Joseph A. Harrison

Concurrent Validation of the Clinical Opiate Withdrawal Scale (COWS) and Single-Item Indices against the Clinical Institute Narcotic Assessment (CINA) Opioid Withdrawal Instrument

INTRODUCTION The Clinical Opiate Withdrawal Scale (COWS) is an 11-item clinician-administered scale assessing opioid withdrawal. Though commonly used in clinical practice, it has not been systematically validated. The present study validated the COWS in comparison to the validated Clinical Institute Narcotic Assessment (CINA) scale. METHOD Opioid-dependent volunteers were enrolled in a residential trial and stabilized on morphine 30 mg given subcutaneously four times daily. Subjects then underwent double-blind, randomized challenges of intramuscularly administered placebo and naloxone (0.4 mg) on separate days, during which the COWS, CINA, and visual analog scale (VAS) assessments were concurrently obtained. Subjects completing both challenges were included (N=46). Correlations between mean peak COWS and CINA scores as well as self-report VAS questions were calculated. RESULTS Mean peak COWS and CINA scores of 7.6 and 24.4, respectively, occurred on average 30 min post-injection of naloxone. Mean COWS and CINA scores 30 min after placebo injection were 1.3 and 18.9, respectively. The Pearsons correlation coefficient for peak COWS and CINA scores during the naloxone challenge session was 0.85 (p<0.001). Peak COWS scores also correlated well with peak VAS self-report scores of bad drug effect (r=0.57, p<0.001) and feeling sick (r=0.57, p<0.001), providing additional evidence of concurrent validity. Placebo was not associated with any significant elevation of COWS, CINA, or VAS scores, indicating discriminant validity. Cronbachs alpha for the COWS was 0.78, indicating good internal consistency (reliability). DISCUSSION COWS, CINA, and certain VAS items are all valid measurement tools for acute opiate withdrawal.

Induction of opioid-dependent individuals onto buprenorphine and buprenorphine/naloxone soluble-films

A sublingual soluble‐film formulation of buprenorphine/naloxone (B/N) has been approved by the US Food and Drug Administration for the treatment of opioid dependency. This preparation provides unit‐dose, child‐resistant packaging amenable to tracking and accountability, offers more rapid dissolution, and has a potentially preferred taste vs. tablets. This study compared the ability of buprenorphine (B) and B/N films to suppress spontaneous withdrawal in opioid‐dependent volunteers. Participants were maintained on morphine and underwent challenge sessions to confirm sensitivity to naloxone‐induced opioid withdrawal. Subjects were randomized to receive either B (16 mg, n = 18) or B/N (16/4 mg, n = 16) soluble films for 5 days. The primary outcome measure was the Clinical Opiate Withdrawal Scale (COWS) score. Thirty‐four subjects completed induction onto soluble films. There was a significant decrease in COWS scores but no significant differences between the groups. The results support the use of B and B/N soluble films as safe and effective delivery methods for opioid induction.

Opioid detoxification via single 7-day application of a buprenorphine transdermal patch: an open-label evaluation

RationaleManaged withdrawal (i.e., detoxification) from opioid dependence is a widespread clinical procedure that is a necessary step for those pursuing abstinence. Buprenorphine is one effective detoxification treatment, however, consensus regarding effective detoxification procedures is lacking.ObjectivesThis study evaluated the efficacy of a buprenorphine transdermal formulation (i.e., patch) in suppressing opioid withdrawal, its safety and tolerability, and its biodelivery when applied for 7 days.MethodsPhysically dependent opioid (heroin) users (n = 12) completed a 10-day opioid detoxification in a residential research unit. Each received a single patch application that remained in place for 7 days. Blood samples were drawn prior to patch application and once daily thereafter. Assessments, four times daily, included: the amount of rescue medications ordered to treat withdrawal discomfort; self-report and observer ratings of opioid withdrawal and agonist effects; and vital sign measures.ResultsOverall, the patch appeared safe and well-tolerated. Buprenorphine plasma levels peaked 48 h after patch application at 0.59 ng/ml. Indices of withdrawal (self-reports, observer ratings, rescue medication) were significantly reduced within 24 h of patch application, continued to decline thereafter, and did not reappear following patch removal.ConclusionsThis study confirms that transdermal buprenorphine is safe and clinically effective, and suggests that a 7-day application may provide an effective and comfortable means of detoxification. This patch formulation would appear to be a useful opioid detoxification treatment by reducing compliance concerns, and administering buprenorphine in a formulation less likely to be diverted to illicit use.

Recruitment techniques for alcohol pharmacotherapy clinical trials: A cost-benefit analysis.

Objectives:Alcohol-use disorders (AUDs) represent a large public health burden with relatively few efficacious pharmacotherapies. Randomized controlled trials (RCTs) for new AUD therapies can be hampered by ineffective recruitment, leading to increased trial costs. The current analyses examined the effectiveness of recruitment efforts during 2 consecutive outpatient RCTs of novel AUD pharmacotherapies conducted between 2009 and 2012. Methods:During an initial phone screen, participants identified an ad source for learning about the study. Qualified persons were then scheduled for in-person screens (IPSs). The present analyses examined demographic differences among the 8 ad sources utilized. Recruitment effectiveness was determined by dividing the number of persons meeting criteria for an IPS by the total number of callers from each ad source. Cost-effectiveness was determined by dividing total ad source cost by number of screens, participants randomized, and completers. Results:A total of 1813 calls resulted in 1005 completed phone screens. The most common ad source was television (34%), followed by print (29%), word-of-mouth (11%), flyer (8%), internet (5%), radio (5%), bus ad (2%), and billboard (1%). Participants reporting bus ads (46%), billboard (44%), or print ads (34%) were significantly more likely than the other sources to meet criteria to be scheduled for IPSs. The most cost-effective ad source was print (

Continuous Abstinence During Early Alcohol Treatment is Significantly Associated with Positive Treatment Outcomes, Independent of Duration of Abstinence.

2506 per completer), whereas bus ad was the least cost-effective (

Human abuse liability assessment of oxycodone combined with ultra-low-dose naltrexone

13,376 per completer). Conclusions:Recruitment in AUD RCTs can be successful using diverse advertising methods. The present analyses favored use of print ads as most cost-effective.

Evaluation of a transdermal buprenorphine formulation in opioid detoxification

Aims Neither the predictive value of early continuous abstinence in alcohol use disorder (AUD) or the point at which this effect may emerge has been evaluated. This analysis of the Combined Pharmacotherapies and Behavioral Interventions (COMBINE) clinical trial evaluated whether abstinence early in treatment was a predictor of longer term abstinence. Methods Participants who stated a goal of total abstinence (N = 954) were dichotomized into Early Abstainer vs. Nonabstainers and were compared on a variety of drinking outcome measures that are frequently used in clinical trial evaluations of alcohol treatment strategies, as a function of duration of early continuous abstinence. Results Significant differences existed for every outcome. Early Abstinence was significantly associated with fewer drinks per drinking day, number of drinking and number of heavy drinking days, and longer time to first drinking and first heavy drinking day. Effects were evident within the first week. The magnitude of all effects increased as the duration of early abstinence (1–4 weeks) increased, though the size of increase varied across the outcomes. Conclusions These data provide evidence that drinking at the beginning of alcohol treatment is significantly and robustly associated with drinking throughout and at the end of a clinical trial treatment for AUD. Early drinking may be a useful early index to identify whether patients are responding positively to a treatment strategy, and provides a useful method for tailoring treatment to patients that is consistent with a personalized medicine approach.