Publications by authors named "Michael Mancino"

22 Publications

  • Page 1 of 1

Clearance of buprenorphine during pregnancy and neonatal outcomes.

Arch Womens Ment Health 2021 Apr 16. Epub 2021 Apr 16.

Department of Psychiatry, University of Wisconsin, Madison, WI, USA.

Buprenorphine is emerging as the preferred pharmacologic treatment for opioid use disorder during pregnancy. We examined the relative plasma clearance of buprenorphine (BUP) across pregnancy. Pregnant women with opioid use disorder participating in a prospective, observational study from 2013 to 2016 on stress in pregnancy who were receiving BUP for opioid use disorder were included. Women with an active eating disorder or suicidal ideation were excluded. Research visits occurred at 4-6-week intervals across pregnancy and the early postpartum period and included medication exposure history and blood samples. All assays for BUP serum concentrations at steady state were completed. Relative weight-adjusted clearance (Cl) was calculated using Cl = (daily dose [mg]/ body weight [kg])/serum concentration [ng/ml]. We collected 112 maternal blood samples from 29 women throughout pregnancy and the postpartum period. Serum concentrations for BUP ranged from < 0.2 to 15.8 ng/ml. Eleven women, with greater than three collected samples, increased their daily dose of BUP during pregnancy; however, there were no significant differences in relative clearance of BUP across this same period. This data suggests that women with opioid use disorder receiving BUP did not demonstrate a significant increase in BUP clearance across pregnancy despite increase in dosages during pregnancy. When selecting an appropriate BUP dosage for management of perinatal opioid use disorder, gestational stage appears not to be an important covariate and should be based on an individualized approach.
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http://dx.doi.org/10.1007/s00737-021-01128-1DOI Listing
April 2021

Development and Validation of a Rapid LC-MS/MS based Method to Quantitate Gabapentin and Buprenorphine in Human Serum.

Rapid Commun Mass Spectrom 2021 Apr 16:e9104. Epub 2021 Apr 16.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, 72205.

Rationale: Gabapentin has shown initial promise as an opioid-sparing medication in pain patients as well as a treatment for opioid withdrawal and LC-MS/MS is often used for clinical monitoring. Despite reports of validated tandem masspectormetric methods for the determination of gabapentin and buprenorphine, mechanisms for the collision-induced fragmentation have not been adequetly described.

Methods: A rapid analytical method has been developed to determine the gabapentinoid, gabapentin, and partial opioid agonist, buprenorphine in 20 microliters of human serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a chromatographic run time of 2 minutes. A simplified sample cleanup procedure using methanol precipitation of serum proteins/lipids followed by evaporation and reconstitution in mobile phase was demonstrated. Gabapentin and buprenorphine were detected following positive ion electrospray ionization using multiple-reaction-monitoring. The internal standard approach was used for quantitation with labeled gabapentin-D10 and buprenorphine-D4 serving as internal standards. Using organic reaction principals and stable isotope labels, collision-induced fragmentation mechanisms for both gabapentin and buprenorphine are proposed. The method was validated according to the FDA Guidance for Industry - Bioanalytical Method Validation.

Results: Accuracy was demonstrated by error values ≤15% for buprenorphine and ≤6% for gabapentin. The inter-day precision was ≤4.88% and 15.59% for gabapentin and buprenorphine and the intra-day precision was ≤5.20% and 11.65% for gabapentin and buprenorphine. The lower limit of quantitation corresponded to 10 ng/mL for gabapentin and 1 ng/mL for buprenorphine in serum. Recoveries were 104% ± 2.55 and 85% ± 2.03 for gabapentin and buprenorphine, respectively.

Conclusions: Concentrations of gabapentin and buprenorphine were determined for 5 authentic human serum samples to further validate the utility of the method and applicable to therapeutic drug monitoring beyond its use as a drug screening assay. Furthermore, new mechanisms for the collision-induced dissociation of gabapentin and buprenorphine have been proposed.
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http://dx.doi.org/10.1002/rcm.9104DOI Listing
April 2021

Feasibility and Preliminary Efficacy of Isradipine During Outpatient Buprenorphine Stabilization and Detoxification: A Pilot Randomized, Placebo-Controlled Trial.

Subst Abuse 2020 23;14:1178221820970926. Epub 2020 Nov 23.

Department of Psychiatry and Behavioral Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Background: Given the immense burden of the widespread use of opioids around the world, exploring treatments that improve drug use outcomes, and craving and withdrawal measures in individuals with opioid use disorder is crucial. This pilot study examined the feasibility and preliminary efficacy of the L-type calcium-channel blocker isradipine (ISR) to improve drug use outcomes, and craving and withdrawal measures during buprenorphine (BUP)/ISR stabilization and subsequent taper in opioid-dependent individuals.

Methods: Participants were stabilized on BUP sublingual tablets within the first 2 days of week 1, were then randomized and inducted on either ISR or placebo, gradually increasing the dose over the next 2 weeks, followed by a 10-day BUP taper during weeks 5-6, and ISR/placebo taper during weeks 7 to 8. Assessments included thrice-weekly measures of craving and withdrawal, as well as vital signs and urine drug screens. Medication compliance was assessed by monitoring number of missed clinic visit days.

Results: Baseline characteristics of participants (n = 25; 60% male, 96% Caucasian, 48% employed, mean age 32.8 years) did not differ significantly between treatment groups (isradipine, n = 11; placebo, n = 14). During the stabilization phase (n = 19), ISR participants had significantly lower rates of illicit opioid-positive urines (treatment × visit:  = -2.16,  = 0.03), as well as reduction in craving intensity ( = -2.50,  = 0.01), frequency ( = -3.43,  < 0.01) and duration ( = -2.51,  = 0.01). ISR was well tolerated with mild adverse effects.

Conclusions: This study was likely underpowered due to being a pilot trial. Although preliminary results suggest ISR may improve BUP-assisted treatment outcomes, concerns about high number of exclusions (n = 11 during taper phase) based on cardiovascular measures as well as ISR-induced changes in vital signs with the immediate release formulation may limit the feasibility of this approach.

Trial Registration: Clinicaltrials.gov identifier NCT01895270. Registered 10 July 2013, https://clinicaltrials.gov/ct2/show/NCT01895270?id=NCT01895270&draw=2&rank=1.
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http://dx.doi.org/10.1177/1178221820970926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686602PMC
November 2020

The utility of a statewide prescription drug-monitoring database vs the Current Opioid Misuse Measure for identifying drug-aberrant behaviors in emergency department patients already on opioids.

Am J Emerg Med 2020 03 17;38(3):503-507. Epub 2019 May 17.

Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR, United States of America.

Background: The most recent guidelines on prescribing opioids from the United States Centers for Disease Control recommend that clinicians not prescribe opioids as first-line therapy for chronic non-cancer pain. If an opioid prescription is considered for a patient already on opioids, prescribers are encouraged to check the statewide prescription drug monitoring database (PDMP). Some additional guidelines recommend screening tools such as the Current Opioid Misuse Measure (COMM) which may also help identify drug-aberrant behaviors.

Objective: To compare the PDMP and the Current Opioid Misuse Measure (COMM), a commonly-recommended screening tool for patients on opioids, in detecting drug-aberrant behaviors in patients already taking opioids at the time of ED presentation.

Methods: Patients on opioids were enrolled prospectively in a mixed urban-suburban ED seeing approximately 65,000 patients per year. The sensitivity, specificity, likelihood ratios, and diagnostic odds ratios of the PDMP and COMM were compared against objective criteria of drug-aberrant behaviors as documented in the electronic medical record (EMR) and medical examiner databases.

Results: Compared to the COMM, the PDMP had similar sensitivity (36% vs 45%) and similar specificity (79% vs 55%), but better positive predictive value, better negative predictive value, and better diagnostic odds ratio. The combination of the PDMP and the COMM did not improve the detection of drug-aberrant behaviors.

Conclusions: The PDMP alone is a more useful as a screening instrument than either the COMM or the combination of the PDMP plus COMM in patients already taking opioids at time of ED presentation. However, the PDMP misses a majority of patients with documented drug-aberrant behaviors in the EMR, and should not be used in isolation to justify whether a particular opioid prescription is appropriate.
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http://dx.doi.org/10.1016/j.ajem.2019.05.035DOI Listing
March 2020

Survey of Treatment Preferences for Opioid Use Disorder.

Jacobs J Addict Ther 2018 27;5(3). Epub 2018 Nov 27.

Department of Psychiatry, University of Arkansas for Medical Sciences, 4301 W Markham Street, Little Rock, AR 72205, USA.

Objectives: This study gathered preliminary information on the initial feasibility of using injection Naltrexone (NTX) therapy in opioid users.

Methods: One hundred opioid users (36% female, 8% minorities, mean age 34.5±11.4 yrs.) undergoing a health screen to determine initial eligibility for an ongoing study completed the survey.

Results: Of the 100 respondents, 26, 16, 16, 1 and 0 reported prior treatment episodes of opioid detoxification, buprenorphine (BUP), methadone (MTD), oral NTX and injection NTX, respectively. Ninety and 71% were interested in participating in a study involving oral and/or injection NTX treatment, respectively. Reasons for not wanting to try injection NTX included fear of needles (n=13), side effects (n=7), lack of pain relief (n=12) and cost (n=3). A significantly higher percentage of those interested in injection NTX had episodes of prior opioid agonist maintenance treatment relative to those uninterested (32.4% vs 10.3%; Chi=5.2, p<0.03). Those preferring injection NTX therapy showed a higher level of interest in this therapy (3.08±1.01 vs 1.62±1.35; Rank Sum p<0.0001) and a lower degree of interest in BUP treatment (2.96±0.93 vs 3.38±0.90; Rank Sum p< 0.03) than those not preferring injection NTX.

Conclusions: These preliminary results suggest that those with prior, failed experience with opioid agonist maintenance treatment are more likely to consider injection NTX therapy, suggesting it may be optimal as a second-line treatment for OUD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530927PMC
November 2018

Moderators of response to sertraline versus placebo among recently abstinent, cocaine dependent patients: A retrospective analysis of two clinical trials.

Am J Addict 2017 Dec 8;26(8):807-814. Epub 2017 Nov 8.

University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Background And Objectives: Moderators of treatment response to serotonin reuptake inhibitor sertraline (SRT) for cocaine dependence were assessed in two randomized, double blind, placebo-controlled clinical trials.

Methods: Generalized estimating equation modeling was performed on data from cocaine-dependent volunteers randomized to receive SRT or placebo (N = 126) who completed >2-week drug-free residential portions of the 12-week trials, in which subsequent outpatient treatment (weeks 3-12) included weekly cognitive behavioral therapy and thrice-weekly supervised urine toxicology.

Primary Outcome Measure: Relapse (2 consecutive cocaine-positive or missing urines) following residential stay. Potential moderators included treatment, sex, age, race, depression measures, baseline cocaine urine result, and alcohol dependence diagnosis (ADDx).

Results: Odds ratios (OR) for relapse showed placebo-treated participants were significantly more likely to relapse than SRT participants. Regardless of treatment condition, participants more likely to relapse were male, and those with lower Hamilton depression ratings, or baseline cocaine-negative urines. Older subjects or those with current ADDx had higher relapse risk than those without ADDx; however, treating older or ADDx participants with SRT reduced cocaine relapse more than placebo.

Discussion And Conclusions: Women or those with more severe cocaine use or depressive symptoms may have fewer cocaine relapses regardless of medication treatment. SRT at 200 mg reduced cocaine relapse more than placebo, especially in older participants or in those with comorbid ADDx.

Scientific Significance: SRT may be efficacious to support relapse prevention among cocaine-dependent patients in the context of brief residential followed by outpatient treatment, especially in older participants or those with comorbid alcohol/cocaine dependence. (Am J Addict 2017;26:807-814).
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http://dx.doi.org/10.1111/ajad.12635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699965PMC
December 2017

Impact of early childhood trauma on retention and phase advancement in an outpatient buprenorphine treatment program.

Am J Addict 2016 10 15;25(7):542-8. Epub 2016 Sep 15.

Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Background: Early adverse life events such as childhood trauma have been linked to development of substance use disorders. The prevalence and impact on treatment of early childhood trauma in opioid-dependent individuals has received limited research attention. The present study examined reported childhood trauma and its relation to retention and adherence in an outpatient buprenorphine treatment program.

Methods: Medical records of individuals who completed childhood trauma questionnaire (CTQ) were reviewed to extract baseline data and demographics (N = 113). Total and subscale CTQ scores were dichotomized to low versus moderate-severe levels of trauma. Treatment course evaluation was based on successful phase advancement and retention in treatment during the first 90 days. Logistic regression models were used to examine associations between CTQ subscales and total score and the two outcomes adjusting for covariates.

Results: Moderate-severe trauma defined by total CTQ score was present in 16% of participants. Logistic regression models showed significant associations between physical and emotional neglect and drop out after adjusting for covariates. Individuals who had never married and those with positive admission urine drug screen for opiates associated significantly with drop out.

Conclusions And Scientific Significance: The results from a convenience sample participating in a university-based buprenorphine treatment program demonstrated significant association between self-reported early childhood trauma and retention during the first 90 days. These findings suggest that addressing early trauma could potentially improve adherence rates leading to reduced disease burden. This study extends the knowledge base on potential predictive factors associated with successful participation in outpatient buprenorphine treatment. (Am J Addict 2016;25:542-548).
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http://dx.doi.org/10.1111/ajad.12437DOI Listing
October 2016

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

J Consult Clin Psychol 2014 Dec 4;82(6):964-72. Epub 2014 Aug 4.

Addiction Recovery Research Center.

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.
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http://dx.doi.org/10.1037/a0037496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244262PMC
December 2014

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

J Consult Clin Psychol 2014 Dec 4;82(6):964-72. Epub 2014 Aug 4.

Addiction Recovery Research Center.

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.
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http://dx.doi.org/10.1037/a0037496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244262PMC
December 2014

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

J Clin Psychopharmacol 2014 Apr;34(2):234-9

From the *Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR; †Department of Psychiatry, VA Boston Healthcare System, Brockton, MA; ‡Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR; and §Department of Psychiatry, Baylor College of Medicine and Michael E DeBakey VA Medical Center, Houston, TX.

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.
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http://dx.doi.org/10.1097/JCP.0000000000000062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068618PMC
April 2014

Randomized, placebo-controlled pilot trial of gabapentin during an outpatient, buprenorphine-assisted detoxification procedure.

Exp Clin Psychopharmacol 2013 Aug 15;21(4):294-302. Epub 2013 Jul 15.

Department of Psychiatry and Behavioral Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

This pilot study examined the efficacy of the N-type calcium channel blocker gabapentin to improve outcomes during a brief detoxification protocol with buprenorphine. Treatment-seeking opioid-dependent individuals were enrolled in a 5-week, double-blind, placebo-controlled trial examining the effects of gabapentin during a 10-day outpatient detoxification from buprenorphine. Participants were inducted onto buprenorphine sublingual tablets during Week 1, were randomized and inducted onto gabapentin or placebo during Week 2, underwent a 10-day buprenorphine taper during Weeks 3 and 4, and then were tapered off gabapentin/placebo during Week 5. Assessments included thrice-weekly opioid withdrawal scales, vitals, and urine drug screens. Twenty-four individuals (13 male; 17 Caucasian, 3 African American, 4 Latino; mean age 29.7 years) participated in the detoxification portion of the study (gabapentin, n = 11; placebo, n = 13). Baseline characteristics did not differ significantly between groups. Self-reported and observer-rated opioid withdrawal ratings were relatively low and did not differ between groups during the buprenorphine taper. Urine results showed a Drug × Time interaction, such that the probability of opioid-positive urines significantly decreased over time in the gabapentin versus placebo groups during Weeks 3 and 4 (OR = 0.73, p = .004). These results suggest that gabapentin reduces opioid use during a 10-day buprenorphine detoxification procedure.
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http://dx.doi.org/10.1037/a0033724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972066PMC
August 2013

Effects of disulfiram on QTc interval in non-opioid-dependent and methadone-treated cocaine-dependent patients.

J Addict Med 2013 Jul-Aug;7(4):243-8

From the Department of Psychiatry and Behavioral Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock.

Objectives: Methadone and cocaine are each known to prolong the QTc interval, a risk factor for developing potentially fatal cardiac arrhythmias. Disulfiram, often administered in the context of methadone maintenance to facilitate alcohol abstinence, has been shown to have some efficacy for cocaine dependence. Disulfiram has differential effects on cocaine and methadone metabolism, but its impact on methadone- or cocaine-induced changes in QTc interval is unclear. Thus, the effects of disulfiram on QTc interval in a subset of cocaine-dependent patients participating in a 14-week, randomized, double-blind, placebo-controlled clinical trial of disulfiram were prospectively determined.

Methods: Opioid-dependent participants were inducted onto methadone (weeks 1-2; MT) and both MT and non-opioid-dependent (UT) participants were randomized to receive disulfiram (weeks 3-14) at one of the following doses: 0, 250, 375, or 500 mg/d. Electrocardio-grams were obtained before study entry and during weeks 2 and 4.

Results: Complete QTc-interval data in 23 MT and 18 UT participants were analyzed. QTc interval tended to be higher in MT participants relative to UT participants, regardless of disulfiram dose and time point, but disulfiram did not differentially alter QTc interval. QTc interval was, however, significantly greater in participants with recent cocaine use than in those with no recent use.

Conclusions: These results suggest that cocaine use and possibly MT status, but not disulfiram, are risk factors for QTc prolongation.
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http://dx.doi.org/10.1097/ADM.0b013e3182928e02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737260PMC
April 2014

Effects of prototypic calcium channel blockers in methadone-maintained humans responding under a naloxone discrimination procedure.

Eur J Pharmacol 2013 Sep 21;715(1-3):424-35. Epub 2013 Mar 21.

Department of Psychiatry and Behavioral Sciences, University of Arkansas for Medical Sciences, 4301 W Markham St., Little Rock, AR 72205, USA.

Accumulating evidence suggests that L-type calcium channel blockers (CCBs) attenuate the expression of opioid withdrawal and the dihydropyridine L-type CCB isradipine has been shown to block the behavioral effects of naloxone in opioid-maintained humans. This study determined whether two prototypic L-type CCBs with differing chemical structures, the benzothiazepine diltiazem and the phenylalkamine verapamil, attenuate the behavioral effects of naloxone in methadone-maintained humans trained to distinguish between low-dose naloxone (0.15 mg/70 kg, i.m.) and placebo under an instructed novel-response drug discrimination procedure. Once discrimination was acquired, diltiazem (0, 30, 60, 120 mg) and verapamil (0, 30, 60, 120 mg), alone and combined with the training dose of naloxone, were tested. Diltiazem alone produced 33-50% naloxone- and novel-appropriate responding at 30 and 60 mg and essentially placebo-appropriate responding at 120 mg. Verapamil alone produced 20-40% naloxone- and 0% novel-appropriate responding. Diltiazem at 60 mg decreased several ratings associated with positive mood and increased VAS ratings of "Bad Drug Effects" relative to placebo, whereas verapamil increased ratings associated with euphoria. When administered with naloxone, diltiazem produced 94-100% naloxone-appropriate-responding with 6% novel-appropriate responding at 60 mg (n=3). When administered with naloxone, verapamil produced 60-80% naloxone- and 0% novel-appropriate responding (n=5). Diltiazem decreased diastolic blood pressure and heart rate whereas verapamil decreased ratings of arousal relative to placebo. These results suggest that CCBs with different chemical structures can be differentiated behaviorally, and that diltiazem and verapamil do not attenuate the discriminative stimulus effects of naloxone in humans at the doses tested.
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http://dx.doi.org/10.1016/j.ejphar.2013.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759565PMC
September 2013

Sertraline delays relapse in recently abstinent cocaine-dependent patients with depressive symptoms.

Addiction 2012 Jan 10;107(1):131-41. Epub 2011 Oct 10.

University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

Aims: Whether the selective serotonin re-uptake inhibitor sertraline at 200 mg/day delays relapse in recently abstinent cocaine-dependent individuals.

Design: The study involved a 12-week, double-blind, placebo-controlled clinical trial with 2-week residential stay followed by 10-week out-patient participation.

Setting: Veterans Affairs residential unit and out-patient treatment research program.

Participants: Cocaine-dependent volunteers (n = 86) with depressive symptoms (Hamilton score > 15), but otherwise no major psychiatric or medical disorder or contraindication to sertraline.

Measurements: Participants were housed on a drug-free residential unit (weeks 1-2) and randomized to receive sertraline or placebo. Participants then participated on an out-patient basis during weeks 3-12 while continuing to receive study medication. Patients participated in a day substance abuse/day treatment program during weeks 1-3 and underwent weekly cognitive behavioral therapy during weeks 4-12. The primary outcome measure was thrice-weekly urine results and the secondary measure was Hamilton Depression scores.

Findings: Pre-hoc analyses were performed on those who participated beyond week 2. Generally, no group differences in retention or baseline characteristics occurred. Sertraline patients showed a trend towards longer time before their first cocaine-positive urine ('lapse', χ(2) = 3.67, P = 0.056), went significantly longer before having two consecutive urine samples positive for cocaine ('relapse', χ(2) = 4.03, P = 0.04) and showed significantly more days to lapse (26.1 ± 16.7 versus 13.2 ± 10.5; Z = 2.89, P = 0.004) and relapse (21.3 ± 10.8 versus 32.3 ± 14.9; Z = 2.25, P = 0.02). Depression scores decreased over time (F = 43.43, P < 0.0001), but did not differ between groups (F = 0.09, P = 0.77).

Conclusions: Sertraline delays time to relapse relative to placebo in cocaine-dependent patients who initially achieve at least 2 weeks of abstinence.
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http://dx.doi.org/10.1111/j.1360-0443.2011.03552.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237722PMC
January 2012

Characterizing methamphetamine withdrawal in recently abstinent methamphetamine users: a pilot field study.

Am J Drug Alcohol Abuse 2011 Mar 11;37(2):131-6. Epub 2011 Jan 11.

Department of Psychiatry, Psychiatric Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

Background: Methamphetamine dependence has become a significant problem, but methamphetamine withdrawal symptoms have not been well studied.

Methods: This prospective observational pilot study was designed to examine withdrawal symptoms, mood, anxiety, cognitive function, and subjective measures of sleep over a 4-week period in six patients entering residential treatment for methamphetamine dependence.

Results: Methamphetamine withdrawal symptoms, mood, and anxiety symptoms all resolve fairly quickly within 2 weeks of cessation of methamphetamine. Sleep was disrupted over the course of the 4-week study. No clinically significant alterations in blood pressure or heart rate were identified. This study did not demonstrate any alterations in cognitive function over the 4 weeks of the residential stay.

Conclusions: This pilot study points toward the need for a double-blind, placebo-controlled amphetamine withdrawal paradigm in humans where changes in sleep, cognitive function, and withdrawal measures can be explored more fully.

Scientific Significance: This study extends the literature by pointing toward a methamphetamine withdrawal syndrome that includes alterations in measures of sleep quality and refreshed sleep, early improvement in depression and anxiety symptoms, most striking during the first week, but persisting into the second week.
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http://dx.doi.org/10.3109/00952990.2010.543998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063384PMC
March 2011

Hypothetical intertemporal choice and real economic behavior: delay discounting predicts voucher redemptions during contingency-management procedures.

Exp Clin Psychopharmacol 2010 Dec;18(6):546-52

Department of Psychiatry, Center for Addiction Research, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

Delay discounting rates are predictive of drug use status, the likelihood of becoming abstinent, and a variety of health behaviors. Rates of delay discounting may also be related to other relevant behaviors associated with addiction, such as the frequency at which individuals redeem contingency management voucher earnings. This study examined the discounting rates of 152 participants in a buprenorphine treatment program for opioid abuse. Participants received up to 12 weeks of buprenorphine treatment combined with contingency management. Participant's drug use was measured via urine specimens submitted three times a week. Successive negative urine specimens were reinforced with increasing amounts of money. After each negative urine specimen, a participant could either redeem his or her earnings or accumulate it in an account. Analysis of the frequency of redemptions showed that participants with higher rates of delay discounting at study intake redeemed their earnings significantly more often than participants with lower rates of discounting. Age and income also predicted redemption rates. We suggest that delay discounting rates can be used to predict redemption behaviors in a contingency management treatment program and that these findings are consistent with the recent theory of the competing neurobehavioral decision systems.
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http://dx.doi.org/10.1037/a0021739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034533PMC
December 2010

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

Drug Alcohol Depend 2011 Jan 15;113(2-3):184-91. Epub 2010 Sep 15.

Psychiatry Dept, University of Arkansas for Medical Sciences, Slot 843, 4301 W Markham St, Little Rock, AR 72205, USA.

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.
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http://dx.doi.org/10.1016/j.drugalcdep.2010.07.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005977PMC
January 2011

Predictors of attrition from a national sample of methadone maintenance patients.

Am J Drug Alcohol Abuse 2010 May;36(3):155-60

Central Arkansas Veterans Healthcare System, North Little Rock, Arkansas, USA.

Background: Methadone substitution therapy is an effective harm reduction treatment method for opioid dependent persons. Ability to retain patients in methadone treatment is an accepted predictor of treatment outcomes.

Objectives: The current study evaluates the roles of psychiatric comorbidity, medical comorbidity, and sociodemographic characteristics as predictors of retention in methadone treatment utilizing retrospective analysis of data from a nationwide sample of patients in methadone treatment in the VA.

Methods: Data were gathered using the VA's national health services use database. A cohort of veterans with a new episode of "opiate substitution" in fiscal year 1999 was identified, and their continuous service use was tracked through fiscal year 2002. The sample included a total of 2,363 patients in 23 VA medical centers. Survival analysis was used to explore factors associated with retention in methadone treatment.

Results: Younger age, having a serious mental illness, being African American, or having race recorded as unknown were associated with lower rates of retention in methadone treatment programs in this population of veterans (controlling for site).

Conclusion: Given that extended methadone treatment is associated with improved outcomes while patients remain in treatment, more longitudinal studies using primary data collection are needed to fully explore factors related to retention. For the VA population specifically, further research is necessary to fully understand the relationship between race/ethnicity and treatment retention.

Scientific Significance: This is the first retention study the authors are aware of that utilizes data from a nationwide, multisite, population of participants in methadone treatment.
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http://dx.doi.org/10.3109/00952991003736389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314423PMC
May 2010

Effect of PTSD diagnosis and contingency management procedures on cocaine use in dually cocaine- and opioid-dependent individuals maintained on LAAM: a retrospective analysis.

Am J Addict 2010 Mar-Apr;19(2):169-77

Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

This randomized clinical trial retrospectively examined the effect of post-traumatic stress disorder (PTSD) and contingency management (CM) on cocaine use in opioid and cocaine dependent individuals maintained on high or low-dose LAAM randomly assigned to CM or a yoked-control condition. Cocaine-positive urines decreased more rapidly over time in those without PTSD versus those with PTSD in the noncontingency condition. In participants with PTSD, CM resulted in fewer cocaine-positive urines compared to the noncontingent condition. This suggests that CM may help improve the potentially worse outcomes in opioid- and cocaine-dependent individuals with PTSD compared to those without PTSD. (Am J Addict 2010;00:1-9).
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http://dx.doi.org/10.1111/j.1521-0391.2009.00025.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472706PMC
July 2010

Open-label pilot study of modafinil for methamphetamine dependence.

J Clin Psychopharmacol 2009 Oct;29(5):488-91

Medical Department, Community Counseling Services Inc, Hot Springs, AR, USA.

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.
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http://dx.doi.org/10.1097/JCP.0b013e3181b591e0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610177PMC
October 2009

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

Pharmacol Biochem Behav 2008 Oct;90(4):787-96

Department of Psychiatry and Behavioral Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

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.
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http://dx.doi.org/10.1016/j.pbb.2008.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577173PMC
October 2008

Quality-adjusted health status in veterans with posttraumatic stress disorder.

J Nerv Ment Dis 2006 Nov;194(11):877-9

Department of Psychiatry, Central Arkansas Veterans Healthcare System, and the Division of Health Services Research, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

This study evaluated the quality-adjusted health status in veterans with posttraumatic stress disorder (PTSD). In a cross-sectional study veterans diagnosed with PTSD completed a quality-adjusted health status measure (Quality of Well-Being Self-Administered [QWB-SA] scale), PTSD symptom severity measures (Mississippi Scale for Combat-Related PTSD and Clinician-Administered PTSD Scale), and a depression severity measure (Beck Depression Inventory). Significant inverse relationships were identified between the QWB-SA and PTSD severity measures as well as between the QWB-SA and depression severity measures in this sample. Demonstration of these relationships suggests that greater symptom severity is associated with lower quality-adjusted health status in veterans with PTSD. More importantly, the QWB-SA was designed for use in cost-effectiveness analyses and may be useful in assessing the relative value of PTSD interventions compared with other mental and physical health interventions.
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http://dx.doi.org/10.1097/01.nmd.0000244686.79689.21DOI Listing
November 2006