A case of buprenorphine-precipitated withdrawal managed with high-dose buprenorphine.

BACKGROUND: Buprenorphine-naloxone has a very high affinity for the mu-receptor and can cause precipitated opioid withdrawal, typically more severe than withdrawal that occurs naturally, when administered while a full mu-opioid receptor agonist remains in a person's system. To avoid precipitated withdrawal, one needs to be in mild to moderate opioid withdrawal at the time of buprenorphine-naloxone induction. Recently, there have been reported cases of precipitated withdrawal occurring in patients taking fentanyl knowingly or unknowingly, despite them being in adequate opioid withdrawal at the time of induction. When this occurs, the current recommendation is to provide 2 mg of buprenorphine-naloxone every 1-2 hours. OBJECTIVES: Describe a case of successful management of buprenorphine-precipitated withdrawal with escalation of the dose of buprenorphine and highlight implications for future management. METHODS: We present a case of a patient with a history of opioid use disorder who was in moderate opioid withdrawal at the time of buprenorphine-naloxone induction and experienced precipitated withdrawal after buprenorphine-naloxone administration. RESULTS: High-dose buprenorphine-naloxone was given to the patient and precipitated withdrawal subsided after receiving a total of 20 mg. On the next day, the patient had no symptoms of opioid withdrawal and is currently maintained on 16 mg/day. CONCLUSION: With the rising prevalence of fentanyl-laced drugs, increased instances of precipitated withdrawal are likely to be encountered. In cases of precipitated withdrawal, giving a high dose of buprenorphine-naloxone rapidly is safe and will allow rapid reversal of withdrawal symptoms.

Alcohol Withdrawal Syndrome: Outpatient Management.

Approximately one-half of patients with alcohol use disorder who abruptly stop or reduce their alcohol use will develop signs or symptoms of alcohol withdrawal syndrome. The syndrome is due to overactivity of the central and autonomic nervous systems, leading to tremors, insomnia, nausea and vomiting, hallucinations, anxiety, and agitation. If untreated or inadequately treated, withdrawal can progress to generalized tonic-clonic seizures, delirium tremens, and death. The three-question Alcohol Use Disorders Identification Test-Consumption and the Single Alcohol Screening Question instrument have the best accuracy for assessing unhealthy alcohol use in adults 18 years and older. Two commonly used tools to assess withdrawal symptoms are the Clinical Institute Withdrawal Assessment for Alcohol Scale, Revised, and the Short Alcohol Withdrawal Scale. Patients with mild to moderate withdrawal symptoms without additional risk factors for developing severe or complicated withdrawal should be treated as outpatients when possible. Ambulatory withdrawal treatment should include supportive care and pharmacotherapy as appropriate. Mild symptoms can be treated with carbamazepine or gabapentin. Benzodiazepines are first-line therapy for moderate to severe symptoms, with carbamazepine and gabapentin as potential adjunctive or alternative therapies. Physicians should monitor outpatients with alcohol withdrawal syndrome daily for up to five days after their last drink to verify symptom improvement and to evaluate the need for additional treatment. Primary care physicians should offer to initiate long-term treatment for alcohol use disorder, including pharmacotherapy, in addition to withdrawal management.

Transition of Patients with Opioid Use Disorder from Buprenorphine to Extended-Release Naltrexone: A Randomized Clinical Trial Assessing Two Transition Regimens.

BACKGROUND AND OBJECTIVE: When patients seek to discontinue buprenorphine (BUP) treatment, monthly injectable extended-release naltrexone (XR-NTX) may help them avoid relapse. The efficacy of low ascending doses of oral NTX vs placebo for patients transitioning from BUP to XR-NTX is evaluated in this study. METHODS: In a phase 3, hybrid residential/outpatient study, clinically stable participants with opioid use disorder (N = 101), receiving BUP for more than or equal to 3 months and seeking antagonist treatment, were randomized (1:1) to 7 residential days of descending doses of BUP and low ascending doses of oral NTX (NTX/BUP, n = 50) or placebo (PBO-N/BUP, n = 51). Both groups received standing ancillary medications and psychoeducational counseling. Following negative naloxone challenge, participants received XR-NTX (day 8). The primary endpoint was the proportion of participants who received and tolerated XR-NTX. RESULTS: There was no statistical difference between groups for participants receiving a first dose of XR-NTX: 68.6% (NTX/BUP) vs 76.0% (PBO-N/BUP; P = .407). The mean number of days with peak Clinical Opiate Withdrawal Scale (COWS) score less than or equal to 12 during the treatment period (days 1-7) was similar for NTX/BUP and PBO-N/BUP groups (5.8 vs 6.3; P = .511). Opioid withdrawal symptoms during XR-NTX induction and post-XR-NTX observation period (days 8-11) were mild and similar between groups (mean peak COWS score: NTX/BUP, 5.1 vs PBO-N/BUP, 5.4; P = .464). Adverse events were mostly mild/moderate. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Low ascending doses of oral NTX did not increase induction rates onto XR-NTX compared with placebo. The overall rate of successful induction across treatment groups supports a brief BUP taper with standing ancillary medications as a well-tolerated approach for patients seeking transition from BUP to XR-NTX. (Am J Addict 2020;00:00-00).

Topical Steroid Withdrawal: A Case Series of 10 Children.

Concerns about topical steroid withdrawal are causing some patients to cease long-term topical corticosteroid therapy, however, little is known about the ensuing clinical outcomes. This qualitative case series studied 10 children whose parents stopped their chronic topical corticosteroid use and subsequently developed features typically reported in adults experiencing topical steroid withdrawal. Patients were seen in an Australian general practice between April 2014 and October 2018, with follow-up periods ranging from 18 months to 4 years. Symptoms were difficult initially for the children and their families, however, all ultimately improved. At the final review, 4 of the children had clear skin and another 4 had symptoms consistent with their original, pre-treatment atopic dermatitis. More research is required into long-term topical corticosteroid use and its discontinuation, including topical steroid withdrawal, particularly in the pediatric population.

Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment.

BACKGROUND AND OBJECTIVES: The opioid crisis has taken an immense toll in the United States. On average, five lives are lost to an opioid overdose every hour of the day; estimated costs associated with opioid misuse exceed $500 billion annually. Illicit opioid discontinuation is the first step in the treatment of opioid use disorder (OUD), and transition to an opioid agonist may initiate treatment. However, discontinuation to abstinence from either OUD directly or following agonist treatment results in severely distressing opioid withdrawal symptoms (OWS). METHODS: This review evaluated studies on the etiology, burden, and management of OWS. RESULTS: Noradrenergic hyperactivity generates many OWS. These OWS can cause patients to relapse during early opioid discontinuation. While agonist therapies are generally first-line for moderate or severe OUD and reduce OWS, prescribing restrictions can limit their availability. DISCUSSION AND CONCLUSIONS: Non-opioid medications to treat OWS provides a gateway into long-term treatment with naltrexone or psychosocial therapies. For opioid dependent patients without OUD, non-opioid treatments like α-2 adrenergic agonists can facilitate opioid tapering. SCIENTIFIC SIGNIFICANCE: For the millions who are physically dependent on opioids, new treatments for OWS can enhance recovery from OUD and prevent relapse. (© 2019 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc.;XX:1-8).

Rapid micro-induction of buprenorphine/naloxone for opioid use disorder in an inpatient setting: A case series.

BACKGROUND AND OBJECTIVES: Buprenorphine/naloxone has been shown to be effective in the treatment of opioid use disorder. Due to its pharmacological properties, induction can be challenging, time-consuming, and result in sudden onset of withdrawal symptoms. METHODS: Retrospective case series (n = 2). RESULTS: Two patients with opioid use disorder were successfully started on buprenorphine/naloxone using a rapid micro-induction technique that did not cause precipitated withdrawal or require preceding cessation of other opioids. DISCUSSION AND CONCLUSIONS: These cases provide an alternative method for starting buprenorphine/naloxone that offers unique benefits compared to protocols previously described in the literature. SCIENTIFIC SIGNIFICANCE: This method can be used to minimize barriers to opioid agonist therapy. (Am J Addict 2019;28:262-265).

The perioperative patient on buprenorphine: a systematic review of perioperative management strategies and patient outcomes.

BACKGROUND: An increasing number of patients with opioid use disorder (OUD) are treated with opioid agonist-antagonists such as buprenorphine/naloxone. Perioperative management of patients on buprenorphine/naloxone is inconsistent and remains a controversial topic with mismanagement posing a significant risk to the long-term health of these patients. METHODS: We performed a systematic literature search involving Medline, Medline In-Process, Embase, Cochrane Central, Cochrane Database of Systematic Reviews, PsycINFO, Web of Science (Clarivate), Scopus (Elsevier), CINAHL (EbscoHosst), and PubMed (NLM). RESULTS: Eighteen studies were included in the final sample, including one controlled study and four observational studies . Neither the controlled study nor the observational studies assessed addiction treatment retention, harm reduction, or long-term mortality rates as primary or secondary outcomes. Of the observational studies, authors showed equivalent peri- and postoperative pain control among buprenorphine continued patients. All but one authors described adequate analgesia among the case reports in which buprenorphine ≤ 16 mg sublingually (SL) daily was continued during the perioperative period. Long-term harm reduction was not reported with only three case reports including any long-term abstinence or relapse rates. CONCLUSIONS: The current understanding of the risks and benefits of continuing or stopping buprenorphine perioperatively is limited by a lack of high-quality evidence. Observational studies and case reports indicate no evidence against continuing buprenorphine perioperatively, especially when the dose is < 16 mg SL daily. In patients with significant potential for relapse, such as those with a recent history of OUD, the discontinuation of buprenorphine should have a strong rationale supported by patient and surgical preferences. Future studies require standardized reporting of median doses, details on the route of delivery, dosing schedules and any dosing changes, and rates of addiction relapse, including long-term morbidity and mortality where possible.

RéSUMé: CONTEXTE: Un nombre croissant de patients présentant un trouble d'utilisation des opioïdes (TUO) sont traités avec des agonistes/antagonistes des opioïdes, tels que la buprénorphine et la naloxone. La gestion périopératoire des patients sous buprénorphine/naloxone n'est pas constante et reste un sujet de controverses; de plus une mauvaise gestion pose un risque significatif pour la santé à long terme de ces patients. MéTHODES: Nous avons effectué une recherche systématique de la littérature dans les bases de données suivantes : Medline, Medline In-Process, Embase, Cochrane Central, Cochrane Database of Systematic Reviews, PsycINFO, Web of Science (Clarivate), Scopus (Elsevier), CINAHL (EbscoHosst) et PubMed (NLM). RéSULTATS: Dix-huit études ont été incluses dans l'échantillon final, y compris une étude contrôlée et quatre études observationnelles. Ni l'étude contrôlée ni les études observationnelles n'ont évalué la continuation du traitement de l'addiction, la réduction des préjudices infligés ou les taux de mortalité à long terme parmi les critères d'évaluation principaux ou secondaires. Dans les études observationnelles, les auteurs ont montré qu'il y avait un contrôle équivalent de la douleur en péri- et postopératoire chez les patients continuant à recevoir de la buprénorphine. Tous les auteurs sauf un ont décrit une analgésie satisfaisante dans les rapports de cas où la buprénorphine sublinguale avec une dose ≤ 16 mg par jour était maintenue pendant la période périopératoire. La réduction des préjudices à long terme n'était pas décrite; seulement trois rapports de cas indiquaient le taux d'abstinence à long terme ou les taux de rechute. CONCLUSIONS: Les connaissances actuelles des risques et avantages de la poursuite ou de l'arrêt de la buprénorphine en période périopératoire sont limitées par le manque de données probantes de grande qualité. Les études observationnelles et les rapports de cas ne fournissent pas de données probantes à l'encontre de la poursuite de la buprénorphine dans la période périopératoire, en particulier quand la dose journalière par voie sublinguale est < 16 mg. Chez les patients présentant un risque significatif de rechute, comme ceux ayant des antécédents récents de TUO, l'arrêt de la buprénorphine devrait être solidement justifié avec le soutien des préférences des patients et des équipes chirurgicales. Les futures études nécessitent une normalisation du rapport des doses médianes, des détails sur les voies d'administration, de la posologie et de sa modification et des taux de rechute, en incluant aussi, chaque fois que possible, les taux de morbidité et mortalité à long terme.

Long-term abiraterone withdrawal syndrome.

WHAT IS KNOWN AND OBJECTIVE: Abiraterone acetate (AA) is an androgen receptor axis inhibitor, indicated together with prednisone, for metastatic castration-resistant prostate cancer. Withdrawal syndrome for classical antiandrogen treatments is well known, but not so known for AA. Abiraterone withdrawal syndrome (AWS) could be related to simultaneous prednisone discontinuation or to an androgenic effect of AA metabolites. CASE DESCRIPTION: A case is described of a patient with long-term AWS without prednisone discontinuation. The clinical and prostate-specific antigen (PSA) response allowed an 8-month delay in docetaxel treatment. WHAT IS NEW AND CONCLUSION: Prednisone did not play a role in AWS in this case. The long-term response allowed a delay in future treatment.

Gradual Versus Abrupt Smoking Cessation: A Randomized, Controlled Noninferiority Trial.

BACKGROUND: Most smoking cessation guidelines advise quitting abruptly. However, many quit attempts involve gradual cessation. If gradual cessation is as successful, smokers can be advised to quit either way. OBJECTIVE: To examine the success of quitting smoking by gradual compared with abrupt quitting. DESIGN: Randomized, controlled noninferiority trial. (International Standardized Randomized Controlled Trial Number Register: ISRCTN22526020). SETTING: Primary care clinics in England. PARTICIPANTS: 697 adult smokers with tobacco addiction. INTERVENTION: Participants quit smoking abruptly or reduced smoking gradually by 75% in the 2 weeks before quitting. Both groups received behavioral support from nurses and used nicotine replacement before and after quit day. MEASUREMENTS: The primary outcome measure was prolonged validated abstinence from smoking 4 weeks after quit day. The secondary outcome was prolonged, validated, 6-month abstinence. RESULTS: At 4 weeks, 39.2% (95% CI, 34.0% to 44.4%) of the participants in the gradual-cessation group were abstinent compared with 49.0% (CI, 43.8% to 54.2%) in the abrupt-cessation group (relative risk, 0.80 [CI, 0.66 to 0.93]). At 6 months, 15.5% (CI, 12.0% to 19.7%) of the participants in the gradual-cessation group were abstinent compared with 22.0% (CI, 18.0% to 26.6%) in the abrupt-cessation group (relative risk, 0.71 [CI, 0.46 to 0.91]). Participants who preferred gradual cessation were significantly less likely to be abstinent at 4 weeks than those who preferred abrupt cessation (38.3% vs 52.2%; P = 0.007). LIMITATIONS: Blinding was impossible. Most participants were white. CONCLUSION: Quitting smoking abruptly is more likely to lead to lasting abstinence than cutting down first, even for smokers who initially prefer to quit by gradual reduction. PRIMARY FUNDING SOURCE: British Heart Foundation.

Cannabinoid Poisoning by Hemp Seed Oil in a Child.

We report a case of mild cannabinoid poisoning in a preschool child, after 3-week ingestion of hemp seed oil prescribed by his pediatrician to strengthen his immune system. The patient presented neurological symptoms that disappeared after intravenous hydration. A possible mild withdrawal syndrome was reported after discharge. The main metabolite of Δ-tetrahydrocannabinol was detected in urine, and very low concentration of Δ-tetrahydrocannabinol was detected in the ingested product. This is, as far as we know, the first report of cannabinoid poisoning after medical prescription of hemp seed oil in a preschool child.

Why is buprenorphine coformulated with naloxone?

Combination buprenorphine-naloxone is a cornerstone of outpatient treatment for substance use disorder, and is more widely accessible in primary care. Because oral buprenorphine has been diverted and abused for its euphoric properties, a combination formulation was developed and will trigger withdrawal symptoms if injected IV.

Effects of a Single Lyric Analysis Intervention on Withdrawal and Craving With Inpatients on a Detoxification Unit: A Cluster-Randomized Effectiveness Study.

BACKGROUND: For patients hospitalized on inpatient detoxification units, reducing negative symptoms such as withdrawal and craving is a key treatment area. Although lyric analysis is a commonly utilized music therapy intervention for clients in substance abuse rehabilitation, there is a lack of randomized controlled music therapy studies systematically investigating how lyric analysis interventions can affect patients on a detoxification unit. OBJECTIVE: The purpose of this cluster-randomized effectiveness study was to measure the effects of single-session group lyric analysis interventions on withdrawal and craving with patients on a detoxification unit. A secondary purpose of this study was to determine if relationships existed between treatment effects and participants' familiarity with the song. METHODS: Participants (N = 144) were cluster-randomized to experimental (posttest only) or wait-list control (pretest only) conditions to provide treatment to all participants in an inclusive single-session design. RESULTS: Although participants in the experimental condition had lower withdrawal and craving means than participants in the control condition, these differences were not significant. Familiarity of the song in the lyric analysis was not related to withdrawal or craving. CONCLUSION: Group-based lyric analysis interventions may be effective for temporarily relieving withdrawal and craving in patients on a detoxification unit. Familiarity of the song did not affect results. Implications for clinical practice, suggestions for future research, and limitations are provided.

Does melissa officinalis cause withdrawal or dependence?

INTRODUCTION: Melissa officinalis is a medical and aromatic plant that is used for its hypnotic, sedative, and spasmolytic effects. This report presents a case study of30-year-old patient who was admitted to an emergency department with restlessness, tremor, distractibility, and sweating following a discontinuation of Melissa officinalis consumption. CASE REPORT: In this case, withdrawal symptoms may be related to the dependence effect caused by long-term use of Melissa officinalis. Although Melissa officinalis, a plant, is preferred by many patients as an alternative to pharmaceutical drugs, patients should be made aware that it may have a risk of dependency and can lead to withdrawal symptoms.

[Development of (hypo)mania during discontinuation of venlafaxine in two patients with bipolar disorder]. / Een (hypo)manie tijdens de afbouw van venlafaxine bij twee patiënten met een bipolaire stoornis.

The scientific literature frequently warns that patients with bipolar disorder risk developing a (hypo)mania on starting a course of antidepressants. In this case report, however, two patients with bipolar disorder developed a (hypo)mania while their dosage of venlafaxine was being gradually tapered off. We discuss a pharmacodynamic explanation for the induction of (hypo)mania during discontinuation of venlafaxine. We also discuss alternative explanations, such as a venlafaxine withdrawal syndrome; induction of rapid cycling; difficulties in distinguishing an agitated depression and a dysphoric mania and the naturalistic course of a bipolar disorder.

Antidepressant Tapering Is Not Routine But Could Be.

INTRODUCTION: When antidepressants are discontinued, severe withdrawal symptoms are possible. Some patients have few or no problems stopping, whereas others struggle. That struggle can be minimized or prevented with careful dose tapering. How often is that done? METHODS: Using 7 years of medical records, we determined the percentage of patients who received a prescription for the lowest available dose of their antidepressant before it was discontinued, as an indicator of a deliberate taper. RESULTS: Over that period, 8.9% of patients had evidence of tapering. The percentage increased from 4.9% in 2014 to a plateau around 10% in the past 4 years. DISCUSSION: While reports of severe withdrawal are increasingly recognized and must be addressed, our data suggest that many patients can discontinue their antidepressants without a taper through the lowest dose. However, it is difficult to identify which patients will struggle without a careful taper. A "one-size-fits-all" taper approach is recommended, balancing the need for withdrawal prevention with the need to avoid unnecessary complexity for the majority of patients. The first decrement is key for all patients: it must go well. Thereafter many patients may accelerate but all should receive a prescription for the lowest available dose of their antidepressant.

Antiresorptive drugs (bisphosphonates), atypical fractures and rebound effect: new evidence of similitude.

BACKGROUND: Homeopathy is based on treatment by similitude ('like cures like') administering to sick individuals substances that cause similar symptoms in healthy individuals, employing the secondary and paradoxical action of the organism as therapeutic response. This vital or homeostatic reaction of the organism can be scientifically explained by the rebound effect of drugs, resulting in worsening of symptoms after suspension of treatment. Bisphosphonates (BPs) reduce 'typical' fractures in patients with osteoporosis, but recent studies report 'atypical' fractures of the femur after stopping the BPs, a rebound effect may be the causal mechanism. METHOD: Review of the literature concerning the relationship between atypical femoral fractures and antiresorptive drugs (bisphosphonates), identifying the pathogenesis of this adverse event. RESULTS: Several studies have described multiple cases of 'atypical' low-impact subtrochanteric stress fractures or complete fractures of the femur. These fractures are often bilateral, preceded by pain in the affected thigh, may have a typical X-ray appearance, and may delayed healing. Rebound of osteoclastic activity after suspension of antiresorptive drugs is a plausible mechanism to explain this phenomenon. CONCLUSION: As for other classes of drugs, the rebound effect of antiresorptive drugs supports Hahnemann's similitude principle (primary action of the drugs followed by secondary and opposite action of the organism), and clarifies this 'unresolved' issue. Unfortunately, the rebound effect is little discussed among health professionals, depriving them of important knowledge ensure safe management of drugs.

[SUN's abdominal acupuncture for depression after methamphetamine withdrawal: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect of SUN 's abdominal acupuncture and conventional acupuncture in the treatment of depression after methamphetamine withdrawal. METHODS: A total of 80 female patients with depression after methamphetamine withdrawal were randomly divided into an observation group (40 cases, 1 case dropped off) and a control group (40 cases, 2 cases dropped off). The control group was treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 29), Taichong (LR 3), Shenmen (HT 7), Neiguan (PC 6), Danzhong (GV 17), and the observation group was treated with SUN 's abdominal acupuncture at area 1 of the abdomen and area 8 of the abdomen. Both groups were treated once a day, 30 min each time, 6 days as a course of treatment, 1 day rest between treatment courses, a total of 4 courses of treatment. The scores of withdrawal symptoms, Hamilton depression scale (HAMD), Pittsburgh sleep quality index (PSQI) scale and serum serotonin (5-HT) level were compared between the two groups before and after treatment. RESULTS: After treatment, the scores of withdrawal symptoms, HAMD and the various scores and total score of PSQI scale in the two groups were all lower than before treatment (P<0.01), and the scores of withdrawal symptoms, HAMD and the sleep quality, time to fall asleep, sleep time scores and total score of PSQI in the observation group were lower than the control group (P<0.05, P<0.01). After treatment, the serum 5-HT level of the two groups was increased (P<0.01), and that in the observation group was higher than the control group (P<0.05). CONCLUSION: SUN 's abdominal acupuncture can improve withdrawal symptom, depression and sleep quality, increase serum 5-HT content in treatment of depression after methamphetamine withdrawal, and has better effect than conventional acupuncture.

[Acute benzodiazepine withdrawal delirium].

In this case report we describe a life-threatening episode of delirium in a 51-year-old man. The condition was triggered by an abrupt withdrawal of benzodiazepines. The patient had been taking multiple sedatives for several years but a large proportion of the drugs were not available in Denmark. His general practitioner substituted and prescribed oxazepam and zolpidem for ten days. Afterwards the patient did not have access to benzodiazepines and developed a severe benzodiazepine withdrawal delirium. He was treated with diazepam and olanzapine with gradual dose reduction.

Alcohol withdrawal syndrome: symptom-triggered versus fixed-schedule treatment in an outpatient setting.

AIMS: To investigate whether, in the treatment with chlordiazepoxide for outpatient alcohol withdrawal, there are advantages of symptom-triggered self-medication over a fixed-schedule regimen. METHODS: A randomized controlled trial in outpatient clinics for people suffering from alcohol dependence (AD) and alcohol-related problems; 165 adult patients in an outpatient setting in a specialized alcohol treatment unit were randomized 1:1 to either a symptom-triggered self-medication or tapered dose, using chlordiazepoxide. Alcohol withdrawal symptoms, amount of medication, duration of symptoms, time to relapse and patient satisfaction were measured. Patients assessed their symptoms using the Short Alcohol Withdrawal Scale (SAWS). Patient satisfaction was monitored by the Diabetes Treatment Satisfaction Questionnaire. We used the Well-Being Index and the European addiction severity index for the 1-year follow-up. RESULTS: We found no differences in the quantity of medication consumed, time to relapse, well being or treatment satisfaction. CONCLUSION: Symptom-triggered self-medication was as safe as fixed-schedule medication in treating outpatients with AD and mild to moderate symptoms of AWS. The SAWS is a powerful monitoring tool, because it is brief and permits the subject to log the withdrawal symptoms.