Extended release naltrexone for alcohol use disorders: quasi-experimental effects on mortality and subsequent detoxification episodes.

BACKGROUND: Utilization of extended release naltrexone (XRN) for alcohol use disorders (AUDs) in the U.S. Veterans Health Administration (VHA) has been limited, perhaps due to high cost, lack of established superiority over less expensive alternatives including oral naltrexone, and related formulary restrictions. Despite these barriers, pockets of higher utilization exist in VHA, allowing for the quasi-experimental examination of the effects of XRN on 1-year mortality and number of subsequent detoxification episodes among patients with high rates of psychiatric comorbidities and previous psychosocial and pharmacological addiction treatment. METHODS: Using propensity score-weighted mixed-effects logistic regression, 1-year mortality was compared between patients with AUDs who received XRN in fiscal year 2010 (n = 387) and a random sample of patients with AUDs who did not receive XRN (n = 3,759). Among the subgroup of patients who had at least 1 detoxification episode in the previous year, 1-year mortality and number of subsequent detoxification episodes were compared between those who did and did not receive XRN. RESULTS: Overall, 1-year mortality for the patients receiving XRN was significantly lower than for the comparison group who did not receive XRN (odds ratio [OR] = 0.30; p < 0.001). Among patients with a detoxification episode in the previous year, those receiving XRN had, on average, 0.80 fewer subsequent detoxification episodes (p < 0.001) and significantly lower mortality (OR = 0.78, p < 0.001) in the postindex year. CONCLUSIONS: Among patients with AUDs, those receiving XRN had lower 1-year mortality and fewer detoxifications compared to similar patients not receiving XRN. These results, although observational, support the use of XRN, especially among patients with high rates of psychiatric comorbidities and previous addiction treatment who are still struggling with AUDs and/or facing a period of vulnerability to relapse.

Suicide-specific Safety in the Inpatient Psychiatric Unit.

In total, 75% of suicides reported to the Joint Commission as sentinel events since 1995, have occurred in psychiatric settings. Ensuring patient safety is one of the primary tasks of inpatient psychiatric units. A review of inpatient suicide-specific safety components, inclusive of incidence and risk; guidelines for evidence-based care; environmental safety; suicide risk assessment; milieu observation and monitoring; psychotherapeutic interventions; and documentation is provided. The Veterans Health Administration (VA) has been recognized as an exemplar system in suicide prevention. A VA inpatient psychiatric unit is used to illustrate the operationalization of a culture of suicide-specific safety. We conclude by describing preliminary unit outcomes and acknowledging limitations of suicide-specific inpatient care and gaps in the current inpatient practices and research on psychotherapeutic interventions, observation, and monitoring.

Brain activation to cocaine cues and motivation/treatment status.

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.

Functional neuroimaging studies of alcohol cue reactivity: a quantitative meta-analysis and systematic review.

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.

Naltrexone modification of drinking effects in a subacute treatment and bar-lab paradigm: influence of OPRM1 and dopamine transporter (SLC6A3) genes.

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.

A pilot trial of neuropsychological evaluations conducted via telemedicine in the Veterans Health Administration.

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.

Stability of fMRI striatal response to alcohol cues: a hierarchical linear modeling approach.

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.

Neurocognitive performance, alcohol withdrawal, and effects of a combination of flumazenil and gabapentin in alcohol dependence.

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.

Neural correlates of craving and resisting craving for tobacco in nicotine dependent smokers.

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.

The effect of aripiprazole on cue-induced brain activation and drinking parameters in alcoholics.

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.

Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms.

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.

A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal.

INTRODUCTION: Some anticonvulsants ameliorate signs and symptoms of alcohol withdrawal, but have an unacceptable side effect burden. Among the advantages of using anticonvulsant agents in this capacity is their purported lack of interaction with alcohol that could increase psychomotor deficits, increase cognitive impairment, or increase intoxication. The aim of this study was to evaluate alcohol use and symptom reduction of gabapentin when compared with lorazepam in the treatment of alcohol withdrawal in a double-blinded randomized clinical trial. METHODS: One hundred individuals seeking outpatient treatment of alcohol withdrawal with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) ratings > or =10 were randomized to double-blind treatment with 2 doses of gabapentin (900 mg tapering to 600 mg or 1200 tapering to 800 mg) or lorazepam (6 mg tapering to 4 mg) for 4 days. Severity of alcohol withdrawal was measured by the CIWA-Ar on days 1 to 4 of treatment and on days 5, 7, and 12 post-treatment and alcohol use monitored by verbal report and breath alcohol levels. RESULTS: CIWA-Ar scores decreased over time in all groups; high-dose gabapentin was statistically superior but clinically similar to lorazepam (p = 0.009). During treatment, lorazepam-treated participants had higher probabilities of drinking on the first day of dose decrease (day 2) and the second day off medication (day 6) compared to gabapentin-treated participants (p = 0.0002). Post-treatment, gabapentin-treated participants had less probability of drinking during the follow-up post-treatment period (p = 0.2 for 900 mg and p = 0.3 for 1200 mg) compared to the lorazepam-treated participants (p = 0.55). The gabapentin groups also had less craving, anxiety, and sedation compared to lorazepam. CONCLUSIONS: Gabapentin was well tolerated and effectively diminished the symptoms of alcohol withdrawal in our population especially at the higher target dose (1200 mg) used in this study. Gabapentin reduced the probability of drinking during alcohol withdrawal and in the immediate postwithdrawal week compared to lorazepam.

Aripiprazole effects on alcohol consumption and subjective reports in a clinical laboratory paradigm--possible influence of self-control.

INTRODUCTION: There has been increasing interest in the use of medications that affect the dopamine receptor in the treatment of alcoholism. Aripiprazole has the unique pharmacology of being a partial dopamine agonist serving to stabilize brain dopamine systems in both frontal cortical and subcortical areas. As such, it might act to dampen alcohol reinforcement and craving and/or alter control over alcohol use. The current clinical laboratory study was conducted to evaluate the safety and efficacy of aripiprazole as a potential agent to alter drinking and objective effects of alcohol. METHODS: Thirty nontreatment seeking alcoholics were enrolled in a subacute human laboratory study and received double-blind treatment with up to 15 mg of aripiprazole (n = 15) or identical placebo (n = 15) for 8 days. Tolerability and utility of aripiprazole was monitored during natural drinking over the first 6 days of medication treatment and also during a free choice limited access alcohol consumption paradigm following an initial drink of alcohol in a bar-lab setting on Day 8. RESULTS: Aripiprazole was well tolerated and reduced drinking in nontreatment seeking alcoholics over 6 days of natural drinking--especially in those with lower self control (more impulsive). It also reduced drinks in the bar-lab after a priming drink and broke the link between priming drink induced stimulation and further drinking. During the bar-lab drinking session, there were no differences in subjective high, intoxication, or craving between subjects treated with aripiprazole or placebo. DISCUSSION: This study joins several others in demonstrating the utility of subacute dosing laboratory paradigms for evaluating medication effects in alcoholics. Aripiprazole was well tolerated and lowered alcohol use, especially in those with lower impulse control. Further study is needed to determine the safety and utility of aripiprazole in the treatment of alcoholism and if subgroups of alcoholics are more likely to respond.

Is cocaine desire reduced by N-acetylcysteine?

OBJECTIVE: Animal models suggest that N-acetylcysteine inhibits cocaine-seeking. The present pilot study evaluated whether N-acetylcysteine would suppress reactivity to cocaine-related cues in cocaine-dependent humans. METHOD: In this double-blind, placebo-controlled trial, 15 participants received N-acetylcysteine or placebo during a 3-day hospitalization. Participants were crossed over to receive the opposite condition on a second, identical 3-day stay occurring 4 days later. During each hospital stay, participants completed a cue-reactivity procedure that involved collecting psychophysical and subjective data in response to slides depicting cocaine and cocaine use. RESULTS: While taking N-acetylcysteine, participants reported less desire to use and less interest in response to cocaine slides and watched cocaine slides for less time. CONCLUSIONS: The inhibition of cocaine cue reactivity is consistent with existing preclinical data and supports the use of N-acetylcysteine as a treatment for cocaine dependence.

Predictors of Naltrexone Response in a Randomized Trial: Reward-Related Brain Activation, OPRM1 Genotype, and Smoking Status.

This corrects the article DOI: 10.1038/npp.2017.74.

Predictors of Naltrexone Response in a Randomized Trial: Reward-Related Brain Activation, OPRM1 Genotype, and Smoking Status.

Naltrexone reduces drinking among individuals with alcohol use disorders (AUDs), but it is not effective for everyone. Variability in its effects on reward-related brain activation, genetic variation, and/or cigarette smoking may account for this mixed response profile. This randomized clinical trial tested the effects of naltrexone on drinking and alcohol cue-elicited brain activation, evaluated whether OPRM1 A118G genotype or smoking moderated these effects, and explored whether the effects of medication on cue-elicited activation predicted subsequent drinking. One hundred and fifty-two treatment-seeking individuals with alcohol dependence, half preselected to carry at least one A118G G (Asp) allele, were randomized to naltrexone (50 mg) or placebo for 16 weeks and administered an fMRI alcohol cue reactivity task at baseline and after 2 weeks of treatment. Naltrexone, relative to placebo, significantly reduced alcohol cue-elicited activation of the right ventral striatum (VS) between baseline and week 2 and reduced heavy drinking over 16 weeks. OPRM1 genotype did not significantly moderate these effects, but G-allele carriers who received naltrexone had an accelerated return to heavy drinking after medication was stopped. Smoking moderated the effects of medication on drinking, such that naltrexone was superior to placebo only among smokers. The degree of reduction in right VS activation between scans interacted with medication in predicting subsequent drinking, such that individuals with greater reduction in activation who received naltrexone, but not placebo, experienced the least heavy drinking during the following 14 weeks. These data replicate previous findings that naltrexone reduces heavy drinking and reward-related brain activation among treatment-seeking individuals with AUDs, and indicate that smoking and the magnitude of reduction in cue-elicited brain activation may predict treatment response.

Randomized Controlled Trial Comparing Exercise to Health Education for Stimulant Use Disorder: Results From the CTN-0037 STimulant Reduction Intervention Using Dosed Exercise (STRIDE) Study.

OBJECTIVE: To evaluate exercise as a treatment for stimulant use disorders. METHODS: The STimulant Reduction Intervention using Dosed Exercise (STRIDE) study was a randomized clinical trial conducted in 9 residential addiction treatment programs across the United States from July 2010 to February 2013. Of 497 adults referred to the study, 302 met all eligibility criteria, including DSM-IV criteria for stimulant abuse and/or dependence, and were randomized to either a dosed exercise intervention (Exercise) or a health education intervention (Health Education) control, both augmenting treatment as usual and conducted thrice weekly for 12 weeks. The primary outcome of percent stimulant abstinent days during study weeks 4 to 12 was estimated using a novel algorithm adjustment incorporating self-reported Timeline Followback (TLFB) stimulant use and urine drug screen (UDS) data. RESULTS: Mean percent of abstinent days based on TLFB was 90.8% (SD = 16.4%) for Exercise and 91.6% (SD = 14.7%) for Health Education participants. Percent of abstinent days using the eliminate contradiction (ELCON) algorithm was 75.6% (SD = 27.4%) for Exercise and 77.3% (SD = 25.1%) for Health Education. The primary intent-to-treat analysis, using a mixed model controlling for site and the ELCON algorithm, produced no treatment effect (P = .60). In post hoc analyses controlling for treatment adherence and baseline stimulant use, Exercise participants had a 4.8% higher abstinence rate (78.7%) compared to Health Education participants (73.9%) (P = .03, number needed to treat = 7.2). CONCLUSIONS: The primary analysis indicated no significant difference between exercise and health education. Adjustment for intervention adherence showed modestly but significantly higher percent of abstinent days in the exercise group, suggesting that exercise may improve outcomes for stimulant users who have better adherence to an exercise dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01141608.

Regional Brain Activity in Abstinent Methamphetamine Dependent Males Following Cue Exposure.

BACKGROUND: Neuroimaging of drug-associated cue presentations has aided in understanding the neurobiological substrates of craving and relapse for cocaine, alcohol, and nicotine. However, imaging of cue-reactivity in methamphetamine addiction has been much less studied. METHOD: Nine caucasian male methamphetamine-dependent subjects and nine healthy controls were scanned in a Phillips 3.0T MRI scan when they viewed a randomized presentation of visual cues of methamphetamine, neutral objects, and rest conditions. Functional Imaging data were analyzed with Statistical Parametric Mapping software 5 (SPM 5). RESULTS: Methamphetamine subjects had significant brain activation in the ventral striatum and medial frontal cortex in comparison to meth pictures and neutral pictures in healthy controls (p<0.005, threshold 15 voxels). Interestingly the ventral striatum activation significantly correlated with the days since the last use of meth (r=-0.76, p=0.017). No significant activity was found in healthy control group. CONCLUSION: The preliminary data suggest that methamphetamine dependent subjects, when exposed to methamphetamine-associated visual cues, have increased brain activity in ventral striatum, caudate nucleus and medial frontal cortex which subserve craving, drug-seeking, and drug use.

Health service use among persons with comorbid bipolar and substance use disorders.

OBJECTIVE: This study tested the hypothesis that patients with comorbid bipolar and substance use disorders use health services to a greater extent than patients with either bipolar or substance use disorder alone. METHODS: A retrospective chart review was conducted among patients who used health services at the Ralph H. Johnson Department of Veterans Affairs medical center in Charleston, South Carolina, and had bipolar disorder alone, substance use disorder alone, and comorbid bipolar and substance use disorders. Patients with a psychiatric admission between 1999 and 2003 were included in the study. Information was collected on the use of health services one year before and including the index admission. RESULTS: The records of 106 eligible patients were examined for this study: 18 had bipolar disorder alone, 39 had substance use disorder alone, and 49 had both bipolar and substance use disorders. Compared with the other two groups, the group with comorbid bipolar and substance use disorders was significantly more likely to be suicidal. Compared with the group with bipolar disorder alone, the group with comorbid disorders had significantly fewer outpatient psychiatric visits and tended to have shorter psychiatric hospitalizations. Among patients with an alcohol use disorder, those who also had bipolar disorder were significantly less likely than those with an alcohol use disorder alone to have had an alcohol-related seizure. Patients with comorbid bipolar and substance use disorders were significantly less likely than those with substance use disorder alone to be referred for intensive substance abuse treatment, even though both groups were equally likely to enter and complete treatment when they were referred. CONCLUSIONS: Despite significant functional impairment among patients with comorbid bipolar and substance use disorders, they had significantly fewer psychiatric outpatient visits than those with bipolar disorder alone and were referred for intensive substance abuse treatment significantly less often than those with substance use disorder alone.

Beliefs as a predictor of relapse in alcohol-dependent Turkish men.

OBJECTIVE: The aim of the current study was to evaluate the role of beliefs about alcohol use and craving on predicting relapse as stated in Beck's cognitive theory of alcoholism in detoxified alcohol-dependent patients. METHOD: Seventy male participants who were alcohol dependent according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and who were admitted to an inpatient unit for alcohol detoxification were studied at baseline and at 6 months follow-up. Participants were administered the Structured Clinical Interviews for DSM-IV axis I and DSM-III-R axis II Disorders (SCID-I and SCID-II, respectively), the Beck Anxiety Inventory and the revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). Beliefs about alcohol use were assessed with the Beliefs About Substance Use Inventory and the Craving Beliefs Questionnaire (CBQ). RESULTS: The relapse rate of the study group was 84.1% (58 patients). The age of onset of alcohol dependence and age at first hospitalization were lower in patients who relapsed. The severity of physical dependence and presence of comorbid antisocial personality disorder were higher in the relapse group. In addition, patients who relapsed had higher scores in the CBQ. According to logistic regression analysis, craving beliefs and the degree of physical dependence were predictors of relapse in alcoholic patients. CONCLUSIONS: Our findings suggest that beliefs about craving and the severity of physical dependence may play an important role in relapse of male alcoholic patients. These factors could have a direct clinical application for predicting relapse to drinking in male alcohol-dependent patients.