Opioid Abuse [keywords]
- Anhedonia, depression, anxiety, and craving in opiate dependent patients stabilized on oral naltrexone or an extended release naltrexone implant. [JOURNAL ARTICLE]
- Am J Drug Alcohol Abuse 2016 Jul 19.:1-7.
Naltrexone is a μ-opioid receptor antagonist that blocks opioid effects. Craving, depression, anxiety, and anhedonia are common among opioid dependent individuals and concerns have been raised that naltrexone increases them due to blocking endogenous opioids. Here, we present data that address these concerns.Assess the relationship between affective responses and naltrexone treatment.Opioid dependent patients (N = 306) were enrolled in a three cell (102ss/cell) randomized, double blind, double dummy, placebo-controlled 6-month trial comparing extended release implantable naltrexone with oral naltrexone and placebo (oral and implant). Monthly assessments of affective responses used a Visual Analog Scale for opioid craving, the Beck Depression Inventory, Spielberger Anxiety Test, and the Ferguson and Chapman Anhedonia Scales. Between-group outcomes were analyzed using mixed model analysis of variance (Mixed ANOVA) and repeated measures and the Tukey test for those who remained and treatment and did not relapse, and between the last measure before dropout with the same measure for those remaining in treatment.Depression, anxiety, and anhedonia were elevated at baseline but reduced to normal within the first 1-2 months for patients who remained in treatment and did not relapse. Other than a slight increase in two anxiety measures at week two, there were no significant between-group differences prior to treatment dropout.These data do not support concerns that naltrexone treatment of opioid dependence increases craving, depression, anxiety or anhedonia.
- Acceptability of the use of cellular telephone and computer pictures/video for "pill counts" in buprenorphine maintenance treatment. [Journal Article]
- J Opioid Manag 2016 May-Jun; 12(3):217-20.
As part of a comprehensive plan to attempt to minimize the diversion of prescribed controlled substances, many professional organization and licensing boards are recommending the use of "pill counts." This study sought to evaluate acceptability of the use of cellular phone and computer pictures/video for "pill counts" by patients in buprenorphine maintenance treatment.Patients prescribed buprenorphine/naloxone were asked a series of questions related to the type(s) of electronic communication to which they had access as well as their willingness to use these for the purpose of performing a "pill/film count."Of the 80 patients, 4 (5 percent) did not have a phone at all. Only 28 (35 percent) had a "smart phone" with some sort of data plan and Internet access. Forty (50 percent) of the patients had a phone with no camera and 10 (12.5 percent) had a phone with a camera but no video capability. All patients said that they would be willing to periodically use the video or camera on their phone or computer to have buprenorphine/naloxone pills or film counted as long as the communication was protected from electronic tampering.With the advent of applications for smart phones that allow for Health Insurance Portability and Accountability Act of 1996-compliant picture/video communication, a number of things can now be done that can enhance patient care as well as reduce the chances of misuse/diversion of prescribed medications. This could be used in settings where a larger proportion of controlled substances are prescribed including medication assisted therapy for opioid use disorders and pain management programs.
- Risk factors for opioid misuse in adolescents and young adults with focus on oncology setting. [Journal Article]
- J Opioid Manag 2016 May-Jun; 12(3):205-16.
Prescription opioid use has increased in recent decades. Although opioids provide effective pain control, their use may be associated with the risk of misuse. Opioid misuse (OM) is prevalent among adolescents and young adults (AYAs). Opioids are necessary to treat cancer-related pain; however, oncology patients are not immune to medication misuse. Research examining OM among AYAs with cancer is scarce. This article examines the risk factors described in the general adult and adolescent medication abuse literature and aims to provide recommendations for practice in the AYA oncology population. The following risk factors should be examined in AYA oncology patients to determine their relevance: age, sex, behavioral and academic problems, psychological conditions, and a history of illicit drug use/abuse. To maintain the delicate balance of providing adequate pain relief while protecting patients from the risk of OM, clinicians must consider potential risk factors, motivating factors, and individual behaviors. Placing these challenges in perspective, this review provides clinical considerations, recommendations, and intervention strategies for OM prevention in AYA oncology patients.
- Abuse deterrence testing: A dose ratio escalation study examining naloxone coadministered with intravenous hydromorphone in non-treatment-seeking, opioid-dependent drug users. [Journal Article]
- J Opioid Manag 2016 May-Jun; 12(3):165-80.
To assess the reduction in intravenous (IV) abuse potential of hydromorphone from different dose ratio combinations with naloxone in opioid-dependent drug users.Randomized, blinded, dose ratio escalation study.Single center.Following conversion to a stable IV dose of hydromorphone, 12 non-treatment-seeking, opioid-dependent subjects were randomly assigned and received at least one dose of study drug; seven subjects received all five study treatments. Five subjects withdrew early from the treatment phase: adverse events (2) and participant decision (3).Participants underwent a dose-selection phase to stabilize on an individualized hydromorphone dose. Stable subjects were dosed intravenously on 5 consecutive days. The dose received was one of five hydromorphone/naloxone dose ratios that included the combination of hydromorphone and placebo naloxone. Hydromorphone/naloxone treatment always involved increasing dose ratios of naloxone (8:1, 6:1, 4:1, and 2:1) with the hydromorphone-placebo naloxone treatment randomly assigned within the sequence of dose ratios.Drug Liking visual analog scale (VAS), Objective Opioid Withdrawal Scale (OOWS) and Subjective Opioid Withdrawal Scale (SOWS).Hydromorphone/naloxone placebo produced subjective effects typical of opioid administration, while hydromorphone/naloxone dose ratios were associated with significant increases in SOWS and OOWS scores (p < 0.05). Compared with hydromoprophone/naloxone placebo, naloxone reduced the effects of hydromorphone on most measures, including Drug Liking VAS, the antagonism was greatest for the 4:1 and 2:1 ratios.This study was an ethical investigation of the abuse deterrence potential of four hydromorphone/naloxone dose ratios. The IV coadministration of commercially available IV solutions of hydromorphone and naloxone in 4:1 and 2:1 ratios had statistically greater reductions of abuse-related opioid effects and triggers of withdrawal symptoms and there was a convergence of subjective and objective pharmacodynamic results and safety findings. An oral modified-release product, developed with a 2:1 hydromorphone/naloxone ratio, may have important public health benefits by reducing high-risk, IV abuse of prescription opioids, while providing pain relief when ingested orally and used in accordance with the Product Monograph.
- Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial. [Journal Article, Research Support, Non-U.S. Gov't]
- JAMA 2016 Jul 19; 316(3):282-90.
The effectiveness of buprenorphine treatment of opioid dependence is limited by suboptimal medication adherence, abuse, and diversion.To determine whether 6-month buprenorphine implants are noninferior to daily sublingual buprenorphine as maintenance treatment for opioid-dependent patients with stable abstinence.Outpatient, randomized, active-controlled, 24-week, double-blind, double-dummy study conducted at 21 US sites from June 26, 2014, through May 18, 2015. Outpatients were prescribed daily sublingual buprenorphine for 6 months or more, were abstinent while taking 8 mg/d or less of sublingual buprenorphine for 90 days or longer, and were determined to be clinically stable by their physician.Participants were randomized to receive sublingual buprenorphine plus 4 placebo implants or sublingual placebo plus four 80-mg buprenorphine hydrochloride implants (expected efficacy, 24 weeks).The primary end point was between-group difference in proportion of responders (≥4 of 6 months without opioid-positive urine test result [monthly and 4 times randomly] and self-report). The noninferiority established for the lower bound of the 95% confidence interval was greater than -0.20 (P < .025). Secondary end points included cumulative percentage of negative opioid urine results, abstinence, and time to first illicit opioid use. Safety was assessed by adverse event reporting.Of 177 participants (mean age, 39 years; 40.9% female), 90 were randomized to sublingual buprenorphine with placebo implants and 87 to buprenorphine implants with sublingual placebo; 165 of 177 (93.2%) completed the trial. Eighty-one of 84 (96.4%) receiving buprenorphine implants and 78 of 89 (87.6%) receiving sublingual buprenorphine were responders, an 8.8% difference (1-sided 97.5% CI, 0.009 to ∞; P < .001 for noninferiority). Over 6 months, 72 of 84 (85.7%) receiving buprenorphine implants and 64 of 89 (71.9%) receiving sublingual buprenorphine maintained opioid abstinence (hazard ratio, 13.8; 95% CI, 0.018-0.258; P = .03). Non-implant-related and implant-related adverse events occurred in 48.3% and 23% of the buprenorphine implant group and in 52.8% and 13.5% of participants in the sublingual buprenorphine group, respectively.Among adults with opioid dependence maintaining abstinence with a stable dose of sublingual buprenorphine, the use of buprenorphine implants compared with continued sublingual buprenorphine did not result in an inferior likelihood of remaining a responder. However, the study population had an exceptionally high response rate in the control group, and further studies are needed in broader populations to assess the efficacy in other settings.clinicaltrials.gov Identifier: NCT02180659.
- Two cases of intoxication with new synthetic opioid, U-47700. [JOURNAL ARTICLE]
- Clin Toxicol (Phila) 2016 Jul 19.:1-5.
Novel substances often referred to as "designer drugs" have emerged as drugs of abuse, and recognition of these is difficult as routine blood and urine screening tests do not detect these agents. U-47700 is a synthetic selective μ-opioid agonist that can be bought online for as little as $40 per gram. We report two patients presenting after insufflation of U-47700, with subsequent confirmation of this substance in urine samples.A 26-year-old man and 24-year-old woman insufflated a substance they believed to be "synthetic cocaine." The man was found down with cyanosis and agonal respirations. He was intubated and taken to hospital where he recovered well with supportive care. The woman presented with anxiety, tremors and drowsiness and was admitted for observation. Urine samples from both patients were analyzed using GC/MS/MS and LC/QToF, and U-47700 was isolated in both cases. No other opioids were detected.These cases are concerning because U-47700 is a relatively new agent that is easy to obtain over the internet and has the potential to cause significant morbidity and mortality.
- Buprenorphine Initiation and Linkage to Outpatient Buprenorphine do not Reduce Frequency of Injection Opiate Use Following Hospitalization. [Journal Article]
- J Subst Abuse Treat 2016 Sep.:68-73.
Buprenorphine has established effectiveness for outpatient treatment of opioid use disorder. Our previously published STOP (Suboxone Transition to Opiate Program) trial showed that buprenorphine induction, stabilization, and linkage to outpatient treatment in opioid-dependent inpatients (injection and non-injection drug users) decreased illicit opioid use over 6months. The present study was a planned subgroup analysis of injection opiate users from STOP.To determine if inpatient buprenorphine initiation and linkage to outpatient buprenorphine reduce injection opiate users' frequency of injection opiate use (IOU).Inpatient injection opiate users at a safety-net hospital were randomized to buprenorphine linkage (induction, stabilization, bridge prescription, and facilitated referral to outpatient treatment) or detoxification (5-day inpatient buprenorphine taper). Conditional fixed-effects Poisson regression was used to estimate the effects of intervention on 30-day (self-report) at 1, 3, and 6months, measured using 30-day timeline follow-back. The secondary outcome was linkage effectiveness, measured as % presenting to initial outpatient buprenorphine visits after hospital discharge.Analysis was limited to persons (n=62 randomized to detoxification and n=51 to linkage) with baseline IOU. There were no significant differences in age, ethnicity, or baseline IOU frequency. At follow-up, linkage patients (70.6%) were significantly more likely (p<0.001) to present to initial buprenorphine visits than detoxification patients (9.7%). However, there was no significant between group difference in the rate of IOU at 1- (IRR=0.73, p=0.32), 3- (IRR=1.20, p=0.54), or 6-month (IRR=0.73, p=0.23) follow-ups. Using person-day analysis, participants self-reported IOU on 5.8% of follow-up days in which they used prescription buprenorphine and 37.5% of non-buprenorphine days. Using a generalized estimating equation, the estimated odds of IOU was 4.57 times higher (p<0.001) on non-buprenorphine days.Despite STOP's success in linking patients who inject opiates to outpatient buprenorphine, the intervention did not significantly decrease their IOU frequency. Injection opiate users will require a more intensive protocol to sustain outpatient buprenorphine treatment and decrease injection with its attendant risks.
- Hepatic Safety of Buprenorphine in HIV-Infected and Uninfected Patients With Opioid Use Disorder: The Role of HCV-Infection. [Journal Article]
- J Subst Abuse Treat 2016 Sep.:62-7.
Individuals with HIV and hepatitis C (HCV) infection, alcohol use disorder, or who are prescribed potentially hepatotoxic medications may be at increased risk for buprenorphine (BUP) associated hepatotoxicity.We examined a cohort of HIV-infected and uninfected patients receiving an initial BUP prescription between 2003 and 2012. We compared changes in alanine and aspartate aminotransferases (ALT and AST) and total bilirubin (TB) stratified by HIV status. We identified cases of liver enzyme elevation (LEE), TB elevation (TBE), and conducted chart review to assess for cases of drug induced liver injury (DILI) and death. We examined associations between age, sex, race, HIV-infection, HCV-infection, alcohol use disorder, and prescription of other potentially heptatotoxic medications with the composite endpoint of LEE, TBE, and DILI.Of 666 patients prescribed BUP, 36% were HIV-infected, 98% were male, 60% had RNA-confirmed HCV infection, 50% had a recent diagnosis of alcohol use disorder, and 64% were prescribed other potentially hepatotoxic medications. No clinically significant changes were observed in median ALT, AST and TB and these changes did not differ between HIV-infected and uninfected patients. Compared with uninfected patients, HIV-infected (OR 7.3, 95% CI 2.1-26.1, p=0.002), HCV-infected (OR 4.9 95% CI 1.6-15.2, p=0.007) or HIV/HCV co-infected patients (OR 6.9, 95%CI 2.1-22.2, p=0.001) were more likely to have the composite endpoint of LEE, TB elevation or DILI, in analyses that excluded 60 patients with evidence of pre-existing liver injury. 31 patients had LEE, 14/187 HIV-infected and 17/340 uninfected (p=0.25); 11 had TBE, including 9/186 HIV-infected and 2/329 uninfected (p=0.002); 8 experienced DILI, 4/202 HIV-infected and 4/204 uninfected (p=0.45). There were no significant associations with alcohol use disorder or prescription of other potentially hepatotoxic medications after adjustment for HIV/HCV status.Liver enzymes and TB are rarely elevated in HIV-infected and uninfected patients receiving BUP. Risk of hepatotoxicity was greater in individuals infected with HIV, HCV, or HIV/HCV co-infection, who may benefit from increased monitoring.
- Reasons for Benzodiazepine Use Among Persons Seeking Opioid Detoxification. [Journal Article]
- J Subst Abuse Treat 2016 Sep.:57-61.
Over the past decade, patients admitted to addiction treatment programs have reported increasing rates of concurrent opioid and benzodiazepine (BZD) use. This drug combination places individuals at high risk for accidental overdose. Little is known about reasons for BZD use among individuals seeking treatment for opioid use disorders.We surveyed consecutive persons initiating inpatient opioid detoxification and identified 176 out of 438 who reported BZD use in the past 30 days and/or had a positive toxicology.Forty percent of persons surveyed used a BZD in the month prior to admission, and 25% of these met criteria for BZD dependence (DSM IV). BZD users averaged 32.0 years of age, 63.6% were male, 85.2% used heroin, and reported, on average, 13.3 (±11.2) days of BZD use during the past month. Alprazolam (Xanax) was the most commonly used BZD (52%), and buying it on the street the most common source (48%). The most commonly reported reason for BZD use was 'to manage anxiety' (42.6%), followed by 'to get or enhance a high' (27.7%), 'to help with sleep' (11.4%), and 'to decrease opioid withdrawal' (10.2%). The most common reason for BZD use was significantly associated (p<.001) with most likely source of BZDs, with persons who got their BZDs from a prescriber (23%) more likely to report BZD anxiety as their primary reason for use, while persons who bought BZDs on "the street" (48%) had the highest likelihood of reporting using BZD to get or enhance a high. Participants using BZDs most commonly for anxiety did not endorse lower anxiety than those using BZDs for other reasons.Two in five persons seeking detoxification for an opioid use disorder used a BZD in the prior month. Anxiety was the most common reason patients reported using a benzodiazepine, but they also reported using BZDs to enhance a 'high' and manage opioid withdrawal. Evidence-based discussions about the risks of combining BZDs and opioids, and alternatives to BZDs should be a high priority in detoxification settings.