An open-label pilot study of aripiprazole for male and female veterans with chronic post-traumatic stress disorder who respond suboptimally to antidepressants.

Emerging data suggest that second-generation antipsychotics such as aripiprazole may be effective in the treatment of post-traumatic stress disorder (PTSD). However, few clinical trials have used aripiprazole in PTSD, and data are limited on its use in Veterans with PTSD. The objective of this pilot trial was to investigate the safety and efficacy of aripiprazole in Veterans with PTSD. Ten individuals (five men and five women) meeting the Diagnostic and statistical manual of mental disorders, 4th ed., PTSD criteria participated in this 12-week, open-label, flexibly dosed monotherapy trial. The dose range of aripiprazole was 5-30 mg/day, titrated to tolerability and clinical response. The primary outcome measure was the Clinician-Administered PTSD Scale. Additional outcomes included the Short PTSD Rating Interview, the Treatment Outcome PTSD Scale (Top-8), the Davidson Trauma Scale, the Positive and Negative Syndrome Scale, the Beck Depression Inventory-Fast Screen, and Clinical Global Impressions-Improvement. Eight participants completed the study, and aripiprazole was generally well tolerated and associated with a significant improvement in PTSD symptoms, as measured by the Clinician-Administered PTSD Scale (primary outcome measure) and by the Short PTSD Rating Interview, the Treatment Outcome PTSD Scale, and the Davidson Trauma Scale. An improvement was also observed on all three Positive and Negative Syndrome Scale subscales and the Beck Depression Inventory-Fast Screen, and the average Clinical Global Impressions-Improvement ratings indicated that patients were 'much improved'. These promising initial results merit further investigation in a larger, randomized-controlled trial.

Executive function deficits in acute stroke.

OBJECTIVES: To establish the frequency of executive dysfunction during acute hospitalization for stroke and to examine the relationship of that dysfunction to stroke severity and premorbid characteristics. DESIGN: Inception cohort study. SETTING: Inpatient wards at a Veterans Affairs hospital. PARTICIPANTS: Consecutive sample of inpatients with radiologically or neurologically confirmed stroke. Final sample included 47 patients screened for aphasia and capable of neuropsychologic testing. Two nonstroke inpatient control samples (n=10 each) with either transient ischemic attack (TIA) or multiple stroke risk factors were administered the same research procedure and tests. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Composite cognitive impairment ratio (CIR), calculated from 8 scores indicative of executive function on 6 neuropsychologic tests by dividing number of tests completed into the number of scores falling below cutoff point, defined as 1.5 standard deviations below normative population mean. RESULTS: Stroke patients had a mean CIR of .61, compared with .48 for TIAs and .44 for stroke-risk-only. Analysis of variance revealed that CIRs of stroke-risk-only patients but not TIAs were lower than those of the stroke patients (P=.02). Impairment frequencies were at least 50% for stroke patients on most test scores. The Symbol Digit Modalities Test (75% impairment) and a design fluency measure distinguished stroke from nonstroke patients. CIR was not related to stroke severity in the stroke patient sample, but was related to estimated premorbid intelligence. CONCLUSIONS: Executive function deficits are common in stroke patients. The data suggest that limitations in information processing due to these deficits may require environmental and procedural accommodations to increase rehabilitation benefit.

Executive functioning early in abstinence from alcohol.

BACKGROUND: Executive dysfunction is among the cognitive impairments that may persist after abstinence in alcohol-dependent persons. The type(s) and extent of executive dysfunction early in abstinence have not been well characterized, but they may have important implications for the evolution of behavioral treatment strategies. METHODS: To determine which aspects of executive functioning were impaired in early abstinence, we administered memory and executive function tests to veterans who successively presented for treatment at an outpatient substance abuse clinic. We then compared the neuropsychological performance of these recovering alcoholics (n = 27) with that of age-matched primary care outpatients (n = 18). We also examined group differences in self-evaluation of cognitive decline and evaluated associations between drinking history and cognitive impairment in the index group. RESULTS: We found that the normal and alcohol-dependent groups differed on abstract reasoning, memory discrimination, and effectiveness on timed tasks. Patients in the alcohol-dependent sample were also more likely to perceive themselves as cognitively impaired. It is interesting to note that the duration of alcohol use did not relate to neuropsychological test performance, but recent quantity consumed and days of sobriety were associated with nonverbal abstract reasoning ability. CONCLUSIONS: Executive functions are impaired early in abstinence and should, therefore, be taken into account when early behavioral treatments are being developed.

The effect of poststroke cognitive impairment on rehabilitation process and functional outcome.

OBJECTIVES: To determine whether cognitive impairment affects access to, or quality of, rehabilitation services, and to examine the effects of functional outcomes in stroke patients. DESIGN: Secondary analysis of prospective cohort of stroke patients followed for 6 months after stroke. SETTINGS: Eleven large-volume US Department of Veterans Affairs hospitals nationwide. PARTICIPANTS: Stroke patients (N=272) who were candidates for rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Rehabilitation process variables were examined for patients assessed as cognitively impaired or unimpaired according to education-adjusted Mini-Mental State Examination score. Functional outcomes were performance of activities of daily living (ADLs), measured by the FonFIM, and instrumental activities of daily living (IADLs), measured by Lawton, at 6-month follow-up. RESULTS: Compliance with guidelines and receipt of and interval to postacute treatment initiation did not differ between cognitively impaired and unimpaired patients. Although most cognition-related treatment elements were similar for both groups, cognitive goals were more frequently charted in impaired patients. Controlling for baseline function and rehabilitation process, cognitively impaired patients had worse IADL performance at 6 months than did unimpaired patients; cognition did not significantly influence ADL performance. CONCLUSIONS: Quality of, and access to, rehabilitative care was equivalent for patients with and without cognitive impairment. Despite a similar rehabilitation process, cognitively impaired stroke patients experienced worse recovery of IADLs.

Performance of recently detoxified patients with alcoholism on a neuropsychological screening test.

OBJECTIVE: Early in recovery from alcoholism, cognitive deficits may compromise patients' utilization of rehabilitative information. Cognitive impairment in a sample of newly detoxified inpatients with alcoholism was examined using the Neurobehavioral Cognitive Status Examination (NCSE). METHODS: Consecutively admitted psychiatric inpatients (N=233) with an alcohol-related primary diagnosis (63% male, mean age 46.3) were administered the NCSE following medical stabilization. Within-samples differences between age and diagnostic groups were examined and scores were compared to normative samples. RESULTS: Inpatients older than 50 demonstrated significant cognitive deficits for all scales except Attention. In comparison with normative samples, patients with alcoholism produced lower scores, with the most pronounced deficits among middle-aged patients. In alcohol-abusing patients with medical comorbidities, language deficits and more severe memory deficits were observed. Abuse severity or comorbid psychiatric disorder produced no differences in NCSE scores. CONCLUSIONS: Neuropsychological screening following detoxification in patients diagnosed with an alcohol disorder reflected the effects of increased age and medical comorbidity. Our finding of frequent deficits in abstraction, comprehension, and memory suggests that cognitive-behavioral treatments for inpatients may be less effective if cognitive impairment is not considered.

Delayed neuropsychologic dysfunction after liver transplantation for acute liver failure: a matched, case-controlled study.

Although several studies have identified posttransplant neurologic sequelae in patients with acute liver failure (ALF), the effects of these sequelae on neuropsychologic functioning after transplant is unknown. This study compared neuropsychologic functioning of ALF patients with chronic liver disease patients after liver transplantation. After liver transplantation, seven ALF patients were compared with a matched control group of patients who had been transplanted for chronic liver disease. The patients were matched by gender, age (within 5 years), and time since transplantation (within 2 years). Patients completed a 2-hour battery of tests, which included measures of attention, memory, motor performance, abstract conceptualization, and visuospatial perception. There were no significant differences between the groups on measures of socioeconomic status or education. Significant differences were found on three separate tests: WAIS-III Vocabulary, WAIS-III Similarities, and WMS-III Paired Associate Learning II. Although these tests measure distinct functions (vocabulary knowledge, abstract conceptualization, and delayed verbal recall), they may be influenced by broader verbal functions, such as verbal fluency, conceptualization, and the ability to articulate ideas. When patients were asked what functions had noticeably deteriorated since transplantation, nearly all complained of memory difficulties, and there was no difference between groups. However, more ALF than chronic liver disease (CLD) patients complained of concentration difficulties. The results of this study suggest that ALF patients may experience more neuropsychologic dysfunction after transplant. Further studies are required to expand on these initial observations with the potential to improve patient care and referral to appropriate rehabilitative services.