Reward Responsiveness in Patients with Opioid Use Disorder on Opioid Agonist Treatment: Role of Comorbid Chronic Pain.

OBJECTIVE: Evidence suggests that blunted reward responsiveness may account for poor clinical outcomes in both opioid use disorder (OUD) and chronic pain. Understanding how individuals with OUD and comorbid chronic pain (OUD+CP) respond to rewards is, therefore, of clinical interest because it may reveal a potential point of behavioral intervention. METHODS: Patients with OUD (n = 28) and OUD+CP (n = 19) on opioid agonist treatment were compared on: 1) the Probabilistic Reward Task (an objective behavioral measure of reward response bias) and 2) ecological momentary assessment of affective responses to pleasurable events. RESULTS: Both the OUD and the OUD+CP groups evidenced an increase in reward response bias in the Probabilistic Reward Task. The rate of change in response bias across blocks was statistically significant in the OUD group (B = 0.06, standard error [SE] = 0.02, t = 3.92, P < 0.001, 95% confidence interval [CI]: 0.03 to 0.09) but not in the OUD+CP group (B = 0.03, SE = 0.02, t = 1.90, P = 0.07, 95% CI: -0.002 to 0.07). However, groups did not significantly differ in the rate of change in response bias across blocks (B = 0.03, SE = 0.02, t = 1.21, P = 0.23, 95% CI: -0.02 to 0.07). Groups did not significantly differ on state measures of reward responsiveness (P's ≥0.50). CONCLUSIONS: Overall, findings across objective and subjective measures were mixed, necessitating follow-up with a larger sample. The results suggest that although there is a reward response bias in patients with OUD+CP treated with opioid agonist treatment relative to patients with OUD without CP, it is modest and does not appear to translate into patients' responses to rewarding events as they unfold in daily life.

Craving mediates the association between momentary pain and illicit opioid use during treatment for opioid-use disorder: an ecological momentary assessment study.

AIM: To assess the role of momentary pain on opioid craving and illicit opioid use among individuals receiving opioid agonist treatment. DESIGN: Observational study using ecological momentary assessment. SETTING: The National Institute of Drug Abuse Intramural Research Program in the United States. PARTICIPANTS: Fifty-six adults who qualified for opioid agonist treatment. MEASUREMENTS: Participants completed randomly prompted assessments of pain severity, stress, negative mood, opioid craving and illicit opioid use for a mean of 66 days [standard deviation (SD) = 27]. Urine samples were collected two to three times/week throughout. FINDINGS: Almost 70% of participants reported moderate average pain severity in the past 24 hours at intake and 35% of participants reported chronic pain. There were no significant differences in percent of opioid-positive urine samples (P = 0.73) and average level of opioid craving during the study period (P = 0.91) among opioid agonist treatment only patients versus opioid agonist treatment patients with chronic pain. However, momentary pain severity significantly predicted concurrent opioid craving [B = 0.02, 95% confidence interval (CI) = 0.01, 0.04], over and above stress and negative mood. Momentary opioid craving, in turn, significantly predicted illicit opioid use that was assessed in the next moment [odds ratio (OR) = 1.72, 95% CI = 1.12, 2.64), while controlling for autocorrelation and the effects of pain, negative mood and stress. Momentary opioid craving significantly mediated the prospective association between momentary pain and illicit opioid use (95% CI = 0.003, 0.032). Exploratory analysis revealed that momentary pain severity also significantly moderated the momentary association between stress and opioid craving (B = 0.02, 95% CI = 0.00, 0.04), such that when momentary pain severity increased, the association between the two intensified. CONCLUSIONS: Among people receiving opioid agonist treatment, momentary pain appears to be indirectly associated with illicit opioid use via momentary opioid craving.

Multimodal assessment of sleep in men and women during treatment for opioid use disorder.

BACKGROUND: Sleep disturbance is common in patients with opioid use disorder (OUD) receiving medication for addiction treatment. Differences between patients on the two primary agonist medications-methadone and buprenorphine-are not well understood. METHODS: In patients receiving either methadone or buprenorphine treatment for OUD, we examined sleep continuity and architecture using ambulatory monitoring to gather both an objective measure (daily sleep EEG; M = 5.76 days, SD = 1.46) and a subjective measure (daily sleep diary; M = 54.10 days, SD = 25.10) of sleep. RESULTS: Patients treated with buprenorphine versus methadone did not differ on any measure of sleep continuity or architecture. Women had longer EEG-derived total sleep time than men (d = -0.68, 95 % CI -1.32 to -0.09), along with lower %N2 (d = 0.94, 95 % CI 0.34-1.64) and greater %N3 (d = -0.94, 95 % CI -1.61 to -0.32). Self-reported sleep differed from EEG-derived estimates: wake after sleep onset was greater by EEG than by diary (d = 2.58, 95 % CI 1.74-3.63), and total sleep time and sleep efficiency were lower by EEG than by diary (d for sleep time = 2.93, 95 % CI 2.06-4.14; d for efficiency = 1.69, 95 % CI 0.98-2.49). CONCLUSIONS: Patients treated with buprenorphine or methadone did not substantively differ in ambulatory measures of sleep. With both medications, there was a discrepancy between objective and subjective sleep measures. Further confirmatory evidence would inform the development of sleep-related recommendations for OUD patients undergoing agonist treatment.

Aripiprazole for cocaine abstinence: a randomized-controlled trial with ecological momentary assessment.

Aripiprazole blocks psychostimulant seeking in a rat model of relapse. However, in humans, it may increase ongoing use. We tested aripiprazole specifically for relapse prevention. Methadone-maintained outpatients who were abstinent from cocaine in weeks 11-12 were randomized to double-blind aripiprazole (15 mg daily) or placebo in weeks 13-27 after 12 weeks of contingency management. Participants reported craving through ecological momentary assessment. We stopped the trial because very few (18/41) participants fulfilled the abstinence criterion. The results suggested that aripiprazole delayed lapse [hazard ratio (HR)=0.45, 95% confidence interval (CI)=0.14-1.42, P=0.17] and relapse (HR=0.31, 95% CI=0.07-1.27, P=0.10), but the effects did not reach statistical significance. Unexpectedly, the proportion of participants reporting cocaine craving was higher in the aripiprazole group (Fisher's exact P=0.026), although the frequency of craving was similar in the aripiprazole and placebo groups (1.89 vs. 1.16%, reffect=0.43, 95% CI=-0.08-0.76). The results suggest that in recently abstinent cocaine users, aripiprazole might delay relapse, but might also slightly increase craving. Difficulty in trial implementation underscores the fact that initial abstinence from cocaine is not a trivial hurdle.

Continuous in-the-field measurement of heart rate: Correlates of drug use, craving, stress, and mood in polydrug users.

BACKGROUND: Ambulatory physiological monitoring could clarify antecedents and consequences of drug use and could contribute to a sensor-triggered mobile intervention that automatically detects behaviorally risky situations. Our goal was to show that such monitoring is feasible and can produce meaningful data. METHODS: We assessed heart rate (HR) with AutoSense, a suite of biosensors that wirelessly transmits data to a smartphone, for up to 4 weeks in 40 polydrug users in opioid-agonist maintenance as they went about their daily lives. Participants also self-reported drug use, mood, and activities on electronic diaries. We compared HR with self-report using multilevel modeling (SAS Proc Mixed). RESULTS: Compliance with AutoSense was good; the data yield from the wireless electrocardiographs was 85.7%. HR was higher when participants reported cocaine use than when they reported heroin use (F(2,9)=250.3, p<.0001) and was also higher as a function of the dose of cocaine reported (F(1,8)=207.7, p<.0001). HR was higher when participants reported craving heroin (F(1,16)=230.9, p<.0001) or cocaine (F(1,14)=157.2, p<.0001) than when they reported of not craving. HR was lower (p<.05) in randomly prompted entries in which participants reported feeling relaxed, feeling happy, or watching TV, and was higher when they reported feeling stressed, being hassled, or walking. CONCLUSIONS: High-yield, high-quality heart-rate data can be obtained from drug users in their natural environment as they go about their daily lives, and the resultant data robustly reflect episodes of cocaine and heroin use and other mental and behavioral events of interest.

Clonidine Maintenance Prolongs Opioid Abstinence and Decouples Stress From Craving in Daily Life: A Randomized Controlled Trial With Ecological Momentary Assessment.

OBJECTIVE: The authors tested whether clonidine blocks stress-induced seeking of heroin and cocaine. The study was also intended to confirm translational findings from a rat model of drug relapse by using ecological momentary assessment of patients' stress to test hypotheses about clonidine's behavioral mechanism of action. METHOD: The authors conducted a randomized double-blind placebo-controlled clinical trial with 208 opioid-dependent patients at an outpatient buprenorphine clinic. The 118 participants (57%) who maintained abstinence during weeks 5-6 were continued on buprenorphine and randomly assigned to receive clonidine (N=61) or placebo (N=57) for 14 weeks. Urine was tested thrice weekly. Lapse was defined as any opioid-positive or missed urine test, and relapse as two or more consecutive lapses. Time to lapse and relapse were examined with Cox regressions; longest period of abstinence was examined with a t test, and ecological momentary assessment data were examined with generalized linear mixed models. RESULTS: In an intent-to-treat analysis, clonidine produced the longest duration (in consecutive days) of abstinence from opioids during the intervention phase (34.8 days [SD=3.7] compared with 25.5 days [SD=2.7]; Cohen's d=0.38). There was no group difference in time to relapse, but the clonidine group took longer to lapse (hazard ratio=0.67, 95% CI=0.45-1.00). Ecological momentary assessment showed that daily-life stress was partly decoupled from opioid craving in the clonidine group, supporting the authors' hypothesized mechanism for clonidine's benefits. CONCLUSIONS: Clonidine, a readily available medication, is useful in opioid dependence not just for reduction of withdrawal signs, but also as an adjunctive maintenance treatment that increases duration of abstinence. Even in the absence of physical withdrawal, it decouples stress from craving in everyday life.

Smartphone Delivery of Mobile HIV Risk Reduction Education.

We sought to develop and deploy a video-based smartphone-delivered mobile HIV Risk Reduction (mHIVRR) intervention to individuals in an addiction treatment clinic. We developed 3 video modules that consisted of a 10-minute HIVRR video, 11 acceptability questions, and 3 knowledge questions and deployed them as a secondary study within a larger study of ecological momentary and geographical momentary assessments. All 24 individuals who remained in the main study long enough completed the mHIVRR secondary study. All 3 videos met our a priori criteria for acceptability "as is" in the population: they achieved median scores of ≤2.5 on a 5-point Likert scale; ≤20% of the individuals gave them the most negative rating on the scale; a majority of the individuals stated that they would not prefer other formats over video-based smartphone-delivered one (all P < 0.05). Additionally, all of our video modules met our a priori criteria for feasibility: ≤20% of data were missing due to participant noncompliance and ≤20% were missing due to technical failure. We concluded that video-based mHIVRR education delivered via smartphone is acceptable, feasible and may increase HIV/STD risk reduction knowledge. Future studies, with pre-intervention assessments of knowledge and random assignment, are needed to confirm these findings.