MIRECC / CoE
VISN 1 New England MIRECC Past Clinical Efficacy Research
Medications
Analysis of an Academic Detailing Intervention at the VA Connecticut Healthcare System
Contact: Robert Rosenheck, M.D. (Robert.Rosenheck@va.gov)
An intervention consisting of educational academic detailing that also required a provider decision-making survey was employed at the VA Connecticut Healthcare System between October 2007-May 2009 to encourage use of generic antipsychotics. The intervention was implemented throughout the facility which provided outpatient and inpatient treatment to approximately 10,000 Veterans with mental illnesses annually during this period. The survey involved all antipsychotic prescribers (psychiatric physicians, advanced practice registered nurses, and physician assistants) at the medical center. The survey was completed at the time any on-patent second generation antipsychotic was ordered as a new, non-refill prescription for an outpatient and was electronically delivered as part of the medication ordering system at the time any new prescription was submitted. Survey completion was required before the prescription could be electronically sent to the pharmacy. Therefore, 100% of providers writing second generation antipsychotic prescriptions were assumed to have been surveyed regarding 100% of Veteran patients receiving those medications. Findings: The intervention had no effect on prescribing over the 18 months of the study, but it has yielded considerable information about physician prescribing.
Collaborator: Eric Hermes, M.D., MPH (Eric.Hermes@va.gov)
Publications: (1) Hermes, E.D., Sernyak, M.J., & Rosenheck, R.A. (2012). Impact of a program encouraging the use of generic antipsychotics. The American Journal of Managed Care, 18(8), e307-314; (2) Hermes, E.D., Sernyak, M.J., & Rosenheck, R.A. (2013). Use of second-generation antipsychotic agents for sleep and sedation: A provider survey. Sleep, 36(4), 597-600; (3) Hermes, E.D., Sernyak, M.J., & Rosenheck, R.A. (2013). Prescription of second-generation antipsych0tics: Responding to treatment risk in real-world practice. Psychiatric Services, 64(3), 238-244; and (4) Hermes, E.D., Sernyak, M.J., & Rosenheck, R.A. (2014). The use of second generation antipsychotics for posttraumatic stress disorder in a US Veterans Health Administration Medical Center. Epidemiology and Psychiatric Sciences, 23(3), 281-288.
Assessment of Non-Inferiority of Perphenazine and Three Second-Generation Antipsychotics in Chronic Schizophrenia
Contact: Robert Rosenheck, M.D. (Robert.Rosenheck@va.gov)
Non-inferiority analysis, to evaluate whether one treatment is clinically equivalent to another effective treatment, has not been applied to schizophrenia trials or specifically to the comparison of first- and second-generation antipsychotics (FGAs and SGAs). The purpose of this study was to assess the non-inferiority of the FGA perphenazine to three SGAs (olanzapine, risperidone, and quetiapine) in controlling psychotic symptoms. The study design included secondary, post-hoc non-inferiority analysis of a double blind randomized clinical trial, the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), with a non-inferiority margin derived from published literature. Fifty-seven U.S. sites, including academic and community outpatient clinics, participated. From a total cohort of 1,460 patients, we examined data from the 1,049 in the randomization that excluded patients with tardive dyskinesia and included perphenazine, olanzapine, risperidone, and quetiapine. To assess non-inferiority as conservatively as possible, the smallest published value for the minimally clinically important difference (MCID) on the Positive and Negative Syndrome Scale (PANSS), then reduced further by 25% (6.3 PANSS points), was used as a non-inferiority margin. This margin was used to assess non-inferiority based on the Bonferroni-adjusted 95% two-sided confidence interval (CI) of the difference in symptoms between three pairs of treatments (perphenazine less each SGA) calculated through mixed models. When the upper limit of the 95% CI of the PANSS difference, measured as FGA less SGA, is smaller than the non-inferiority margin, the FGA was considered non-inferior to the SGA. Findings: Perphenazine was noninferior to all three SGAs during 18 months of intention-to-treat analysis and in several subanalyses. Noninferiority can be evaluated from studies designed as superiority trials. Power was available in the CATIE to conduct noninferiority analysis.
Collaborator: Haiqun Lin, Ph.D. (Haiqun.Lin@yale.edu)
Publication: Rosenheck, R., & Lin, H. (2014). Non-inferiority of perphenazine vs. three second-generation antipsychotics in chronic schizophrenia. Journal of Nervous and Mental Disease, 202(1), 18-24.
Effect of Second-Generation Antipsychotics on Caregiver Burden in Alzheimer's Disease
Contact: Somaia Mohamed, M.D., Ph.D. (Somaia.Mohamed@va.gov)
Alzheimer's disease (AD) imposes a severe burden upon patients and their caregivers. Severity of psychiatric symptoms and behavioral disturbances is an important determinant of caregivers' experience of burden. These symptoms may be improved with atypical antipsychotic treatment. In this study, data from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) trial were used to evaluate the effect of atypical antipsychotics versus placebo on the experiences of caregivers of outpatients with AD. We compared the effect of atypical antipsychotic drugs (olanzapine, risperidone, or quetiapine considered together as a group) versus placebo on the experiences of caregivers of AD outpatients (diagnosed according to DSM-IV-TR). We also evaluated whether improvement in patients' psychiatric and behavioral symptoms mediated the relationship between drug treatment and caregiver burden. The CATIE-AD trial, conducted from April 2001 through November 2004, included outpatients (mean age=77.9 years [SD=7.5 years]) in usual care settings and assessed treatment effectiveness over a 9-month period at 42 U.S. sites. In a set of secondary analyses, data from CATIE-AD participants, who had at least 1 post-baseline outcome assessment, and data from their caregivers were examined in an intention-to-treat (ITT) analysis (n=361). A phase 1-only analysis was conducted, including only observations while patients were receiving the initially randomized drug (n=153). The Burden Interview, the Beck Depression Inventory, and the Neuropsychiatric Inventory (NPI) Caregiver Distress Scale were used to evaluate caregiver burden. Findings: In both ITT and phase 1-only analyses, caregivers of patients treated with second-generation antipsychotics scored significantly lower than caregivers of patients receiving placebo on both the Burden Interview (P=.0090) and the NPI Caregiver Distress Scale (P=.0209). These differences appeared to have been mediated by lower levels of agitation, hostility, and psychotic distortions. In AD patients with symptoms of psychosis, agitation, or aggressive behavior, medications can have a small but significant impact on caregiver burden.
Publication: Mohamed, S., Rosenheck, R., Lyketsos, C.G., Kaczynski, R., Sultzer, D.L., & Schneider, L.S. (2012). Effect of second-generation antipsychotics on caregiver burden in Alzheimer's disease. Journal of Clinical Psychiatry, 73(1), 121-128.
Galantamine’s Effects on Nicotine Responses in Smokers
Contact: Mehmet Sofuoglu, M.D., Ph.D. (Mehmet.Sofuoglu@va.gov)
Galantamine (GAL), a reversible and competitive inhibitor of acetylcholinesterase, is used clinically in the treatment of Alzheimer's dementia. Some preclinical and clinical studies support the potential efficacy of cholinesterase inhibitors for smoking cessation, although their effects on the behavioral and physiological responses to nicotine have not been examined. The goal of this study was to characterize GAL's actions on multiple outcomes, including withdrawal severity and cognitive performance, as well as subjective and physiological responses to nicotine administered intravenously. A total of 12 smokers participated in a double-blind, placebo-controlled, crossover study. Smokers had two 4-day treatment periods, assigned in random sequence, to GAL (8 mg/day) or placebo treatment. On day 4 of each treatment phase, smokers had an experimental session in which they received an intravenous (IV) dose of saline or 1 mg/70 kg nicotine, 1 h apart, in a random order. Findings: GAL attenuated the self-reported rating of “craving for cigarettes” and prevented decrements in performance in a Go/No-Go task. In response to IV nicotine, GAL treatment attenuated the self-report ratings of “like the drug effects,” “good drug effects,” “bad drug effects,” and “stimulated.” These findings support the potential utility of GAL as a treatment for smoking cessation.
Publication: Sofuoglu, M., Herman, A.I., Li, Y., & Waters, A.J. (2012). Galantamine attenuates some of the subjective effects of intravenous nicotine and improves performance on a Go No-Go task in abstinent cigarette smokers: A preliminary report. Psychopharmacology, 224(3), 413-420.
Naltrexone and SSRI in Alcoholics with Post-Traumatic Stress Disorder and/or Depressive Disorders
Contact: Ismene Petrakis, M.D. (Ismene.Petrakis@va.gov) and Nitigna Desai, M.D. (Nitigna.Desai@va.gov)
The purpose of this study is to evaluate the effects of paroxetine, desipramine, and naltrexone in reducing alcohol use in alcohol-dependent Veterans with current depressive disorder or post-traumatic stress disorder (PTSD). One hundred Veterans who have comorbid alcohol dependence and PTSD or depression were recruited for the study. The Veterans were randomized in a double-blind fashion to one of four cells. We compared paroxetine versus desipramine and naltrexone versus placebo. The antidepressant was started at a low dose and titrated upward on a fixed schedule. The target dose was 40mg for paroxetine and 250 mg for desipramine. Minimum dosage permitted for study retention was 20mg for paroxetine and 150mg for desipramine. Pharmacological treatments lasted 13 weeks. Psychosocial treatment involved medication compliance therapy, using the Microelectric Event Monitoring (MEMS) bottlecaps. The primary baseline and outcome measures of major interest included: frequency and quantity of alcohol consumption; self-reported cravings; self-reported psychiatric and emotional distress; diagnostic assessment of psychiatric symptoms; and side effects. These outcomes were measured by the following: self-assessments; Timeline Followback; Hamilton Depression and Anxiety Scales; Clinician-Administered PTSD Scale (CAPS); Addiction Severity Index (ASI); Quality of Life; breathalyzer tests; and monthly liver function tests. The specific aim of this study was to compare the relative effectiveness of paroxetine versus desipramine and naltrexone versus placebo in reducing the quantity and frequency of alcohol consumption in individuals with co-occurring alcohol dependence and PTSD or depression. Findings: Paroxetine did not show statistical superiority to desipramine for the treatment of PTSD symptoms. However, desipramine was superior to paroxetine with respect to study retention and alcohol use outcomes. Naltrexone reduced alcohol craving relative to placebo, but it conferred no advantage on drinking use outcomes. Although the serotonin uptake inhibitors are the only FDA-approved medications for the treatment of PTSD, the current study suggests that norepinephrine uptake inhibitors may present clinical advantages when treating male Veterans with PTSD and alcohol dependence. However, naltrexone did not show evidence of efficacy in this population.
Publication: Petrakis, I.L., Ralevski, E., Desai, N., Trevisan, L., Gueorguieva, R., Rounsaville, B., & Krystal, J.H. (2012). Noradrenergic vs. serotonergic antidepressant with or without naltrexone for Veterans with PTSD and comorbid alcohol dependence. Neuropsychopharmacology, 37, 996-1004.
Prescribing Psychotropics Without Psychiatric Diagnoses in Non-VA and VA Settings
Contact: Robert Rosenheck, M.D. (Robert.Rosenheck@va.gov)
Recent reports have raised concern that many primary care patients are prescribed antidepressants with no justifying psychiatric diagnosis. This study used a private insurance claims database to examine the prescription of diverse classes of psychotropic medications without a psychiatric diagnosis across age groups. MarketScan® claims data for 2009 were used to identify privately insured individuals who filled a prescription for at least one psychotropic medication (n=5.1 million patients). Bivariate and multivariate analyses were used to compare the proportion of these patients without any psychiatric or justifying medical diagnosis during the entire year across age groups and among patients who received specialty mental health care and those who did not. Analyses were repeated for six different classes of psychotropic medications. Findings: Altogether, 58% of individuals prescribed a psychotropic medication in 2009 had no psychiatric diagnosis during the year the prescription(s) were filled, with the highest proportions among those aged 50-64 (69%) and those who did not receive any mental health specialty care. Logistic regression found patients aged 50-64 to be 2.7 times more likely than younger patients to be prescribed a psychotropic without a psychiatric diagnosis. Medical indications for use and severity of general medical comorbidities were only weakly related to absence of a psychiatric diagnosis and did not alter these age trends. Conclusions: In a large private claims database, the majority of recipients of psychotropic medication lacked a justifiable indication for such use, especially older patients and those not utilizing mental health specialty care. This unwarranted exposure to serious adverse events or incomplete documentation of psychiatric diagnoses deserves further study and remediation. This study is being replicated in the VA health care system.
Collaborators: Ilse Weichers, M.D., MPP and Paul Kirwin, M.D.
Publication: Wiechers, I.R., Leslie, D.L., & Rosenheck, R.A. (2013). Prescribing psychotropic medications to patients without a psychiatric diagnosis. Psychiatric Services, 64(12), 1243–1248.
Progesterone for Postpartum Cocaine Relapse
Contact: Mehmet Sofuoglu, M.D., Ph.D. (Mehmet.Sofuoglu@va.gov)
Pre-clinical data show that estrogen increases the likelihood of stimulant self-administration. Progesterone has the opposite effect and can reverse the effect of estradiol. Pregnancy, which is characterized by high circulating progesterone levels, is associated with decreased substance use. Unfortunately, drug use increases again after delivery. The incremental decrease in drug use over the course of pregnancy as progesterone levels increase, and the escalation in drug use after delivery when progesterone levels drop, suggests the possibility that progesterone influences drug use. This project was a double-blind, randomized, placebo-controlled trial that obtained preliminary data on the efficacy of oral micronized progesterone for postpartum women with a history of cocaine dependence or abuse. We recruited 50 postpartum women who abused cocaine either during the 6 months before or in pregnancy. Postpartum participants were randomized to receive either oral micronized progesterone (100 mgs BID) or placebo for 12 weeks. We conducted a post-treatment follow-up visit 3 months after the last treatment visit. Each week, we collected a substance use calendar and urine for cocaine metabolite analysis. Findings: Preliminary analysis indicated that participants randomized to progesterone lowered their cocaine use more than did those randomized to placebo (treatment by time F=5.41; p=.02). Participants assigned to progesterone, as compared to placebo, were less likely to submit a urine that was positive for cocaine (treatment wald=11.7, p=.003). Forty-one women were abstinent at baseline, and 12 relapsed during the 12-week study period. If the positive results found in this study are replicated in a larger cohort, this may constitute a viable treatment option for postpartum cocaine users. A manuscript reporting these findings is in preparation.
Publication: Yonkers, K.A., Forray, A., Nich, C., Carroll, K.M., Hine, C., Merry, B.C., Shaw, H., Shaw, J., & Sofuoglu, M. (2014). Progesterone reduces cocaine use in postpartum women with a cocaine use disorder: A randomized, double-blind study. The Lancet Psychiatry, 1(5), 360-367.
Randomized Clinical Trial of Long-Acting Injectable Risperidone and Oral Antipsychotics in Unstable Chronic Schizophrenia
Contact: Robert Rosenheck, M.D. (Robert.Rosenheck@va.gov)
VA patients with schizophrenia and schizoaffective disorder, who were hospitalized within the past two years or judged to be at risk of hospitalization from increasing psychiatric service use, were randomly assigned to long-acting injectable (LAI) risperidone (Risperdal Consta ® bi-weekly 25-50 mg/injection) or to the psychiatrist’s choice of oral antipsychotics and followed for up to two years. The primary intention-to-treat endpoint was VA or non-VA psychiatric re-hospitalization. Symptoms, quality of life, and global functioning were assessed through blinded video conference interviews. Findings: The results found that participants (n=369) were hospitalized either at randomization (40%) or within the previous two years (55%), or they were at current risk of hospitalization (5%). LAI risperidone showed no superiority to oral antipsychotics on time to first psychiatric hospitalization (p=.39). Mixed models showed no significant superiority for LAI risperidone on psychiatric symptoms, quality of life, or the Personal and Social Performance (PSP) measure of global functioning, all assessed blindly via video interview or on standard measures of neurological side effects. However, LAI patients reported more adverse events at the injection site and extrapyramidal symptoms. This first randomized trial suggests that Risperdal Consta ® may not offer significant health benefits and may have greater side effect risks and should perhaps be used cautiously in the VA health care system. Continuing analyses have looked at cost-effectiveness, sub-group responses, and the minimally clinically important difference (MCID) of the Positive and Negative Symptom Scale (PANSS).
Publications: (1) Rosenheck, R.A., Krystal, J.H., Lew, R., Barnett, P.G., Fiore, L., Valley, D., Thwin, S.S., Vertrees, J.E., Liang, M.H., & CSP555 Research Group. (2011). Long-acting risperidone and oral antipsychotics in unstable schizophrenia. New England Journal of Medicine, 364(9), 842-851; (2) Barnett, P.G., Scott, J.Y., Krystal, J.H., Rosenheck, R.A., for the CSP 555 Research Study Group. (2012). Cost and cost-effectiveness in a randomized trial of long-acting risperidone for schizophrenia. Journal of Clinical Psychiatry, 73(5), 696-702; and (3) Thwin, S.S., Hermes, E., Lew, R., Barnett, P., Liang, M., Valley, D., & Rosenheck, R. (2013). Assessment of the minimum clinically important difference in quality of life in schizophrenia measured by the Quality of Well-Being Scale and disease-specific measures. Psychiatric Research, 209(3), 291-296.
Risperidone Treatment for Refractory Combat-Related Post-Traumatic Stress Disorder
Contacts: John Krystal, M.D. (John.Krystal@va.gov) and Robert Rosenheck, M.D. (Robert.Rosenheck@va.gov)
This CSP #504 study evaluated the efficacy and durability of benefit of risperidone in the treatment of Veterans with military service-related chronic post-traumatic stress disorder (PTSD). The primary hypothesis of the study was that risperidone would reduce symptoms of PTSD, relative to placebo, in Veterans with military service-related chronic PTSD who were partial- or non-responders to antidepressant medications. The main objective of the study was to assess the efficacy of the atypical antipsychotic, risperidone, in treating Veterans with military service-related chronic PTSD who had an inadequate antidepressant treatment response, using a placebo-controlled, double-blind design. If risperidone was effective, we expected improvement in the secondary consequences of PTSD for Veterans and for the VA health care system. The secondary endpoints included determination of whether risperidone is a safe and feasible treatment for Veterans with military service-related chronic PTSD and addressed important clinical dimensions of this disorder: (1) safety and tolerability of risperidone in this special Veteran population; (2) compliance with risperidone prescriptions; and (3) whether depression, paranoia, violent behavior, sleep disturbance, substance abuse, quality of life, and cognitive impairments improve with risperidone treatment. The study was a 6-month, randomized, double-blind, placebo-controlled multicenter trial conducted between February 2007 and February 2010 at 23 Veterans Administration outpatient medical centers. Of the 367 Veteran patients screened, 296 were diagnosed with military-related PTSD and had ongoing symptoms despite at least 2 adequate SRI treatments, and 247 contributed to analysis of the primary outcome measure. The primary endpoint was change in the score on the Clinician-Administered PTSD Scale (CAPS). Findings: Change in CAPS scores from baseline to 24 weeks in the risperidone group was -16.3 (95% CI, -19.7 to -12.9) and in the placebo group, -12.5 (95% CI, -15.7 to -9.4); the mean difference was 3.74 (95% CI, -0.86 to 8.35; t = 1.6; P = .11). Mixed model analysis of all time points also showed no significant difference in CAPS score (risperidone: mean, 64.43; 95% CI, 61.98 to 66.89, vs placebo: mean, 67.16; 95% CI, 64.71 to 69.62; mean difference, 2.73; 95% CI, -0.74 to 6.20; P = .12). Risperidone did not reduce symptoms of depression (MADRS mean difference, 1.19; 95% CI, -0.29 to 2.68; P = .11) or anxiety (HAMA mean difference, 1.16; 95% CI, -0.18 to 2.51; P = .09; patient-rated CGI mean difference, 0.20; 95% CI, -0.06 to 0.45; P = .14; observer-rated CGI mean difference, 0.18; 95% CI, 0.01 to 0.34; P = .04), or increase quality of life (SF-36V physical component mean difference, -1.13, 95% CI, -2.58 to 0.32; P = .13; SF-36V mental component mean difference, -0.26; 95% CI, -2.13 to 1.61; P = .79). Adverse events were more common with risperidone vs placebo, including self-reported weight gain (15.3% vs 2.3%), fatigue (13.7% vs 0.0%), somnolence (9.9% vs 1.5%), and hypersalivation (9.9% vs 0.8%), respectively. The conclusion was that, among Veteran patients with military-related PTSD with SRI-resistant symptoms, 6-month treatment with risperidone compared with placebo did not reduce PTSD symptoms.
Publication: Krystal, J.H., Rosenheck, R.A., Cramer, J.A., Vessicchio, J.C., Jones, K.M., Vertrees, J.E., Horney, R.A., Huang, G.D., Stock, C. & Veterans Affairs Cooperative Study No. 504 Group. (2011). Adjunctive risperidone treatment for antidepressant-resistent symptoms of chronic military service-related PTSD: A randomized trial. JAMA: The Journal of the American Medical Association, 306(5), 493-502.
Secondary Analysis of CATIE Trial Data
Contact: Robert Rosenheck, M.D. (Robert.Rosenheck@va.gov)
The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) was designed to compare the effectiveness and cost-effectiveness of available second generation antipsychotics in a large, National Institute of Mental Health–funded, randomized double-blind trial at 57 US sites, including both academic and community providers. Participants were 18-65 years of age with a diagnosis of schizophrenia. Individuals diagnosed with schizoaffective disorder, a cognitive disorder, or who had only one schizophrenic episode were excluded. Treatment comparisons in CATIE were divided into phases. In phase 1, participants were randomized to double-blind treatment with one of 5 atypical antipsychotics, not including clozapine, and followed for up to 18 months or until treatment was discontinued for any reason. Participants who discontinued phase 1 could enter phase 2 unless their phase 1 treatment was perphenazine wherein they could enter phase 1B where they were randomly assigned double-blind treatment with olanzapine, quetiapine, or risperidone. If participants discontinued treatment in phase 1B, they then entered phase 2. Details of the study design have been presented elsewhere. Data analyses focused on the dually diagnosed and other participants.
Collaborator: Eric Hermes, M.D., MPH (Eric.Hermes@va.gov)
Publications: (1) Kerfoot, K.E., Rosenheck, R.A., Petrakis, I.L., Swartz, M.S., Keefe, R.S., McEvoy, J.P., Stroup, T.S., and CATIE Investigators. (2011). Substance use and schizophrenia: Adverse correlates in the CATIE study sample. Schizophrenia Research, 132(2-3), 177-182; (2) Hermes, E., Nasrallah, H., Davis, V., Meyer, J., McEvoy, J., Goff, D., Davis, S., Stroup, T. S., Swartz, M., Lieberman, J., & Rosenheck, R. (2011). The association between weight change and symptom reduction in the CATIE schizophrenia trial. Schizophrenia Research, 128(1-3), 166-170; (3) Hermes, E. & Rosenheck, R.A. (2012). Predictors of antipsychotic dose changes in the CATIE schizophrenia trial. Psychiatry Research, April 19 [Epub ahead of print]; (4) Hermes, E. & Rosenheck, R.A. (2012). Choice of randomization to clozapine versus other second generation antipsychotics in the CATIE schizophrenia trial. Journal of Psychopharmacology, 26(9), 1194-2000; (5) Hermes, E.D., Sokoloff, D., Stroup, T.S., & Rosenheck, R.A. (2012). Minimum clinically important difference in the Positive and Negative Syndrome Scale with data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Journal of Clinical Psychiatry, 73(4), 526-532.
Treatment with Acamprosate in Individuals with Schizophrenia and Comorbid Alcoholism
Contact: Ismene Petrakis, M.D. (Ismene.Petrakis@va.gov)
Alcohol use disorders (AUD) are common conditions in individuals with schizophrenia. Acamprosate is a recently approved treatment for alcoholism, and it may be advantageous over other treatments for individuals with schizophrenia since is not metabolized in the liver, and it can be used safely with other psychotropic medications. There are only few reports in the current literature evaluating the efficacy of medications available for the treatment of alcoholism in individuals with schizophrenia, and the efficacy and safety of acamprosate have never been studied in this vulnerable group. The aim of this study was to evaluate the safety and efficacy of acamprosate for individuals with alcohol dependence and comorbid schizophrenia. We evaluated the efficacy of acamprosate (1998 mg/day) versus placebo in reducing alcohol consumptions and schizophrenic symptoms in individuals diagnosed with alcohol dependence (AD) and schizophrenia. This was a 12-week randomized, double-blind study. Twenty-three participants with a current diagnosis of AD and schizophrenia were enrolled. Findings: Data analyses revealed a decrease in drinking outcomes over the treatment period but no superiority of acamprosate to placebo. However, acamprosate was more successful than placebo in reducing craving. There was no change in cognitive functioning over time in this sample of patients with schizophrenia and no differences between acamprosate and placebo in how they affected cognitive performance.
Publications: (1) Ralevski, E., O’Brien, E., Jane, J.S., Dwan, R., Dean, E., Edens, E., Arnaout, B., Keegan, K., Drew, S., & Petrakis, I. (2011). Treatment with acamprosate in patients with schizophrenia spectrum disorders and comorbid alcohol dependence. Journal of Dual Diagnosis, 7(1-2), 64-73; and (2) Ralevski, E., O’Brien, E., Jane, J.S., Dwan, R., & Petrakis, I. (2011). Effects of acamprosate on cognition in a treatment study of patients with schizophrenia spectrum disorders and comorbid alcohol dependence. Journal of Nervous and Mental Disease, 199(7), 499-505.
Psychosocial Interventions
Benefits Counseling to Preserve Function Among Disability Applicants
Contact: Marc Rosen, M.D. (Marc.Rosen@va.gov)
Website: http://www.behaviorchange.yale.edu/index.html
This study will address the problem that Veterans with psychiatric disabilities who apply for and receive disability benefits go on to work less than those whose claims are denied. The key questions are: (1) Do Veterans assigned to benefits counseling engage in more days of work and work-related activity over time than those assigned to the control condition?; (2) Do attitudes about disability benefits differ between the treatment groups over time, and does a change in attitudes mediate benefits counseling’s effects? This is a 6-month randomized clinical trial comparing 60 Veterans assigned to benefits counseling to 60 Veterans assigned to the control condition, VA orientation. Benefits counseling, a therapy designed to foster involvement in work and work-related activities, also involves engaging Veterans in VA rehabilitative services, clarifying that work does not foreclose receiving benefits and addressing barriers to working. The control condition, VA orientation, involves a brief description of available VA health care services. Assessments for all participants will be conducted 4 times over a 6-month period. The primary outcome measure will be the number of days spent in work-related activities. Attitudes about disability benefits will be rated to determine if benefits counseling is, as hypothesized, associated with decreasing concern about losing benefits and if such a change mediates benefits counseling’s effects. Findings: The study has been completed and the main results have been submitted for publication. A secondary analysis has been published which found that Veterans endorsed high levels of agreement with statements that working would lead to loss of benefits. Veterans with substance use agreed more strongly that they would rather turn down a job offer than lose financial benefits. The greater preference for disability payments among substance-using Veterans may reflect a realistic concern that they are particularly likely to have difficulty maintaining employment. The widespread concern among Veterans that work will lead to loss of VA disability payments is striking given the ambiguity about how likely loss of benefits actually is and should be addressed during the service-connection application process.
Publications: (1) Rosen, M.I. (2010). Guest editorial: Compensation examinations for PTSD—An opportunity for treatment? Journal of Rehabilitation Research & Development, 47(5), xv-xxii; and (2) Meshberg-Cohen, S., Reid-Quiñones, K., Black, A.C., & Rosen, M.I. (2014). Veterans' attitudes toward work and disability compensation: Associations with substance abuse. Addictive Behaviors, 39(2), 445-448.
Impact of Supported Employment Vs. Standard Vocational Rehabilitation in Veterans with PTSD
Principal Investigator: Lori Davis, M.D., Tuscaloosa VA (Lori.Davis@va.gov)
Contacts: Charles Drebing, Ph.D. (Charles.Drebing@va.gov) and Lisa Mueller, Ph.D. (Lisa.Mueller@va.gov)
This multi-site, randomized study evaluated the impact on occupational functioning of the Individual Placement and Support (IPS) model of supported employment (SE) on Veterans with post-traumatic stress disorder (PTSD) compared to standard vocational rehabilitation (VR) programs. Veterans who met inclusion criteria were randomized to either SE or VR. Occupational functioning was determined primarily by whether the Veteran could obtain and maintain competitive employment and, secondarily, by time worked and wages earned for those employed. Outcomes were assessed over a fixed 12-month observation period as percent participants employed at least one week and monthly employment rates. In addition, health outcomes, PTSD symptoms, sobriety, other psychiatric symptoms, and other health-related quality of life measures were evaluated. Given the increased numbers of Veterans returning from Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Freedom (OEF/OIF/OND) who often experience PTSD symptoms and confront unemployment upon their military discharge, this study is timely and has critical implications for clinical care and mental health policy. Findings: During the 12-month study, 76% of the IPS participants gained competitive employment, compared with 28% of the VR participants (number needed to treat=2.07; χ2=19.84, df=1, p<.001). Veterans assigned to IPS also worked substantially more weeks than those assigned to VR (42% versus 16% of the eligible weeks, respectively; Mann-Whitney z test p<.001) and earned higher 12-month income (mean±SD income of $9,264±$13,294 for IPS versus $2,601±$6,009 for VRP; Mann-Whitney z test p<.001) during the 12-month period. Veterans with PTSD who received IPS were 2.7 times more likely to gain competitive employment than those who received VR. Because work is central to recovery, these results should assist stakeholders in planning improved services for Veterans with PTSD.
Publication: Davis, L.L., Leon, A.C., Toscano, R., Drebing, C.E., Ward, L.C., Parker, P.E., Kashner, T.M., & Drake, R.E. (2012). A randomized controlled trial of supported employment among Veterans with post-traumatic stress disorder. Psychiatric Services, 63(5), 464-470.
Mindfulness and Acceptance-Based Smoking Cessation Treatment for Veterans with Post-Traumatic Stress Disorder
Contact: Megan M. Kelly, Ph.D. (Megan.Kelly1@va.gov)
Veterans with post-traumatic stress disorder (PTSD) have high rates of smoking and significant difficulties with quitting. Acceptance and mindfulness-based techniques may enhance smoking cessation approaches for Veterans with PTSD as they are designed to improve emotion regulation skills related to coping with elevated negative affect and withdrawal symptoms associated with quit attempts. The primary aim of this study was to develop and evaluate Acceptance and Commitment Therapy for Veterans with Comorbid PTSD and Tobacco Use (ACT-VPT). This treatment specifically targets elevated negative affect and distress intolerance associated with quit attempts in Veterans with PTSD. The research study involved the development of an ACT treatment for smokers with PTSD and an evaluation of this treatment using an open trial format. Nineteen Veterans with current PTSD and smoking = 15 cigarettes/day participated in an open trial of ACT-VPT. Participants attended nine weekly individual counseling sessions and received eight weeks of the nicotine patch. Primary outcomes included expired-air carbon monoxide confirmed seven-day point prevalence abstinence, number of cigarettes/day at the end of treatment, and PTSD symptoms on the PTSD Checklist (PCL). Intent-to-treat analyses examined pre-treatment to post-treatment scores on the PCL. Findings: At the end of treatment (one month after targeted quit date), 37% (7/19) of participants were abstinent from smoking, 37% (7/19) were abstinent from smoking at the one month follow-up, and 16% (3/19) were abstinent at the three month follow-up. Subjects reduced from 26 cigarettes/day at baseline to 10 cigarettes/day at the end of treatment (p<.001), and 15 cigarettes/day at the 3-month follow-up (p=.002). PTSD symptoms significantly decreased from baseline to the end of treatment (p<.001), and continued to remain significantly decreased at the 3-month follow-up (p=.011). The retention rate (74%), client satisfaction ratings and qualitative feedback from subjects indicated that the treatment was acceptable. Although preliminary, these results suggest that ACT-PT is a promising smoking cessation treatment for Veterans with PTSD. Longer follow-up and randomized controlled studies are needed. A manuscript of these findings is in preparation.
Publication: Kelly, M. M., Latta, R., & Gimmestad, K. (2012). Acceptance and mindfulness-based tobacco cessation interventions for individuals with mental health disorders. Journal of Dual Diagnosis, 8, 89-98.
Supported Education for OIF/OEF/OND Veterans with PTSD
Principal Investigator: Marsha Ellison, Ph.D., UMass Memorial Medical Center
Contact: Lisa Mueller, Ph.D. (Lisa.Mueller@va.gov) and Charles Drebing, Ph.D. (Charles.Drebing@va.gov)
Many Operation Iraqi Freedom/Enduring Freedom/New Dawn (OIF/OEF/OND) Veterans with psychiatric disabilities and co-occurring substance abuse possess educational aspirations. However, many OIF/OEF/OND Veterans are unsuccessful in finding employment or are locked into entry-level jobs because of limited education and disability adjustment. Even with current increases in GI Bill funding, returning Veterans face non-financial barriers blocking their pursuit of educational goals. Supported education is a recovery-based rehabilitation intervention that is new to VA health care system (VA) services and responds to an expressed but unmet need among returning Veterans with war-related trauma. We propose that supported education practices, merged with VA disability and vocational services, will increase the completion of post-secondary education courses, degrees, or certificate programs that will in turn significantly improve OIF/OEF/OND Veterans later employment outcomes. The goal of this study is to develop culturally informed Supported Education Training Curricula and Implementation Guidelines for a supported education service designed for returning Veterans with post-traumatic stress disorder (PTSD). Using a participatory action research approach, a needs assessment and an implementation assessment for supported education were conducted. Data were collected through focus groups with Veterans, including two with Hispanic Veterans. Additional data for the implementation assessment were collected via key informant interviews with local and national VA leaders and administrators in mental health and vocational rehabilitation services. Findings: We completed focus groups and interviews with OIF/OEF/OND Veterans with PTSD (n=31), key informant interviews, and development team meetings with stakeholders (VA clinicians, college administrators, peer support providers, state providers of Veterans services, etc.). Results indicate that the following elements are important to assist Veterans with PTSD to succeed in educational settings: peer support and mentoring on and off campus; outreach in homes and community; benefits counseling and advocacy; on-campus services for Veterans; case management; clinical and education services coordination; and college readiness training.
Publication: Ellison, M.L., Mueller, L., Smelson, D., Corrigan, P.W., Torres-Stone, R., Bokhour, B.G., Najavits, L.M., Vessella, J., & Drebing, C. (2012). Supporting the education goals of post 9/11 Veterans with self-reported PTSD symptoms: A needs assessment. Psychiatric Rehabilitation Journal, 35, 209-217.
Use of a Modified Version of Cognitive Processing Therapy for the Treatment of Patients Diagnosed with Post-Traumatic Stress Disorder and Alcohol Dependence
Contact: Ismene Petrakis, M.D. (Ismene.Petrakis@va.gov)
The purpose of this study was to improve symptoms of post-traumatic stress disorder (PTSD) and alcohol use disorders for Veterans diagnosed with these conditions. This study proposed to use cognitive processing therapy without the written exposure account (CPT-C) with modifications to address alcohol misuse in Veterans with PTSD. Veterans were recruited as participants from the VA Connecticut Healthcare System. All participants received CPT-C for 12 weeks by experienced CPT-C clinicians. Participants underwent a thorough eligibility screening, weekly assessments, and a post-treatment follow-up visit. Participants were compensated for their participation. Twenty historical controls diagnosed with PTSD and alcohol use disorders were used. This study’s findings will help advance understanding about effective treatments for Veterans with co-occurring PTSD and alcohol use disorders.
Publication: McCarthy, E. & Petrakis, I. (2011). Case report on the use of cognitive processing therapy-cognitive, enhanced to address heavy alcohol use. Journal of Traumatic Stress, 24(4), 474-478.
