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Background: Modafinil is a medication approved for narcolepsy and shift work sleep disorder. It has both dopaminergic and glutamatergic activity that could be useful for the treatment of cocaine dependence. Modafinil has reduced cocaine subjective effects and cocaine self-administration in human laboratory trials and has reduced cocaine use in cocaine dependent patients in some clinical trials., Methods: This was an 8-week, double blind, placebo controlled clinical trial involving 94 cocaine dependent subjects. Subjects received 300mg of modafinil or identical placebo daily along with weekly individual therapy. The primary outcome measure was cocaine use measured by self-report, and confirmed by twice weekly urine benzoylecgonine tests (UBT). Additional outcome measures included cocaine craving measured by the Brief Substance Craving Scale and global improvement measured by the Clinical Global Impression Scale (CGI)., Results: The odds ratio (OR) in favor of abstinence for modafinil vs. placebo was 2.54 (p=. 03) and modafinil-treated subjects were significantly more likely than placebo-treated subjects to be abstinent from cocaine during the last 3 weeks of the trial, 23% vs. 9%, χ(2)=3.9, p<.05. Modafinil treated subjects were more likely to report very low levels of cocaine craving intensity and duration on the Brief Substance Craving Scale (OR=2.04, p=.03 and OR 1.06, p=.03 respectively). Modafinil-treated subjects were also more likely than placebo-treated subjects to rate themselves as "very much improved" on the CGI (OR=2.69, p=.03)., Conclusion: Modafinil may be an efficacious treatment for cocaine dependence., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Alcohol use, abuse and dependence remain a pressing public health problem. Based on its mechanism of action, varenicline seemed to be a likely candidate for treating alcohol dependence., Methods: Alcohol dependent subjects (n=40) were enrolled in a 13-week double-blind placebo controlled clinical trial. Subject visits were once per week. At each visit, subjects were tested for breath alcohol levels, provided self-report data on alcohol and nicotine use, and on mood and craving. In addition, subjects received once a week medical management (MM)., Results: There was no difference between varenicline and placebo treated groups on any of the drinking outcomes. Compared to placebo-treated subjects, varenicline treated subjects had decreased rates of alcohol craving and cigarette smoking, as well as greater mood improvements during the later part of the study (weeks 6-13). In addition, among subjects who were cigarette smokers, those treated with varenicline were significantly less likely to report heavy drinking during the trial., Conclusions: Although varenicline was not significantly more effective than placebo at reducing drinking during the trial, its effects on alcohol craving and mood suggest that future investigation of the mechanism of action of varenicline, as well as additional clinical studies may be warranted. In particular, the findings regarding the influence of smoking status on heavy drinking among varenicline-treated subjects should be investigated in future studies., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Topiramate increases GABAergic activity and antagonizes the AMPA/kainate subtype of glutamate receptors. Through these mechanisms of action, topiramate may reduce alcohol and cocaine reward and may reduce alcohol and cocaine craving. Topiramate has been shown to reduce drinking in persons with alcohol dependence, and reduce relapse in stimulant-dependent patients. The current trial was intended to test the ability of topiramate to promote cocaine and alcohol abstinence among patients addicted to both drugs., Methods: The study was a double-blind, placebo-controlled, 13-week trial involving 170 cocaine and alcohol dependent subjects. After achieving a period of cocaine and alcohol abstinence, subjects were randomized to topiramate, 300 mg daily, or identical placebo capsules. In addition, subjects received weekly individual psychotherapy. Primary outcome measures included self-reported alcohol and cocaine use, and thrice weekly urine drug screens. Secondary outcome measures included cocaine and alcohol craving, Addiction Severity Index results, cocaine withdrawal symptoms, and clinical global improvement ratings., Results: Topiramate was not better than placebo in reducing cocaine use on the a priori primary outcome measure, or in reducing alcohol use. Topiramate was not better than placebo in reducing cocaine craving. Topiramate-treated subjects, compared to placebo-treated subjects, were more likely to be retained in treatment and more likely to be abstinent from cocaine during the last three weeks of the trial. Subjects who entered treatment with more severe cocaine withdrawal symptoms responded better to topiramate., Discussion: Topiramate plus cognitive behavioral therapy may reduce cocaine use for some patients with comorbid cocaine and alcohol dependence., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Addiction susceptibility and treatment responsiveness are greatly influenced by genetic factors. Sequence variation in genes involved in the mechanisms of drug action have the potential to influence addiction risk and treatment outcome. The opioid receptor system is involved in mediating the rewarding effects of cocaine and opioids. The μ-opioid receptor (MOR) has traditionally been considered the primary target for opioid addiction. The MOR, however, interacts with and is regulated by many known MOR interacting proteins (MORIPs), including the δ-opioid receptor (DOR)., Methods: The present study evaluated the contribution of OPRD1, the gene encoding the DOR, to the risk of addiction to opioids and cocaine. The association of OPRD1 polymorphisms with both opioid addiction (OA) and cocaine addiction (CA) was analyzed in African American (OA n=336, CA n=503) and European American (OA n=1007, CA n=336) populations., Results: The primary finding of this study is an association of rs678849 with cocaine addiction in African Americans (allelic p=0.0086). For replication purposes, this SNP was analyzed in a larger independent population of cocaine addicted African Americans and controls and the association was confirmed (allelic p=4.53 × 10(-5); n=993). By performing a meta-analysis on the expanded populations, the statistical evidence for an association was substantially increased (allelic p=8.5 × 10(-7)) (p-values non-FDR corrected)., Conclusion: The present study suggests that polymorphisms in OPRD1 are relevant for cocaine addiction in the African American population and provides additional support for a broad role for OPRD1 variants in drug dependence., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Cocaine use, abuse and dependence remains a pressing public health problem. Based on its mechanism of action, varenicline, an alpha4beta2 partial agonist seemed to be a likely candidate for treating cocaine dependence., Methods: Cocaine dependent participants (n=37) were enrolled in a 9-week double-blind placebo controlled clinical trial. Varenicline was titrated up to a target dose of 1mg BID during the first week of medication., Results: Varenicline was associated with lower odds of cocaine use than placebo (OR=2.02, p=0.08), as measured by thrice-weekly urinalysis results. Compared to placebo-treated participants, varenicline treated participants had significantly decreased rates of cocaine reward, as measured by the Multiple Choice Procedure (MCP) (p=0.02)., Conclusions: Varenicline appears to decrease cocaine use and reward, suggesting that further investigation of varenicline may be warranted., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

This study examined the relationship of the therapeutic alliance and treatment outcomes for alcohol-dependent patients receiving naltrexone or placebo and one of three different types of clinical interventions, including two medical-based (non-specialty) treatments. This is a secondary analysis of a 24-week randomized, placebo-controlled, clinical trial of 100mg/day of naltrexone or placebo for patients with DSM-IV alcohol dependence. Patients were also randomized to one of three interventions: (1) medication clinic only, (2) medication clinic plus BRENDA (an intervention promoting pharmacotherapy), or (3) medication clinic plus cognitive behavioral therapy (CBT). Early in treatment, patients and clinicians completed the working alliance inventory (WAI). Regression analyses were conducted to determine the predictive validity of the WAI on percent days abstinent and percent of sessions attended over the clinical trial. In the medication clinic only condition, the clinicians' WAI total score was marginally correlated to percent of visits attended (p=.057) but not percent days abstinent. In the medication clinic plus BRENDA condition, clinicians' WAI total score was positively correlated with percent days abstinent (p=.013) but not percent visits attended. No significant relationships were found between the WAI scores and either outcome measure in the CBT condition or for any of the patient rated assessments. To our knowledge, this is the first published report providing some support for the importance of the therapeutic alliance in medical interventions for alcohol dependence but only in the context of the clinicians' ratings. The absence of other effects underscores the need for further research.

The use of antidepressant pharmacotherapy to treat patients with co-occurring depression and alcohol dependence is controversial. There is a stigma attached to giving medications to alcohol-dependent persons. Also, empirical evidence is sparse and inconsistent, which discourages the use of antidepressants in these patients. Historically, it has been a challenge to accurately diagnose a depressive disorder in the presence of alcohol dependence. In addition, early clinical studies were fraught with methodological problems; however, improved diagnostic assessments are now available, and in the last decade, results from well-controlled trials appear to support the use of antidepressants in this patient population in the specific role of relieving depressive symptoms. The majority of these trials also demonstrate that antidepressants have relatively little impact on reducing heavy drinking in this patient population, even though the medications reduce depressive symptoms. Newer approaches to treating patients with co-occurring depression and alcohol dependence suggest adding to the antidepressant a pharmacotherapy that directly impacts drinking. The findings from this review better define the action of antidepressants in patients with co-occurring depression and alcohol dependence as specific to reducing depressive symptoms, and these medications and their action on mood have little impact on treating the co-occurring alcohol dependence.

Vasopressin may be involved in normal memory functions and may alleviate certain memory impairments. In this study, the usefulness of vasopressin to relieve electroconvulsive therapy (ECT)-induced memory impairment was evaluated using a placebo-controlled, random assignment, double-blind design. Patients were 33 depressives receiving bilateral ECT. Vasopressin, in a nasal spray, was administered q.i.d. from the first through the fifth ECT. Extensive memory testing evaluated both retrograde and anterograde amnesia; ratings of depression and patient ratings of subjective memory complaints were also obtained. Results did not show statistically significant evidence of benefit from vasopressin, though a number of comparisons were in the predicted direction. The role of vasopressin in reducing memory impairment of various types remains to be elucidated.

The Squire Self-rating Scale of Memory Function was administered to 28 depressed inpatients before and after electroconvulsive therapy (ECT), with random assignment to bilateral or unilateral electrode placement. Several memory changes differentiated between bilateral and unilateral ECT following treatment (p less than 0.05). Memory complaints arising from ECT were distinguished from those due to depression.

Dexamethasone, compared to placebo in a double-blind study, failed to prevent the memory deficiency that typically accompanies electroconvulsive therapy (ECT) (n = 48 patients treated for DSM-III diagnosed major depressive disorder). Rather, the administration of the drug was associated with attention (p less than 0.02) and short-term memory (p less than 0.0003) difficulties in both bilateral and unilateral ECT patients. Bilateral ECT plus dexamethasone patients had significantly less improvement (p less than 0.05) in their depression (measured by the Hamilton Depression Scale) compared to bilateral ECT plus placebo patients. These depression differences were not seen among unilateral ECT patients.

The number of electroconvulsive therapy (ECT) stimulations over a course of treatment that resulted in brief or no seizure activity was evaluated for depressed patients (N = 58, treated for DSM-III diagnosed major depressive disorder) who had been randomly assigned to either bilateral or unilateral nondominant ECT in a double-blind study. Comparable treatment efficacy between both groups was found. Although there were no group differences in brief seizures, unilateral nondominant ECT resulted in more missed seizures (p less than 0.01) and required more restimulations than bilateral ECT. Of 27 unilateral ECT patients, 63% had at least one missed seizure over the course of treatment, compared to 29% of 31 bilateral ECT patients (p less than 0.02). Although more missed seizures occurred early in treatment, brief seizures occurred later in treatment. As missed seizures are not always detected clinically, it is possible that without seizure monitoring, patients with unilateral nondominant ECT will not improve at the same rate as patients with bilateral ECT. Lack of seizure monitoring in the clinic is one likely explanation for the discrepancy between a number of research studies reporting equivalent efficacy for bilateral and unilateral ECT and the clinical impression that bilateral ECT is more effective.