A randomized trial of combined citalopram and naltrexone for nonabstinent outpatients with co-occurring alcohol dependence and major depression.

Despite the high rate of co-occurrence of major depression and alcohol dependence, the role of pharmacotherapy in their treatment remains unclear. In the new era of naltrexone for alcohol dependence, it is notable that only 1 study to date has examined the efficacy of antidepressant medication prescribed concurrently with naltrexone. We aimed to determine whether combining naltrexone with citalopram produced better treatment outcomes than naltrexone alone in patients with co-occurring alcohol dependence and depression, and to investigate whether either sex or depression type (independent or substance-induced depression) moderated treatment response. Participants were 138 depressed alcohol-dependent adults who were not required to be abstinent at the commencement of the trial. They were randomized to 12 weeks of citalopram or placebo, plus naltrexone and clinical case management. Treatment was well attended, and medications were reasonably well tolerated with high adherence rates. Substantial improvements in both mood and drinking occurred in both groups, with no significant differences between groups on any of the mood or drinking outcome measures, whether or not other variables were controlled for. No interaction effect was found for independent/substance-induced depression status, whereas there was a marginal effect found by sex, with greater improvement in 1 drinking outcome measure (percent days abstinent) in women taking citalopram. These findings suggest that citalopram is not a clinically useful addition to naltrexone and clinical case management in this treatment population. Independent/substance-induced depression status did not predict treatment response. Findings for sex were equivocal.

Movies as a vehicle to teach addiction medicine.

Dependence on a substance and the role of medical practitioners in this health problem can be perceived as an enigma. Movies, as a tool for teaching, can be a powerful means of engaging, clarifying and educating students within the addiction medicine arena. Popular mythologies and stereotypes of drug use (including alcohol) and users in cinema can be explored within a learning environment aiding the understanding of this complex topic, thereby improving the therapeutic commitment to addiction medicine. There is a responsibility of the teacher to use this tool with care so as not to perpetuate the mythologies of addiction as often portrayed within commercial cinema. Tried and tested use of this potent educational aid, with suggestions for further development, are outlined in this article.

A longitudinal evaluation of medical student knowledge, skills and attitudes to alcohol and drugs.

AIM: To examine the knowledge, skills and attitudes of medical students to alcohol and drugs as training progresses. DESIGN: A longitudinal, prospective, cohort-based design. SETTING: The four schools of medicine in New Zealand. PARTICIPANTS: All second-year medical students (first year of pre-clinical medical health sciences) in New Zealand were administered a questionnaire which was repeated in the fourth (first year of significant clinical exposure) and then sixth years (final year). A response rate of 98% in the second year, 75% in the fourth year and 34% in the sixth year, with a total of 637 respondents (47.8% male) and an overall response rate of 68%. QUESTIONNAIRE: The questionnaire consisted of 43 questions assessing knowledge and skills -- a mixture of true/false and scenario stem-based multiple-choice questions and 25 attitudinal questions scored on a Likert scale. Demographic questions included first language, ethnicity and personal consumption of alcohol and tobacco. FINDINGS: The competence (knowledge plus skills) correct scores increased from 23.4% at the second year to 53.6% at the fourth year to 71.8% at the sixth year, being better in those students who drank alcohol and whose first language was English (P < 0.002). As training progressed the student's perceptions of their role adequacy regarding the effectiveness of the management of illicit drug users diminished. For example, at second year 21% and at sixth year 51% of students felt least effective in helping patients to reduce illicit drug use. At the sixth year, 15% of sixth year students regarded the self-prescription of psychoactive drugs as responsible practice. CONCLUSION: Education on alcohol and drugs for students remains a crucial but under provided part of the undergraduate medical curriculum. This research demonstrated that while positive teaching outcomes were apparent, further changes to medical student curricula need to be considered to address specific knowledge deficits and to increase the therapeutic commitment and professional safety of medical students to alcohol and drugs.

Anterior Cingulate Implant for Alcohol Dependence: Case Report.

BACKGROUND AND IMPORTANCE: Alcohol dependence is related to dysfunctional brain processes, in which a genetic background and environmental factors shape brain mechanisms involved with alcohol consumption. Craving, a major component determining relapses in alcohol abuse, has been linked to abnormal brain activity. CLINICAL PRESENTATION: We report the results of a treatment-intractable, alcohol-addicted patient with associated agoraphobia and anxiety. Functional imaging studies consisting of functional magnetic resonance imaging and resting-state electroencephalogram were performed as a means to localize craving-related brain activation and for identification of a target for repetitive transcranial magnetic stimulation and implant insertion. Repetitive transcranial magnetic stimulation of the dorsal anterior cingulate cortex with a double-cone coil transiently suppressed his very severe alcohol craving for up to 6 weeks. For ongoing stimulation, 2 "back-to-back" paddle electrodes were implanted with functional magnetic resonance imaging neuronavigation guidance for bilateral dorsal anterior cingulate cortex stimulation. Using a recently developed novel stimulation design, burst stimulation, a quick improvement was obtained on craving, agoraphobia, and associated anxiety without the expected withdrawal symptoms. The patient has remained free of alcohol intake and relieved of agoraphobia and anxiety for over 18 months, associated with normalization of his alpha and beta activity on electroencephalogram in the stimulated area. He perceives a mental freedom by not being constantly focused on alcohol. CONCLUSION: This case report proposes a new pathophysiology-based target for the surgical treatment of alcohol dependence and suggests that larger studies are warranted to explore this potentially promising avenue for the treatment of intractable alcohol dependence with or without anxiety and agoraphobia. ABBREVIATIONS: ACC, anterior cingulate cortexBOLD, blood oxygen level dependentdACC, dorsal anterior cingulate cortexDBS, deep brain stimulationEEG, electroencephalogramfMRI, functional magnetic resonance imagingrTMS, repetitive transcranial magnetic stimulationSMA, supplementary motor areaTMS, transcranial magnetic stimulation.

Switching Opioid-Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics.

The aim of this study was to switch patients established on methadone opioid substitution therapy (OST) to morphine over 1 week. Subjects established on daily methadone OST (mean dose 60 mg/day) were switched to morphine slow-release capsules, dosed at 4× the previous total daily methadone dose, for 6 days, then given morphine syrup dosed q3h. All 27 subjects enrolled in this study completed the switch from methadone to morphine. Opioid withdrawal symptoms (OWS) peaked within 12-24 hours of starting morphine, and 24/27 subjects required higher daily morphine doses (mean 5.2× multiple). Pharmacokinetic evaluation showed that 91% of methadone was cleared during this time, with a mean elimination half-life of 59 hours. The most frequent treatment-emergent non-OWS adverse events were headache, nausea, constipation, and neck pain. The method described here appears to be a safe and acceptable approach to switch subjects from methadone to morphine.

Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients.

Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and Cmax and was slowly eliminated (mean t1/2 range, 24-30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL), with the largest observed mean effect of ∼16, 28, and 42 milliseconds in the 60-, 120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120-mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure-controlled multiple-dose noribogaine studies are planned that will address these safety and design issues.