Use of Naltrexone in the Treatment of Alcohol Use Disorders in Patients with Concomitant Major Mental Illness

Abstract

We report the use of naltrexone for treatment of alcohol use disorder in patients with major psychiatric illness. We reviewed the records of 72 mentally ill outpatients treated with naltrexone for alcohol use disorders at a community mental health center. The psychiatric diagnoses included major depression (n = 37), schizophrenia (n = 17), bipolar illness (n = 11), schizoaffective disorder (n = 7), and gender identity disorder (n = 4). Sixty-one patients (85%) had histories of psychiatric hospitalization. Total retention in naltrexone treatment for at least eight weeks was 81.9%: 5 (6.9%) were lost to follow-up, and 8 (11.1%) discontinued the medication because of side effects, primarily nausea. Patients showed good clinical response to naltrexone, with 82% reducing their drinking by at least 75%, and only 17% relapsing at eight weeks. We conclude that naltrexone is useful in the treatment of dually-disordered patients. The hypothesis that clinical response to naltrexone is facilitated by active alcohol drinking during treatment is discussed.     

Naltrexone and disulfiram in patients with alcohol dependence and current depression

OBJECTIVE: Although disulfiram and naltrexone have been approved by the Food and Drug Administration for the treatment of alcoholism, no medications have been approved for individuals with alcohol dependence and comorbid psychiatric disorders. In particular, the effect of these medications on alcohol use outcomes and on specific psychiatric symptoms is still unknown in patients with the most common co-occurring disorder, major depression. METHOD: Two hundred fifty-four patients with a major Axis I psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in an outpatient medication study conducted at 3 Veterans Administration outpatient clinics. Randomization included (1) open randomization to disulfiram or no disulfiram, and (2) double-blind randomization to naltrexone or placebo. This resulted in 4 groups: (1) naltrexone alone, (2) placebo alone, (3) disulfiram and naltrexone, and (4) disulfiram and placebo. Primary outcomes were measures of alcohol use. Secondary outcomes included psychiatric symptoms assessed by the Hamilton Depression Rating Scale, alcohol craving, gamma-glutamyltransferase levels, and adverse events. RESULTS: One hundred thirty-nine subjects (54.7%) met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression. There was no relationship between the diagnosis of depression and medication treatment on alcohol use outcomes, psychiatric symptoms, or the reporting of side effects for these medications. There was a significant interaction between diagnosis, medication group, and craving, where subjects with depression on disulfram reported lower craving over time than subjects with depression on naltrexone. CONCLUSIONS: The results suggest that disulfiram and naltrexone are safe pharmacotherapeutic agents for dually diagnosed individuals with depression for the treatment of alcohol use disorders.     

Gender differences in treatment and clinical characteristics among patients receiving extended release naltrexone

Further research is needed to investigate real-world acceptability of extended-release naltrexone for alcohol and opioid use disorders, and potential gender differences. This study examines treatment and clinical characteristics among men and women receiving extended-release naltrexone in a large, publicly funded substance use disorder treatment system (N = 465; 52% female). Patient demographics, treatment characteristics, and the number of extended-release naltrexone doses received were collected from administrative data and treatment program staff. Additionally, patients provided information on experiences with extended-release naltrexone in an open-ended format at 1, 2, and 3 weeks following their first injection. For a subsample of patients (N = 220), alcohol/opioid cravings and specific adverse effects were also assessed. Compared to men, women reported experiencing a higher rate and mean number of adverse effects. Overall, craving scores showed substantial reductions over time. However, among patients taking extended-release naltrexone for alcohol use, women showed a significantly greater reduction in craving scores compared to men. No gender differences were observed in the number of extended-release naltrexone doses received. Although women may have a greater need for additional support in managing early adverse effects, extended-release naltrexone as an adjunct to psychosocial treatment may be an acceptable and promising treatment approach for both men and women, and particularly for women prescribed extended-release naltrexone for alcohol use. This study contributes further information on patients’ experiences during the early course of extended-release naltrexone treatment in real-world settings. Understanding these experiences may assist policy makers and treatment providers in addressing challenges of implementing this treatment into wider practice.     

Sustained-release bupropion versus naltrexone in the treatment of pathological gambling: a preliminary blind-rater study

BACKGROUND: Pathological gambling (PG) is a relatively common and highly disabling impulse control disorder. A range of psychotherapeutic agents, including selective serotonin reuptake inhibitors, mood stabilizers, and opioid antagonists, has been shown to be effective in the treatment of PG. The use of selective serotonin reuptake inhibitors and opioid antagonists for PG is consistent with the observation that PG shares features of both the obsessive-compulsive spectrum disorders and addictive disorders. The aim of the study is to compare the effectiveness of sustained-release bupropion versus naltrexone in the treatment of PG. METHODS: Thirty-six male pathological gamblers were enrolled in our study. A comprehensive psychiatric diagnostic evaluation was performed at baseline on all patients, and patients were screened for symptoms of gambling, depression, and anxiety using the South Oaks Gambling Screen, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression-Severity Scale. In addition, the patients completed self-report questionnaires about their demographic status. Patients were randomized in 2 groups and received either naltrexone (n = 19) or sustained-release bupropion (n = 17) for 12 weeks in a parallel fashion. Treatment response was monitored using the Clinical Global Impression-Improvement Scale which was performed at weeks 2, 4, 8, and 12. Patients were also assessed for the presence of gambling behavior via an unstructured interview, which was also performed at weeks 2, 4, 6, 8, and 12. Raters were blind to the study treatment. RESULTS: The majority of patients responded well to the drug treatment. Twelve of 17 patients in the sustained-release bupropion group completed the 12-week study, and 13 of 19 naltrexone patients completed the study. Nine (75%) of the 12 completers were rated as full responders in the sustained-release bupropion group versus 10 (76%) of 12 in the naltrexone group. Three (25%) of 12 completers in the bupropion group were rated as partial responders. In the naltrexone group, 3 (23%) of 13 completers were rated as partial responders. Full response was defined as the absence of gambling for a 2-week duration together with improvement on the Clinical Global Impression-Improvement Scale. Partial response was defined as a decrease in the frequency of gambling behavior and a decrease in the amount of money spent on gambling. CONCLUSION: This preliminary study shows that sustained-release bupropion may be effective as naltrexone in the treatment of PG. Further studies are needed to confirm our findings.     

Patient characteristics and treatment implications of marijuana abuse among bipolar alcoholics: results from a double blind, placebo-controlled study

OBJECTIVE: Marijuana abuse, primarily a disorder of adolescents and young adults, is highly prevalent among patients with severely ill psychiatric population, especially those with bipolar disorder. Additional marijuana abuse may impact on the clinical presentation of bipolar illness and may potentially act as mediator of treatment response in this population. However, the characterization of bipolar disorder patients with additional marijuana abuse and the impact of such abuse on treatment outcome has been rarely examined. The aim of this study was to characterize bipolar alcoholic patients with comorbid marijuana abuse and test the impact of marijuana abuse on alcohol and mood outcome of patients with bipolar disorder and comorbid alcohol dependence. METHOD: We conducted secondary analyses of a randomized, double blind, placebo-controlled trial testing valproate in 52 bipolar alcoholics. Subjects had a comprehensive assessment at baseline using structured diagnostic assessments, and they were then assessed every 2 weeks for 24 weeks. RESULTS: Twenty-five subjects (48%) reported marijuana abuse. Those with co-occurring marijuana abuse were younger, had fewer years of education, and had significantly higher number of additional psychiatric comorbidity. They also had more severe alcohol and other drug use and were significantly more likely to present in the manic phase. The mixed model indicated that the placebo-treated marijuana abuse group had the worst alcohol use outcome. CONCLUSIONS: Marijuana abuse among patients with bipolar disorder and alcohol dependence is associated with higher degree of severity of alcohol and other drugs of abuse and may negatively impact on alcohol treatment outcome.     

Nefazodone treatment of major depression in alcohol-dependent patients: a double-blind, placebo-controlled trial

Depression is the most common comorbid psychiatric illness in patients with alcohol dependence. This double-blind study tested the efficacy of nefazodone versus placebo for the treatment of depression in actively drinking alcohol-dependent patients who were also participating in weekly group treatment for alcoholism. Sixty-four subjects with major depression disorder and alcohol dependence with a history of at least one prior episode of depression when not drinking were randomly assigned to receive 12 weeks of either nefazodone or placebo and participated in a weekly psychoeducational group on alcoholism. Subjects were assessed every 2 weeks for depression, anxiety, side effects, and drinking frequency. Subjects taking nefazodone were significantly more likely to complete the study (62%) than those taking placebo (34%). Analyses of covariance using drinks per week as a time-dependent covariate showed lower Hamilton Rating Scale for Depression scores at week 8 for end-point analysis and at weeks 8 and 12 for completers. The endpoint analysis demonstrated a significantly greater response in the nefazodone group (48%) than in the placebo group (16%). Both groups showed a similarly significant decrease in the average number of alcoholic drinks consumed per day over the course of the study. Although the number of adverse effects was significantly greater for the nefazodone group, there were no severe adverse events, and nefazodone was well tolerated. Nefazodone is a safe and effective antidepressant to use in a population of alcohol-dependent patients with depression who have a high degree of comorbidity. Nefazodone treatment was superior to placebo in alleviating depression in these patients but did not add any advantage over the psychoeducational group in terms of drinking outcomes.     

An evaluation of hepatic enzyme elevations among HIV-infected released prisoners enrolled in two randomized placebo-controlled trials of extended release naltrexone

Extended-release naltrexone (XR-NTX), an approved treatment for opioid or alcohol dependence, is a once-monthly injectable formulation of naltrexone. Hepatotoxicity concerns have limited its use, necessitating further investigation. This study aims to examine hepatic enzyme levels in participants of 2 randomized placebo-controlled trials (RCTs) of XR-NTX. Hepatic transaminases were measured in 85 patients enrolled in RCTs of XR-NTX among HIV-infected prisoners, transitioning to the community and receiving treatment for either dependence on alcohol (52.9%), opioids (44.7%) or both (16.5%). Baseline characteristics included HCV co-infection (55.7%), antiretroviral therapy (81%), mental illness (39%) and receiving psychiatric medications (34.1%). Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) were not statistically different between persons randomized to placebo (N = 24) and XR-NTX (N = 61) arms. These results confirm that XR-NTX is safe to use among opioid and alcohol dependent HIV-infected released prisoners receiving ART with high rates of co-morbid HCV infection and mental illness.     

Relations among parental substance use, violence exposure and mental health: the national survey of adolescents

OBJECTIVE: To study the relations among parental substance use, violence exposure and psychopathology in a nationally representative sample of adolescents. METHOD: Random digit dialing methodology was used to obtain a nationally representative sample of 4023 adolescents, ages 12-17. Telephone surveys, conducted in 1995, assessed demographics, parental substance use, violence exposure, and three psychiatric disorders: major depressive disorder (MDE), posttraumatic stress disorder (PTSD), and substance abuse/dependence (SA/D). RESULTS: Obtained prevalence rates included: 8.2% for sexual assault, 22.5% for physical assault, and 39.7% for witnessing violence at home or in the community. Substance use by a family member was reported by 18.4% (n=721) of adolescents, with 50.6% reporting parental alcohol use and 19.1% (n=138) reporting parental drug use. Consistent with hypotheses, violence exposure and parental substance use, particularly parental alcohol abuse, were independently associated with outcomes. Additionally, parental substance use emerged as a moderator for MDE, PTSD, and SA/D; however, the moderating relations varied according to the outcome variable investigated. CONCLUSIONS: Violence-exposed adolescents reporting parental alcohol or drug use had the highest rates of psychiatric diagnoses.     

Drinking behavior and motivation for treatment among alcohol-dependent liver transplant candidates

Alcohol misuse is the second most common indication for liver transplantation in the United States. Our post-transplant alcoholism treatment trial suggested that current interventions might not be transferable to liver transplantees. We sought to identify differences between patients awaiting liver transplantation and alcoholics entering treatment without severe liver disease. Thirty transplant patients were compared to thirty naltrexone study patients on medical status, alcohol and drug use, alcohol craving, motivation for treatment, psychiatric symptoms, and psychosocial problems. Lifetime alcohol consumption was greater for transplant patients compared to naltrexone patients. In contrast to the naltrexone group, transplant patients denied craving for alcohol and showed little motivation for alcoholism treatment. Groups did not differ on other psychosocial measures. Liver transplant patients differ from patients in alcoholism treatment trials on measures of alcohol consumption, alcohol craving and motivation for treatment. Alcoholism interventions should accommodate their medical condition and boost motivation for continued abstinence.     

Gender differences with high-dose naltrexone in patients with co-occurring cocaine and alcohol dependence

This is a randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy of a higher-than-typical daily dose of naltrexone (150 mg/day), taken for 12 weeks, in 164 patients (n = 116 men and n = 48 women) with co-occurring cocaine and alcohol dependence. Patients were stratified by gender and then randomly assigned to either naltrexone or placebo, and to either cognitive–behavioral therapy or a type of medical management. The two primary outcomes were cocaine use and alcohol use. Significant Gender × Medication interactions were found for cocaine use via urine drug screens (three way, with time) and self-reports (two way) for drug severity (two way) and alcohol use (two way). The type of psychosocial treatment did not affect outcomes. Thus, 150 mg/day naltrexone added to a psychosocial treatment resulted in reductions in cocaine and alcohol use and drug severity in men, compared to higher rates of cocaine and alcohol use and drug severity in women.     

Improving clinical outcomes for naltrexone as a management of problem alcohol use

Despite being a relatively effective and safe treatment, the clinical management of alcohol abuse/dependence by oral naltrexone can be compromised due to the patient''s non-compliance with daily use of this medication. Over the past decade an increasing body of research has suggested that the use of sustained release depot naltrexone preparations can overcome this issue and deliver improved clinical outcomes. However, at the same time, research findings from diverse areas of pharmacogenetics, neurobiology and behavioural psychology have also been converging to identify variables including genetic markers, patient psychosocial characteristics and drug use history differences, or clusters of these variables that play a major role in mediating the response of alcohol abuse/dependent persons to treatment by naltrexone. While this article does not attempt to review all available data pertaining to an individual alcohol dependent patient''s response to treatment by naltrexone, it does identify relevant research areas and highlights the importance of data arising from them. The characterization of clinical markers, to identify those patients who are most likely to benefit from naltrexone and to tailor a more individual naltrexone treatment, will ultimately provide significant benefit to both patients and clinicians by optimizing treatment outcome.     

Trends in Opioid Use Disorder Diagnoses and Medication Treatment Among Veterans With Posttraumatic Stress Disorder

Objective: Despite long-standing interest in posttraumatic stress disorder (PTSD) and opioid use disorder comorbidity, there is a paucity of data on the prevalence of opioid use disorder in patients with PTSD. Therefore, there is limited understanding of the use of medications for opioid use disorder in this population. We determined the prevalence of diagnosed opioid use disorder and use of medications for opioid use disorder in a large cohort of patients with PTSD. Methods: We obtained administrative and pharmacy data for veterans who initiated PTSD treatment in the Department of Veterans Affairs (VA) between 2004 and 2013 (N = 731,520). We identified those with a comorbid opioid use disorder diagnosis (2.7%; n = 19,998) and determined whether they received a medication for opioid use disorder in the year following their initial clinical PTSD diagnosis (29.6%; n = 5,913). Using logistic regression, we determined the predictors of receipt of opioid use disorder medications. Results: Comorbid opioid use disorder diagnoses increased from 2.5% in 2004 to 3.4% in 2013. Patients with comorbid opioid use disorder used more health services and had more comorbidities than other patients with PTSD. Among patients with PTSD and comorbid opioid use disorder, use of medications for opioid use disorder increased from 22.6% to 35.1% during the same time period. Growth in the use of buprenorphine (2.0% to 22.7%) was accompanied by relative decline in use of methadone (19.3% to 12.7%). Patients who received buprenorphine were younger and more likely to be rural, White, and married. Patients who received methadone were older, urban, unmarried, from racial and ethnic minorities, and more likely to see substance abuse specialists. While use of naltrexone increased (2.8% to 8.6%), most (87%) patients who received naltrexone also had an alcohol use disorder. Controlling for patient factors, there was a substantial increase in the use of buprenorphine, a substantial decrease in the use of methadone, and no change in use of naltrexone across years. Conclusions: Opioid use disorder is an uncommon but increasing comorbidity among patients with PTSD. Patients entering VA treatment for PTSD have their opioid use disorder treated with opioid agonist treatments in large and increasing numbers. There is a need for research both on the epidemiology of opioid use disorder among patients with PTSD and on screening for opioid use disorder.     

Quality of life in veterans with alcohol dependence and co-occurring mental illness

Quality of life is negatively impacted by diagnosis of mental illness. Those with mental illness report problems in physical, psychological, cognitive, social, and occupational functioning. This study was designed to examine changes in quality of life in veterans with dual diagnoses. All veterans participated in a treatment study designed to treat alcohol dependence with naltrexone, disulfiram, and the combination of naltrexone/disulfiram or placebo for 12 weeks. Quality of life was assessed before treatment and at the end of treatment. Quality of life improved for all veterans and the improvement was more significant for those who abstained from alcohol throughout treatment. Severity of psychiatric symptom was associated with worse quality of life. This study demonstrates the importance of addressing social functioning in veterans with dual diagnosis.     

Sertraline treatment of co-occurring alcohol dependence and major depression

BACKGROUND: Major depressive disorder occurs commonly in association with alcohol dependence, both in clinical samples and in the community. Efforts to treat major depressive disorder in alcoholics with antidepressants have yielded mixed results. This multicenter, double-blind, placebo-controlled trial of sertraline was designed to address many of the potential methodological shortcomings of studies of co-occurring disorders. METHOD: Following a 1-week, single-blind, placebo lead-in period, 328 patients with co-occurring major depressive disorder and alcohol dependence were randomly assigned to receive 10 weeks of treatment with sertraline (at a maximum dose of 200 mg/d) or matching placebo. Randomization was stratified, based on whether initially elevated scores on the 17-item Hamilton Depression Rating Scale declined with cessation of heavy drinking, resulting in a sample of 189 patients with Hamilton Depression Rating Scale scores > or =17 (group A) and 139 patients with Hamilton Depression Rating Scale scores < or =16 (group B). RESULTS: Both depressive symptoms and alcohol consumption decreased substantially over time in both groups. There were no reliable medication group differences on depressive symptoms or drinking behavior in either group A or B patients. CONCLUSION: Despite careful attention to methodological considerations, this study does not provide consistent support for the use of sertraline to treat co-occurring major depressive disorder and alcohol dependence. The high rate of response among placebo-treated patients may help to explain these findings. Further research is needed to identify efficacious treatments for patients with these commonly co-occurring disorders.     

Targeted use of naltrexone without prior detoxification in the treatment of alcohol dependence: a factorial double-blind, placebo-controlled trial

Several studies have shown the opioid antagonist naltrexone to be effective when combined with psychosocial therapies for the treatment of patients who are dependent on alcohol with fixed medication and time (12 weeks). In this study, 121 nonabstinent outpatients with alcohol dependence (DSM-IV) were treated with sessions of cognitive coping skills (N = 67) or supportive therapy (N = 54) and either naltrexone 50 mg/day (N = 63) or placebo (N = 58) daily for the first 12 weeks and thereafter for 20 weeks only when craving alcohol (i.e., targeted medication) in a prospective one-center, dual, double-blind, randomized clinical trial. The dropout rate for all subjects was 16.5% during the first 12-week period and approximately twice that level by the end of the study. There were no significant group differences in study completion and therapy participation rates. After the continuous medication (12 weeks), the coping/naltrexone group had the best outcome, and coping/placebo had the worst. This difference remained during the targeted medication period (the following 20 weeks). Naltrexone was not better than placebo in the supportive groups, but it had a significant effect in the coping groups: 27% of the coping/naltrexone patients had no relapses to heavy drinking throughout the 32 weeks, compared with only 3% of the coping/placebo patients. The authors' data confirm the original finding of the efficacy of naltrexone in conjunction with coping skills therapy. In addition, their data show that detoxification is not required and that targeted medication taken only when craving occurs is effective in maintaining the reduction in heavy drinking.     

A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients.

This study examined the association between two specific polymorphisms of the gene encoding the mu-opioid receptor and treatment outcomes in alcohol-dependent patients who were prescribed naltrexone or placebo. A total of 82 patients (71 of European descent) who were randomized to naltrexone and 59 who were randomized to placebo (all of European descent) in one of three randomized, placebo-controlled clinical trials of naltrexone were genotyped at the A(+118)G (Asn40Asp) and C(+17)T (Ala6Val) SNPs in the gene encoding the mu-opioid receptor (OPRM1). The association between genotype and drinking outcomes was measured over 12 weeks of treatment. In subjects of European descent, individuals with one or two copies of the Asp40 allele treated with naltrexone had significantly lower rates of relapse (p=0.044) and a longer time to return to heavy drinking (p=0.040) than those homozygous for the Asn40 allele. There were no differences in overall abstinence rates (p=0.611), nor were there differences in relapse rates or abstinence rates between the two genotype groups among those assigned to placebo. These preliminary results are consistent with prior literature demonstrating that the opioid system is involved in the reinforcing properties of alcohol and that allelic variation at OPRM1 is associated with differential response to a mu-receptor antagonist. If replicated, these results would help to identify alcohol-dependent individuals who may be most likely to respond to treatment with naltrexone.     

Co-morbidity and cannabis use in a mental health trust in South East England

AIM: The prevalence of co-morbidity (severe mental illness and substance) may be less in rural and semi-rural areas than inner cities. The aims were therefore to measure the prevalence of co-morbidity among patients of attending a mental health service in a semi-rural area South East England. DESIGN AND PARTICIPANTS: Cross-sectional prevalence survey of 1,808 patients with detailed assessments from a representative sample of 373 patients identified as having a combination of severe mental illness and substance misuse. Interviews with key workers were performed using validated methods from the COSMIC study. RESULTS: The response rates equalled or exceeded 90% for the various parts of the study. One-tenth of patients attending the Community Mental Health Teams (CMHTs) reported problematic use of illicit drugs and 17% reported alcohol problems in the past year. 22% of Community Drug and Alcohol Service (CDAS) clients reported a severe mental illness and 46% reported some other form of psychiatric disorder. Of patients with a combined diagnosis of mental illness and substance misuse, cannabis use was 4-fold more common amongst patients attending the CMHT than CDAS (33% vs. 8%) while use of amphetamine was five-fold higher in the CMHT group (10% vs. 2%). Patients with concurrent psychiatric and substance misuse problems represent a similar proportion of the aggregate caseload of both treatment services with observed prevalence amongst the CDAS and CMHT patients with a diagnosis for anxiety disorder (18% vs. 26%), minor depression (42% vs. 32%), personality disorders (32% vs. 36%), histories of self-harm (52% vs. 46%) and violence (33% vs. 30%) respectively. CONCLUSIONS: Co-morbidity is common in clients amongst CMHT and CDAS clients although use of cannabis was significantly more common in CMHT clients than in CDAS clients.     

Divalproex in the treatment of impulsive aggression: efficacy in cluster B personality disorders.

Impulsive aggressive behavior is common in psychiatric disorders and accounts for significant morbidity and mortality. However, little systematic treatment data exist from placebo-controlled trials for this symptom domain. This was a multicenter, randomized, double-blind, placebo-controlled study in which outpatients with a score of > or =15 on the Aggression scale of the Overt Aggression Scale-Modified (OAS-M) and who fulfilled DSM-IV criteria for Cluster B personality disorder (n=96), intermittent explosive disorder (n=116), or post-traumatic stress disorder (n=34) were randomized to divalproex sodium or placebo for 12 weeks duration. Based on average OAS-M Aggression scores over the last 4 weeks of treatment, a treatment effect was not observed in the intent-to-treat data set (combined across the three psychiatric disorders), but was observed in both intent-to-treat and evaluable data sets for patients with Cluster B personality disorders. In the Cluster B evaluable data set, statistically significant treatment differences favoring divalproex were also observed for component items of the OAS-M Aggression score, including verbal assault and assault against objects, as well as OAS-M Irritability score, and Clinical Global Impression (CGI)-Severity at multiple time points throughout the study. No treatment group difference was noted for overall premature discontinuation rate; however, across psychiatric diagnoses, 21 (17%) patients in the divalproex group prematurely discontinued because of an adverse event, as compared to 4 (3%) patients in the placebo group (p <0.001). While a treatment effect was not observed when all diagnostic groups were combined, in a large subgroup of patients with Cluster B disorders, divalproex was superior to placebo in the treatment of impulsive aggression, irritability, and global severity.     

A double-blind, placebo-controlled, randomized pilot study comparing quetiapine with placebo, associated to naltrexone, in the treatment of alcohol-dependent patients

The objective of this study was to determine whether quetiapine plus naltrexone is more effective than naltrexone alone for the treatment of alcohol-dependent patients. This was a double-blind, randomized clinical trial where eligible alcohol-dependent patients were randomized to receive naltrexone (50mg/day) plus quetiapine (25-200mg/day) or naltrexone (50mg/day) plus placebo for 12 weeks, and afterwards patients received naltrexone alone during 4 additional weeks. The primary efficacy measures were percent days abstinent, drinks per drinking day, and the relapse rate. Sixty-two patients received a single-blind treatment with placebo plus naltrexone, and they were thereafter randomly assigned to quetiapine plus naltrexone (n=30) or placebo plus naltrexone (n=32). Eleven (36.7%) patients in the quetiapine-treated group and 4 (12.5%) patients in the placebo-treated group withdrew before they completed 12 weeks of treatment. There were no statistically significant differences for any primary drinking outcomes between treatment groups. Both regimens were well tolerated. This study failed to demonstrate any additional benefit from the combination of quetiapine and naltrexone compared to naltrexone alone on drinking outcomes.