Sex differences in daily life stress and craving in opioid-dependent patients.

BACKGROUND: Responses to stress and drug craving differ between men and women. Differences in the momentary experience of stress in relation to craving are less well-understood. OBJECTIVES: Using ecological momentary assessment (EMA), we examined sex differences in real-time in two areas: (1) causes and contexts associated with stress, and (2) the extent to which stress and drug cues are associated with craving. METHODS: Outpatients on opioid-agonist treatment (135 males, 47 females) reported stress, craving, and behavior on smartphones for 16 weeks. They initiated an entry each time they felt more stressed than usual (stress event) and made randomly prompted entries 3 times/day. In stress-event entries, they identified the causes and context (location, activity, companions), and rated stress and craving severity. RESULTS: The causes reported for stress events did not differ significantly by sex. Women reported arguing and being in a store more often during stress events, and men reported working more often during stress events, compared to base rates (assessed via random prompts). Women showed a greater increase in opioid craving as a function of stress (p < 0.0001) and had higher stress ratings in the presence of both stress and drug cues relative to men (p < 0.01). Similar effects were found for cocaine craving in men (p < 0.0001). CONCLUSION: EMA methods provide evidence based on real-time activities and moods that opioid-dependent men and women experience similar contexts and causes for stress but differ in stress- and cue-induced craving. These findings support sex-based tailoring of treatment, but because not all participants conformed to the overall pattern of sex differences, any such tailoring should also consider person-level differences.

Stress, craving and mood as predictors of early dropout from opioid agonist therapy.

BACKGROUND: Treatment with opioid agonists is effective for opioid use disorder, but early discontinuation of treatment is a major obstacle to success. Intensive longitudinal methods - which take many repeated measurements over time, usually in the field- have provided unique insight into the effects of stress, mood and craving on drug use while people are being treated; these methods might also be useful for studying the processes that lead people to drop out of treatment. METHODS: Ecological momentary assessment (EMA) was conducted for up to 17 weeks by obtaining multiple electronic diary entries per day from 238 participants being treated with methadone or buprenorphine-naloxone. Survival analysis was used to study two outcomes: dropping out of treatment and noncompliance with EMA self-report requirements. Self-reports of stress, craving, and mood were used as time-varying predictors. Demographic and psychosocial variables measured with the Addiction Severity Index at the start of treatment were used as time-invariant predictors. RESULTS: Dropping out of treatment was more likely in participants with more reported hassles (a measure of stress), higher levels of cocaine craving, lower levels of positive mood, a recent history of emotional abuse, a recent history of being bothered frequently by psychological problems, and with buprenorphine rather than methadone as their medication. In contrast, study noncompliance was not significantly associated with any of the variables analyzed. CONCLUSIONS: Assessment of stress, craving and mood during treatment might identify people who are at greater risk of dropping out, and therapeutic interventions targeting these processes might increase retention.

End-of-day reports of daily hassles and stress in men and women with opioid-use disorder: Relationship to momentary reports of opioid and cocaine use and stress.

BACKGROUND AND AIMS: Stress can be validly assessed "live" or by a summary evaluation of the very recent past. Using smartphone-based ecological momentary assessment (EMA) combined with end-of-day (EOD) entries, we assessed the association between daily hassles, stressful events and use of opioids and cocaine, in opioid- and cocaine-using men and women. METHODS: For up to 16 weeks, 161 outpatients in opioid-agonist treatment who reported cigarette smoking carried smartphones on which they reported stressful events (SEs) and drug use (DU) and completed an EOD questionnaire to report hassles encountered throughout the day, current perceived stress, cigarettes/day, and current mood. We compared EOD responses on days with and without SE and DU reports and on days when thrice-weekly urine drug screens indicated opioid or cocaine use or abstinence. RESULTS: Participants (N = 161) made 11,544 EOD entries; EMA SEs were reported on 861 (7.5%) days, and DUs on 1685 (14.6%) days. The most frequently reported hassles in EOD entries were "not enough money" (31.4% of daily reports) and maintaining abstinence (18.7%). Total EOD hassles showed small but statistically significant associations [odds ratios (95% CIs)] with EMA SEs [1.09 (1.06-1.13)], DUs [1.08 (1.06-1.10)], and urine-positive opioid [1.06 (1.04-1.09)] and cocaine [1.03 (1.00-1.06)] results. Men and women had similar rates (mean/day (SD)) of hassles: men 2.25 (3.55); women 2.55 (3.76) (F1,159 = 0.53, p = 0.47). CONCLUSIONS: Daily hassles, reported at the end of the day, are associated with both same-day stressful events and drug use. Monitoring hassles and devising specific coping strategies might be useful therapeutic targets.

Before and after: craving, mood, and background stress in the hours surrounding drug use and stressful events in patients with opioid-use disorder.

RATIONALE: Ecological momentary assessment (EMA) of specific events usually focuses more on antecedents and concomitants than on aftermaths. OBJECTIVES: To examine mental state both before and after discrete episodes of stress and drug use. METHODS: For up to 16 weeks, outpatients on opioid-agonist treatment carried smartphones on which they initiated entries for stressful events (SEs) or lapses to drug use (DUs), and thrice daily when randomly prompted (RPs). Participants rated their stress, opioid craving, cocaine craving, and moods. RP entries within 5 h of an event were analyzed and compared to other RPs. RESULTS: Stress, negative mood, and craving were generally higher before and after DUs and SEs compared to background levels in participants with at least one DU (n = 149) or SE (n = 158). Before DUs, there were increases in negative mood, opioid craving, and cocaine craving, but not background stress. Before SEs, there were increases in background stress, opioid craving, and cocaine craving, but not negative mood. These changes were more variable after events than before. Neither DUs nor SEs were significantly related to positive mood. CONCLUSIONS: Stress increased before stressful-event entries, but was less evident before drug use. Craving increased in the hours before drug use and stressful events-and remained elevated in the hours after either event. These results suggest a stronger link between drug use and craving than between drug use and stress. Lapses to drug use did not improve mood or reduce stress, at least not at our 1-h-bin time resolution, suggesting that if such benefits exist, they are brief.

Exacerbated Craving in the Presence of Stress and Drug Cues in Drug-Dependent Patients.

In addiction, risk factors for craving and use include stress and drug-related cues. Stress and cues have additive or more-than-additive effects on drug seeking in laboratory animals, but, surprisingly, seem to compete with one another (ie, exert less-than-additive effects) in human laboratory studies of craving. We sought heretofore elusive evidence that human drug users could show additive (or more-than-additive) effects of stress and cues on craving, using ecological momentary assessment (EMA). Outpatients (N=182) maintained on daily buprenorphine or methadone provided self-reports of stress, craving, mood, and behavior on electronic diaries for up to 16 weeks. In three randomly prompted entries (RPs) per day, participants reported the severity of stress and craving and whether they had seen or been offered opioids, cocaine, cannabis, methamphetamine, alcohol, or tobacco. In random-effects models controlling for between-person differences, we tested effects of momentary drug-cue exposure and stress (and their interaction) on momentary ratings of cocaine and heroin craving. For cocaine craving, the Stress × Cue interaction term had a positive mean effect across participants (M=0.019; CL95 0.001-0.036), denoting a more-than-additive effect. For heroin, the mean was not significantly greater than 0, but the confidence interval was predominantly positive (M=0.019; CL95 -0.007-0.044), suggesting at least an additive effect. Heterogeneity was substantial; qualitatively, the Stress × Cue effect appeared additive for most participants, more than additive for a sizeable minority, and competitive in very few. In the field, unlike in human laboratory studies to date, craving for cocaine and heroin is greater with the combination of drug cues and stress than with either alone. For a substantial minority of users, the combined effect may be more than additive.

Context and craving during stressful events in the daily lives of drug-dependent patients.

RATIONALE: Knowing how stress manifests in the lives of people with substance-use disorders could help inform mobile "just in time" treatment. OBJECTIVES: The purpose of this paper is to examine discrete episodes of stress, as distinct from the fluctuations in background stress assessed in most EMA studies. METHODS: For up to 16 weeks, outpatients on opioid-agonist treatment carried smartphones on which they initiated an entry whenever they experienced a stressful event (SE) and when randomly prompted (RP) three times daily. Participants reported the severity of stress and craving and the context of the report (location, activities, companions). Decomposition of covariance was used to separate within-person from between-person effects; r effect sizes below are within-person. RESULTS: Participants (158 of 182; 87%) made 1787 stress-event entries. Craving for opioids increased with stress severity (r effect = 0.50). Stress events tended to occur in social company (with acquaintances, 0.63, friends, 0.17, or on the phone, 0.41) rather than with family (spouse, -0.14; child, -0.18), and in places with more overall activity (bars, 0.32; outside, 0.28; walking, 0.28) and more likelihood of unexpected experiences (with strangers, 0.17). Being on the internet was slightly protective (-0.22). Our prior finding that being at the workplace protects against background stress in our participants was partly supported in these stressful-event data. CONCLUSIONS: The contexts of specific stressful events differ from those we have seen in prior studies of ongoing background stress. However, both are associated with drug craving.

Substance use and hepatitis C: an ecological momentary assessment study.

OBJECTIVE: The objective of this study was to assess craving and mood related to opioid and cocaine use among asymptomatic hepatitis C virus (HCV)+ and HCV- methadone patients who have not started antiviral treatment. METHODS: In this 28-week prospective ecological momentary assessment (EMA) study, 114 methadone-maintained, heroin- and cocaine-abusing individuals reported from the field in real time on their mood, craving, exposure to drug-use triggers, and drug use via handheld computers. RESULTS: Sixty-one percent were HCV+; none were overtly symptomatic or receiving HCV treatment. HCV status was not associated with age, sex, race, or past-30-day or lifetime heroin or cocaine use. In event-contingent EMA entries, HCV+ individuals more often attributed use to having been bored, worried, or sad; feeling uncomfortable; or others being critical of them compared with HCV- participants. In randomly prompted EMA entries, HCV+ participants reported significantly more exposure to drug-use triggers, including handling ≥$10, seeing cocaine or heroin, seeing someone being offered/use cocaine or heroin, being tempted to use cocaine, and wanting to see what would happen if they used just a little cocaine or heroin. CONCLUSIONS: HCV+ individuals experienced more negative moods and more often cited these negative moods as causes for drug use. HCV+ individuals reported greater exposure to environmental drug-use triggers, but they did not more frequently cite these as causes for drug use. The EMA data reported here suggest that HCV+ intravenous drug users may experience more labile mood and more reactivity to mood than HCV- intravenous drug users. The reason for the difference is not clear, but HCV status may be relevant to tailoring of treatment.

Real-time tracking of neighborhood surroundings and mood in urban drug misusers: application of a new method to study behavior in its geographical context.

BACKGROUND: Maladaptive behaviors may be more fully understood and efficiently prevented by ambulatory tools that assess people's ongoing experience in the context of their environment. METHODS: To demonstrate new field-deployable methods for assessing mood and behavior as a function of neighborhood surroundings (geographical momentary assessment; GMA), we collected time-stamped GPS data and ecological momentary assessment (EMA) ratings of mood, stress, and drug craving over 16 weeks at randomly prompted times during the waking hours of opioid-dependent polydrug users receiving methadone maintenance. Locations of EMA entries and participants' travel tracks calculated for the 12 before each EMA entry were mapped. Associations between subjective ratings and objective environmental ratings were evaluated at the whole neighborhood and 12-h track levels. RESULTS: Participants (N=27) were compliant with GMA data collection; 3711 randomly prompted EMA entries were matched to specific locations. At the neighborhood level, physical disorder was negatively correlated with negative mood, stress, and heroin and cocaine craving (ps<.0001-.0335); drug activity was negatively correlated with stress, heroin and cocaine craving (ps .0009-.0134). Similar relationships were found for the environments around respondents' tracks in the 12h preceding EMA entries. CONCLUSIONS: The results support the feasibility of GMA. The relationships between neighborhood characteristics and participants' reports were counterintuitive and counter-hypothesized, and challenge some assumptions about how ostensibly stressful environments are associated with lived experience and how such environments ultimately impair health. GMA methodology may have applications for development of individual- or neighborhood-level interventions.

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.

Real-time electronic diary reports of cue exposure and mood in the hours before cocaine and heroin craving and use.

CONTEXT: In ecological momentary assessment (EMA), participants electronically report their activities and moods in their daily environments in real time, enabling a truly prospective approach to the study of acute precipitants of behavioral events. Ecological momentary assessment has greatly enhanced the study of tobacco addiction, but its use has rarely been attempted in individuals with cocaine or heroin addiction. OBJECTIVE: To prospectively monitor the acute daily life precipitants of craving for and use of cocaine and heroin. DESIGN: Cohort study. PARTICIPANTS: A volunteer sample of 114 cocaine- and heroin-abusing outpatients who were being treated with methadone provided EMA data on handheld electronic devices for 14 918 person-days (mean, 130.9; range, 6-189 days per participant). Of these outpatients, a total of 102 (63 men, 39 women) provided acute precraving and/or preuse data and were thus included in the present analyses. MAIN OUTCOME MEASURES: Changes in reports of mood and exposure to 12 putative drug-use triggers at random intervals during the 5 hours preceding each self-reported episode of drug craving or use, analyzed via repeated-measures logistic regression (generalized linear mixed models). RESULTS: During the 5 hours preceding cocaine use or heroin craving, most of the 12 putative triggers showed linear increases. Cocaine use was most robustly associated with increases in participants reporting that they "saw [the] drug" (P < .001), were "tempted to use out of the blue" (P < .001), "wanted to see what would happen if I used" (P < .001), and were in a good mood (P < .001). Heroin craving was most robustly associated with increases in reports of feeling sad (P < .001) or angry (P = .01). Cocaine craving and heroin use showed few reliable associations with any of the putative triggers assessed. CONCLUSIONS: These findings confirm that polydrug-abusing individuals can provide behavioral data in their daily environments using handheld electronic devices and that those data can reveal orderly patterns, including prospectively detectable harbingers of craving and use, which may differ across drugs.

Automation in an addiction treatment research clinic: computerised contingency management, ecological momentary assessment and a protocol workflow system.

INTRODUCTION AND AIMS: A challenge in treatment research is the necessity of adhering to protocol and regulatory strictures while maintaining flexibility to meet patients' treatment needs and to accommodate variations among protocols. Another challenge is the acquisition of large amounts of data in an occasionally hectic environment, along with the provision of seamless methods for exporting, mining and querying the data. DESIGN AND METHODS: We have automated several major functions of our outpatient treatment research clinic for studies in drug abuse and dependence. Here we describe three such specialised applications: the Automated Contingency Management (ACM) system for the delivery of behavioural interventions, the transactional electronic diary (TED) system for the management of behavioural assessments and the Protocol Workflow System (PWS) for computerised workflow automation and guidance of each participant's daily clinic activities. These modules are integrated into our larger information system to enable data sharing in real time among authorised staff. RESULTS: ACM and the TED have each permitted us to conduct research that was not previously possible. In addition, the time to data analysis at the end of each study is substantially shorter. With the implementation of the PWS, we have been able to manage a research clinic with an 80 patient capacity, having an annual average of 18,000 patient visits and 7300 urine collections with a research staff of five. Finally, automated data management has considerably enhanced our ability to monitor and summarise participant safety data for research oversight. DISCUSSION AND CONCLUSIONS: When developed in consultation with end users, automation in treatment research clinics can enable more efficient operations, better communication among staff and expansions in research methods.

Pharmacy informatics in controlled substances research.

Pharmacies have become essential components in support of clinical research. Their operations become highly complex when preponderance of prescriptions is composed of controlled substances. Application of informatics will result in more efficient operations. We present the Pharmacy Information Management System (PIMS) that includes a set of decision support systems to address the pharmacy challenges and is integrated into our electronic health record system.

A clinical recruiting management system for complex multi-site clinical trials using qualification decision support systems.

A clinical recruiting management system with qualification decision support systems was developed to increase the efficiency of screening and evaluation of participants during a recruiting process whereby recruiting for various protocols are conducted at multiple sites by different groups with process interdependencies. This system is seamlessly integrated into our enterprise-scale Human Research Information System (HuRIS), encompassing research participants' electronic health records (EHR), with real-time access to the clinical trial data.

A high-level specification for adaptive ecological momentary assessment: real-time assessment of drug craving, use and abstinence.

In psychological research, efforts to capture day-to-day human experience traditionally relied on pen-and-paper diaries and questionnaires. Some current studies, however, incorporate handheld computers, which provide researchers with many options and advantages in addition to providing more reliable data. One advantage of using handheld computers is the programmability of the electronic diary, which, compared to old-fashioned paper diaries, affords the researchers with a wealth of possibilities. An important possibility is to construct a built-in mechanism in the computer-administered questionnaires that would allow transparent branching, in which question presentation is contingent on participants' answers to previous questions. The major hurdle in implementing such an approach is the limitations of the platform used for such assessments: inexpensive "low-end" handheld devices. We propose a high-level specification which enables non-programming researchers to "branch" their questionnaires without modifications to the source code in a highly user-friendly fashion, with backtracking capability and very modest hardware requirements. A finite state automaton approach was implemented, we believe for the first time, to create an auto-trigger mechanism for the real-time evaluation of the conditions. This solution provides our investigators with the capacity to administer efficient assessments that are dynamically customized to reflect participants' behaviors without the need for any post-production programming.