Factors associated with use of opioid rescue medication after surgery.

BACKGROUND: Opioid exposure after surgery increases risk of persistent opioid use. Here, we characterize at-home use of opioid rescue medication during 1-2 days after outpatient surgery (N=270) in a postoperative opioid-sparing context at a Norwegian hospital. METHODS: The postsurgical pain management plan included non-steroidal anti-inflammatory drugs and up to six pills of 5 mg oxycodone as rescue analgesics. In this observational study we assessed risk factors for taking rescue opioids after surgery, by comparing patients who did, with those who did not. RESULTS: Only 35% (N=228) of patients reported taking rescue opioids 1-2 days after discharge. Patients taking rescue opioids after surgery (opioid-takers) differed from non-takers by prevalence of preoperative chronic pain (>3 months; 74% vs 48%), higher pain severity and interference before and after surgery, reporting lower ability to cope with postsurgical pain, higher nervousness about the surgery, being younger, and having received more opioid analgesics in the recovery room. Exploratory predictive modeling identified opioid administration in the recovery room as the most important predictor of at-home rescue medication use. Follow-up after >4 months indicated low acute pain levels (mean±SD = 1.1±1.8), with only four patients (2%, N=217) reporting opioid analgesic use. CONCLUSION: Factors related to at-home rescue medication use closely mirrored known risk factors for persistent opioid use after surgery, such as prior chronic pain, prior substance use, affective disturbances, and pain severity before surgery. These findings are potential targets in patient-centered care. Nevertheless, and reassuringly, findings are consistent with the idea that opioid-sparing postsurgical care can prevent large-scale chronic opioid use.

Opioid antagonism in humans: a primer on optimal dose and timing for central mu-opioid receptor blockade.

Non-human animal studies outline precise mechanisms of central mu-opioid regulation of pain, stress, affiliation and reward processing. In humans, pharmacological blockade with non-selective opioid antagonists such as naloxone and naltrexone is typically used to assess involvement of the mu-opioid system in such processing. However, robust estimates of the opioid receptor blockade achieved by opioid antagonists are missing. Dose and timing schedules are highly variable and often based on single studies. Here, we provide a detailed analysis of central opioid receptor blockade after opioid antagonism based on existing positron emission tomography data. We also create models for estimating opioid receptor blockade with intravenous naloxone and oral naltrexone. We find that common doses of intravenous naloxone (0.10-0.15 mg/kg) and oral naltrexone (50 mg) are more than sufficient to produce full blockade of central MOR (>90% receptor occupancy) for the duration of a typical experimental session (~60 min), presumably due to initial super saturation of receptors. Simulations indicate that these doses also produce high KOR blockade (78-100%) and some DOR blockade (10% with naltrexone and 48-74% with naloxone). Lower doses (e.g., 0.01 mg/kg intravenous naloxone) are estimated to produce less DOR and KOR blockade while still achieving a high level of MOR blockade for ~30 min. The models and simulations form the basis of two novel web applications for detailed planning and evaluation of experiments with opioid antagonists. These tools and recommendations enable selection of appropriate antagonists, doses and assessment time points, and determination of the achieved receptor blockade in previous studies.

Stress recovery with social support: A dyadic stress and support task.

How does social support bolster resilience? Here, we present a new dyadic paradigm to study causal mechanisms of acute and ecologically valid social support in the laboratory. The Dyadic Stress and Support Task (DSST) consists of a psychosocial stress phase and a recovery phase. During DSST stress, a pair of participants take turns to perform public speaking and mental arithmetic in front of a panel. Unable to see or touch each other, they witness each other's performance and feedback. During DSST recovery, the pair either interact freely with each other for 5 min (social support condition) or interact separately with an experimenter (non-support condition). To establish the validity of the DSST, we tested 21 pairs of long-term close friends in a pilot study. Primary outcome measures were ratings of affective state and bodily arousal (VAS scales 0-100). Secondary outcome measures were heart rate and salivary cortisol. DSST stress successfully induced subjective Stress Activation, increased Negative Affect and decreased Positive Affect. We also observed increased heart rate and salivary cortisol. After DSST recovery, Stress Activation and Negative Affect ratings were reduced in both groups. Positive Affect was completely restored to pre-stress baseline levels in the Social support group, while remaining significantly lower in the Non-support group. The DSST successfully induced stress and negative affect and captured stress recovery in both groups. Free-form interaction with the friend enhanced recovery of affective state, supporting the validity of spontaneous interaction between friends as a model of social support.

Assessment of Anhedonia in Adults With and Without Mental Illness: A Systematic Review and Meta-analysis.

Importance: Anhedonia, a reduced capacity for pleasure, is described for many psychiatric and neurologic conditions. However, a decade after the Research Domain Criteria launch, whether anhedonia severity differs between diagnoses is still unclear. Reference values for hedonic capacity in healthy humans are also needed. Objective: To generate and compare reference values for anhedonia levels in adults with and without mental illness. Data Sources: Web of Science, Scopus, PubMed, and Google Scholar were used to list all articles from January 1, 1995 to July 2, 2019, citing the scale development report of a widely used anhedonia questionnaire, the Snaith-Hamilton Pleasure Scale (SHAPS). Searches were conducted from April 5 to 11, 2018, and on July 2, 2019. Study Selection: Studies including healthy patients and those with a verified diagnosis, assessed at baseline or in a no-treatment condition with the complete 14-item SHAPS, were included in this preregistered meta-analysis. Data Extraction and Synthesis: Random-effects models were used to calculate mean SHAPS scores and 95% CIs separately for healthy participants and patients with current major depressive disorder (MDD), past/remitted MDD, bipolar disorder, schizophrenia, substance use disorders, Parkinson disease, and chronic pain. SHAPS scores were compared between groups using meta-regression, and traditional effect size meta-analyses were conducted to estimate differences in SHAPS scores between healthy and patient samples. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Main Outcomes and Measures: Self-reported anhedonia as measured by 2 different formats of the SHAPS (possible ranges, 0-14 and 14-56 points), with higher values on both scales indicating greater anhedonia symptoms. Results: In the available literature (168 articles; 16 494 participants; 8058 [49%] female participants; aged 13-72 years), patients with current MDD, schizophrenia, substance use disorder, Parkinson disease, and chronic pain scored higher on the SHAPS than healthy participants. Within the patient groups, those with current MDD scored considerably higher than all other groups. Patients with remitted MDD scored within the healthy range (g = 0.1). This pattern replicated across SHAPS scoring methods and was consistent across point estimate and effect size analyses. Conclusions and Relevance: The findings of this meta-analysis indicate that the severity of anhedonia may differ across disorders associated with anhedonia. Whereas anhedonia in MDD affects multiple pleasure domains, patients with other conditions may experience decreased enjoyment of only a minority of life's many rewards. These findings have implications for psychiatric taxonomy development, where dimensional approaches are gaining attention. Moreover, the SHAPS reference values presented herein may be useful for researchers and clinicians assessing the efficacy of anhedonia treatments.

Anhedonia in chronic pain and prescription opioid misuse.

BACKGROUND: Both acute and chronic pain can disrupt reward processing. Moreover, prolonged prescription opioid use and depressed mood are common in chronic pain samples. Despite the prevalence of these risk factors for anhedonia, little is known about anhedonia in chronic pain populations. METHODS: We conducted a large-scale, systematic study of anhedonia in chronic pain, focusing on its relationship with opioid use/misuse, pain severity, and depression. Chronic pain patients across four distinct samples (N = 488) completed the Snaith-Hamilton Pleasure Scale (SHAPS), measures of opioid use, pain severity and depression, as well as the Current Opioid Misuse Measure (COMM). We used a meta-analytic approach to determine reference levels of anhedonia in healthy samples spanning a variety of countries and diverse age groups, extracting SHAPS scores from 58 published studies totaling 2664 psychiatrically healthy participants. RESULTS: Compared to healthy samples, chronic pain patients showed higher levels of anhedonia, with ~25% of patients scoring above the standard anhedonia cut-off. This difference was not primarily driven by depression levels, which explained less than 25% of variance in anhedonia scores. Neither opioid use duration, dose, nor pain severity alone was significantly associated with anhedonia. Yet, there was a clear effect of opioid misuse, with opioid misusers (COMM ⩾13) reporting greater anhedonia than non-misusers. Opioid misuse remained a significant predictor of anhedonia even after controlling for pain severity, depression and opioid dose. CONCLUSIONS: Study results suggest that both chronic pain and opioid misuse contribute to anhedonia, which may, in turn, drive further pain and misuse.