VISN 1 New England MIRECC Current Clinical Efficacy Research
Cholinergic Enhancement as a Treatment for Nicotine Addiction
Contact: Mehmet Sofuoglu, M.D., Ph.D. (Mehmet.Sofuoglu@va.gov)
The purpose of this study is to characterize the dose-dependent effects of galantamine (GAL) as a treatment for nicotine dependence in treatment-seeking smokers GAL is a cholinesterase inhibitor that is approved for the treatment of Alzheimer's disease. We propose a double-blind, placebo-controlled, outpatient study with a between-groups design. Seventy-two male and female smokers will be randomly assigned to one of the 3 treatment conditions, including GAL (8 or 16 mg/day) or placebo. The dose of GAL will be gradually increased to the target doses over a 2-week period. On week 3, following overnight abstinence from smoking, participants will have a laboratory session in which they will have the option of cigarette self-administration. Smokers who quit smoking before the session will not be asked to participate in the self-administration session. After the lab session is completed, smokers will be maintained on their randomized medication condition for an additional 4-week period. Smokers will have a quit date at the beginning of the treatment period and will receive weekly brief behavioral treatment for 4 weeks. Additionally, at the beginning of Week 3, participants will be given a personal digital assistant (PDA) that will administer ecological momentary assessments (EMA). The medication will be tapered after the end of the 4-week period. Participants will be contacted by phone at one week and one month after treatment termination to inquire about any adverse events and their smoking status. The study is the participant recruitment stage.
Cognitive Enhancement as a Target for Cocaine Pharmacotherapy
Contact: Mehmet Sofuoglu, M.D., Ph.D. (Mehmet.Sofuoglu@va.gov)
The goals of this study are to determine if: (1) galantamine (8 or 16 mg/day) is more effective than placebo in reducing cocaine use as measured by cocaine urine results and self-report days of use; (2) galantamine (8 or 16 mg/day) is more effective than placebo in improving attention, assessed with the Rapid Visual Information Processing (RVIP) and the Simple Reaction Time (SRT) tests; and (3) improvement in attention during the first four weeks of treatment will mediate galantamine’s efficacy in reducing cocaine use. This is a double-blind, placebo-controlled, 12-week randomized clinical trial. Participants are men and women between the ages of 18 and 55 who have used cocaine more than once per week in the previous 30 days and fulfill criteria for current cocaine dependence according to DSM-IV. 120 cocaine-dependent men and women will be randomized to one of three treatment groups: placebo (n=40), 8 mg/day (n=40), and 16 mg/day (n=40) of extended release (ER) galantamine. The initial dose of galantamine will be 8 mg/day as a single dose, as recommended for clinical use. For those participants assigned to 16 mg/day, the dose of galantamine will be increased to 16 mg at the end of week 4. Treatment groups will remain on their full dosage through week 12. All participants will receive contingency management (CM) targeting compliance with treatment. The results of this study may lead to development of effective pharmacotherapies for cocaine addiction.
Effectiveness of Zonisamide in Treating Alcohol Dependent Veterans
Contacts: Albert Arias, M.D. (Albert.Arias@va.gov) or Nitigna Desai, M.D. (Nitigna.Desai@va.gov)
The objective of this project is to study the effectiveness of zonisamide as a treatment to reduce harmful drinking in Veterans with moderate to severe alcohol use disorder. We also plan to explore genetic variation and other subject characteristics as potential moderators of zonisamide response. We propose a medium sized (N = 160), 16-week, randomized, double-blind, placebo-controlled, effectiveness study of zonisamide in reducing heavy drinking and improving outcomes in a representative population of heavy-drinking Veterans with moderate to severe alcohol use disorder. This study will take place in the outpatient setting with participants that are regular heavy drinkers. Participants will be randomized to placebo or the anticonvulsant zonisamide and titrated to a target dose of 500mg daily of the medication over 7 weeks. The active treatment phase is 9 weeks at the target dose. Participants will then be tapered off the medication over 2 weeks and seen at 3 months post-endpoint for a follow-up. We will collect DNA for genotyping and pharmacogenetic analysis. We expect to confirm findings from pilot studies supporting the efficacy of the medication and also that it is highly effective in a representative sample of Veterans who often have comorbid psychiatric disorders. The primary outcome is the percentage of participants with no heavy drinking days in the last 4 weeks of treatment. We may find ways to predict which Veteran patients will respond the best to zonisamide. This is a clinical trial in a representative and generalizable sample. Thus, the results will give a good example of the effectiveness of the medication in treating Veterans with alcohol use problems.
IV Nicotine Self-administration: Dose Ranging and Sex Differences in Smokers
Contact: Mehmet Sofuoglu, M.D., Ph.D. (Mehmet.Sofuoglu@va.gov)
The purpose of this study is to characterize the reinforcing threshold and dose-response curve for intravenous (IV) nicotine self-administration in male and female smokers with or without nicotine dependence. The reinforcing effects of nicotine will be determined by the number of IV nicotine self-administrations. In this double-blind, placebo-controlled, crossover study, the main outcomes will be threshold dose (the minimum dose of nicotine that is self-administered more than placebo) and the slope of dose-response for nicotine self-administration (changes in nicotine self-administration for per unit change in nicotine dose). This study will examine the minimum doses of nicotine needed to maintain nicotine use in male and female smokers. Tobacco addiction is the most important preventable cause of death in the U.S. The results of this study would be vital to the development of science-based tobacco control policies that may gradually reduce the nicotine in cigarettes to an amount below the addictive threshold.
Publication: DeVito, E.E., Herman, A.I., Waters, A.J., Valentine, G.W., & Sofuoglu, M. (2014). Subjective, physiological, and cognitive responses to intravenous nicotine: Effects of sex and menstrual cycle phase. Neuropsychopharmacology, 39(6), 1431-1440.
Mecamylamine for the Treatment of Alcohol Dependence
Contact: Ismene Petrakis, M.D. (Ismene.Petrakis@va.gov)
Alcohol dependence is the most prevalent psychiatric disorder and also one of the most costly health care problems faced by society. Although there are three medications approved by the Food and Drug Administration (FDA) to treat alcoholism, all three have limitations, so the development of new medications is of high clinical importance. Nicotine and alcohol dependence are linked by a high rate of comorbidity, a synergistic effect of nicotine and ethanol use and a common neurobiology. In fact, acetylcholine nicotinic receptors (nAChR), which are important in nicotine dependence, may also play a crucial role in alcohol dependence. Preclinical and human laboratory studies have suggested that a drug known to block nicotine receptors, mecamylamine hydrochloride (Inversine), decreases alcohol use and craving. We conducted a pilot study evaluating the effects of mecamylamine on ethanol use in alcohol dependent individuals, approximately 60% of whom were smokers. Our preliminary data suggests that there is a significant interaction between smoking status and medication on the alcohol use outcome heavy drinking days with a large effect size. There is a trend toward significance in the outcome drinking days where non-smokers treated with mecamylanine had better outcomes compared to non-smokers treated with placebo. No participants spontaneously reported quitting smoking. One hundred and eighty-four individuals with alcohol dependence will be randomly assigned to receive either a standard dose of mecamylamine (10 mg daily) or a matching placebo every day for a total of twelve weeks. Outcomes include ethanol intake as measured by the Time Line Followback Method, craving as measured by the Obsessive Compulsive Drinking Scale, psychiatric distress, and side effect burden. In addition, we will evaluate smoking behavior in smokers who are not trying to abstain from smoking. We predict that non-smokers will have a better response to mecamylamine than smokers. This is the first study conducted to evaluate mecamylamine as a potential pharmacotherapeutic agent for alcohol dependence.
Menthol’s Effects on the Nicotine Reinforcement in Smokers
Contact: Mehmet Sofuoglu, M.D., Ph.D. (Mehmet.Sofuoglu@va.gov)
Evidence from epidemiological studies suggests that menthol is a potential contributor to the development and maintenance of tobacco addiction. Menthol may have a special role in tobacco addiction given that nicotine, compared to other drugs of abuse, is a relatively weak reinforcer, and other reinforcers combined with nicotine may facilitate development and maintenance of addiction. The potential reinforcing properties of menthol have not been examined with systematic studies in controlled settings. The overall goal of this project is to examine the reinforcing effects of menthol in combination with nicotine. To reach this goal, this proposal will examine if acute menthol administration via e-cigarette, compared to control flavors, will change the reinforcing effects of pure nicotine administered intravenously. We are proposing a double-blind, placebo-controlled study enrolling 60 smokers, 30 menthol and 30 non-menthol cigarette smokers, matched for race, gender, and level of nicotine intake. Using a crossover design, each smoker will be tested under low or high dose of menthol or non-menthol flavors. Menthol will be administered concurrently with nicotine (saline, 5 µg/kg and 10 µg/kg). The results of this study will contribute to the knowledge needed to develop science-based policies regarding menthol as an additive in cigarettes.
Minocycline Treatment for Cocaine Users
Contact: Mehmet Sofuoglu, M.D., Ph.D. (Mehmet.Sofuoglu@va.gov)
The goal of this study is to evaluate the safety and potential efficacy of minocycline as a pharmacotherapy for cocaine dependence. Minocycline is a tetracycline derivative antibiotic that also inhibits nitric oxide (NO) production. NO serves as a second messenger for the dopamine and NMDA type glutamate receptor mediated effects including the rewarding effects of stimulant drugs. Minocycline may have utility as a treatment for cocaine addiction. This is a 14-week clinical trial in which 60 cocaine dependent individuals will be randomly assigned to 200 or 400 mg/day of minocycline or placebo. The main outcome measure will be cocaine urine results which will be obtained three times per week during the study. Cocaine addiction is a major health problem with no proven medication treatment. Thus, development of effective pharmacotherapies for cocaine addiction will have great public health implications both for Veterans and non-Veterans.
Collaborator: Caroline Arout, Ph.D. (Caroline.Arout@va.gov)
Randomized Controlled Trial of an N-methyl-D-aspartate Antagonist Ketamine in Comorbid Depression and Alcohol Dependence
Contact: Gihyun Yoon, M.D. (Gihyun.Yoon@va.gov)
The present study is investigating the use of the glutamate receptor (N-methyl-D-aspartate or NMDA) antagonist, ketamine, as a novel experimental therapy for the treatment of co-occurring depression and alcoholism in participants with depression and alcohol dependence. The primary objective is improvement in standard depression scores. Key secondary outcomes are safety, tolerability, and drinking behavior. Recruitment and data collection are ongoing.
Retroactive Chart Review of Veterans Receiving Vivitrol or Suboxone for Opioid Use Disorder
Contact: Shane Kraus, Ph.D. (Shane.Kraus@va.gov)
The need for effective opioid addiction treatment is imminent in this time of increasing deaths due to opioid overdose. Vivitrol is an injectable extended-release formulation of naltrexone, an opioid antagonist, used in the treatment of alcohol and opioid use disorders. Research suggests that Vivitrol is an effective and safe treatment for both alcohol and opioid use disorders. Unfortunately, most past trials have excluded individuals with dual diagnosis. Buprenorphine (Suboxone) is an approved medication for the treatment of opioid use disorder. Suboxone is available in a tablet form and taken daily to address issues of craving and opioid withdrawal, and it has been shown to reduce opioid overdose and relapse. Additional research is needed to examine the demographic and psychiatric differences of Veterans seeking treatment for opioid use disorder. More precisely, additional research is needed to compare the effectiveness of Vivitrol and Suboxone for the treatment of opioid use disorder among Veterans, many of whom are high risk for accidental overdose or relapse. This current project is a retroactive medical chart review to evaluate the effectiveness of Vivitrol (380 mg administered once a month) and Suboxone (4/1 mg - 24/6 mg administered daily) in the treatment of opioid use disorder among Veterans who received treatment at the Edith Nourse Rogers Memorial Veterans Hospital’s Veterans Center for Addiction Treatment between July 2015 – June 2016. The study seeks to examine the relationships among medication adherence (e.g., length of time taking medication), treatment outcomes (e.g., negative urine screens), and demographic and clinical characteristics of Veterans prescribed Vivitrol or Suboxone for an opioid use disorder. Using exploratory analyses, we hope to identify risk factors associated with poor treatment outcomes. In doing so, we can develop new treatment interventions for Veterans at risk for accidental overdose and chronic relapse.
Stress Reactivity in Individuals Receiving Pharmacological Treatment for PTSD and Alcohol Dependence (AD)
Contact: Elizabeth Ralevski, Ph.D. (Elizabeth.Ralevski@va.gov)
This project tests whether pharmacotherapy that targets both symptoms of post-traumatic stress disorder (PTSD) and alcohol dependence (AD) can attenuate the stress response, and how the attenuation of a stress response will affect relapse and outcome. The study design consists of three phases. In Phase I, all participants will participate in three laboratory sessions to determine their reactivity to stress. Stress reactivity will be measured using traumatic experiences, stressful non-trauma experiences, and neutral experiences presented randomly. Phase II is a randomized clinical trial evaluating prazosin versus placebo for 12 weeks in a double-blind, controlled fashion in an outpatient setting. The treatment will last for 12 weeks and outcomes will include symptoms of PTSD and alcohol use. Phase III will be conducted during the 12th and final week on medication while participants are still receiving prazosin or placebo. PTSD and alcoholism are commonly occurring issues among Veterans. The findings from this study will help advance understanding about effective treatments for these disorders in the Veteran population. Recruitment and data collection are ongoing.
Use of Prazosin for Treatment of Individuals with Alcohol Dependence (AD) and Post-Traumatic Stress Disorder (PTSD)
Contact: Ismene Petrakis, M.D. (Ismene.Petrakis@va.gov) and Nitigna Desai, M.D. (Nitigna.Desai@va.gov)
Alcohol dependence (AD) is the most common comorbid diagnosis among men with PTSD. The comorbidity of PTSD and alcoholism is associated with more severe PTSD symptoms, higher rates of alcohol relapse, higher rates of psychosocial and medical problems and psychiatric hospitalizations than the rates in non-comorbid patients with PTSD. There is evidence of common neurobiological mechanisms that underlie both PTSD and alcohol dependence and involve abnormalities of the noradrenergic system. The use of an alpha-1 adrenergic receptor antagonist represents a novel approach to treatment that may target symptoms of both PTSD and alcohol dependence. Prazosin is an alpha-1 adrenergic receptor antagonist that has been used successfully in the treatment of trauma nightmares and sleep disturbance in combat Veterans with PTSD. Prazosin has also been used in a pilot study for the treatment of alcohol dependence in which it decreased the number of drinking days as compared to placebo. These findings suggest that treatment with prazosin can be effective in reducing the symptoms of PTSD and alcohol consumption in individuals with these comorbid disorders, but it has not yet been rigorously tested. We wish to evaluate whether treatment with the alpha-1 adrenergic receptor antagonist, prazosin, will be more effective than placebo in Veterans with PTSD and comorbid AD in ameliorating the symptoms of PTSD and in reducing alcohol use. This study is a double-blind, randomized 13-week clinical trial. The experimental population consists of 120 Veterans with PTSD and comorbid alcohol dependence recruited at VA Connecticut Healthcare System and the Edith Nourse Rogers Memorial Veterans Hospital. The objective of this study is to evaluate the efficacy of prazosin (16mg) versus placebo in reducing alcohol consumption and decreasing symptoms of PTSD in Veterans with comorbid AD and PTSD. Participants are assigned to either prazosin or placebo in a double-blind fashion. This project will be the first to compare prazosin to placebo as an effective treatment for reducing alcohol consumption and PTSD symptoms in individuals with both AD and PTSD. This is a common type of dual diagnosis in Veterans and is a particular concern for returning Operations Iraqi Freedom/Enduring Freedom/New Dawn (OIF/OEF/OND) Veterans. The study is currently in the data analysis stage and a manuscript is being prepared for publication.
Publication: Petrakis, I., Desai, N., Gueorguieva, R., Arias, A., O'Brien, E., Jane, J.S., Sevarino, K., Southwick, S., & Ralevski, E. (2016). Prazosin for Veterans with post-traumatic stress disorder (PTSD) and co-morbid alcohol dependence: A clinical trial. Alcoholism, Clinical and Experimental Research, 40(1), 178-186.
Zonisamide in Addition to Enhanced Cognitive Processing Therapy-C (E-CPT-C) for Veterans with PTSD and Comorbid Alcohol Dependence
Contact: Ismene Petrakis, M.D. (Ismene.Petrakis@va.gov)
Post-traumatic stress disorder (PTSD) is prevalent among individuals who have experienced combat, so is of particular relevance to the returning Veterans from Iraq/Afghanistan. Many individuals with PTSD also suffer from other disorders, and one of the most common is alcohol dependence (AD). The new cohort of Iraq and Afghanistan combat Veterans also has relatively high rates of alcohol and substance abuse. The treatment of alcohol dependence among Veterans with PTSD is of high clinical importance. While there are four Food and Drug Administration (FDA) approved medications to treat alcohol dependence, there are limitations for all of them. Limitations include: for disulfiram: lack of acceptability; for oral naltrexone: lack of efficacy in Veterans with PTSD; for IM naltrexone (Vivitrol): prohibitive cost; and for acamprosate: lack of efficacy in large U.S. trials. The development of new medications to treat alcohol dependence is a priority for the Department of Defense and the Veterans Healthcare Administration (VHA). The anticonvulsants are the most efficacious new medications for the treatment of alcohol dependence. Most of the data is with topiramate, where double-blind, randomized, single and multisite studies show that topiramate is more efficacious than placebo at reducing the percentage of heavy drinking days and promoting abstinence. Studies show that topiramate also attenuates comorbid PTSD symptoms, and improves quality of life. However, topiramate has serious side effects including cognitive side effects. Zonisamide is an anticonvulsant, with similar properties to topiramate. A pilot study, conducted by a member of our team, of zonisamide suggests that zonisamide’s effects are similar to those of topiramate with fewer side effects, particularly cognitive effects. Cognitive processing therapy (CPT) was developed for the treatment of PTSD and currently, CPT is being rolled out nationally in a large dissemination project by VHA and the Department of Defense (DoD) as one of two gold standards for the treatment of PTSD. Our group has been developing an “Enhanced CPT-C (E-CPT-C)” a new standardized 12-week therapy that integrates CPT-C (cognitive therapy only version of CPT) with coping skills training for AD that can more effectively and simultaneously treat PTSD and AD. In piloting this new treatment, our group has developed a manual for its use and is rigorously testing its efficacy with standardized scales evaluating symptoms for PTSD (Clinician Administered PTSD Symptom Scale-CAPS) and alcohol consumption using the Time Line Follow-back Method, as well as mood ratings and quality of life data. The compatibility of E-CPT-C with medications to treat alcohol dependence is unknown. We propose to conduct a 12-week pilot study for the feasibility and efficacy of zonisamide (400mg) vs. placebo as an adjunct to E-CPT-C for Veterans with PTSD and comorbid AD. Participants (n=30) will be Veterans who meet DSM-IV diagnosis of PTSD and comorbid AD. Participants will be randomized (using a 3:1 ratio) to zonisamide 400mg or placebo for 12 weeks. Medication will be titrated upward to minimize side effects. Eligible participants will also be enrolled in E-CPT-C therapy. Assessments of alcohol use outcomes, symptoms of PTSD, and side effects will occur weekly. The study will evaluate efficacy, safety, tolerability and side effect profile including cognitive effect of zonisamide. Results from this trial will determine whether zonisamide warrants a larger clinical trial. If it is indicated, we have an ongoing collaboration with: (1) the Edith Nourse Rogers Memorial Veterans Hospital; and (2) have established a collaboration with Dr. Steve Batki at the University of California and San Francisco VA who has agreed to conduct a randomized trial in collaboration with the principle investigator. The study is in the participant recruitment stage.
Centralized Off-Site AdheRence Enhancement Program (CARE)
Contact: Marc Rosen, M.D. (Marc.Rosen@va.gov)
Individuals who use drugs or alcohol and do not adequately adhere to antiretroviral medication have sub-optimal outcomes, but effective interventions for them are lacking. We seek to develop and pilot an intervention program delivered by phone and supported by information technology that combines contingency management for medication adherence and a cognitive-behavioral approach to both adherence to antiretroviral therapy and abstinence from substances of abuse. The intervention, Centralized Off-Site AdheRence Enhancement Program (CARE), builds on the published finding that adherence was robustly improved and viral load was significantly reduced among individuals who received cash-reinforcement for opening MEMS-capped bottles to take prescribed medication on time. CARE involves transmission of bottle-opening data with real time operation from SimPill bottles to a website system which generates messages to participants indicating the amount of cash-reinforcement earned if medication is taken within a specified time window or forsaken if medication is missed. Reinforcement for medication-taking will be wired to debit cards that participants will be given to receive the payments. This contingent reinforcement of medication-taking will be coupled with 12 sessions of cognitive-behavioral therapy (CBT) conducted by phone and also assisted by the website which will generate CBT-related text messages, reminders, and scheduling information from a menu of choices negotiated by the participant and therapist. Development of CARE will proceed in 3 stages, with revisions of the intervention at each stage. First, the web system and therapy manuals will be developed. Second, 12 weeks of CARE will be pre-piloted in 10 participants with sub-optimal adherence and recent risky alcohol use and/or stimulant misuse. Qualitative and quantitative data will be collected concerning acceptability, usability, and perceived efficacy of components of CARE. Procedures and logistics will be evaluated and modified if necessary. Third, CARE will be pilot-tested in a 12-week randomized controlled trial in which the control arm only involves phone-based counseling focusing first on adherence and then on abstinence. Retention of effects will be examined during a 12-week follow-up period. CARE has the potential to be among the first interventions that: (1) delivers both reinforcement and counseling remotely; (2) improves outcomes among substance users without providing opioid substitution or other extremely intensive interventions; and (3) utilizes a cognitive-behavioral approach targeting both non-adherence and substance abuse. Because CARE is delivered by a therapist who is off-site from the participant's clinic, CARE can be effectively delivered from any distance and is a scalable treatment for individuals in whom medication adherence is crucial. This study is in the data analysis phase.
Publication: Moore, B.A., Rosen, M.I., Wange, Y., Shen, J., Ablondi, K., Sullivan, A., Guerrero, M., Siqueiros, L., Daar, E.S., Liu, H. (2015). A remotely-delivered CBT and contingency management therapy for substance using people with HIV. AIDS and Behavior, 19(Suppl 2), 156-162.
Dialectical Behavior Therapy Skills Group for Suicidal Veterans: Pilot
Contact: Suzanne Decker, Ph.D. (Suzanne.Decker@va.gov)
The overall goal of the study is to conduct a pilot clinical intervention study on a psychosocial skills training intervention, Dialectical Behavior Therapy Skills Training Group (DBT-SG), to reduce chronic suicidal ideation and improve social and emotional functioning among Veterans with psychiatric disorders. This goal will be accomplished through a structured training program on the conduct of clinical outcomes research, DBT-SG intervention fidelity rating, and manuscript and grant preparation. The training program will be coordinated by local mentors with expertise in clinical outcomes research and the DBT-SG intervention. The proposed CDA-1 pilot study will examine the feasibility, acceptability, and preliminary efficacy of DBT-SG, a group skills training intervention that has been associated with reductions in suicidal ideation and emotion dysregulation in individuals with chronic suicidal ideation. As an estimated 18 Veterans die by suicide per day, interventions to address chronic suicidal ideation are critically needed. While VA has several systems in place to manage acute suicidal ideation and risk, some Veterans demonstrate chronic suicidal ideation, placing them at elevated risk. These Veterans may not respond to short-term treatments or may not be eligible for existing evidence-based treatments at VA. Problems in emotion dysregulation and social functioning are strong predictors of suicidal ideation, therefore, skills-training interventions that can help Veterans improve their functioning in these areas are promising avenues for investigation and are consistent with VA’s emphasis on recovery. The DBT-SG intervention is a manualized component of a larger and more complex treatment, Dialectical Behavior Therapy, identified as a promising treatment for suicidal Veterans that has been associated with significant reductions in suicidality and improvement in social functioning in adults with multiple psychiatric disorders. The proposed pilot study would be the first to examine the more resource-efficient DBT-SG intervention as an adjunct to treatment as usual in for Veterans with chronic suicidal ideation, and is based on a clinical pilot conducted by the applicant at the proposed research site at VA Connecticut Healthcare System. For the proposed pilot study, 12 Veterans with chronic suicidal ideation will receive the DBT-SG intervention in addition to routine treatment as usual for chronically suicidal Veterans. The study’s primary aims are to determine feasibility and acceptability of this intervention in VA setting and to determine DBT-SG’s preliminary efficacy. Feasibility will be determined by subject participation and retention in treatment, and acceptable intervention fidelity as rated by the gold-standard DBT Adherence Rating Scale. Acceptability will be determined by positive satisfaction ratings provided by participating Veterans and their primary mental health providers. A preliminary estimate of DBT-SG efficacy to reduce suicidal ideation, decrease emotion dysregulation, and improve social functioning will be obtained through use of a multiple-baseline across-subjects design and weekly measures of these outcomes. This design strategy allows each subject to serve as his or her own control and is uniquely suited for examination of a pilot intervention. Exploratory aims for the proposed pilot study include examination of changes in Veteran suicidal behavior, effective coping, and psychiatric symptoms.
Effectiveness of Motivational Interviewing Supervision in Community Programs
Contact: Steve Martino, Ph.D. (Steve.Martino@va.gov)
The virtual requirement that substance abuse treatment programs use evidence-based treatments (EBTs) has prompted the development of dissemination strategies to promote EBT technology transfer. Implementation research, clinical trial training methods, and clinician training studies suggest that clinical supervision that involves direct observation, fidelity rating-based feedback, and coaching of therapeutic skills is a promising dissemination approach. However, clinical supervision delivered within substance abuse treatment programs by on-site supervisors has never been directly tested in a randomized controlled trial to determine the impact of supervision on both clinician EBT skills and client treatment outcomes. Recent results from two NIDA CTN protocols testing the effectiveness of motivational interviewing (MI) have shown that community program clinicians can learn to deliver MI with fidelity when receiving MI supervision from their program supervisors after workshop training. Also, their implementation of MI early in treatment improves client retention and primary substance use outcomes. A MI supervision manual entitled, Motivational Interviewing Assessment: Supervisory Tools for Enhancing Proficiency (MIA: STEP), was developed from these protocols and has begun to be widely distributed by NIDA in partnership with SAMHSA for community program use. The effectiveness of the MIA: STEP supervision approach is unknown. This study directly tested the effectiveness of MIA: STEP supervision on clinician MI fidelity and on client outcomes by randomly assigning 60 clinicians and 420 substance-using outpatients from 12 community programs within Connecticut to one of two conditions in which clinicians in both conditions delivered a one-session MI intervention to clients as they entered treatment. The conditions were: (1) workshop training plus MIA: STEP supervision; and (2) workshop training alone with no supervision beyond standard supervisory practices used at each program. This project was the first randomized trial to examine the impact of clinical supervision in an empirically based treatment on both clinician and client outcomes. Moreover, because it provided workshop training and supervision completely within the context of community programs and utilized in-house program supervisors, it will provide a rigorous evaluation of a feasible model for disseminating EBTs such as MI within the VA health care system. A manuscript regarding the findings of this project is in preparation.
Implementation of a Computer-based Cognitive Behavioral Therapy for Insomnia Among Veterans with Non-Psychotic Mental Health Disorders
Contact: Eric Hermes, M.D. (Eric.Hermes@va.gov)
Insomnia is very common in Veterans, especially among those with non-psychotic mental illnesses such as substance abuse, post-traumatic stress disorder, and depression. Insomnia is commonly treated with sedative-hypnotic medications which have significant side effects and costs. However, controlled trials of CBT treatments for insomnia (CBTi) have shown improved effectiveness and more enduring positive outcomes compared to pharmacotherapy. Computer-based versions of CBTi may increase accessibility, increase the quality of service delivery, and decrease medication costs. Congress has mandated that VHA, through the Veterans’ Mental Health and Other Care Improvements Act of 2008, increase the implementation of computer-based therapies. However, there have been no systematic studies of the acceptability or implementation of computer-based treatment for insomnia among Veterans. Computer-based therapy for insomnia is an entirely new treatment option for VA, targeting a mental health problem that is very common and for which the current treatment paradigm comes with significant risks. In spite of the recent development and initial implementation of computer-based treatments for other mental health disorders among Veterans, their outcomes have yet to be systematically evaluated. Veterans may benefit from improved sleep and reduced severity of their primary psychiatric disorders as well as a decrease in the amount of sedative-hypnotics used. Support techniques and best practices developed will apply to computer-based treatments across the VISN 1 and VA as a whole and will form the basis for further evaluation through a controlled trial. Recruitment and Veteran participation in the study are now complete. Data analysis is ongoing.
Improving Functional Outcomes of Veterans with PTSD and Tobacco Dependence
Contact: Megan M. Kelly, Ph.D. (Megan.Kelly1@va.gov)
Mindfulness and acceptance-based smoking cessation treatments are ideal for individuals with PTSD because of their success at reducing anxiety, reducing nicotine withdrawal severity, and improving smoking cessation outcomes by enhancing relapse prevention. The primary aim of this study is to evaluate Acceptance and Commitment Therapy for Veterans with PTSD and Tobacco Addiction (ACT-PT). This treatment will specifically target elevated anxiety sensitivity and distress intolerance associated with quit attempts in Veterans with PTSD. The primary research objective of this study is to evaluate a novel ACT smoking cessation treatment for Veterans with PTSD (ACT-PT). This proposed research project involves the evaluation of ACT-PT using a randomized controlled pilot study. Therapeutic progress will be broadly assessed with measures of tobacco use, smoking urges, mood, quality of life, and other measures. Fifty participants will be randomly assigned to ACT-PT and the nicotine patch (n=25) or a standard smoking cessation treatment, Freedom from Smoking (FFS) and the nicotine patch (n=25). We will evaluate the feasibility and acceptability of ACT-PT compared to FFS. The preliminary efficacy of ACT-PT will also be explored. We will conduct a randomized controlled pilot study comparing ACT-PT to a standard smoking cessation treatment, Freedom from Smoking (FFS) and the nicotine patch in Veteran smokers with PTSD (n=50). The pilot study will assess the feasibility, acceptability, and preliminary efficacy of the newly designed intervention. Participants in the ACT-PT condition will receive 10 50-minute sessions and 8 weeks of nicotine patch. Participants randomized to FFS will receive 10 50-minute sessions and 8 weeks of nicotine patch. We will examine the effects of ACT-PT on smoking cessation outcomes, PTSD, depression, and quality of life. We expect that participants treated with ACT-PT will have significantly higher rates of abstinence than participants in FFS. It is also expected that participants treated with ACT-PT will have significantly greater improvement in PTSD symptoms and quality of life than participants in FFS.
Publication: Kelly, M.M., Sido, H., Forsyth, J.P., Ziedonis, D., Kalman, D., & Cooney, J.L. (2015). A pilot feasibility study of an Acceptance and Commitment Therapy smoking cessation treatment for Veterans with posttraumatic stress disorder. Journal of Dual Diagnosis, 11, 50-55.
In-Home Messaging Device to Deliver Combined Behavioral Substance Abuse Treatments to Veterans
Contact: Steve Martino, Ph.D. (Steve.Martino@va.gov)
This study evaluated the feasibility and efficacy of providing post-hospital follow-up care for Veterans with alcohol dependence using an in-home messaging device (IHMD) to provide automated monitoring and brief daily automated counseling experiences. VA has invested heavily in IHMDs for medical conditions requiring frequent monitoring, following evidence of improved health outcomes among Veterans with diabetes and those with chronic heart failure, thereby reducing the number of hospital admissions in both groups. Overall, Veterans report that IHMD interventions are highly reliable, easy to understand and use, and improve communication with their health care providers. However, the efficacy of IHMDs for substance abuse treatment has not been tested in randomized controlled trials. Dr. Martino and Dr. Elizabeth Santa Ana, a former MIRECC Fellow, have written 28 substance abuse treatment dialogues adapted from material used within the Combined Behavioral Intervention manual used in Project COMBINE. Dialogues assess drug and alcohol use on a daily basis and include interventions based on motivational interviewing, cognitive behavioral therapy, and twelve-step facilitation strategies. We conducted a pilot study that evaluated the feasibility and efficacy of the 28-day IHMD substance abuse treatment dialogues. Data collection for this project is complete and data analysis is ongoing. A manuscript regarding the findings is in preparation. One paper describing the development and initial acceptability of the IHMD has been published.
Publication: Santa Ana, E.J., Stallings, D.L., Rounsaville, B.J., & Martino, S. (2013). Development of an in-home telehealth program for outpatient Veterans with substance use disorders. Psychological Services, 10, 304-314.
Progressive Goal Attainment Program for Veterans
Contact: Jack Tsai, Ph.D. (Jack.Tsai2@va.gov)
This is a pilot study of a new 10-week behavioral intervention called the Progressive Goal Attainment Program (PGAP) which has been found to be effective in vocational rehabilitation for disabled adults, but it has not tested on the Veteran population. Together with MDRC, the sponsor and partner research institution, and the Michael E. DeBakey VA Medical Center, this study will determine whether PGAP is feasible and effective in helping homeless Veterans with disabilities seek and find jobs. A two-site randomized controlled trial will be conducted with approximately 200 homeless Veterans referred by VA psychosocial rehabilitation services over one year. Participants will be randomized to either PGAP or regular VA vocational rehabilitation services. Data on job-seeking behaviors, employment, mental health, and social integration will be collected at baseline, 4 weeks into the program, 10 weeks at program completion, and at 6-month follow-up. Mixed linear regression models will be used to examine outcomes between groups. Qualitative interviews will also be conducted with participants and clinicians to understand their experiences with PGAP. VA psychosocial programs will refer Veterans interested in obtaining vocational rehabilitation services. After obtaining informed consent, the Veterans will then be randomly assigned to PGAP or regular VA vocational services. A sample size of approximately 50 participants each in the PGAP and control group is expected at each site. PGAP is a manualized intervention that involves clients meeting with a PGAP coach weekly to plan and schedule activities towards employment. The main outcomes assessed will be engagement in job-related activities and subjective measures of mental health and social integration.
Collaborators: MDRC and Anthony Kerrigan, Ph.D. (Michael E. DeBakey VA Medical Center)
Project Start: Screening to Augment Referral to Treatment
Contact: Steve Martino, Ph.D. (Steve.Martino@va.gov)
Substance abuse, and the general medical consequences of use, are associated with high costs to both individuals and society. Unfortunately, less than one-third of individuals who are drug dependent and 6% of those who abuse drugs ever receive treatment. Such discouraging statistics illustrate the need for new strategies to identify and provide treatment interventions for individuals with substance use disorders. General medical settings have the advantage of reaching large numbers of individuals. In these settings, standardized screening, brief interventions, and referral to treatment (SBIRT) approaches have led to modest reductions in alcohol and tobacco use. However, it is not clear whether SBIRT: (1) leads to reductions in other drugs of abuse; and (2) increases attendance to specialty substance abuse treatment. Experts believe that the situation regarding treatment is worse for women than for men. The preferred and predominant primary care setting among women is a reproductive health setting. In the spirit of a primary care approach, the American College of Obstetricians and Gynecologists recommends SBIRT to determine if women abuse substances and help them reduce or stop their use. However, there have been no studies to date that examine the effectiveness of SBIRT for substances (other than alcohol or tobacco) in a reproductive health setting. Moreover, it not clear how these interventions should be delivered (nurse-led vs. computer-assisted) to make them most acceptable to individuals and feasible to deliver. Health screening and promotion are hallmarks of nursing care and fully consistent with SBIRT. However, nurses often have limited time in which to address the range of medical, gynecological, and obstetrical patient care issues and must be trained to deliver SBIRT. Advances in technology and the increased acceptance of computerized interventions constitute a possible solution to these barriers. SBIRT, delivered either by nurse or computer, would be a strong addition to a primary care clinician’s therapeutic armamentarium for substance abusers, but the utility, efficacy, and cost effectiveness of these alternative approaches need to be tested against usual care. We are using obstetric-gynecological clinics to conduct a randomized clinical trial that compares two SBIRTS, delivered either by a trained nurse or by computer, to usual care. As part of this trial, we are including outcomes that allow us to assess the cost effectiveness of these three conditions. Our primary aims are to assess whether SBIRT, based upon motivational interviewing and delivered either by computer or a trained nurse, leads to decreased use of a participant’s primary drug of abuse and promotes substance abuse treatment utilization for the primary drug of abuse. In addition, we will compare the relative cost-effectiveness of the three interventions. Enrollment was completed with 450 randomized client participants, 71 randomized clinician participants, and 22 supervisors, all from 11 community substance abuse treatment programs. We completed data collection and are currently in the data analysis phase.
Supported Employment: Motivational Enhancement for Entry and Outcome
Contact: Lisa Mueller, Ph.D. (Lisa.Mueller@va.gov)
This 3-year project tested the impact of an intervention aimed at improving entry in VA supported employment (SE) and competitive employment outcomes for Veterans with serious mental illnesses. We investigated the effect of a 6-session motivational interviewing intervention for Veterans and their significant others on SE utilization, SE participation, and employment outcomes as well as the factors related to these outcomes according to the health belief model. Veterans from the Edith Nourse Rogers Memorial Veterans Hospital who were eligible for supported employment but not enrolled in the program completed a baseline evaluation and then received information about VA vocational services. Participants were randomly assigned to adapted motivational interviewing for supported employment (AMI-SE) or a control condition where participants received basic support and education about VA and non-VA psychiatric rehabilitation and recovery services. The results of this project will provide VA policymakers, VA investigators, and non-VA vocational rehabilitation specialists with findings and recommendations regarding: (a) the utility of an extended motivational interviewing protocol for Veterans and their significant others; and (b) topic areas for the development of additional strategies to improve access and outcomes in SE. If effective, the AMI-SE protocol could be provided by clinicians or case managers of Veterans with serious mental illnesses to increase rates of entry in SE as well as rates of competitive employment. A total of 2440 Veterans were screened, 382 were eligible, and 238 of those eligible were offered to participate in the study through study staff or one of their VA providers. Ninety-one participants completed a baseline assessment. Study recruitment and data collection are complete. Findings: Data analysis is ongoing. Preliminary analyses conducted on the 81 participants who completed at least one session with research staff (42 randomized to intervention and 39 to control) indicate that those in the MI condition were significantly more likely to enter SE (38%) than participants in the control condition (5%), (chi-square = 12.72, p<.001). Collaborators: Robert Rosenheck, M.D. and Sandra Resnick, Ph.D. (VISN 1 New England MIRECC); Lori Davis, M.D. (Tuscaloosa VAMC); Gary Rose, Ph.D.; and Shirley Glynn, Ph.D. (VA Greater Los Angeles Healthcare System—West LA Campus).
Three Strategies for Implementing Motivational Interviewing on Medical Inpatient Units: See One, Do One, Order One
Contact: Steve Martino, Ph.D. (Steve.Martino@va.gov)
General medical hospitals provide care for a disproportionate share of patients who abuse or are dependent upon substances. This group is among the most costly to treat and has the poorest medical and substance use outcomes. Hospitalization provides a unique opportunity to identify and motivate patients to address their substance use problems in that the patients are: (1) accessible; (2) have time for an intervention; and (3) are often admitted for complications related to substance use that renders hospitalization a “teachable moment.” We propose to conduct a randomized controlled trial using quantitative and qualitative methods in order to examine the effectiveness of three different strategies for integrating motivational interviewing (MI) into the practice of physician assistants (PAs) working within Yale-New Haven Hospital’s general medical hospitalist service. Specifically, we will randomize 30 PAs to one of three conditions: (1) a continuing medical education workshop that provides background and “shows” PAs how to conduct MI (the control condition, called SEE ONE); (2) a “see one, do one” apprenticeship model involving workshop training plus live supervision of bedside practice (DO ONE); and (3) ordering MI from CL after learning about it in a workshop (ORDER ONE). Following the respective MI trainings, each PA will be assessed for the provision of MI to 40 study-eligible inpatients, recruited by the research team after admission to our general medical units. The primary aims of the study are to assess: (1) the uptake of MI by PAs; (2) the integrity of MI when PAs use it on the medical units; and (3) the relative costs and cost-effectiveness of the three different implementation strategies. Qualitative assessment of implementation facilitators and barriers will also be evaluated in this study. The results of this study have implications for training VA medical staff in MI who frequently work with Veterans that have substance use disorders. Participant recruitment is ongoing for both patients and medical care providers.
Transitional and Supported Employment Interventions for Veterans with Non-Psychotic Comorbid Disorders
Contacts: Charles Drebing, Ph.D. (Charles.Drebing@va.gov)
This project will investigate whether the outcomes of either of two common VA vocational rehabilitation services, transitional employment (TE) services or supported employment (SE) services, can be enhanced by integrating them into a single intervention. Using an equipoise stratified random assignment approach, Veterans entering VA vocational rehabilitation services are assigned to one of three conditions: TE alone; SE alone; or TE integrated with SE. Participants are followed for 24 months to document the treatment outcome in terms of employment and broader clinical outcomes. A total of 200 Veterans will be recruited from Veterans entering VA vocational rehabilitation services. Participants must have a dual diagnosis and a vocational problem. The interventions consist of two existing VA vocational rehabilitation services (TE and SE) as well as a new intervention consisting of an integrated form of TE and SE. Employment rates for the three interventions is the primary outcome, with Veterans’ preference and willingness to accept the various services as a key secondary outcome. At completion, the results of this project will provide VA policymakers, VA investigators, and non-VA vocational rehabilitation specialists with findings and recommendations regarding: (a) Veterans’ preference and acceptance for TE vs. SE; and (b) the relative efficacy of an integrated form of TE and SE compared to either TE or SE alone. The results will provide evidence to guide how VA uses the two existing vocational rehabilitation models to achieve better clinical and employment outcomes. The study is the recruitment and data collection stage.
Web-Delivered Acceptance & Commitment Therapy for Smokers with Bipolar Disorder
Contact: Megan M. Kelly, Ph.D. (Megan.Kelly1@va.gov)
Up to 70% of adults with bipolar disorder smoke, compared with only 20% of the general population. Quit rates for smokers with bipolar disorder are less than half that of smokers without psychiatric disorders (17% vs. 43%). Key barriers to improving quit rates in this group are: (1) the belief that smoking helps to manage psychiatric symptoms, which is reported by 50% of smokers with bipolar disorder and is not addressed in standard cessation counseling, and (2) limited access to tobacco treatment within the mental health care system. New treatment approaches are greatly needed to address both of these barriers. Web-based Acceptance and Commitment Therapy (ACT) is a new model of smoking cessation treatment that more than doubled quit rates compared to the current standard for web-based treatments, the U.S. government’s Smokefree.gov site (23% vs. 10%). Adding nicotine replacement therapy (NRT), an effective and accessible pharmacotherapy, and targeting this intervention to address the major barriers to quitting for smokers with bipolar disorder could significantly improve the extremely low quit rates. This project involves development and pilot testing of a targeted, web-based ACT intervention for smokers with bipolar disorder (WebQuit Plus). The study will be conducted in two phases. The first phase will consist of intervention development and website usability testing (n=12). The second phase will be a pilot randomized, controlled trial at three sites within the National Network of Depression Centers (NNDC), comparing WebQuit Plus (n=30) to Smokefree.gov (n=30). Both interventions will be delivered in combination with the nicotine patch. A primary aim of the study is to determine feasible procedures for conducting a larger, multi-site efficacy trial within the NNDC, with primary feasibility targets of enrolling an average of 2 participants per month at each site and retaining at least 70% of participants through the 1-month post-treatment follow-up, with similar retention in each treatment group. Another primary aim is to compare WebQuit Plus to Smokefree.gov on treatment satisfaction and utilization, ACT’s theory-based mechanism of change (i.e., acceptance of smoking triggers), smoking cessation outcomes, and bipolar disorder symptoms at the end of the 10-week treatment period and at 1-month post-treatment follow-up. This intervention development study is significant and innovative in two key respects: (1) it applies a promising new treatment with a novel mechanism of action for smoking cessation (i.e., acceptance of psychiatric symptom-related smoking triggers) to the problem of low quit rates among smokers with bipolar disorder; and (2) the intervention is web-based, making it potentially cost-effective and easily disseminated to mental health care settings. If found to be effective in the larger trial that would be informed by this pilot trial, WebQuit Plus could have an immediate, positive impact on the low quit rates and high prevalence of smoking in adults with bipolar disorder.