Relapse Prevention Medications Research Articles

The influence of concomitant antidepressant and antipsychotic medication on antidepressant effect and seizure duration of electroconvulsive therapy.

A significant proportion of patients with a depressive disorder show resistance to pharmacological and psychotherapeutic antidepressant treatments. Electroconvulsive therapy (ECT) is still one of the most effective treatment methods, especially in the acute phase. In everyday clinical practice, this usually accompanies pharmacological treatment. It has been shown that pharmacological treatment following acute ECT treatment reduces the rate of relapses. However, the effect of various antidepressants (ADs) and antipsychotics (APs) on the effect during the course of ECT has rarely been investigated. In this retrospective chart review study, the data of 104 depressive patients treated with ECT were examined. We analyzed the influence of concomitant administration of AD and AP or no psychotropic medication on the effect of ECT using the Montgomery-Åsberg Depression Rating Scale (MADRS). We further analyzed the influence of the ADs Bupropion, Venlafaxine, and Sertraline or no AD and the influence of augmentation with Aripiprazole or Quetiapine or Olanzapine. Psychotropic medication did not have an impact on antidepressant efficacy of ECT as measured with the MADRS scores. In addition, the comparison between the antidepressant or antipsychotic medications themselves did not show any significant difference. However, we found a significantly different seizure duration depending on the antidepressant substance that patients received during ECT (p = .008). ECT treatment itself led to a highly significant reduction of 13.3 points in the MADRS (p <.001). Taken together, our study underlines that concomitant psychotropic medication while doing electroconvulsive therapy does not bare the risk of prolonged seizure duration or does it reduce the effectiveness of ECT. To the best of our knowledge, this study is the first to examine the effect of treatment with antidepressants in combination with antipsychotics while doing ECT. In light of our results, this combination therapy is safe and effective. Bearing in mind the delay in onset of antidepressant action of medication and the importance of antidepressant medication for relapse prevention, this study further supports the recommendation that psychotropic medication should be given in adjunction to ECT.

Management of alcohol use disorder in patients with chronic liver disease.

Alcohol use disorder (AUD) rates have risen dramatically in the United States, resulting in increasing rates of alcohol-associated liver disease (ALD), but many patients struggle to access alcohol use treatment. AUD treatment improves outcomes, including mortality, and represents the most urgent means by which care can be improved for those with liver disease (including ALD and others) and AUD. AUD care for those with liver disease involves 3 steps: detecting alcohol use, diagnosing AUD, and directing patients to alcohol treatment. Detecting alcohol use can involve questioning during the clinical interview, the use of standardized alcohol use surveys, and alcohol biomarkers. Identifying and diagnosing AUD are interview-based processes that should ideally be performed by a trained addiction professional, but nonaddiction clinicians can use surveys to determine the severity of hazardous drinking. Referral to formal AUD treatment should be made, especially where more severe AUD is suspected or identified. Therapeutic modalities are numerous and include different forms of one-on-one psychotherapy, such as motivational enhancement therapy or cognitive behavior therapy, group therapy, community mutual aid societies (such as Alcoholics Anonymous), inpatient addiction treatment, and relapse prevention medications. Finally, integrated care approaches that build strong relationships between addiction professionals and hepatologists or medical providers caring for those with liver disease are crucial to improving care for this population.

Alcohol use disorder in community management of chronic liver diseases.

Rising rates of alcohol use disorder (AUD) combined with increases in alcohol-related liver disease (ALD) and other liver disease have resulted in the need to develop alcohol management strategies at all levels of patient care. For those with pre-existing liver disease, whether ALD or others, attention to alcohol use treatment and abstinence becomes critical to avoiding worsening liver-related consequences. Modalities to help patients reduce or stop alcohol include screening/brief intervention/referral to treatment, various therapeutic modalities including cognitive behavioral therapy, motivational enhancement therapy and 12-step facilitation, and alcohol relapse prevention medications. Harm reduction approaches versus total abstinence may be considered, but for those with existing ALD, particularly advanced ALD (cirrhosis or acute alcoholic hepatitis), total abstinence from alcohol is the recommendation, given clear data that ongoing alcohol use worsens mortality and liver-related morbidity. For certain populations, alcohol cessation is even more critically important. For those with hepatitis C or NAFLD, alcohol use accelerates negative liver-related outcomes. In women, alcohol use accelerates liver damage and results in worsened liver-related mortality. Efforts to integrate AUD and liver disease care are urgently needed and can occur at several levels, with establishment of multidisciplinary ALD clinics for fully integrated co-management as an important goal.

Service Users' Views and Experiences of Alcohol Relapse Prevention Treatment and Adherence: New Role for Pharmacists?

AimsTo understand service users' views and experiences of alcohol relapse prevention medication, views of a telephone behavioural modification intervention delivered by pharmacists and the use of Contingency Management (CM) to support acamprosate adherence following assisted alcohol withdrawal.MethodsFour focus groups were conducted within four alcohol treatment and recovery groups across England (UK), with service users with lived experience of alcohol dependence (26 participants). Semi-structured topic guide was used to explore participants' views and experiences of alcohol relapse prevention medication, a telephone behavioural modification medication intervention delivered by pharmacists, and the use of CM to support acamprosate adherence. These were audio-recorded, transcribed verbatim and thematically analysed inductively and deductively.ResultsFour themes were identified: concerns about support and availability of alcohol relapse prevention medication; lack of knowledge and understanding about acamprosate treatment; positive perceptions of acamprosate adherence telephone support from pharmacists; and negative perceptions of CM to support acamprosate adherence. There were misunderstandings about acamprosate's mode of action and strong negative beliefs about CM. However, most were positive about pharmacists' new role to support acamprosate adherence.ConclusionThis study highlighted challenges service users face to commence alcohol relapse prevention medication. It appears service users could benefit from a pharmacist-led telephone intervention to improve understanding about acamprosate medication, particularly, if delivered in an engaging and motivating way.

A87 CHANGES IN CLINICIAN KNOWLEDGE, COMFORT, PREPAREDNESS, AND ATTITUDES ABOUT ALCOHOL USE DISORDER AND CIRRHOSIS AFTER A BRIEF EDUCATIONAL INTERVENTION

BackgroundAlcohol use disorder (AUD) is increasing in prevalence and has a substantial impact on morbidity and mortality in people with cirrhosis. The use of screening, brief intervention and referral to treatment (SBIRT) and relapse prevention medications (e.g. acamprosate) are recommended by recent guidelines. Unfortunately, many clinicians report insufficient training to feel confident using these interventionsAimsWe aimed to compare the effect of a brief educational intervention on AUD knowledge, comfort, attitudes, and preparedness in clinicians who provide care to patients with cirrhosis.MethodsClinicians were invited to participate in a 1.5-hour educational session conducted by a hepatologist and addiction medicine specialist. The session included information about SBIRT and pharmacotherapy. Pre-training knowledge, comfort, and practice behaviors were assessed using previously published questions. Baseline attitudes were measured using the Short Alcohol and Alcohol Problems Perception Questionnaire. Participants were invited to repeat the questionnaires immediately post-training and statistical analysis conducted.ResultsEighty-two clinicians attended the session. Among the 38 attendees who completed both the pre- and post-questionnaires, 34% were GIs/internists, 45% were family medicine physicians, and the remainder (21%) did not specify or were not prescribers. Scores for self-reported intention and preparedness to treat AUD, comfort, and knowledge improved significantly from the pre-training phase. Attitudes also improved from the pre-training phase, with significant improvements in the SAAPPQ subscales of role adequacy (p=0.03) and motivation (p=0.04).ConclusionsRecognizing the small sample size, a brief educational session demonstrated promising results in the promotion of knowledge, attitudes, preparedness, and comfort for clinicians managing AUD in patients with cirrhosis. Feedback from these sessions will be used to design an accredited educational series for roll-out in 2022.Table 1. Paired samples t-test pre and post preparedness, intention and comfort questionsPre-test mean (SD)Post-test mean (SD)P-valueEffect size IntentionTo screen every patient for AUD5.0 (1.2)5.7 (.74)<0.0010.702Provide medical advice about AUD5.4 (1.0)5.8 (0.56)0.0970.494Provide a brief intervention5.3 (.93)5.7 (.68)0.0090.491Prescribe anti-relapse medications4.6 (1.5)5.2 (1.2)0.0280.442PreparednessTo screen and diagnose AUD3.3 (.85)3.8 (.39)0.001.756To provide a brief intervention2.8 (.91)3.6 (.50)<0.0011.09To refer patients for treatment3.0 (.96)3.6 (.50)0.001.784ComfortPrescribing Acamprosate2.4 (.82)3.2 (.75)<0.0011.018Prescribing Baclofen2.2 (.62)3.0 (.68)<0.0010.279Prescribing Gabapentin2.5 (.65)3.1 (.67)<0.0010.909Funding AgenciesAlberta Innovates Health Solutions

Knowledge, Attitudes, and Beliefs about Relapse Prevention Research Involving Bupropion among Current and Former Pregnant Individuals Who Smoke.

While many individuals quit smoking during pregnancy, most relapse within one year postpartum. Research into methods to decrease smoking relapse postpartum has been hampered by difficulties with recruitment. We conducted individual interviews with pregnant women (N = 22) who were interested in quitting smoking while pregnant about their attitudes regarding smoking and quitting during pregnancy, clinical trial participation, and smoking cessation medication use. Participants were aware of the risks of smoking while pregnant. Many wanted to quit smoking before delivery. Few used empirically supported treatments to quit. While research was viewed positively, interest in taking on new commitments postpartum and taking a medication to prevent relapse was low. Medication concerns were evident among most participants, especially among those planning to breastfeed. Further, several women noted medication was unnecessary, as they did not believe they would relapse postpartum. Financial incentives, childcare, and fewer and/or remote visits were identified as facilitators to participating in research. However, these factors did not outweigh women's concerns about medication use and time commitments. Women are aware that quitting smoking during pregnancy and remaining smoke-free postpartum are important. However, beliefs that personal relapse risk is low and that medications are dangerous reduced enthusiasm for taking medication for postpartum relapse prevention. Future medication trials should educate women about the high likelihood of relapse, prepare to answer detailed questions about risks of cessation medications, and connect with participants' clinicians. For new mothers, studies conducted remotely with few scheduled appointments would reduce barriers to participation.

Extended-release naltrexone for youth with opioid use disorder

BackgroundFew published research studies have examined the effectiveness of extended-release naltrexone (XR-NTX) for the treatment of opioid use disorder (OUD) among adolescents and young adults. MethodsThis two-group randomized controlled trial recruited 288 youth, ages 15–21, with moderate/severe OUD from a residential addiction treatment program in Baltimore, Maryland. The study randomized the youth within the first week of treatment entry to receive either XR-NTX or treatment-as-usual (TAU; either buprenorphine maintenance treatment or treatment without OUD medication following medically managed withdrawal) prior to discharge, with continued treatment in the community for 6 months. However, due to various reasons spanning patients' and caregivers' preferences and constraints, considerable participant nonadherence to randomized condition occurred (i.e., only 30% of the participants randomized to XR-NTX received an initial injection, while 27% of participants randomized to TAU received an XR-NTX injection at treatment discharge, instead of their assigned treatment). The study used generalized linear mixed modeling (GLiMM) to examine self-reported 90-day opioid, cocaine, marijuana, and alcohol use as well as DSM-5 OUD criteria on “intention-to-treat” (as randomized), “as-received” (XR-NTX vs. not XR-NTX), and “as-medicated” (XR-NTX vs. buprenorphine vs. no medication) bases. ResultsThe condition x time interactions in the intention-to-treat analyses failed to reach significance for past-90-day self-reported use of illicit opioids, cocaine, marijuana, or alcohol, or in meeting DSM-5 OUD criteria at 3 or 6 months [all ps > 0.05]. However, these findings are of limited interpretive value due to participant nonadherence to their randomized condition. When the study analyzed results by the treatment received at discharge, the “as-received” group x time interaction for illicit opioid use was significant [p = .003], with the XR-NTX group reporting less opioid use in the past 90 days at 3 and 6 months. Participants who received their first XR-NTX dose at inpatient discharge (n = 82) received, on average, 1.3 subsequent injections in the community over the 6-month study follow-up period. Only 2 of the 82 study participants received XR-NTX continuously through the 6-month postdischarge follow-up period. Twelve serious adverse events (SAEs) occurred during the study, but the study determined that only 1 was possibly study related (hepatitis C/elevated liver function test results). ConclusionNone of the condition x time interactions in the intention-to-treat analyses reached significance. Participants' nonadherence may have contributed to the failure to reject the null hypothesis. Irrespective of randomized condition, participants who received XR-NTX for OUD demonstrated low retention in treatment, receiving an average of only 1.3 subsequent injections, yet reported less opioid use at follow-up than participants who did not received XR-NTX. Treatment programs should consider XR-NTX as a treatment option for youth motivated to receive it. Future research should focus on building developmentally informed strategies to improve uptake of and adherence to relapse prevention medication in this population.

Feasibility and early experience of a novel multidisciplinary alcohol-associated liver disease clinic

BackgroundAlcohol cessation improves mortality in alcohol-associated liver disease (ALD), but access to treatment is limited. To address this gap, implementation and early feasibility and outcomes of a multidisciplinary ALD clinic are described. MethodsThe clinic comprised a hepatologist, psychiatrist, psychologist, nurse, and social worker. Patients included those with alcohol-associated cirrhosis or acute alcoholic hepatitis who were not in the transplant evaluation process, who had less than 6 months’ sobriety and willingness to engage in alcohol use treatment. Psychosocial metrics in addition to routine hepatic function labs were collected. Treatment plans were tailored based on patient preferences and needs after multidisciplinary discussion. Results89 patients were referred from both inpatient and outpatient settings, with 51 seen during the initial year. 38 remained active in clinic (4 died, 6 discharged, 3 moved to transplant clinic). 55% were women, 88% were white, 61% had private insurance. 49% had alcoholic hepatitis. 71% were decompensated. 80% had severe alcohol use disorder (AUD) and 84% had at least 1 comorbid psychiatric or substance use disorder. 63% chose one-on-one AUD treatment, 57% were prescribed relapse prevention medications. Mean MELD-Na score improved from baseline of 14 (SD 6.6) to 11.3 at 6 months (p=0.01). Hospital utilization significantly declined when comparing 6 months before to 6 months after initial visit (emergency department visits: 0.51 to 0.20 per person-month; inpatient admission: 0.34 to 0.14 per person-month; (β= -0.89, 95% CI -1.18 to -0.60). ConclusionsA multidisciplinary ALD clinic was feasible with encouraging early outcomes. Further research should explore ways to expand this model and increase clinic capacity.

Commentary on Farnum et al.: Agonist maintenance in Ukraine-ambivalence, success and moving forward.

Agonist maintenance arrived late in Ukraine and shared many of the issues that occurred when methadone was introduced in the United States. It has been well-accepted by patients and could have a meaningful impact on the spread of HIV if the number of patients receiving it is substantially increased. The paper by Farnum et al. on methadone and buprenorphine maintenance in Ukraine is an important contribution to a growing literature on the use of these therapies in former Soviet states [1]. The usual approach in Ukraine has followed the Russian model, where using a medication with opioid agonist effects is against the law. Treatment is provided in specialized addiction (‘narcology’) hospitals that are part of the National Health system, although some patients are treated by private practitioners in a fee-for-service arrangement. Upon treatment admission, patients are detoxified with non-opioid medications, receive 2–4 weeks of cognitive behavioral or relapse prevention therapy, relaxation exercises, social work services and employment counseling, and are referred to local health centers for continuing care after discharge. Treatment is voluntary, and patients can leave at any time and be re-admitted if needed, usually after relapsing. The basic idea is to help patients to stop using drugs. The model was developed for alcohol dependence but high relapse rates, unsterile injecting practices and the rapid spread of HIV showed its limitations in Ukraine when used for opioid addiction [2]. Health authorities and clinicians were aware of the findings from methadone and buprenorphine studies [3-5] and of later studies showing that agonist maintenance reduced HIV risk and infection [6]. Regulations were changed to allow agonist therapy and, like the United States, when methadone treatment began in the late 1960s, it was a major policy change and accompanied by strict new regulations that were later modified to make treatment more accessible. Also like the United States, some providers viewed agonist maintenance as ineffective (‘substituting beer for whiskey or vodka’), and residential programs did not offer or even continue it for patients who were receiving it, although that practice has been changing due to the opioid epidemic. The finding that higher methadone doses are associated with better retention is identical to US studies, as is the gap between treatment need and participation, although that gap is greater in Ukraine than in the United States. The average 75% retention on methadone in Ukraine at 12 months is higher than the approximate 50% retention at 6–12 months in a meta-analysis of methadone treatment in the United States, Australia and China [7], and is also consistent with the findings of a National Institute of Drug abuse (NIDA)-funded study in Kiev, where 47 of 50 patients chose to continue methadone after their 20-week follow-up [8]. The 89% buprenorphine retention in Ukraine at 12 months is much greater than the 43% retention at 24 weeks in a recent US study [9]. Collectively, these findings show that attitudinal barriers and processes associated with the introduction of agonist maintenance in Ukraine bear similarities to the processes associated with the introduction of methadone maintenance in the United States. Importantly, agonist maintenance is being well accepted by patients, and has the potential to reduce the spread of HIV if treatment can be expanded to include a larger proportion of opioid addicted individuals. Not to be overlooked while focusing on dosing outcomes is the role of psychosocial treatments. Papers by Bejerot [10], and Dole [11], from a 1980 NIDA Research Monograph, point to craving as the root of the chronic, relapsing nature of opioid addiction and explain the apparent paradox of patients completing treatment, then returning to prior behaviors and relapsing. Bejerot describes an addiction as beginning with occasional use that at some point, in some individuals, becomes a craving that results in compulsive use with remissions and relapses even after periods of extended remission [12, 13]. He associates the change from occasional to compulsive with a range of factors, but a problem that is stubbornly persistent once established. Many psychosocial interventions have been developed to address craving and the associated behaviors [14-18], but opioid-addicted patients usually drop out unless in a controlled environment or the psychosocial treatment is combined with an effective relapse prevention medication. An additional advantage of medication is that it works quickly to reduce drug use, overdose deaths and HIV risk behavior. How long medication needed is unknown, but probably varies widely among patients. Developing medications, vaccines or other interventions that safely erase the craving would be a wonderful achievement. None.

Smartphone-delivered self-management for first-episode psychosis: the ARIES feasibility randomised controlled trial

ObjectivesTo test the feasibility and acceptability of a randomised controlled trial (RCT) to evaluate a Smartphone-based self-management tool in Early Intervention in Psychosis (EIP) services.DesignA two-arm unblinded feasibility RCT.SettingSix NHS...

Treatment Trajectories During and After a Medication Trial for Opioid Use Disorder: Moving from Research as Usual to Treatment as Usual.

The effectiveness of treatment incorporating relapse prevention medications for opioid use disorder (OUD) is typically examined in research using rigidly predefined endpoints of success versus failure, usually over a single episode of care. But this perspective may not adequately portray the nonlinear trajectories typical of real-world treatment courses in this chronic, remitting, and relapsing disorder. This descriptive study examined 12-month treatment trajectories of n = 60 patients enrolled at a single site of a larger multisite randomized controlled trial examining the comparative effectiveness of buprenorphine versus extended-release naltrexone. While the parent study provided medication treatment through the research protocol for 6 months, this study documents treatment up to 12 months, including medications, provided through standard community resources (treatment as usual) outside of the protocol. Some patients continued medications past the end of the study intervention, whereas others did not. Some patients initiated medications other than the one assigned by the study. Some patients switched from 1 medication to the other. Many patients returned to treatment after 1 or more periods of dropout and/or relapse. Patients utilized multiple episodes of bed-based care, including short-term acute residential and long-term residential treatment, and also recovery housing supports. Described trajectories are also depicted graphically. At 12 months, while rates of continuous treatment retention were low (8%), rates of cross-sectional treatment engagement including return to treatment after drop out were higher (35%). This description of nonlinear treatment trajectories highlights the potential benefits of flexibility and optimism in the promotion of re-engagement, despite interim outcomes that might traditionally be considered "failure" endpoints.

A double blind placebo controlled randomized clinical trial of the efficacy and safety of pregabalin in induction of remission in patients with alcohol dependence

To study the efficacy of pregabalin for relapse prevention and reduction of drinking in patients with alcohol dependence. One hundred recently detoxified out-patients with alcohol dependence were randomly assigned to one of two treatment groups. Patients of the first group (n=50; 38 men, 12 women, age 43.0±1.27) received pregabalin (150 mg once a day at night time) for 3 months, while patients of the second group (n=50; 45 men, 5 women, age 45.92±1.4) received identically looking placebo. All patients received standardized manualized weekly counseling (medical management). Drinking was measured on the weekly basis with Time Line Follow Back technique and GGT enzyme activity. Also, craving for alcohol, depression, and anxiety were measured weekly with the number of scales. Kaplan-Meier survival analysis demonstrated significantly higher retention in treatment and in remission in the pregabalin group (lower drop out and relapse rate) mediana (CL)-12 (10.4-13.6) weeks in the pregabalin group vs. 6 (4.5-7.5) in the placebo group, Log Rank Mantel-Cox test = 0.005). Proportion of patients, who completed treatment in the pregabalin group, was significantly higher compared to the placebo group: 50% vs. 24%. Mean duration of participation in the treatment program was also higher in the pregabalin group: 9.1±0.5 weeks vs. 7.1±0.5 in the placebo group. General linear model demonstrated the significant treatment group effect on: (1) total alcohol consumption (TAC) (mean grams of alcohol per day) with lower TAC in the pregabalin group and (2) on the number of heavy drinking days (NHDD) with lower NHDD in the pregabalin group. Mean NHDD per patient for the period of participation in the study was lower in the pregabalin group (3.6±0.7 vs. 6.4±0.8; p=0.009), while the mean number of abstinent (sober) days was higher (55.9±3.6 vs. 40.0±3.3; p=0.001). No significant differences between the two groups were found in the scores on craving for alcohol, depression and anxiety scales. GGT activity was also similar in both groups throughout the study with no significant between group differences. The rate of adverse events (sleepiness, dizziness, and headache) was insignificantly higher in the pregabalin group compared with the placebo group. All adverse events were mild, gradually disappeared, and did not require any medication. Results of this study provide evidence that pregabalin in a low dose of 150 mg per day is an effective and safe medication for relapse prevention and reduction of drinking in patients with alcohol dependence.

Gender Disparities in Alcohol Use Disorder Treatment Among Privately Insured Patients with Alcohol‐Associated Cirrhosis

The burden of alcohol-associated cirrhosis (AC) is high, and though alcohol cessation improves mortality, many patients fail to engage in alcohol use disorder (AUD) treatment and continue drinking. Our aim was to determine rates, predictors, and outcomes of AUD treatment utilization in AC patients with private insurance. We collected data from persons with AC (diagnosed by ICD-9/ICD-10 codes), aged 18 to 64years, enrolled in the Truven MarketScan Commercial Claims and Encounters database (2009 to 2016). We determined rates and predictors of substance abuse treatment visits as well as rates of alcohol relapse prevention medication prescriptions, weighted to the national employer-sponsored insured population. Effects of AUD treatment utilization on decompensation rates were calculated using proportional hazards regression with propensity score adjustment. A total of 66,053 AC patients were identified, 32% were female, and mean age at diagnosis was 54.5years. About 72% had insurance coverage for substance abuse treatment. Overall, AUD treatment utilization rates were low, with only 10% receiving a face-to-face mental health or substance abuse visit and only 0.8% receiving a Food and Drug Administration (FDA)-approved relapse prevention medication within 1year of index diagnosis. Women were less likely to receive a face-to-face visit (hazard ratio [HR] 0.84, p<0.001) or an FDA-approved relapse prevention medication (0.89, p=0.05) than men. AC patients who had a clinic visit for AUD treatment or used FDA-approved relapse medication showed decreased risk of decompensation at 1year (HR 0.85, p<0.001 for either). AUD treatment utilization is associated with lower decompensation rates among privately insured patients with AC. Women were less likely to utilize AUD treatment visits. Efforts to reduce gender-specific barriers to treatment are urgently needed to improve outcomes.

Home-based delivery of XR-NTX in youth with opioid addiction

Early experience with relapse prevention medications in the treatment of opioid addiction in youth has been positive, but barriers to effectiveness and broader adoption have included problems with adherence and retention, and lack of evidence or consensus about implementation. In particular there is relatively little known about either the effectiveness of extended release naltrexone (XR-NTX) in youth, or optimal models of care for its delivery. The purpose of this study is to report on a pilot initiative to improve the effectiveness of XR-NTX by delivering doses at home with assertive outreach to patients enrolled in a community treatment outpatient program. This is a naturalistic case series based on retrospective chart abstractions of 14 young adults (mean age=20.5), who enrolled in the pilot program, and in particular, the 9 who received home-based doses of XR-NTX. They are compared to a historical group of patients (n=21) prior to the pilot, who were referred to receive standard clinic-based doses of XR-NTX. Home-based administration was viewed favorably by patients and families. Although the small sample size is not amenable to statistical analysis, patients in the home based group, compared to the historical clinic-based group, received a greater number of doses overall and over 16 weeks of treatment, had longer retention, and attended similar numbers of clinic-based counseling sessions. These preliminary findings suggest that home-based delivery of XR-NTX and assertive outreach are feasible and promising in this critical target population, may compare favorably to clinic-based treatment as usual, and should be explored further in more rigorous evaluations.

Naltrexone ameliorates functional network abnormalities in alcohol‐dependent individuals

Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50‐mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly‐drug‐dependent individuals compared with 36 healthy volunteers. Graph theoretic and network‐based statistical analysis of resting‐state functional magnetic resonance imaging (MRI) data revealed that alcohol‐dependent subjects had reduced functional connectivity of a dispersed network compared with both poly‐drug‐dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol‐dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly‐substance‐dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology.

Socioeconomic and geographic disparities in access to pharmacotherapy for alcohol dependence

A higher rate of alcohol-attributable morbidity and mortality exists in remote and socioeconomically disadvantaged regions of Australia. This study aimed to explore the dispensing pattern of pharmacotherapy for alcohol dependence across these groups. A retrospective cohort study of patients (aged 15–84) dispensed acamprosate or naltrexone (July 2009–June 2013) was conducted. Observed dispensing rates were obtained for 541 local government areas (LGA) of Australia. Expected dispensing was based on national rates and age standardized to each LGA. Mean dispensing ratios (observed to expected) for each medicine over the period were calculated for remoteness and socioeconomic disadvantaged groups. For both medications, the mean dispensing ratio significantly differed across geographical groups and across socioeconomic groups (p's<0.05). For naltrexone and acamprosate, respectively, the mean dispensing ratio in remote areas was 6 and 9 times less than for the major cities. The mean dispensing ratio for both medications in the most socially disadvantaged areas was approximately 5 times less than that of the most disadvantaged areas. Our data highlight geographical and socioeconomic disparities in Australia regarding access to pharmacological treatment for alcohol use disorder. Targeted strategies aimed at bridging the gap of accessibility for relapse prevention medications are required.

Opioid Use Disorders.

Opioid use and addiction in adolescents and young adults is a health problem of epidemic proportions, with devastating consequences for youth and their families. Opioid overdose is a life-threatening emergency that should be treated with naloxone, and respiratory support if necessary. Overdose should always be an opportunity to initiate addiction treatment. Detoxification is often a necessary, but never sufficient, component of treatment for OUDs. Treatment for OUDs is effective but treatment capacity is alarmingly limited and under-developed. Emerging consensus supports the incorporation of relapse prevention medications such as buprenorphine and extended release naltrexone into comprehensive psychosocial treatment including counseling and family involvement.

Combination of Levo-Tetrahydropalmatine and Low Dose Naltrexone: A Promising Treatment for Prevention of Cocaine Relapse.

Relapse to drug use is often cited as the major obstacle in overcoming a drug addiction. Whereas relapse can occur for a myriad of reasons, it is well established that complex neuroadaptations that occur over the course of addiction are major factors. Cocaine, as a potent dopamine transporter blocker, specifically induces alterations in the dopaminergic as well as other monoaminergic neurotransmissions, which lead to cocaine abuse and dependence. Evidence also suggests that adaptations in the endogenous opioids play important roles in pathophysiology of cocaine addiction. Following this evidence, we investigated a combination medication, levo-tetrahydropalmatine (l-THP) and low dose naltrexone (LDN), targeting primarily dopaminergic and endogenous opioid systems as a cocaine-relapse-prevention treatment. In the present study Wistar rats were used to assess the effects ofl-THP and LDN on cocaine self-administration, drug-seeking behavior during cocaine reinstatement, spontaneous locomotion, and effects on the endogenous opioid system. We determined that the combination ofl-THP and LDN reduces drug-seeking behavior during reinstatement more potently thanl-THP alone. Additionally, the combination ofl-THP and LDN attenuates the sedative locomotor effect induced byl-THP. Furthermore, we revealed that treatment with the combination ofl-THP and LDN has an upregulatory effect on both plasmaβ-endorphin and hypothalamic POMC that was not observed inl-THP-treated groups. These results suggest that the combination ofl-THP and LDN has great potential as an effective and well-tolerated medication for cocaine relapse prevention.

Pharmacological interventions for alcohol relapse prevention

Alcohol dependence is a chronic, debilitating disorder that is an important public health problem worldwide. Combined psychological and pharmacological treatment packages produce best outcomes in its management. In this paper we discuss the three NICE – approved relapse prevention medications used in treatment of alcohol dependence: acamprosate, naltrexone and disulfiram. We review the pharmacological profile, mode of action, pharmacokinetics, and safety and tolerability of each of these pharmacological interventions. We discuss how each intervention can be used in clinical practice and review the efficacy of each drug. No one drug is clearly superior to the other, and clinical factors and patient choice should inform the choice of drug. KEY WORDS : Alcohol; Dependence; Pharmacological treatment

Ask the Expert: Substance-Related and Addictive Disorders

Ask the Expert: Substance-Related and Addictive Disorders