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ABSTRACT: BACKGROUND: The ability to predict potential for relapse to substance use following treatment could be very useful in targeting aftercare strategies. Recently, a number of investigators have focused on using neural activity measured by fMRI to predict relapse propensity. The purpose of the present study was to use fMRI to investigate prospective associations between brain reactivity to cocaine and response inhibition cues and relapse to cocaine use. METHODS: Thirty cocaine-dependent participants with clean cocaine urine drug screens (UDS) completed a baseline fMRI scan, including a cocaine-cue reactivity task and a go no-go response inhibition task. After participating in a brief clinical trial of d-cycloserine for the facilitation of cocaine-cue extinction, they returned for a one-week follow-up UDS. Associations between baseline activation to cocaine and inhibition cues and relapse to cocaine use were explored. RESULTS: Positive cocaine UDS was significantly associated with cocaine-cue activation in the right putamen and insula, as well as bilateral occipital regions. Associations between positive cocaine UDS and activation to no-go cues were concentrated in the postcentral gyri, a region involved in response execution. CONCLUSIONS: Although preliminary, these results suggest that brain imaging may be a useful tool for predicting risk for relapse in cocaine-dependent individuals. Further, larger-scale naturalistic studies are needed to corroborate and extend these findings.
Drug and alcohol dependence 05/2013; · 3.60 Impact Factor
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ABSTRACT: BACKGROUND: The development of addiction is marked by a pathological associative learning process that imbues incentive salience to stimuli associated with drug use. Recent efforts to treat addiction have targeted this learning process using cue exposure therapy augmented with d-cycloserine (DCS), a glutamatergic agent hypothesized to enhance extinction learning. To better understand the impact of DCS-facilitated extinction on neural reactivity to drug cues, the present study reports fMRI findings from a randomized, double-blind, placebo-controlled trial of DCS-facilitated cue exposure for cocaine dependence. METHODS: Twenty-five participants completed two MRI sessions (before and after intervention), with a cocaine-cue reactivity fMRI task. The intervention consisted of 50mg of DCS or placebo, combined with two sessions of cocaine cue exposure and skills training. RESULTS: Participants demonstrated cocaine cue activation in a variety of brain regions at baseline. From the pre- to post-study scan, participants experienced decreased activation to cues in a number of regions (e.g., accumbens, caudate, frontal poles). Unexpectedly, placebo participants experienced decreases in activation to cues in the left angular and middle temporal gyri and the lateral occipital cortex, while DCS participants did not. CONCLUSIONS: Three trials of DCS-facilitated cue exposure therapy for cocaine dependence have found that DCS either increases or does not significantly impact response to cocaine cues. The present study adds to this literature by demonstrating that DCS may prevent extinction to cocaine cues in temporal and occipital brain regions. Although consistent with past research, results from the present study should be considered preliminary until replicated in larger samples.
Drug and alcohol dependence 03/2013; · 3.60 Impact Factor
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ABSTRACT: RATIONALE: Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism. OBJECTIVES: This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy. METHODS: Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task. RESULTS: There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking. CONCLUSIONS: These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.
Psychopharmacology 02/2013; · 4.08 Impact Factor
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ABSTRACT: Posttraumatic stess disorder (PTSD) is associated with functional impairment, co-occurring diagnoses, and increased health care utilization. Associated high demand for health care services is an important contributor to the large public-health cost of PTSD. Treatments incorporating exposure therapy are efficacious in ameliorating or eliminating PTSD symptoms. Accordingly, the Veterans Health Administration has made significant investments toward nationwide dissemination of a manualized exposure therapy protocol, prolonged exposure (PE). PE is effective with veterans; however, the relationship between PE and mental health service utilization is unknown. The current study investigates PE as it relates to actual tracked mental health service utilization in an urban VA medical center. A sample of 60 veterans with a diagnosis of PTSD was used to examine mental health service utilization in the 12-months prior to and 12-months after being offered PE. Hierarchical Linear Models and traditional repeated-measures ANOVA were used to estimate R2- and d-type effect sizes for service utilization. Associated estimated cost saving are reported. PE was associated with large reductions in symptoms and diagnosis remission. Treatment was also associated with statistically significant, large reductions in mental health service utilization for veterans who completed treatment. Findings suggest that expanding access to PE can increase access to mental health services in general by decreasing ongoing demand for specialty care clinical services. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
Psychological Services 11/2012; · 1.08 Impact Factor
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ABSTRACT: Abstract Introduction: Many veterans live in rural areas distant from Veterans Affairs Medical Centers (VAMCs) and receive primary medical care from community-based outpatient clinics (CBOCs). These veterans often must travel great distances to the nearest VAMC for neuropsychological evaluations, resulting in poor access to care, travel reimbursement costs, fee-basis evaluations of uncontrolled quality, and driving safety concerns. Return trips for feedback compound complications. Accordingly, we initiated a pilot trial of neuropsychological evaluation and feedback via telemedicine (i.e., clinical videoconferencing). Subjects and Methods: Participants were veterans referred for neuropsychological evaluation from a rural CBOC 115 miles from the regional VAMC. All veterans were given the choice to undergo evaluation at the CBOC via telemedicine or in-person at the VAMC. Telemedicine equipment allowed presentation of digitized material with simultaneous patient observation. Testing materials were organized in numbered folders and given to veterans by CBOC clerks immediately prior to evaluation. Clerks returned completed materials via facsimile. Results: Fifteen veterans from the rural CBOC were seen for neuropsychological evaluation. Eight chose telemedicine evaluation. Groups based on evaluation modality appeared similar on demographics, referral basis, resulting neuropsychiatric diagnoses, and follow-through on recommendations. No significant technical or clinical difficulties were encountered, and veterans reported satisfaction with telemedicine. All veterans requested feedback via telemedicine. Conclusions: Neuropsychological evaluation via telemedicine is feasible and appears comparable to in-person evaluation. Experiences are encouraging and consistent with the broader literature on the acceptance of and satisfaction with clinical videoconferencing. Future studies will assess possible psychometric issues in clinical populations.
Telemedicine and e-Health 10/2012; · 1.42 Impact Factor
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ABSTRACT: Variation at a single nucleotide polymorphism in the μ-opioid receptor gene (OPRM1), A118G (Asn40Asp), may moderate naltrexone (NTX) effects in alcohol dependence. Both NTX and A118G variation have also been reported to affect alcohol cue-elicited brain activation. This study investigated whether sub-acute NTX treatment and A118G genotype interacted in their effects on cue-elicited activation of the ventral striatum (VS), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). Secondarily, variation at a variable number tandem repeat polymorphism in the dopamine transporter gene (DAT1/SLC6A3), which has been associated with increased reward-related activation in VS, was analyzed as a moderator of medication and A118G effects. Seventy-four non-treatment-seeking alcohol-dependent individuals, half preselected to carry at least one copy of the A118G G (Asp) allele, were randomized to NTX (50 mg) or placebo for 7 days, and performed an fMRI alcohol cue reactivity task on day 6. Region-of-interest analyses indicated no main effects of medication or A118G genotype. However, these factors interacted in their effects on OFC activation, such that, among NTX-treated individuals, G-allele carriers had less activation than A-allele homozygotes. DAT1 variation also moderated medication/A118G effects. There was a three-way interaction between medication and A118G and DAT1 genotypes on VS activation, such that, among G-allele carriers who received NTX, DAT1 10-repeat-allele (10R) homozygotes had less activation than 9-repeat-allele (9R) carriers. Further, 10R homozygotes who received NTX had less mPFC activation than 9R carriers. Polymorphic variation in OPRM1 and DAT1 should be considered in future studies of NTX, particularly regarding its effects on reward processing.Neuropsychopharmacology advance online publication, 3 October 2012; doi:10.1038/npp.2012.195.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2012; · 6.99 Impact Factor
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ABSTRACT: This study examined the impact of a computer simulation designed to provide the opportunity for individuals with alcohol use disorders (AUDs) to practice relapse prevention skills. Participants were 41 male veterans enrolled in an intensive outpatient substance abuse treatment program. Participants were randomly assigned to either view educational slides about treatment for AUD or play a simulation videogame for eight sessions within 12weeks. Participants were assessed at a 4-week follow-up visit. Outcome measures included relapse rates as well as ratings on the Obsessive Compulsive Drinking Scale (OCDS) and a custom-designed relapse prevention self efficacy scale. While rates of relapse did not differ between groups, those who played the game showed overall reductions in ratings on the OCDS, as well as higher ratings of self-efficacy at week 8, suggesting that the videogame simulation may be a useful adjunct to AUD treatment.
Journal of substance abuse treatment 09/2012; · 2.90 Impact Factor
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ABSTRACT: A comprehensive understanding of the neurobiology of alcohol cue reactivity is critical in identifying the neuropathology of alcohol use disorders (AUD) and developing treatments that may attenuate alcohol craving and reduce relapse risk. Functional neuroimaging studies have identified many brain areas in which alcohol cues elicit activation. However, extant studies have included relatively small numbers of cases, with AUD of varying severity, and have employed many different cue paradigms. We used activation likelihood estimation, a quantitative, coordinate-based meta-analytic method, to analyze the brain areas activated by alcohol-related cues across studies, and to examine whether these areas were differentially activated between cases and controls. Secondarily, we reviewed correlations between behavioral measures and cue-elicited activation, as well as treatment effects on such activation. Data analyzed were from 28 studies of 679 cases and 174 controls. Among cases, alcohol cues elicited robust activation of limbic and prefrontal regions, including ventral striatum, anterior cingulate and ventromedial prefrontal cortex. As compared to controls, cases demonstrated greater activation of parietal and temporal regions, including posterior cingulate, precuneus and superior temporal gyrus. Cue-elicited activation of ventral striatum was most frequently correlated with behavioral measures and most frequently reduced by treatment, but these results were often derived from region-of-interest analyses that interrogated only limbic regions. These findings support long-standing theories of mesolimbic involvement in alcohol cue processing, but suggest that cue-elicited activation of other brain areas may more clearly differentiate cases from controls. Prevention and treatment for AUD should consider interventions that may reduce cue-elicited activation of these areas.
Addiction Biology 05/2012; · 4.83 Impact Factor
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ABSTRACT: BACKGROUND: Naltrexone is moderately effective for the treatment of alcohol dependence, but there is great individual variability. The opioid receptor (OPRM1) single nucleotide polymorphism (SNP) asn40asp has been shown to alter alcohol and naltrexone response in animals and humans. In addition, the brain opioid and dopamine systems interact and might underlie drinking and craving. This study investigated the effects of the OPRM1 SNP and dopamine transporter (DAT) variable number of tandem repeat (VNTR) genetic differences on drinking, alcohol effects, and naltrexone response under controlled conditions in nontreatment-seeking alcoholics. METHODS: Two hundred and sixty-five nontreatment-seeking individuals with alcohol dependence were genotyped a priori for the OPRM1 asn40asp SNP and post hoc for DAT (SLC6A3) 9 and 10 VNTRs. Asp40 carriers (n = 43) and matched asn40 homozygotes (n = 40) were randomized to naltrexone or placebo for 7 days before receiving a priming drink and limited-access alcohol consumption in a bar-lab setting. Effects of genotypes on natural drinking as well as drinking, alcohol effects, and response to naltrexone in the bar-lab setting were examined by genotype. RESULTS: There were no significant main effects of naltrexone or OPRM1 genotype, or any medication by OPRM1 interaction, on drinking variables. However, in individuals who had at least one DAT 9 VNTR, and who were also OPRM1 asn40 homozygotes, naltrexone reduced drinks/d consumed under natural conditions (p = 0.006), but not in the bar-lab. OPRM1 asn40 homozygotes (p = 0.028) and DAT 9 VNTR carriers (p = 0.032) had more stimulation to alcohol after the priming drink. CONCLUSIONS: This study does not support a salient role for the OPRM1 asp40 alone in predicting drinking or naltrexone effects. However, although exploratory and in need of replication, it introduces the possibility that epistasis between the OPRM1 gene and DAT gene might need to be taken into account when examining differential genetic response to alcohol or medication treatment, especially in early-stage alcoholics.
Alcoholism Clinical and Experimental Research 05/2012; · 3.34 Impact Factor
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ABSTRACT: Divalproex, a GABA agonist, may be a useful agent in the treatment of tobacco dependence. Cue reactivity assessment paradigms are ideally suited to explore basic mechanisms underlying the pharmacological effects of medications that purport to have efficacy for smoking cessation. Our primary goal in the current study was to examine the effects of divalproex on in-treatment reactivity to smoking-relevant and affective cues, and to determine if these reactions were predictive of posttreatment smoking behavior. There were 120 nicotine dependent smokers enrolled in an 8-week double-blind clinical trial and randomly assigned to either divalproex or placebo conditions. Of these, 72 smokers (60% female) who achieved a minimal level of abstinence underwent an in-treatment cue reactivity assessment. Contrary to expectations, divalproex was associated with greater craving and arousal during smoking cue presentation. Divalproex also inhibited cardiovascular response to pleasant cues. Although no significant differences in cessation-related outcomes between divalproex- and placebo-treated participants were observed, cue-elicited craving to smoke predicted end-of-treatment and posttreatment smoking rates. These findings suggest that in-treatment cue reactivity assessment may proactively and dynamically inform ongoing treatment as well as provide a tool for screening potential medications for smoking cessation.
Experimental and Clinical Psychopharmacology 04/2012; 20(4):293-301. · 2.58 Impact Factor
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ABSTRACT: Motivation to change is believed to be a key factor in therapeutic success in substance use disorders; however, the neurobiological mechanisms through which motivation to change impacts decreased substance use remain unclear. Existing research is conflicting, with some investigations supporting decreased and others reporting increased frontal activation to drug cues in individuals seeking treatment for substance use disorders. The present study investigated the relationship between motivation to change cocaine use and cue-elicited brain activity in cocaine-dependent individuals using two conceptualizations of 'motivation to change': (1) current treatment status (i.e. currently receiving versus not receiving outpatient treatment for cocaine dependence) and (2) self-reported motivation to change substance use, using the Stages of Change Readiness and Treatment Eagerness Scale. Thirty-eight cocaine-dependent individuals (14 currently in treatment) completed a diagnostic assessment and an fMRI cocaine cue-reactivity task. Whole-brain analyses demonstrated that both treatment-seeking and motivated participants had lower activation to cocaine cues in a wide variety of brain regions in the frontal, occipital, temporal and cingulate cortices relative to non-treatment-seeking and less motivated participants. Future research is needed to explain the mechanism by which treatment and/or motivation impacts neural cue reactivity, as such work could potentially aid in the development of more effective therapeutic techniques for substance-dependent patients.
Addiction Biology 03/2012; · 4.83 Impact Factor
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ABSTRACT: There is significant support for exposure therapy as an effective treatment for posttraumatic stress disorder (PTSD) across a variety of populations, including veterans; however, there is little empirical information regarding how veterans of different war theaters respond to exposure therapy. Accordingly, questions remain regarding therapy effectiveness for treatment of PTSD for veterans of different eras. Such questions have important implications for the dissemination of evidence based treatments, treatment development, and policy. The current study compared treatment outcomes across 112 veterans of the Vietnam War, the first Persian Gulf War, and the wars in Afghanistan and Iraq. All subjects were diagnosed with PTSD and enrolled in prolonged exposure (PE) treatment. Veterans from all three groups showed significant improvement in PTSD symptoms, with veterans from Vietnam and Afghanistan/Iraq responding similarly to treatment. Persian Gulf veterans did not respond to treatment at the same rate or to the same degree as veterans from the other two eras. Questions and issues regarding the effectiveness of evidence based treatment for veterans from different eras are discussed.
Psychological Services 02/2012; 9(1):16-25. · 1.08 Impact Factor
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ABSTRACT: Craving is a significant factor which can lead to relapse during smoking quit attempts. Attempts to resist urges to smoke during cue-elicited craving have been shown to activate regions in the brain associated with decision-making, anxiety regulation and visual processing. In this study, 32 treatment-seeking, nicotine-dependent smokers viewed blocks of smoking and neutral cues alternating with rest periods during magnetic resonance imaging scanning in a 3T Siemens scanner (Siemens AG, Erlangen, Bavaria, Germany). While viewing cues or control images, participants were instructed either to 'allow yourself to crave' or 'resist craving.' Data were analyzed with FSL 4.1.5, focused on the smoking cues versus neutral cues contrast, using cluster thresholding (Z > 2.3 and corrected cluster threshold of P = 0.05) at the individual and group levels. During the Crave condition, activation was seen on the left anterior cingulated cortex (LACC), medial prefrontal cortex, left middle cingulate gyrus, bilateral posterior cingulated gyrus and bilateral precuneus, areas associated with attention, decision-making and episodic memory. The LACC and areas of the prefrontal cortex associated with higher executive functioning were activated during the Resist condition. No clear distinctions between group crave and resist analyses as a whole were seen without taking into account specific strategies used to resist the urge to smoke, supporting the idea that craving is associated with some degree of resisting the urge to smoke, and trying to resist is almost always accompanied by some degree of craving. Different strategies for resisting, such as distraction, activated different regions. Understanding the underlying neurobiology of resisting craving to smoke may identify new foci for treatments.
Addiction Biology 07/2011; 16(4):654-66. · 4.83 Impact Factor
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ABSTRACT: Background: Among some alcohol-dependent individuals, early alcohol abstinence is marked by alcohol withdrawal (AW), a phenomenon mediated by GABA and glutamate signaling. We previously reported that a combination of 2 medications that affect GABA and glutamate tone, gabapentin and flumazenil, more effectively reduced drinking among individuals with higher pretreatment AW (Anton et al., 2009). This study evaluated whether this finding is related to changes in neurocognitive performance, which is also affected by cortical GABA and glutamate tone.Methods: Neurocognitive performance was assessed at baseline and twice during the first week of treatment among 60 alcohol-dependent participants in the previously published clinical trial.Results: AW was associated with poorer baseline performance on 4 of 8 measures, and individuals with higher baseline AW who received the gabapentin and flumazenil combination demonstrated greater improvement on a measure of response inhibition than those with lower AW or those who received a combination of placebos. Improvement in response inhibition during the first week and medication group interacted in their effect on subsequent drinking, such that improvement predicted greater abstinence only among individuals who received gabapentin and flumazenil. Improvement on other neurocognitive measures was neither differentially impacted by medication or baseline AW nor related to subsequent drinking.Conclusions: Taken together, these data suggest that acute AW accounts for a small proportion of variance in neurocognitive performance, that gabapentin and flumazenil slightly improve response inhibition during early abstinence, and that such improvement may somewhat reduce later drinking. However, these medications may not affect other neurocognitive domains.
Alcoholism Clinical and Experimental Research 05/2011; 35(11):2030 - 2038. · 3.34 Impact Factor
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ABSTRACT: Naltrexone, an efficacious medication for alcohol dependence, does not work for everyone. Symptoms such as insomnia and mood instability that are most evident during early abstinence might respond better to a different pharmacotherapy. Gabapentin may reduce these symptoms and help prevent early relapse. This clinical trial evaluated whether the combination of naltrexone and gabapentin was better than naltrexone alone and/or placebo during the early drinking cessation phase (first 6 weeks), and if so, whether this effect persisted.
A total of 150 alcohol-dependent individuals were randomly assigned to a 16-week course of naltrexone alone (50 mg/day [N=50]), naltrexone (50 mg/day) with gabapentin (up to 1,200 mg/day [N=50]) added for the first 6 weeks, or double placebo (N=50). All participants received medical management.
During the first 6 weeks, the naltrexone-gabapentin group had a longer interval to heavy drinking than the naltrexone-alone group, which had an interval similar to that of the placebo group; had fewer heavy drinking days than the naltrexone-alone group, which in turn had more than the placebo group; and had fewer drinks per drinking day than the naltrexone-alone group and the placebo group. These differences faded over the remaining weeks of the study. Poor sleep was associated with more drinking in the naltrexone-alone group but not in the naltrexone-gabapentin group, while a history of alcohol withdrawal was associated with better response in the naltrexone-gabapentin group.
The addition of gabapentin to naltrexone improved drinking outcomes over naltrexone alone during the first 6 weeks after cessation of drinking. This effect did not endure after gabapentin was discontinued.
American Journal of Psychiatry 03/2011; 168(7):709-17. · 12.54 Impact Factor
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ABSTRACT: In functional magnetic resonance imaging (fMRI) studies of alcohol-dependent individuals, alcohol cues elicit activation of the ventral and dorsal aspects of the striatum (VS and DS), which are believed to underlie aspects of reward learning critical to the initiation and maintenance of alcohol dependence. Cue-elicited striatal activation may represent a biological substrate through which treatment efficacy may be measured. However, to be useful for this purpose, VS or DS activation must first demonstrate stability across time. Using hierarchical linear modeling (HLM), this study tested the stability of cue-elicited activation in anatomically and functionally defined regions of interest in bilateral VS and DS. Nine non-treatment-seeking alcohol-dependent participants twice completed an alcohol cue reactivity task during two fMRI scans separated by 14 days. HLM analyses demonstrated that, across all participants, alcohol cues elicited significant activation in each of the regions of interest. At the group level, these activations attenuated slightly between scans, but session-wise differences were not significant. Within-participants stability was best in the anatomically defined right VS and DS and in a functionally defined region that encompassed right caudate and putamen (intraclass correlation coefficients of .75, .81, and .76, respectively). Thus, within this small sample, alcohol cue-elicited fMRI activation had good reliability in the right striatum, though a larger sample is necessary to ensure generalizability and further evaluate stability. This study also demonstrates the utility of HLM analytic techniques for serial fMRI studies, in which separating within-participants variance (individual changes in activation) from between-participants factors (time or treatment) is critical.
NeuroImage 02/2011; 56(1):61-8. · 5.89 Impact Factor
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ABSTRACT: The Veteran's Health Administration (VHA) has launched a large-scale initiative to promote prolonged exposure (PE) therapy, an evidence-based treatment for PTSD. While existing randomized controlled trials (RCTs) unambiguously support the efficacy of PE in civilian and some military populations, there is a need to better understand the course of treatment for combat Veterans of the current wars receiving PE in normative mental healthcare settings. The current study investigates 65 Veterans receiving care at an urban VA medical center. All Veterans were diagnosed with PTSD via a structured interview and treated with PE. Measures of PTSD and depression were collected pre- and post-treatment and every two sessions during treatment. Dependent means t-tests were used to estimate pre- and post-treatment d-type effect sizes. Additionally, hierarchical linear models (HLM) were used to investigate treatment effects over time, relationships between patient characteristics and outcomes, and to provide estimates of R(2)-type effect sizes. Results indicate that PE in regular VA mental healthcare contexts can be as effective as when implemented in carefully conducted RCTs.
Journal of anxiety disorders 11/2010; 25(3):397-403. · 2.68 Impact Factor
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ABSTRACT: Because the effects of alcohol and its environmental cues on brain dopamine have been implicated in the maintenance of heavy drinking, drugs that modify dopamine might be useful in reducing drinking or promoting abstinence. The goal of the current study was to use an established brain imaging paradigm to explore the effect of aripiprazole (final dose 15 mg over a 14-day period), a dopamine stabilizer medication, on alcohol cue-induced brain activation and drinking in alcoholics. Non-treatment-seeking alcoholics were randomly assigned aripiprazole (n = 14) or identical placebo (n = 16) and reported their alcohol use while taking study medication for 14 days before an alcohol cue-induced brain functional magnetic resonance imaging study. In a Philips 3.0-T magnetic resonance imaging scanner, subjects were given a sip of alcohol before viewing a randomized presentation alcoholic- and nonalcoholic-beverage photographs while subjects rated their urge to drink. During photograph presentation, changes in regional brain activity were measured, and differences between viewing alcoholic beverage and nonalcoholic beverages were compared within and between groups. Brain activity analysis revealed increased activation for placebo-treated subjects in the right ventral striatum (P < 0.005; threshold 15 voxels), while there was a blunting of activation in this area in the aripiprazole-treated subjects. Aripiprazole-treated subjects, compared with placebo-treated subjects, also had significantly less heavy drinking during the 14-day medication period. The study provides both novel and valuable information regarding the effect of aripiprazole on cue-induced brain activation and voluntary drinking during treatment.
Journal of clinical psychopharmacology 08/2010; 30(4):365-72. · 5.09 Impact Factor
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ABSTRACT: Among both civilian and veteran populations, substance use disorders (SUDs) and anxiety disorders frequently co-occur. One of the most common comorbid anxiety disorder is posttraumatic stress disorder (PTSD), a condition which may develop after exposure to traumatic events, such as military combat. In comparison with the general population, rates of both SUDs and PTSD are elevated among veterans. Recent data show that soldiers returning from Iraq and Afghanistan demonstrate high rates of co-occurring SUDs, PTSD, and traumatic brain injury. Careful assessment of these conditions is critical and may be complicated by symptom overlap. More research targeting integrated interventions for these conditions is needed to establish optimal treatments.
Journal of Addiction Medicine 12/2009; 3(4):179-88. · 1.95 Impact Factor
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ABSTRACT: Improved treatment of alcohol dependence is a high priority, including defining subtypes that might respond differently. We evaluated a medication combination of intravenous flumazenil (FMZ) and oral gabapentin (GBP) in alcoholics who did and did not exhibit pretreatment alcohol withdrawal (AW) symptoms. Sixty alcohol-dependent individuals (44 with low AW and 16 with high AW) were randomized to receive FMZ (2 mg of incremental bolus for 20 minutes for 2 consecutive days) and GBP (up to 1200 mg nightly for 39 days) or their inactive placebos. Alcohol withdrawal was measured for the first 2 days, and drinking, sleep parameters, and adverse events were monitored during weekly evaluations, along with behavioral counseling sessions. Percent days abstinent (PDA) during treatment and time to first heavy drinking (TFHD) day were primary outcome variables. There was an interaction between the pretreatment AW status and the medication group on PDA (P = 0.0006) and TFHD (P = 0.06). Those in the high AW group had more PDA and more TFHD if treated with active medications, whereas those in the low AW group had more PDA and more TFHD if treated with placebo. This interaction remained for those totally abstinent (P = 0.03) and was confirmed by percent carbohydrate-deficient transferrin values. In addition, the pattern of response remained up to 8 weeks after treatment. In addition, in those with high AW, greater improvement in AW symptoms was observed in the active medication group compared with the placebo group. These results suggest a differential response to FMZ/GBP treatment, depending on pretreatment AW status that should be taken into account during future treatment trials.
Journal of clinical psychopharmacology 09/2009; 29(4):334-42. · 5.09 Impact Factor
