Naldemedine-induced opioid withdrawal syndrome with severe psychiatric symptoms in an advanced cervical cancer patient without brain metastasis

Objective Naldemedine, an oral peripheral μ-opioid receptor antagonist, was developed for the treatment of constipation, a side effect of opioid use. Naldemedine is not generally recognized as causing opioid withdrawal in which associated symptoms affecting the central nervous system. Method From the series of cancer patients undergoing symptom management, we report a case treated with naldemedine for constipation in relation to the use of opioids for cancer pain and who displayed severe psychological symptoms associated with withdrawal immediately after the use of naldemedine. Results The patient was a 36-year-old woman diagnosed with cervical cancer Stage IIB, PS3. When the patient, who was using oxycodone hydrochloride hydrate (80 mg/day) for ileal pain, was started on naldemedine for constipation, she complained of sweating after just 5 min and hallucinations after 1 h. The patient also displayed physical/behavioral abnormalities such as diarrhea and hyperactivity, and psychological abnormalities such as aggression toward staff. Despite the psychiatric symptoms worsening over time, there were no abnormalities in terms of blood biochemical data, and no brain metastasis was observed on MRI. Based on the Clinical Opiate Withdrawal Scale, these symptoms were judged to indicate opioid withdrawal. Naldemedine was discontinued due to naldemedine-related opioid withdrawal syndrome and, thereafter, the psychiatric symptoms diminished, with no recurrence of similar symptoms observed to date. Significance of results If mental and behavioral abnormalities occur in patients receiving naldemedine, it is necessary to consider the possibility of opioid withdrawal syndrome as a differential diagnosis.

Acupuncture for Opioid Dependence Patients Receiving Methadone Maintenance Treatment: A Network Meta-Analysis

Objectives: Opioid dependence has been a threat to public health for hundreds of years. With the increasing number of studies on acupuncture-related therapies for opioid dependence patients receiving methadone maintenance treatment (MMT), its effect of acupuncture therapy in treating MMT patients remains controversial. Therefore, we conducted a multiple-treatments meta-analysis, and incorporated both direct and indirect comparisons, in order to discover the most effective treatment for opioid dependence patients receiving MMT.Methods: Five English databases and three Chinese databases were searched from its inception to August 20, 2020, in order to compare the effects of acupuncture-related therapies and MMT, which was summarized as Western medicine (WM) in the following texts. The quality of studies was assessed according to Cochrane's risk of bias tool 5.1.0, and a pair-wise meta-analysis, cumulative meta-analysis, and the network meta-analysis was performed using the R software (Version 3.6.1) and STATA (Version 14.0). The primary outcome was the effective rate, which was calculated by the ratio of detoxifying patients to the total. The secondary outcome was the Modified Himmelsbach Opiate Withdrawal Scale (MHOWS).Results: A total of 20 trials were included, which consisted of comparisons among WM, traditional Chinese medicine (TCM), and the four types of acupuncture, namely, manual acupuncture (MA), electro-acupuncture (EA), auricular acupuncture (AA), and transcutaneous electrical acupoint stimulation (TEAS). Though none of the trials were at low risk of bias. In the pair-wise meta-analysis, no statistically significant differences were observed in terms of the effective rate. Furthermore, MA was more efficacious than WM, EA, and TEAS in MHOWS, with mean differences (MDs) of (−8.59, 95% CI: −15.96 to −1.23, P < 0.01), (−6.15, 95% CI: −9.45 to −2.85, P < 0.05), and (−10.44, 95% CI: −16.11 to −4.77, P < 0.05), respectively. In the network meta-analysis, MA was more effective than WM (RR: 1.40, 95% CI: 1.05 to 1.99) on the effective rate, and (MD: −5.74, 95% CI: −11.60 to −0.10) on MHOWS. TEAS was more effective than WM (MD: −15.34, 95% CI: −27.34 to −3.46) on MHOWS. Synthetically, MA had the highest probability to rank first in treating opioid dependence.Conclusions: The existing evidence shows that acupuncture related-therapies may effectively be used for treating patients receiving MMT, and that manual acupuncture may be the best choice for opioid dependence among all kinds of acupuncture-related therapies. Nevertheless, reducing the relapse and promoting the recovery of opioid dependence need more efforts from not only the medical industry but also government support, security system, and educational popularization. To strengthen the assurance of acupuncture-related therapies in the treatment of opioid dependence, we expected that clinical trials with high quality would be conducted, to provide more confident evidence.

A case of a mixed overdose involving kratom (Mitragyna speciosa) leading to serotonin syndrome

Objective: Drug overdose deaths have risen precipitously over the past two years in the United States. Polysubstance overdose with opiates and amphetamines have been of particular concern. Kratom (Mitragyna speciosa) is an unregulated widely available herb with both stimulant and opiate μ-receptor activity. Studies suggest that its use is quickly increasing. Case: We describe a patient who presented to a psychiatric hospital with a mixed toxic syndrome due to chronic kratom and prescribed SSRI use compounded by acute intake of methamphetamine. The patient displayed psychosis, tremulousness, myoclonus, and extreme anxiety. Her clinical picture was consistent with both serotonin syndrome and opiate withdrawal. Conclusion: We call attention to this case because polysubstance overdoses are common, and kratom is widely available. Complex toxic presentations that involve kratom are likely to be increasingly encountered.

Methadone initiation in a bridge clinic for opioid withdrawal and opioid treatment program linkage: a case report applying the 72-hour rule

Background In the United States, methadone for opioid use disorder (OUD) is limited to highly regulated opioid treatment programs (OTPs), rendering it inaccessible to many patients. The “72-hour rule” allows non-OTP providers to administer methadone for emergency opioid withdrawal management while arranging ongoing care. Low-barrier substance use disorder (SUD) bridge clinics provide rapid access to buprenorphine but offer an opportunity to treat acute opioid withdrawal while facilitating OTP linkage. We describe the case of a patient with OUD who received methadone for opioid withdrawal in a bridge clinic and linked to an OTP within 72 h. Case presentation A 54-year-old woman with severe OUD was seen in a SUD bridge clinic requesting OTP linkage and assessed with a clinical opiate withdrawal scale (COWS) score of 12. She reported daily nasal use of 1 g heroin/fentanyl. Prior OUD treatment included buprenorphine-naloxone, which was only partially effective. Her acute opioid withdrawal was treated with a single observed oral dose of methadone 20 mg. She returned the following day with persistent opioid withdrawal (COWS score 11) and was treated with methadone 40 mg. On day 3, the patient was successfully admitted to a local OTP, where she remained engaged 3 months later. Conclusions While patients continue to face substantial access barriers, bridge clinics can play an important role in treating opioid withdrawal, building partnerships with OTPs to initiate methadone on demand, and preventing life-threatening delays to methadone treatment. Federal policy reform is urgently needed to make methadone more accessible to people with OUD.

Decreasing Length of Stay in Opioid Withdrawal

Introduction: In 2017, more than 1,200 opioid-related deaths were reported in Virginia, with slightly fewer in 2018, at 1,193 deaths. The current opioid crisis has placed a strain on an already limited number of mental health (MH) inpatient beds. The industry standard for assessment and treatment of opioid withdrawal symptoms, in the inpatient setting, is the Clinical Opiate Withdrawal Scale (COWS), and yet some units continue to utilize the Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA-Ar) for this population. Aim: The purpose of this nurse-led performance improvement project was to implement COWS in the inpatient MH setting and improve length of stay (LOS) by 1 day. Method: In 2018, in a large federal teaching facility in the mid-Atlantic region, the COWS was implemented to replace the CIWA-Ar for opioid withdrawal, with the focus on decreasing LOS. Prior to implementation of COWS, LOS on the inpatient MH unit for opioid withdrawal was 8.6 days, which was higher than the ~6- to 7-day LOS for surrounding private sector hospitals. Individual electronic medical records were reviewed for LOS and completion of COWS and pertinent details were discussed daily with nursing staff and monthly with the interdisciplinary team. Baseline data were collected from April 2017 to March 2018, with data collection continuing through the project implementation, April to September 2018. Results: Completion of COWS on 100% of patients admitted with opioid withdrawal and a decrease in LOS from 8.6 to 4.7 days was found, a 45% reduction. Conclusion: The nurse-driven performance improvement project affected business acumen, through decreased LOS, as well as quality of care, through better symptom management.

Shaping and delivering services in primary care: benzodiazepine and opiate withdrawal service

This article looks at the development of the benzodiazepine and opiate withdrawal service (BOWS) based in addiction services in London. The service was created to implement a manageable and sustainable model that would treat patients with benzodiazepine and codeine-based dependencies. It was envisaged the service would effectively treat patients in GP practices in two boroughs in London. The article outlines what is possible in terms of treatment for patients with issues of opioid dependency, by examining two in-depth case studies. It also illustrates what is possible for nurses in the modern NHS and can be used as a resource to shape and deliver services with positive patient outcomes. Nurses should be seen as shaping and delivering care in the NHS. This is a role that should be promoted to a greater degree, wherever possible.

CRHCeA→VTA inputs inhibit the positive ensembles to induce negative effect of opiate withdrawal

Plasticity of neurons in the ventral tegmental area (VTA) is critical for establishment of drug dependence. However, the remodeling of the circuits mediating the transition between positive and negative effect remains unclear. Here, we used neuronal activity-dependent labeling technique to characterize and temporarily control the VTA neuronal ensembles recruited by the initial morphine exposure (morphine-positive ensembles, Mor-Ens). Mor-Ens preferentially projected to NAc, and induced dopamine-dependent positive reinforcement. Electrophysiology and rabies viral tracing revealed the preferential connections between the VTA-projective corticotrophin-releasing hormone (CRH) neurons of central amygdala (CRHCeA→VTA) and Mor-Ens, which was enhanced after escalating morphine exposure and mediated the negative effect during opiate withdrawal. Pharmacologic intervention or CRISPR-mediated repression of CRHR1 in Mor-Ens weakened the inhibitory CRHCeA→VTA inputs, and alleviated the negative effect during opiate withdrawal. These data suggest that neurons encoding opioid reward experience are inhibited by enhanced CRHCeA→VTA inputs induced by chronic morphine exposure, leading to negative effect during opiate withdrawal, and provide new insight into the pathological changes in VTA plasticity after drug abuse and mechanism of opiate dependence.

The Impact of Zinc Supplementation on Oxidative Stress and Inflammatory Biomarkers in Opioid Addicts-Withdrawal Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Background Opioid withdrawal can induce oxidative stress in opioid addicts. This interventional study aimed to investigate the effect of zinc supplementation on the oxidative profile of patients with an opioid withdrawal syndrome. Methods In the current study, 40 patients aged 18 to 65 years with opioid withdrawal syndrome were randomly assigned to intervention and control groups, each with 20 subjects. In addition to standard treatment, the intervention group received 30 mg of zinc daily, while the control group was given a placebo for one month. They were evaluated using Beck Depression Inventory (BDI), Clinical Opiate Withdrawal Scale (COWS), and Young Mania Rating Scale (YMRS) for withdrawal symptoms. Moreover, other parameters included catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and levels of total antioxidant capacity (TAC), total thiol groups (TTG), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA). Results The rate of withdrawal symptoms (COWS) was statistically significantly lower in the treated group in comparison to the control group (P < 0.05). In the treatment group, the levels of TAC, CAT, SOD, and GPx increased significantly compared to the control group (P < 0.05). In the treatment group compared to the control group, there was a statistically significant decrease in hs-CRP, MDA, and TNFα (P < 0.05). Conclusions The results revealed that zinc supplementation could effectively reduce withdrawal symptoms by increasing antioxidant activity and reducing the lipid peroxidation index.

Shaping and delivering services in primary care: benzodiazepine and opiate withdrawal service

Dependency on benzodiazepine and opiates is an increasing problem. Jeff Fernandez uses case studies to show how a nurse-led addiction service based in primary care can improve patient outcomes This article looks at the development of the benzodiazepine and opiate withdrawal service (BOWS) based in addiction services in London. The service was created to implement a manageable and sustainable model that would treat patients with benzodiazepine and codeine-based dependencies. It was envisaged the service would effectively treat patients in GP practices in two boroughs in London. The article outlines what is possible in terms of treatment for patients with issues of opioid dependency, by examining two in-depth case studies. It also illustrates what is possible for nurses in the modern NHS and can be used as a resource to shape and deliver services with positive patient outcomes. Nurses should be seen as shaping and delivering care in the NHS. This is a role that should be promoted to a greater degree, wherever possible.