15 mg. PET imaging indicated that a PDE10A enzyme occupancy of up to 92.8% was achieved with a ~24 h half-life. CONCLUSIONS: The preclinical and clinical data presented here support the study of EM-221 in phase 2 trials of Tourette syndrome and other movement disorders.
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Hidrolasas Diéster Fosfóricas , Síndrome de Tourette , Adulto , Animales , Perros , Femenino , Humanos , Masculino , Ratas , Trastornos del Movimiento/tratamiento farmacológico , Inhibidores de Fosfodiesterasa/farmacología , Inhibidores de Fosfodiesterasa/uso terapéutico , Hidrolasas Diéster Fosfóricas/metabolismo , Tomografía de Emisión de Positrones , Ratas Sprague-Dawley , Síndrome de Tourette/tratamiento farmacológico , HaplorrinosRESUMEN
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 < 0.0500). Over half (56.8%) of caregivers experienced a change in employment because of caregiving. The percentage of patients requiring full-time caregiving increased across the PKAN severity spectrum (range, 11.1-100%; P = 0.0021). CONCLUSIONS: PKAN diagnosis was often delayed, most probably due to low awareness. Considerable burden of functional impairment and high healthcare utilization were found across the PKAN severity spectrum.
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Neurodegeneración Asociada a Pantotenato Quinasa/genética , Actividades Cotidianas , Adolescente , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Niño , Femenino , Pruebas Genéticas , Humanos , Imagen por Resonancia Magnética , Masculino , Neurodegeneración Asociada a Pantotenato Quinasa/diagnóstico por imagen , Clase Social , Encuestas y CuestionariosRESUMEN
BACKGROUND/AIMS: Pantothenate kinase-associated neurodegeneration is a rare neurodegenerative disease with a variable clinical phenotype. Fosmetpantotenate is in clinical development as a replacement therapy that targets the underlying cause of pantothenate kinase-associated neurodegeneration. The FOsmetpantotenate Replacement Therapy pivotal trial-an ongoing phase 3, randomized, double-blind, placebo-controlled, multicenter trial-examines the efficacy and safety of fosmetpantotenate in patients with pantothenate kinase-associated neurodegeneration aged 6-65 years. The FOsmetpantotenate Replacement Therapy trial required the development and validation of a novel patient-reported outcome measure specifically relevant to pantothenate kinase-associated neurodegeneration. The Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living scale was developed to assess activities of daily living related to motor functioning in patients with pantothenate kinase-associated neurodegeneration to evaluate clinically meaningful change as the primary efficacy endpoint in clinical trials. This article describes the design of the FOsmetpantotenate Replacement Therapy pivotal trial and the development of the Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living scale. METHODS: A systematic, iterative process consistent with the US Food and Drug Administration guidance and advice from the Committee for Medicinal Products for Human Use at the European Medicines Agency was used to evaluate and adapt or remove scale items of an existing widely used instrument for movement disorders to be pantothenate kinase-associated neurodegeneration-specific, and to create new items. Modification of scale items was based on input from international experts, patient advocacy leaders, and primary caregivers. A clinimetric study of the Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living scale conducted in patients with pantothenate kinase-associated neurodegeneration or their caregivers (N = 40 at first assessment; N = 39 at second assessment) demonstrated high content and construct validity and excellent test-retest reliability over an approximately 2-week period. The Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living scale was developed to be broadly useful within clinical and research settings in the examination of patient response to pantothenate kinase-associated neurodegeneration therapies. RESULTS: Approximately 82 patients will be enrolled in the ongoing FOsmetpantotenate Replacement Therapy pivotal trial. Change from baseline in Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living score over the 24-week double-blind period is the primary efficacy endpoint for the FOsmetpantotenate Replacement Therapy trial. Treatment effect will be evaluated using a mixed model for repeated measures analysis to assess data from all visits simultaneously. CONCLUSION: The development and implementation of the Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living scale in the FOsmetpantotenate Replacement Therapy trial illustrates the feasibility and potential patient benefit of putting into practice the current regulatory guidance on the use of patient-reported outcomes in clinical trials. These processes can be broadly applied to clinical trial methodology that requires newly created or revised patient-reported outcome measures to evaluate outcome change as a primary efficacy endpoint. The goal of such measures in patients with pantothenate kinase-associated neurodegeneration is to facilitate development of disease-modifying therapeutics in multiple drug development programs.
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Actividades Cotidianas , Neurodegeneración Asociada a Pantotenato Quinasa/tratamiento farmacológico , Ácido Pantoténico/análogos & derivados , Medición de Resultados Informados por el Paciente , Complejo Vitamínico B/uso terapéutico , Adolescente , Adulto , Anciano , Niño , Ensayos Clínicos Fase III como Asunto , Método Doble Ciego , Humanos , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Ácido Pantoténico/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Resultado del Tratamiento , Adulto JovenRESUMEN
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.
RESUMEN
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.
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OBJECTIVE: 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. METHOD: 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 score >50 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 difference <12.5 points in CAPS score) to prolonged exposure. RESULTS: All therapies had large within-group effect sizes (d values, 1.32-1.88). Rates of response, defined as an improvement of >30% 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. CONCLUSIONS: 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.
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Terapia Implosiva , Psicoterapia/métodos , Trastornos por Estrés Postraumático/terapia , Adulto , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Terapia por Relajación , Resultado del TratamientoRESUMEN
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 (IC50 = 9 - 100 µM), but was a potent inhibitor of human CYP2B6 (IC50 = 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.
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Antidepresivos/farmacocinética , Compuestos Aza/farmacocinética , Encéfalo/metabolismo , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacocinética , Inhibidores de la Captación de Neurotransmisores/farmacocinética , Animales , Antidepresivos/sangre , Antidepresivos/metabolismo , Hidrocarburo de Aril Hidroxilasas , Compuestos Aza/sangre , Compuestos Aza/metabolismo , Biofarmacia , Proteínas Sanguíneas/metabolismo , Compuestos Bicíclicos Heterocíclicos con Puentes/sangre , Compuestos Bicíclicos Heterocíclicos con Puentes/metabolismo , Células CACO-2 , Permeabilidad de la Membrana Celular , Citocromo P-450 CYP2C19 , Inhibidores Enzimáticos del Citocromo P-450 , Sistema Enzimático del Citocromo P-450/metabolismo , Inhibidores Enzimáticos/farmacología , FMN Reductasa/metabolismo , Hepatocitos/metabolismo , Humanos , Lactamas/metabolismo , Masculino , Microsomas Hepáticos/metabolismo , Monoaminooxidasa/metabolismo , NADP/fisiología , Inhibidores de la Captación de Neurotransmisores/sangre , Inhibidores de la Captación de Neurotransmisores/metabolismo , Unión Proteica , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Insomnia marked by sleep maintenance difficulty is extremely prevalent. Yet, problems staying asleep have been relatively neglected as a research focus compared to problems falling asleep. Insomnia treatment studies typically have not required participants to have a problem specifically with sleep maintenance. It is possible that exclusion of such subjects limits the detection of treatment effects in the overall trial in general, and of effects on sleep maintenance specifically. In order to address these issues we conducted a post hoc analysis of a 6-month placebo-controlled trial in which there were no inclusion criteria that specified sleep maintenance difficulties to assess the variable effects of baseline wake time after sleep onset (WASO - the primary maintenance measure) on the efficacy of eszopiclone 3mg. METHODS: Patients diagnosed with chronic primary insomnia were randomized to eszopiclone 3mg (n=593) or placebo (n=195) nightly for six months. The present analyses of this study consisted of: (1) determination of the distribution of baseline WASO; (2) continuous analysis of the relationship between baseline WASO severity and drug-placebo difference at month 1 and 6; and (3) categorical efficacy analyses of subgroups delimited by the following WASO thresholds: 0, 30, 45, 60, and 90 min. RESULTS: The baseline WASO distribution was: ≤ 30=32.2%; >0 to ≤ 45=41.5%; >30 to ≤ 90=33.0%; >45 to ≤ 90=23.7%; >90=22.6%. A relationship between greater baseline WASO severity and a significantly greater drug-placebo difference in efficacy for WASO was evident in both continuous and categorical analyses. Eszopiclone was found to have significant sleep maintenance efficacy at each time point across the entire range of WASO severity studied. CONCLUSIONS: As illustrated in this analysis, a significant proportion of chronic insomnia patients in efficacy trials that select on the basis of sleep onset latency and total sleep time criteria may have normative-range WASO. However, even in the subgroup with minimal WASO there was a significant sleep maintenance effect. The absence of any sleep maintenance effect in a drug trial may reflect the inclusion of relatively many insomnia patients with no baseline WASO abnormality. However, treatments with therapeutic effects on sleep maintenance, can still demonstrate improvement in sleep maintenance, even in a population not selected for this type of sleep problem, if adequately powered. Future clinical trials intending to examine sleep maintenance should employ WASO selection criteria that would ensure sufficient power to detect a sleep maintenance effect. Drug-placebo difference increased as a function of baseline WASO severity, suggesting that eszopiclone's clinical effectiveness for insomnia may be enhanced in patients with more severe sleep maintenance symptoms.
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Compuestos de Azabiciclo/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Piperazinas/administración & dosificación , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Sueño/efectos de los fármacos , Adulto , Anciano , Enfermedad Crónica , Eszopiclona , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.
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Terapia Implosiva , Paroxetina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Ataques Terroristas del 11 de Septiembre/psicología , Trastornos por Estrés Postraumático/terapia , Terapia Combinada , Método Doble Ciego , Femenino , Humanos , Terapia Implosiva/métodos , Masculino , Persona de Mediana Edad , Ciudad de Nueva York , Escalas de Valoración Psiquiátrica , Trastornos por Estrés Postraumático/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Exposure to reminders of trauma underlies the theory and practice of most treatments for post-traumatic stress disorder (PTSD), yet exposure may not be the sole important treatment mechanism. Interpersonal features of PTSD influence its onset, chronicity, and possibly its treatment. The authors review interpersonal factors in PTSD, including the critical but underrecognized role of social support as both protective posttrauma and as a mechanism of recovery. They discuss interpersonal psychotherapy (IPT) as an alternative treatment for PTSD and present encouraging findings from two initial studies. Highlighting the potential importance of attachment and interpersonal relationships, the authors propose a mechanism to explain why improving relationships may ameliorate PTSD symptoms.
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Relaciones Interpersonales , Apego a Objetos , Psicoterapia , Apoyo Social , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/terapia , Humanos , Psicoterapia/métodos , Trastornos por Estrés Postraumático/psicología , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine whether maternal violence-related posttraumatic stress disorder (PTSD), reflective functioning (RF), and/or quality of mental representations of her child predict maternal behavior within a referred sample of interpersonal violence-exposed mothers and their children (ages 8-50 months). METHOD: Forty-one dyads completed two 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). While 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.
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Mujeres Maltratadas/psicología , Mujeres Maltratadas/estadística & datos numéricos , Violencia Doméstica/psicología , Violencia Doméstica/estadística & datos numéricos , Conducta Materna/psicología , Relaciones Madre-Hijo , Trastornos por Estrés Postraumático , Preescolar , Etnicidad/estadística & datos numéricos , Femenino , Humanos , Lactante , Masculino , Trastornos por Estrés Postraumático/etnología , Trastornos por Estrés Postraumático/etiología , Trastornos por Estrés Postraumático/psicología , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To examine relationships between exposure to trauma, bipolar spectrum disorder (BD) and posttraumatic stress disorder (PTSD) in a sample of primary care patients. METHODS: A systematic sample (n = 977) of adult primary care patients from an urban general medicine practice were interviewed with measures including the Mood Disorders Questionnaire, the PTSD Checklist-Civilian Version, and the Medical Outcomes Study 12-Item Short Form Health Survey. RESULTS: Compared with patients who screened negative for BD (n = 881), those who screened positive (n = 96) were 2.6 times [95% confidence interval (CI): 1.6-4.2] as likely to report physical or sexual assault, and 2.9 times (95% CI: 1.6-5.1) as likely to screen positive for current PTSD. Among those screening positive for BD, comorbid PTSD was associated with significantly worse social functioning. These results controlled for selected background characteristics, current major depressive episode, and current alcohol/drug use disorder. CONCLUSION: In an urban general medicine setting, trauma exposure was related to BD, and the frequency of PTSD among patients with BD appears to be common and clinically significant. These results suggest an unmet need for mental health care in this specific population and are especially important in view of available treatments for BD and PTSD.
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Trastorno Bipolar/epidemiología , Acontecimientos que Cambian la Vida , Atención Primaria de Salud , Trastornos por Estrés Postraumático/epidemiología , Adolescente , Adulto , Anciano , Trastorno Bipolar/psicología , Demografía , Femenino , Humanos , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Oportunidad Relativa , Atención Primaria de Salud/estadística & datos numéricos , Estudios Retrospectivos , Trastornos por Estrés Postraumático/psicología , Encuestas y CuestionariosRESUMEN
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.
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Trastornos de Ansiedad/epidemiología , Aflicción , Trastorno Depresivo Mayor/epidemiología , Pesar , Ataques Terroristas del 11 de Septiembre , Trastornos por Estrés Postraumático/epidemiología , Adaptación Psicológica , Adulto , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/psicología , Estudios Transversales , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Femenino , Encuestas Epidemiológicas , Humanos , Internet , Masculino , Tamizaje Masivo , Análisis Multivariante , Aceptación de la Atención de Salud/estadística & datos numéricos , Inventario de Personalidad , Fumar/epidemiología , Fumar/psicología , Factores Socioeconómicos , Estadística como Asunto , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/psicología , Suicidio/psicología , Estados UnidosRESUMEN
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.
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Miedo/psicología , Psicología/métodos , Riesgo , Ataques Terroristas del 11 de Septiembre/psicología , Terrorismo/psicología , Trastornos de Ansiedad/etiología , Trastornos de Ansiedad/psicología , Humanos , Modelos Psicológicos , Trastornos por Estrés Postraumático/etiología , Trastornos por Estrés Postraumático/psicologíaRESUMEN
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.
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Antidepresivos de Segunda Generación/uso terapéutico , Población Negra/psicología , Trastornos Disociativos/tratamiento farmacológico , Hispánicos o Latinos/psicología , Relaciones Interpersonales , Paroxetina/uso terapéutico , Trastornos por Estrés Postraumático/tratamiento farmacológico , Población Blanca/psicología , Adulto , Antidepresivos de Segunda Generación/efectos adversos , Enfermedad Crónica , Trastornos Disociativos/diagnóstico , Trastornos Disociativos/etnología , Trastornos Disociativos/psicología , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Paroxetina/efectos adversos , Determinación de la Personalidad , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/etnología , Trastornos por Estrés Postraumático/psicología , Población UrbanaRESUMEN
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.
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Desensibilización Psicológica , Difusión de Innovaciones , Difusión de la Información , Trastornos por Estrés Postraumático/terapia , Enfermedad Crónica , Humanos , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/psicología , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Terapia Cognitivo-Conductual , Servicios Comunitarios de Salud Mental , Intervención en la Crisis (Psiquiatría) , Libertad , Entrevista Psicológica , Determinación de la Personalidad/estadística & datos numéricos , Derivación y Consulta/estadística & datos numéricos , Ataques Terroristas del 11 de Septiembre/psicología , Trastornos por Estrés Postraumático/terapia , Adulto , Femenino , Humanos , Masculino , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Ciudad de Nueva York , Psicometría/estadística & datos numéricos , Reproducibilidad de los Resultados , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/psicología , Poblaciones Vulnerables/psicología , Poblaciones Vulnerables/estadística & datos numéricosAsunto(s)
Etiquetado de Medicamentos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , United States Food and Drug Administration , Adolescente , Niño , Comunicación , Femenino , Humanos , Masculino , Investigación , Medición de Riesgo , Percepción Social , Estados Unidos , Prevención del SuicidioRESUMEN
OBJECTIVE: To screen for posttraumatic stress disorder (PTSD) in primary care patients 7-16 months after 9/11 attacks and to examine its comorbidity, clinical presentation and relationships with mental health treatment and service utilization. METHOD: A systematic sample (n=930) of adult primary care patients who were seeking primary care at an urban general medicine clinic were interviewed using the PTSD Checklist: the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire and the Medical Outcome Study 12-Item Short Form Health Survey (SF-12). Health care utilization data were obtained by a cross linkage to the administrative computerized database. RESULTS: Prevalence estimates of current 9/11-related probable PTSD ranged from 4.7% (based on a cutoff PCL-C score of 50 and over) to 10.2% (based on the DSM-IV criteria). A comorbid mental disorder was more common among patients with PTSD than patients without PTSD (80% vs. 30%). Patients with PTSD were more functionally impaired and reported increased use of mental health medication as compared to patients without PTSD (70% vs. 18%). Among patients with PTSD there was no increase in hospital and emergency room (ER) admissions or outpatient care during the first year after the attacks. CONCLUSIONS: In an urban general medicine setting, 1 year after 9/11, the frequency of probable PTSD appears to be common and clinically significant. These results suggest an unmet need for mental health care in this clinical population and are especially important in view of available treatments for PTSD.
Asunto(s)
Atención Primaria de Salud , Trastornos por Estrés Postraumático/epidemiología , Terrorismo/psicología , Adolescente , Adulto , Anciano , Comorbilidad , Femenino , Humanos , Entrevistas como Asunto , Masculino , Servicios de Salud Mental/estadística & datos numéricos , Persona de Mediana Edad , Trastornos por Estrés Postraumático/diagnóstico , Estados Unidos/epidemiologíaRESUMEN
A subsample of 255 male Vietnam veterans from the National Vietnam Veterans Readjustment Study received in-depth psychiatric diagnostic interviews. This paper focuses on the 88 veterans with a war-related onset of PTSD. Among these veterans, the avoidance cluster, especially its symptoms of numbing, was most strongly associated with chronic PTSD; less strongly but also significantly associated was the hyperarousal cluster. Further analyses show that these associations are not artifacts of the relationship of symptom patterns to prewar demographic factors (race/ethnicity, socioeconomic status, age at entry into Vietnam), comorbidity, treatment and compensation seeking, or probable severity of war-related trauma. We conclude that certain symptom profiles may predict enduring pathological responses to trauma and therefore provide targets for intervention efforts.