Mohit P. Chopra

Randomized, double blind, placebo-controlled trial of disulfiram for the treatment of cocaine dependence in methadone-stabilized patients.

UNLABELLED This study examined the dose-related efficacy of disulfiram for treating cocaine dependence in methadone-stabilized cocaine dependent participants. DESIGN One hundred and sixty-one cocaine- and opioid-dependent volunteers were entered into a 14-week, double blind, randomized, placebo-controlled clinical trial at two sites. METHODS Participants were stabilized on methadone during weeks 1-2 and received disulfiram at 0, 62.5, 125 or 250 mg/day during weeks 3-14. All participants also received weekly cognitive behavioral therapy. Thrice-weekly urine samples and weekly self-reported drug use assessments were obtained. RESULTS Baseline subject characteristics, retention and drug use did not differ across groups. Outcome analyses were performed on those who participated beyond week 2. Opioid-positive urine samples and self-reported opioid use did not differ by treatment group. The prevalence of alcohol use was low prior to and during the trial and did not differ by treatment group. Cocaine-positive urines increased over time in the 62.5 and 125 mg disulfiram groups and decreased over time in the 250 mg disulfiram and placebo groups (p < 0.0001). Self-reported cocaine use increased in the 125 mg disulfiram group relative to the other three treatment groups (p = 0.04). CONCLUSIONS Disulfiram may be contraindicated for cocaine dependence at doses <250 mg/day. Whether disulfiram at higher doses is efficacious in reducing cocaine use in dually cocaine and opioid dependent individuals needs to be determined.

Vitamin E and memantine in Alzheimer's disease: Clinical trial methods and baseline data

Alzheimers disease (AD) has been associated with both oxidative stress and excessive glutamate activity. A clinical trial was designed to compare the effectiveness of (i) alpha‐tocopherol, a vitamin E antioxidant; (ii) memantine (Namenda), an N‐methyl‐D‐aspartate antagonist; (iii) their combination; and (iv) placebo in delaying clinical progression in AD.

Open Label Pilot Study of Modafinil for Methamphetamine Dependence

Methamphetamine has become a major public health issue globally, particularly in the United States. Despite this, no effective pharmacotherapy for methamphetamine abuse has been developed to date. This 6-week, open-label pilot clinical trial examined the safety and tolerability of modafinil up to 400 mg/d in 8 methamphetamine-dependent individuals. Subjects were inducted onto modafinil at 400 mg/d for more than 3 days and remained on 400 mg/d for 4.5 weeks. Participants received weekly blister packs and underwent weekly individual cognitive behavioral therapy. Adjunctive contingency management procedures were used to enhance retention. Vital signs and supervised urine samples were obtained thrice weekly, and self-reported drug use and Hamilton anxiety and depression ratings were completed once weekly. Eight subjects (50% female, 100% white, aged 35-52 years) were enrolled. Four completed the 6-week study, 3 completed a portion, and 1 withdrew consent before completing intake. Results showed that systolic blood pressure (t = 1.09, P = 0.28), diastolic blood pressure, (t = 1.18, P = 0.24), and heart rate (t = 1.55, P = 0.13) did not change over time. Scores on the modafinil side effects checklist (t = −2.63, P = 0.01), Hamilton anxiety scale (t = −2.50, P = 0.018), and Hamilton depression scale (t = −3.25, P = 0.003) all decreased over time. The proportion of urine positive for amphetamines did not change over time (t = −0.52, P = 0.61), whereas self-reported methamphetamine use did (t = −2.86, P < 0.005). These results suggest that modafinil at 400 mg/d is safe and tolerable for methamphetamine-dependent individuals.

Buprenorphine medication versus voucher contingencies in promoting abstinence from opioids and cocaine.

During a 12-week intervention, opioid dependent participants (N = 120) maintained on thrice-a-week (M, W, F) buprenorphine plus therapist and computer-based counseling were randomized to receive: (a) medication contingencies (MC = thrice weekly dosing schedule vs. daily attendance and single-day 50% dose reduction imposed upon submission of an opioid and/or cocaine positive urine sample); (b) voucher contingency (VC = escalating schedule for opioid and/or cocaine negative samples with reset for drug-positive samples); or (c) standard care (SC), with no programmed consequences for urinalysis results. VC resulted in better 12-week retention (85%) compared to MC (58%; p = 0.009), but neither differed from SC (76% retained). After adjusting for baseline differences in employment, and compared to SC, the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence (p = 0.030), while the VC group had 2 more total weeks of abstinence (p = 0.048). Drug use results suggest that both the interventions were efficacious, with effects primarily in opioid rather than cocaine test results. Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies.

Adding an Internet-delivered treatment to an efficacious treatment package for opioid dependence.

OBJECTIVE To examine the benefit of adding an Internet-delivered behavior therapy to a buprenorphine medication program and voucher-based motivational incentives. METHOD A block-randomized, unblinded, parallel, 12-week treatment trial was conducted with 170 opioid-dependent adult patients (mean age = 34.3 years; 54.1% male; 95.3% White). Participants received an Internet-based community reinforcement approach intervention plus contingency management (CRA+) and buprenorphine or contingency management alone (CM-alone) plus buprenorphine. The primary outcomes, measured over the course of treatment, were longest continuous abstinence, total abstinence, and days retained in treatment. RESULTS Compared to those receiving CM-alone, CRA+ recipients exhibited, on average, 9.7 total days more of abstinence (95% confidence interval [CI = 2.3, 17.2]) and had a reduced hazard of dropping out of treatment (hazard ratio = 0.47; 95% CI [0.26, 0.85]). Prior treatment for opioid dependence significantly moderated the additional improvement of CRA+ for longest continuous days of abstinence. CONCLUSIONS These results provide further evidence that an Internet-based CRA+ treatment is efficacious and adds clinical benefits to a contingency management/medication based program for opioid dependence.

Self-, collateral- and clinician assessment of depression in persons with cognitive impairment

Objectives: This investigation examined the associations between self-reports, collateral-source reports and a clinicians diagnosis of depression in persons with cognitive impairment. Method: Responses on the Geriatric Depression Scale – 15 (GDS-15) from 162 participants with a diagnosis of Mild Cognitive Impairment (n = 78) or Alzheimers Dementia and a Mini-Mental State score ≥15 (n = 84) were compared with both their collateral sources’ report on either the Neuropsychiatric Inventory Questionnaire (n = 93) and/or the collateral-source GDS-15 (n = 67), or a clinicians diagnosis of Major Depression (MD). Results: Significant differences were seen between self- versus collateral-source reports of depression in these participants. Participants’ reports of loss of interest (anhedonia) significantly increased the odds of disagreement with their collateral sources (OR = 3.78, 95% CI: 1.3–11.2) while reports of negative cognitions significantly decreased the odds of such a disagreement (OR = 0.31, 95% CI: 0.1–0.9). The symptom of anhedonia also showed the strongest association with the clinicians diagnosis of MD. Conclusion: A motivational symptom like loss of interest was seen to play an important role in depression experienced by those with cognitive impairment.

Clinical efficacy of sertraline alone and augmented with gabapentin in recently abstinent cocaine-dependent patients with depressive symptoms.

Background Cocaine dependence is a major public health problem with no available robustly effective pharmacotherapy. This study’s aim was to determine if treatment with sertraline (SERT) or SERT plus gabapentin (GBP) improved treatment retention, depressive symptoms, and/or cocaine use. Methods Depressed cocaine-dependent patients (N = 99) were enrolled in a 12-week, double-blind, randomized, placebo (PLA)-controlled, clinical trial and placed in research beds at a residential treatment facility (Recovery Centers of Arkansas). They were randomized by depressive symptom severity and inducted onto 1 of the following while residing at the Recovery Centers of Arkansas: SERT (200 mg/d), SERT (200 mg/d) plus GBP (1200 mg/d), or PLA. Participants transferred to outpatient treatment at the start of their third week, continued receiving study medications or PLA (weeks 3–12), and participated in weekly individual cognitive behavioral therapy. Compliance was facilitated through the use of contingency management procedures. Supervised urine samples were obtained thrice weekly and self-reported mood weekly. At the end of 12 weeks, participants were tapered off the study medication over 5 days and referred to a local treatment program. Results Sertraline, but not SERT plus GBP, showed a significantly lower overall percentage of cocaine-positive urine samples compared with that of PLA. A significantly greater percentage of participants experienced relapse in the PLA group (88.9%) compared with that of the SERT group (65.2%). Hamilton depression ratings decreased significantly over time regardless of the treatment group. Retention in treatment did not differ significantly between the treatment groups. Conclusions Sertraline plus GBP may not be superior to SERT alone in delaying relapse among abstinent cocaine-dependent individuals undergoing cognitive behavioral therapy.

Sex and opioid maintenance dose influence response to naloxone in opioid-dependent humans: a retrospective analysis.

Pooled self-report and physiological data from 32 male and 15 female methadone or levo-alpha-acetyl methadol (LAAM) maintained volunteers were retrospectively analyzed for individual differences in response to naloxone (0.15 mg/70 kg, IM) and placebo at 20 and 40 min post-injection. Males and females were each divided by the median splitmethadone maintenance dose (MMD, in mg/kg body weight) into high and low MMD groups and MMD was used as a factor in the analyses, along with sex, drug, and time post-drug. Females in the low but not high, MMD group showed naloxone-induced increases in ratings on the Antagonist and Mixed-Action sub-scales of the Adjective Rating Scale, and the Lysergic acid diethyl amine (LSD) sub-scale of the Addiction Research Center Inventory at 20 min post-injection. Males in the high MMD group showed significant naloxone-induced increases in scores of these measures at both post-injection time-points. In addition, low MMD subjects showed more short-lived naloxone-induced increases on Visual Analogue Scale (VAS) Bad and Any drug effects ratings than high MMD subjects. These results suggest that those on a lower MMD, especially women, experience a more intense, but short-lived, response to naloxone, whereas those on a higher MMD experience a more modest, but longer-lasting effect.

Psycho-social outcomes for persons with bipolar-I disorder: Eight-year follow-up of a rural cohort from south India

BACKGROUND Assess psycho-social outcomes in a rural cohort of patients with bipolar-I disorder (BD). METHODS Detailed evaluations were performed using the Longitudinal Interval Follow-up Evaluation (LIFE) assessments of community-based BD patients in southern India. Several subjective and objective outcome measures were examined. RESULTS Only half the cohort could be described as having a good overall outcome, with persistent difficulties in inter-personal relationships in a substantial proportion of patients. Separation or divorce, or co-morbid alcohol dependence impacted a higher proportion of female patients compared to males. CONCLUSIONS In spite of the small cohort size, this longitudinal study indicates mixed outcomes for BD patients in this setting, with several patients showing enduring psycho-social and global impairments. Even though symptomatic recovery for BD patients might be better in developing countries compared to those observed in developed nations, the notion of better psycho-social outcomes for BD in developing countries needs closer re-examination in larger cohorts.