Comparison of Fentanyl, Ketamine, and Lidocaine Combined with Propofol Anesthesia in Patients with Crohn Disease Undergoing Colonoscopy.

BACKGROUND Colonoscopy is the predominant invasive procedure for Crohn disease (CD) patients. Opioids and propofol carry risks of respiratory and cardiovascular complications. This study aimed to evaluate whether substituting fentanyl with ketamine or lidocaine could diminish propofol usage and minimize adverse events. MATERIAL AND METHODS In total, 146 patients with CD scheduled for elective colonoscopy were assigned to anesthesia with fentanyl (n=47), ketamine (n=47), or lidocaine (n=55). Propofol was administered to achieve sufficient anesthesia. Measured outcomes in each group included propofol consumption, hypotension and desaturation incidents, adverse event types, consciousness recovery time, abdominal pain intensity, Aldrete scale, and Post Anaesthetic Discharge Scoring System (PADSS). RESULTS Patients administered fentanyl needed significantly more propofol (P=0.017) than those on ketamine, with lidocaine showing no notable difference (P=0.28). Desaturation was significantly less common in the ketamine and lidocaine groups than fentanyl group (P<0.001). The ketamine group experienced milder reductions in mean arterial (P=0.018) and systolic blood pressure (P<0.001). Recovery metrics (Aldrete and PADSS scores) were lower for fentanyl (P<0.001), although satisfaction and pain levels were consistent across all groups (P=0.797). Dizziness occurred less frequently with lidocaine than fentanyl (17.2%, P=0.018) and ketamine (15.1%, P=0.019), while metallic taste incidents were more prevalent in the lidocaine group (13.5%, P=0.04) than fentanyl group. CONCLUSIONS Using ketamine or lidocaine instead of fentanyl in anesthesia for colonoscopy in patients with CD significantly lowers propofol use, reduces desaturation events, maintains blood pressure more effectively, without increasing hypotension risk, and accelerates recovery, without negatively impacting adverse events or patient satisfaction.

United States marijuana legalization and opioid mortality trends before and during the first year of the COVID-19 pandemic.

BACKGROUND: To determine if marijuana legalization was associated with reduced opioid mortality. STUDY DESIGN: The United States (US) opioid mortality trend during the 2010-2019 decade was compared in states and District of Columbia (jurisdictions) that had implemented marijuana legalization with states that had not. Acceleration of opioid mortality during 2020, the first year of the coronavirus disease 2019 (COVID-19) pandemic, was also compared in recreational and medicinal-only legalizing jurisdictions. METHODS: Joinpoint methodology was applied to the Centers for Disease Control and Prevention WONDER data. Trends in legalizing jurisdictions were cumulative aggregates. RESULTS: The overall opioid and fentanyl death rates and the percentage of opioid deaths due to fentanyl increased more during 2010-2019 in jurisdictions that legalized marijuana than in those that did not (pairwise comparison p = 0.007, 0.05, and 0.006, respectively). By 2019, the all-opioid and fentanyl death rates were 44 and 50 percent greater in the legalizing than in the nonlegalizing jurisdictions, respectively. When the COVID-19 pandemic hit in 2020, jurisdictions that implemented recreational marijuana legalization before 2019 had significantly greater increases in both overall opioid and fentanyl death rates than jurisdictions with medicinal-only legalization. For all-opioids, the mean (95 percent confidence interval) 2019-to-2020 increases were 46.5 percent (36.6, 56.3 percent) and 29.1 percent (20.2, 37.9 percent), respectively (p = 0.02). For fentanyl, they were 115.6 percent (80.2, 151.6 percent) and 55.4 percent (31.6, 79.2 percent), respectively (p = 0.01). CONCLUSIONS: During the past decade, marijuana legalization in the US was associated at the jurisdiction level with a greater acceleration in opioid death rate. An even greater increase in opioid mortality occurred in recreational-legalizing jurisdictions with the onset of the COVID-19 pandemic. Marijuana legalization is correlated with worsening of the US opioid epidemic.

Using part of the initial analgesic dose as the epidural test dose did not delay the onset of labor analgesia: a randomized controlled clinical trial.

BACKGROUND: Epidural test dose for labor analgesia is controversial and varies widely in clinical practice. It is currently unclear whether using a portion of the initial dose for analgesia as the test dose delays the onset time of analgesia, compared to the traditional test dose. METHODS: One hundred and twenty-six parturients who chose epidural analgesia during labor were randomly assigned to two groups. The first dose in group L was 3 ml 1.5% lidocaine, and in the RF group was 10 ml 0.1% ropivacaine combined with 2 µg/ml fentanyl. After 3 min of observation, both groups received 8 ml 0.1% ropivacaine combined with 2 µg/ml fentanyl. The onset time of analgesia, motor and sensory blockade level, numerical pain rating scale, patient satisfaction score, and side effects were recorded. RESULTS: The onset time of analgesia in group RF was similar to that in group L (group RF vs group L, 7.0 [5.0-9.0] minutes vs 8.0 [5.0-11.0] minutes, p = 0.197). The incidence of foot numbness (group RF vs group L, 34.9% vs 57.1%, p = 0.020) and foot warming (group RF vs group L, 15.9% vs 47.6%, p < 0.001) in group RF was significantly lower than that in group L. There was no difference between the two groups on other outcomes. CONCLUSIONS: Compared with 1.5% lidocaine 3 ml, 0.1% ropivacaine 10 ml combined with 2 µg/ml fentanyl as an epidural test dose did not delay the onset of labor analgesia, and the side effects were slightly reduced. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn (ChiCTR2100043071).

Clinical and neuroradiographic features of fentanyl inhalation-induced leukoencephalopathy.

A man in his late 40s with no known past medical history was unresponsive for an unknown period of time. Crushed pills and white residue were found on a nearby table. On presentation he was obtunded and unresponsive to verbal commands but withdrawing to painful stimuli. The initial urine drug screen was negative, but a urine fentanyl screen was subsequently positive with a level of 137.3 ng/mL. MRI of the brain showed reduced diffusivity and fluid attenuated inversion recovery (FLAIR) hyperintensity symmetrically in the bilateral supratentorial white matter, cerebellum and globus pallidus. Alternative diagnoses such as infection were considered, but ultimately the history and workup led to a diagnosis of fentanyl-induced leukoencephalopathy. Three days after admission the patient became able to track, respond to voice and follow basic one-step commands. The patient does not recall the mechanism of inhalation. While there are case reports of heroin-induced leukoencephalopathy following inhaled heroin use and many routes of fentanyl, this is the first reported case of a similar phenomenon due to fentanyl inhalation.

Physiologically based modeling reveals different risk of respiratory depression after fentanyl overdose between adults and children.

Despite a rapid increase in pediatric mortality rate from prescription and illicit opioids, there is limited research on the dose-dependent impact of opioids on respiratory depression in children, the leading cause of opioid-associated death. In this article, we extend a previously developed translational model to cover pediatric populations by incorporating age-dependent pharmacokinetic, pharmacodynamic, and physiological changes compared to adults. Our model reproduced previous perioperative clinical findings that adults and children have similar risk of respiratory depression at the same plasma fentanyl concentration when specific endpoints (minute ventilation, CO2 tension in the blood) were used. However, our model points to a potential caveat that, in a perioperative setting, routine use of mechanical ventilation and supplemental oxygen maintained the blood and tissue oxygen partial pressures in patients and prevented the use of oxygen-related endpoints to evaluate the consequences of respiratory depression. In a community setting when such oxygenation procedures are not immediately available, our model suggests that the higher oxygen demand and reduced cerebrovascular reactivity could make children more susceptible to severe hypoxemia and brain hypoxia, even with the same plasma fentanyl concentration as adults. Our work indicates that when developing intervention strategies to protect children from opioid overdose in a community setting, these pediatric-specific factors may need to be considered.

A confirmed case of xylazine-induced skin ulcers in a person who injects drugs in Miami, Florida, USA.

BACKGROUND: Xylazine is an alpha-2 adrenergic receptor agonist that has emerged as a contaminant in the illicit drug supply of fentanyl. Xylazine use may be suspected in naloxone-resistant overdoses and atypical, chronic wounds in people who use drugs (PWUD). This case is unique because it is the first case to our knowledge describing wound care for a xylazine-induced wound with a confirmatory xylazine test strip (XTS) in the setting of a syringe services program (SSP) and in the state of Florida. CASE PRESENTATION: A 43-year-old woman with a past medical history of severe opioid use disorder and stimulant use disorder presented to a student-run clinic at a Miami SSP for wound care. She had multiple ulcerations diffusely over her bilateral forearms with surrounding erythema and warmth. Seven weeks later, she presented to clinic again for wound care because her wounds had progressed. At this visit, a XTS was used to confirm the presence of xylazine in her urine. Wound care management and harm reduction strategies employed at both visits were informed by best clinical judgement due to lack of formal guidelines at the time. Wound outcomes are unknown as the patient has not returned to clinic. CONCLUSIONS: Many PWUD at highest risk for acute and chronic health consequences of xylazine-adulterated fentanyl do not have access to healthcare outside of low barrier clinics and SSPs due to lack of insurance or mistrust of the traditional healthcare system due to stigma. There is an urgent need for access to XTS for PWUD and clinical practice guidelines for the treatment of xylazine-related wounds in outpatient clinics.

Gastrointestinal adverse effects associated with the use of intravenous oliceridine compared with intravenous hydromorphone or fentanyl in acute pain management utilizing adjusted indirect treatment comparison methods.

Background: In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of treatments versus a common comparator (either placebo or active treatment). For acute pain management, the effects of oliceridine have been compared in clinical trials to morphine but not to fentanyl or hydromorphone. Aim: To assess the comparative safety (specifically differences in the incidence of nausea, vomiting and opioid-induced respiratory depression [OIRD]) between oliceridine and relevant comparators (fentanyl and hydromorphone) through ITC analysis. Methods: A systematic literature review identified randomized clinical trials with oliceridine versus morphine and morphine versus fentanyl or hydromorphone. The ITC utilized the common active comparator, morphine, for the analysis. Results: A total of six randomized controlled trials (oliceridine - 2; hydromorphone - 3; fentanyl - 1) were identified for data to be used in the ITC analyses. The oliceridine data were reported in two studies (plastic surgery and orthopedic surgery) and were also reported in a pooled analysis. The ITC focused on nausea and vomiting due to limited data for OIRD. When oliceridine was compared with hydromorphone in the ITC analysis, oliceridine significantly reduced the incidence of nausea and/or vomiting requiring antiemetics compared with hydromorphone (both orthopedic surgery and pooled data), while results in plastic surgery were not statistically significant. When oliceridine was compared with hydromorphone utilizing data from Hong, the ITC only showed a trend toward reduced risk of nausea and vomiting with oliceridine that was not statistically significant across all three comparisons (orthopedic surgery, plastic surgery and combined). An ITC comparing oliceridine with a study of fentanyl utilizing the oliceridine orthopedic surgery data and combined orthopedic and plastic surgery data showed a trend toward reduced risk that was not statistically significant. Conclusion: In ITC analyses, oliceridine significantly reduced the incidence of nausea and/or vomiting or the need for antiemetics in orthopedic surgery compared with hydromorphone and a non-significant trend toward reduced risk versus fentanyl.

Xylazine: A Drug Adulterant of Clinical Concern.

PURPOSE OF REVIEW: The opioid epidemic has been responsible for significant morbidity and mortality in the USA and worldwide. As a result, it is essential to recognize the threat these potent drugs can cause when illicitly used. Specifically, introducing fentanyl as a drug adulterant has been shown to impact overdose rates drastically. In this regard, the Drug Enforcement Agency recently released a public safety alert announcing the new threat of a new adulterant called xylazine. Xylazine is a powerful animal sedative with a different mechanism of action when compared to illicit opioids such as heroin and fentanyl. Xylazine is typically injected intravenously via a syringe, often in combination with multiple other drugs. One of the most common drugs, xylazine, is taken in combination with fentanyl, with users of this drug combination describing xylazine as prolonging the euphoric sensation produced by fentanyl. RECENT FINDINGS: Xylazine may cause adverse effects such as bradycardia, brief hypertension followed by hypotension, premature ventricular contractions, ataxia, slurred speech, sedation, and respiratory depression. Much of the recent literature on xylazine use in humans comes from case reports and review articles. Related to widespread use in veterinary medicine and increasing circulation in illicit drug markets, there is a critical need for public awareness and additional clinical-based studies to further increase understanding of mediated or modulated pharmacological effects of xylazine in humans. Further research is urgently needed to more clearly understand the implications of unregulated xylazine in the illicit drug market, to formulate public health interventions, and to implement harm reduction strategies.

Efficacy and safety of esketamine combined with propofol for curative endoscopic resection in colorectum: a prospective, randomized controlled trial.

BACKGROUND: Curative endoscopic resection is widely used to treat colonic polyps and early stage cancers. The anesthetic strategy commonly involves the use of propofol combined with a small dose of opioids for sedation. Adverse respiratory or cardiovascular events such as hypotension often occur when attempting to achieve the necessary level of sedation. Several studies have suggested its advantages owing to the anesthetic, analgesic, and sympathomimetic properties of esketamine. However, there are no reports on curative colorectal endoscopic resection. We designed this randomized controlled trial to assess the efficacy and safety of esketamine combined with propofol for sedation in patients undergoing curative colorectal endoscopic resection. METHODS: A total of 166 patients who underwent curative colorectal endoscopic resection were randomly assigned to groups A (propofol + fentanyl) or E (propofol + esketamine). Ideal sedation was assessed using the MOAA/S scale and was achieved using TCI-propofol with different doses of fentanyl and esketamine. The propofol consumption and vasoactive drug dosages were recorded. Sedation-related times, adverse events, and satisfaction were recorded. RESULTS: Of the 160 patients, the total propofol consumption was significantly lower in group E (n = 81) (300 mg) than in group A (n = 79) (350 mg). Hypotension and bradycardia were significantly lower in Group E than in Group A. The groups showed no significant differences in other adverse events, induction time, recovery time, or patient or endoscopist satisfaction. CONCLUSION: Compared to fentanyl, esketamine helps decrease propofol consumption and increases cardiovascular stability during curative colorectal endoscopic resection in American Society of Anesthesiologists Class I-III patients without affecting anesthesia, patient and endoscopist satisfaction, or other adverse events. TRIAL REGISTRATION: The study was retrospectively registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ; registration number: ChiCTR2300069014 on 03/03/2023).

Overdosing in a Motor Vehicle: Examination of Human, Geographic, and Environmental Factors.

BACKGROUND: Fentanyl, a type of opioid, in impaired driving cases increased across cities in the United States. OBJECTIVES: No empirical studies have examined motor vehicle overdoses with fentanyl use. We investigated the magnitude of the motor vehicle overdose problem in Providence, RI, and the environmental, socioeconomic, and geographic conditions associated with motor vehicle overdose occurrence. METHODS: This was a retrospective observational study of emergency medical services data on all suspected opioid overdoses between January 1, 2017, and October 31, 2020. The data contain forced-choice fields, such as age and biological sex, and an open-ended narrative in which the paramedic documented clinical and situational information. The overdoses were geocoded, allowing for the extraction of sociodemographic data from the U.S. Census Bureau's American Community Survey. Seven other data sources were included in a logistic regression to understand key risk factors and spatial patterns of motor vehicle overdoses. RESULTS: Of the 1,357 opioid overdose cases in this analysis, 15.2% were defined as motor vehicle overdoses. In adjusted models, we found a 61% increase in the odds of a motor vehicle overdose involvement for men versus women, a 16.8% decrease in the odds of a motor vehicle overdose for a one-unit increase in distance to the nearest gas station, and a 10.7% decrease in the odds of a motor vehicle overdose for a one-unit increase in distance to a buprenorphine clinic. CONCLUSION: There is a need to understand the interaction between drug use in vehicles to design interventions for decreasing driving after illicit drug use.

Subcutaneous vs intravenous fentanyl for labor pain management: a multicenter randomized controlled trial.

BACKGROUND: Labor pain is the most intense pain a woman will experience during her lifetime. Epidural anesthesia is recommended as the most effective method for pain relief, but it has several limitations. Fentanyl has high analgesic potency with short-acting duration, but the large-scale trials that assessed the effectiveness and safety of it for labor pain management are still limited. OBJECTIVE: This study aimed to compare the effectiveness and harm and maternal satisfaction of subcutaneous vs intravenous fentanyl for labor pain management. STUDY DESIGN: We conducted a multicenter, open-label randomized controlled trial. A total of 226 women were randomized to receive intravenous or subcutaneous fentanyl for labor pain management. Pain scores were evaluated before and after fentanyl administration at 5, 30, and 60 minutes and then every 60 minutes until delivery. The data were analyzed based on the intention-to-treat principle. RESULTS: Both intravenous and subcutaneous fentanyl significantly decreased labor pain from baseline to delivery (overall mean change, -1.39; 95% confidence interval, -1.62 to -1.17; and -0.89; 95% confidence interval, -1.24 to -0.05, respectively). The reduction in the pain score between the 2 groups was not different (overall mean difference, -0.35; 95% confidence interval, -0.76 to 0.05). Maternal satisfaction was high for both intravenous and subcutaneous fentanyl (89.4% and 93.8%, respectively). There was no difference in the maternal satisfaction rate between the 2 groups (relative risk, 0.95; 95% confidence interval, 0.88-1.03). No serious maternal and neonatal adverse effects were observed. CONCLUSION: Both intravenously and subcutaneously administered fentanyl were safe and significantly reduced pain from baseline to delivery among low-risk pregnancies. Maternal satisfaction with the childbirth experience was high regardless of the route of administration of fentanyl. No serious adverse effects of fentanyl were observed in either the mothers or the neonates.

Routes of Drug Use Among Drug Overdose Deaths - United States, 2020-2022.

Preliminary reports indicate that more than 109,000 drug overdose deaths occurred in the United States in 2022; nearly 70% of these involved synthetic opioids other than methadone, primarily illegally manufactured fentanyl and fentanyl analogs (IMFs). Data from the western United States suggested a transition from injecting heroin to smoking IMFs. CDC analyzed data from the State Unintentional Drug Overdose Reporting System to describe trends in routes of drug use in 27 states and the District of Columbia among overdose deaths that occurred during January 2020-December 2022, overall and by region and drugs detected. From January-June 2020 to July-December 2022, the percentage of overdose deaths with evidence of injection decreased 29.1%, from 22.7% to 16.1%, whereas the percentage with evidence of smoking increased 73.7%, from 13.3% to 23.1%. The number of deaths with evidence of smoking increased 109.1%, from 2,794 to 5,843, and by 2022, smoking was the most commonly documented route of use in overdose deaths. Trends were similar in all U.S. regions. Among deaths with only IMFs detected, the percentage with evidence of injection decreased 41.6%, from 20.9% during January-June 2020 to 12.2% during July-December 2022, whereas the percentage with evidence of smoking increased 78.9%, from 10.9% to 19.5%. Similar trends were observed among deaths with both IMFs and stimulants detected. Strengthening public health and harm reduction services to address overdose risk related to diverse routes of drug use, including smoking and other noninjection routes, might reduce drug overdose deaths.

Implementing physics-based digital patient twins to tailor the switch of oral morphine to transdermal fentanyl patches based on patient physiology.

Fentanyl transdermal patches are widely implemented for cancer-induced pain treatment due to the high potency of fentanyl and gradual drug release. However, transdermal fentanyl up-titration for opioid-naïve patients is difficult, which is why opioid treatment is often started with oral/iv morphine. Based on the daily dose of morphine, the initial dose of the fentanyl patch is decided upon. After reaching a stable level of pain, the switch is made from oral/iv morphine to transdermal fentanyl. There are standard calculation tools for transferring from oral/iv morphine to transdermal fentanyl, which is the same for all patients. By considering the variations in the physiology of the patients, a unique switching strategy cannot meet the needs of different patients. This study explores the outcome in terms of pain relief and minute ventilation during opioid therapy. For this, we used physics-based simulations on a virtually-generated population of patients, and we applied the same therapy to all patients. We could show that patients' physiology, such as gender, age, and weight, greatly impact the outcome of the therapy; as such, the correlation coefficient between pain intensity and age is 0.89, and the correlation coefficient between patient's weight and maximum plasma concentration of morphine and fentanyl is -0.98 and -0.97. Additionally, a different combination of the duration of overlap between morphine and fentanyl therapy with different doses of fentanyl was considered for the virtual patients to find the best opioid-switching strategy for each patient. We explored the impact of combining physiological features to determine the best-suited strategy for virtual patients. Our findings suggest that tailoring morphine and fentanyl therapy only based on a limited number of features is insufficient, and increasing the number of impactful physiological features positively influences the outcome of the therapy.

Beyond Traditional Pain Relief: A Review of Alternative Analgesics in Myocardial Infarction Patient Management.

While morphine is the recommended first-line treatment for pain management in patients with acute coronary syndrome, recent studies have raised concerns about its association with adverse outcomes. Morphine has been found to cause delayed antiplatelet effects, decreased ticagrelor absorption, increased platelet reactivity, and compromised efficacy of dual antiplatelet therapy (DAPT). Alternative analgesics, such as lidocaine, fentanyl, and acetaminophen, have begun to emerge as viable alternatives, each with unique mechanisms and potential benefits. Lidocaine is demonstrated to have superior effects in reducing microvascular obstruction and fewer adverse events compared to fentanyl, despite being less effective in pain reduction. Fentanyl, which shows rapid onset and powerful analgesic properties, may interfere with ticagrelor absorption, potentially affecting platelet inhibition. Acetaminophen, a centrally acting analgesic, emerges as a safer alternative with comparable pain relief efficacy and minimal side effects. The results of multiple clinical trials emphasize the significance of customizing pain management approaches to match individual patient profiles and achieving the optimal balance between pain relief and potential adverse outcomes.

Guidelines for Rational Clinical Use of Fentanyl Transdermal Patch.

Pain is one of the most common clinical symptoms of cancer patients, seriously affecting the quality of life of patients and bringing heavy mental and economic burden to families and society. The treatment of cancer pain in China is facing numerous challenges, one of which includes the irrational usage of analgesic drugs in clinical practice. As a strong opioid analgesic, transdermal fentanyl patch has been widely used due to its convenient clinical application and obvious therapeutic effect. Several basic-level hospitals and even general hospitals in China fail to appropriate the application of drugs in clinical application due to the lack of understanding of the pharmacological characteristics and clinical application of fentanyl transdermal patch by medical staff, seriously affecting the treatment quality. Therefore, it is imperative to strengthen the rational use and management of fentanyl transdermal patches. Accordingly, the initiation by the Cancer Rehabilitation and Palliative Treatment Professional Committee of the Hubei Anti-cancer Association launched the compilation of the "Guidelines for Rational Clinical Use of Fentanyl Transdermal Patch" (from now on referred to as the "Guidelines") in Hubei Province, China. The experts in the preparation group are experts in many disciplines, such as medicine, pharmacy, and nursing. The expert group determines the outline, prepares the required regulations, and revises it repeatedly. Moreover, these experts put forward suggestions for revision to strictly control the accuracy and scientific authenticity of the contents of the "Guide". Finally, all experts of the preparation team certify and finalize the draft. This "Guide" prepared by experts of the Cancer Rehabilitation and Palliative Treatment Professional Committee of the Hubei Anti-cancer Association and the expert advisory group with joint efforts, aims to play a positive role in promoting the rational clinical use of fentanyl transdermal patch, reducing the mental and economic burden of patients, and ensuring medical quality and medical safety.

Ketamine for treatment-resistant major depressive disorder: Double-blind active-controlled crossover study.

BACKGROUND: The N-methyl-D-aspartate antagonist ketamine has rapid onset antidepressant activity in treatment-resistant depression (TRD). AIMS: To evaluate mood rating, safety and tolerability data from patients with TRD treated with ketamine and the psychoactive control fentanyl, as part of a larger study to explore EEG biomarkers associated with mood response. METHODS: We evaluated the efficacy and safety of intramuscular racemic ketamine in 25 patients with TRD, using a double-blind active-controlled randomized crossover design. Ketamine doses were 0.5 and 1 mg/kg, and the psychoactive control was fentanyl 50 mcg, given at weekly intervals. RESULTS/OUTCOMES: Within 1 h of ketamine dosing, patients reported reduced depression and anxiety ratings, which persisted for up to 7 days. A dose-response profile for ketamine was noted for dissociative side effects, adverse events and changes in blood pressure; however, changes in mood ratings were broadly similar for both ketamine doses. Overall, 14/25 patients (56%) were responders (⩾50% reduction at 24 h compared with baseline) for either ketamine dose for the Hospital Anxiety and Depression Scale (HADS), and 18/25 (72%) were responders for the HADS-anxiety scale. After fentanyl, only 1/25 (HADS-depression) and 3/25 (HADS-anxiety) were responders. Ketamine was generally safe and well tolerated in this population. CONCLUSIONS: Our findings add to the literature confirming ketamine's activity against depressive and anxiety symptoms in patients with TRD.

Characterizing Opioid Withdrawal Experiences and Consequences Among a Community Sample of People Who Use Opioids.

BACKGROUND: Opioid withdrawal symptoms are a highly salient and consequential health condition experienced by people who use opioids (PWUO). This study utilized qualitative interviews to explore opioid withdrawal experiences and consequences among PWUO in Los Angeles County, USA. METHODS: Semi-structured qualitative interviews were conducted with 22 PWUO (aged 27-63 years) between May 2021 and May 2022. Participants self-reported opioid and injection drug use in the last 30 days. We employed an inductive thematic approach to systematically code and synthesize textual interview data. RESULTS: Participants experienced withdrawal symptoms frequently, with many going to great lengths to avoid them. Withdrawal pain was described as incapacitating and interfered with PWUO's ability to sustain regular employment and ensure stable housing. Avoiding withdrawal was described as influential in driving decisions to continue using opioids. Mechanisms for managing withdrawal included using other substances to the point of sedation. PWUO who transitioned from heroin to fentanyl use revealed more frequent, painful, and faster onset of withdrawal symptoms. Adverse withdrawal experiences and fear of precipitated withdrawal from buprenorphine were barriers to treatment initiation and continuation. CONCLUSION: Withdrawal symptoms among PWUO increase health risk. Improved strategies to treat opioid withdrawal are urgently needed. Solutions such as safe supply and intentional opioid withdrawal interventions (educational trainings, withdrawal comfort kits) are needed to improve withdrawal management and reduce opioid-related harm.