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Case report: The lesson from opioid withdrawal symptoms mimicking paraganglioma recurrence during opioid deprescribing in cancer pain.

ABSTRACT: Pain is one of the predominant and troublesome symptoms that burden cancer patients during their whole disease trajectory: adequate pain management is a fundamental component of cancer care. Opioid are the cornerstone of cancer pain relief therapy and their skillful management must be owned by physicians approaching cancer pain patients. In light of the increased survival of cancer patients due to advances in therapy, deprescription should be considered as a part of the opioid prescribing regime, from therapy initiation, dose titration, and changing or adding drugs, to switching or ceasing. In clinical practice, opioid tapering after pain remission could be challenging due to withdrawal symptoms' onset. Animal models and observations in patients with opioid addiction suggested that somatic and motivational symptoms accompanying opioid withdrawal are secondary to the activation of stress-related process (mainly cortisol and catecholamines mediated). In this narrative review, we highlight how the lack of validated guidelines and tools for cancer patients can lead to a lower diagnostic awareness of opioid-related disorders, increasing the risk of developing withdrawal symptoms. We also described an experience-based approach to opioid withdrawal, starting from a case-report of a symptomatic patient with a history of metastatic pheochromocytoma-paraganglioma.

SUBMITTER: Ruggiero E

PROVIDER: S-EPMC10556467 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Case report: The lesson from opioid withdrawal symptoms mimicking paraganglioma recurrence during opioid deprescribing in cancer pain.

Ruggiero Elena E Pambuku Ardi A Caccese Mario M Lombardi Giuseppe G Gallio Ivan I Brunello Antonella A Ceccato Filippo F Formaglio Fabio F

Frontiers in pain research (Lausanne, Switzerland) 20230922

Pain is one of the predominant and troublesome symptoms that burden cancer patients during their whole disease trajectory: adequate pain management is a fundamental component of cancer care. Opioid are the cornerstone of cancer pain relief therapy and their skillful management must be owned by physicians approaching cancer pain patients. In light of the increased survival of cancer patients due to advances in therapy, deprescription should be considered as a part of the opioid prescribing regime ...[more]

PMID: 37810433

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Project description:Δ(9)-Tetrahydrocannbinol (THC), the primary active constituent of Cannabis sativa, has long been known to reduce opioid withdrawal symptoms. Although THC produces most of its pharmacological actions through the activation of CB(1) and CB(2) cannabinoid receptors, the role these receptors play in reducing the variety of opioid withdrawal symptoms remains unknown. The endogenous cannabinoids, N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), activate both cannabinoid receptors but are rapidly metabolized by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. The objective of this study was to test whether increasing AEA or 2-AG, via inhibition of their respective hydrolytic enzymes, reduces naloxone-precipitated morphine withdrawal symptoms in in vivo and in vitro models of opioid dependence. Morphine-dependent mice challenged with naloxone reliably displayed a profound withdrawal syndrome, consisting of jumping, paw tremors, diarrhea, and weight loss. THC and the MAGL inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) dose dependently reduced the intensity of most measures through the activation of CB(1) receptors. JZL184 also attenuated spontaneous withdrawal signs in morphine-dependent mice. The FAAH inhibitor N-(pyridin-3-yl)-4-(3-(5-(trifluoromethyl)pyridin-2-yloxy)benzyl)-piperdine-1-carboxamide (PF-3845) reduced the intensity of naloxone-precipitated jumps and paw flutters through the activation of CB(1) receptors but did not ameliorate incidence of diarrhea or weight loss. In the final series of experiments, we investigated whether JZL184 or PF-3845 would attenuate naloxone-precipitated contractions in morphine-dependent ilea. Both enzyme inhibitors attenuated the intensity of naloxone-induced contractions, although this model does not account mechanistically for the autonomic withdrawal responses (i.e., diarrhea) observed in vivo. These results indicate that endocannabinoid catabolic enzymes are promising targets to treat opioid dependence.

Project description:BackgroundHigh-dose long-term opioid treatment for chronic non-cancer pain (CNCP) has become an increasing burden in industrialised countries. Opioid tapering and withdrawal in patients with CNCP remain challenging. This study evaluated a two-phase inpatient opioid withdrawal (OW) programme aimed at safely discontinuing opioid use in CNCP patients.MethodsThis prospective observational study was conducted from 2018 to 2023 at a Swiss tertiary care centre, involving CNCP patients on long-term opioid therapy (≥ 6 months, ≥ 100 mg morphine equivalent daily dose) who had failed outpatient withdrawal attempts. The programme consisted of a withdrawal phase (Phase 1) followed by multimodal pain rehabilitation (Phase 2). Outcomes included the proportion of patients opioid-free after Phase 2 (primary) and at 3 months, pain intensity changes, and adverse events (secondary).ResultsAmong the 38 enrolled patients (58% female, median age 54 years [IQR 49, 62]), 34 (89%) completed both phases, and 32 (84%) were opioid-free at the end of Phase 2. At 3 months, 23 patients (61%) remained opioid-free, while 4 (11%) resumed opioids, and 11 (29%) were lost to follow-up. Median pain intensity remained stable after discharge. One patient died by suicide 10 days post-withdrawal.ConclusionsThis two-phase inpatient withdrawal and rehabilitation programme enabled most CNCP patients to discontinue opioids without increased pain intensity, with a majority remaining opioid-free at 3 months. These findings highlight the importance of ongoing psychological support and careful patient selection in OW management.Significance statementThis study introduces a structured inpatient opioid withdrawal model tailored for chronic non-cancer pain patients on high-dose opioid therapy, demonstrating that high cessation rates can be achieved without worsening pain intensity. By addressing the gap in care for patients who fail outpatient tapering, this research provides clinical insights into optimising withdrawal protocols and highlights the need for targeted resource allocation for intensive, multidisciplinary pain management. These findings support evidence-based decision-making in designing more effective opioid tapering strategies.

Project description:Background and aimsResearch from cohorts of individuals with recreational cannabis use indicates that cannabis withdrawal symptoms are reported by more than 40% of those using regularly. Withdrawal symptoms are not well understood in those who use cannabis for medical purposes. Therefore, we prospectively examined the stability of withdrawal symptoms in individuals using cannabis to manage chronic pain.Design, setting, participantsUsing latent class analysis (LCA) we examined baseline cannabis withdrawal to derive symptom profiles. Then, using latent transition analysis (LTA) we examined the longitudinal course of withdrawal symptoms across the time points. Exploratory analyses examined demographic and clinical characteristics predictive of withdrawal class and transitioning to more or fewer withdrawal symptoms over time. A cohort of 527 adults with chronic pain seeking medical cannabis certification or re-certification was recruited between February 2014 and June 2015. Participants were recruited from medical cannabis clinic waiting rooms in Michigan, USA. Participants were predominantly white (82%) and 49% identified as male, with an average age of 45.6 years (standard deviation = 12.8).MeasurementsBaseline, 12-month and 24-month assessments of withdrawal symptoms using the Marijuana Withdrawal Checklist-revised.FindingsA three-class LCA model including a mild (41%), moderate (34%) and severe (25%) symptom class parsimoniously represented withdrawal symptoms experienced by people using medical cannabis. Stability of withdrawal symptoms using a three-class LTA at 12 and 24 months ranged from 0.58 to 0.87, with the most stability in the mild withdrawal class. Younger age predicted greater severity and worsening of withdrawal over time.ConclusionsAdults with chronic pain seeking medical cannabis certification or re-certification appear to experience mild to severe withdrawal symptoms. Withdrawal symptoms tend to be stable over a 2-year period, but younger age is predictive of worse symptoms and of an escalating withdrawal trajectory.

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Case report: The lesson from opioid withdrawal symptoms mimicking paraganglioma recurrence during opioid deprescribing in cancer pain.

Publications

Case report: The lesson from opioid withdrawal symptoms mimicking paraganglioma recurrence during opioid deprescribing in cancer pain.

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