Withdrawal catastrophizing scale: initial psychometric properties and implications for the study of opioid use disorder and hyperkatifeia.

Background: Discovery of modifiable factors influencing subjective withdrawal experience might advance opioid use disorder (OUD) research and precision treatment. This study explores one factor - withdrawal catastrophizing - a negative cognitive and emotional orientation toward withdrawal characterized by excessive fear, worry or inability to divert attention from withdrawal symptoms.Objectives: We define a novel concept - withdrawal catastrophizing - and present an initial evaluation of the Withdrawal Catastrophizing Scale (WCS).Methods: Prospective observational study (n = 122, 48.7% women). Factor structure (exploratory factor analysis) and internal consistency (Cronbach's α) were assessed. Predictive validity was tested via correlation between WCS and next-day subjective opiate withdrawal scale (SOWS) severity. The clinical salience of WCS was evaluated by correlation between WCS and withdrawal-motivated behaviors including risk taking, OUD maintenance, OUD treatment delay, history of leaving the hospital against medical advice and buprenorphine-precipitated withdrawal.Results: WCS was found to have a two-factor structure (distortion and despair), strong internal consistency (α = .901), and predictive validity - Greater withdrawal catastrophizing was associated with next-day SOWS (rs (99) = 0.237, p = .017). Withdrawal catastrophizing was also correlated with risk-taking behavior to relieve withdrawal (rs (119) = 0.357, p < .001); withdrawal-motivated OUD treatment avoidance (rs (119) = 0.421, p < .001), history of leaving the hospital against medical advice (rs (119) = 0.373, p < .001) and buprenorphine-precipitated withdrawal (rs (119) = 0.369, p < .001).Conclusion: This study provides first evidence of withdrawal catastrophizing as a clinically important phenomenon with implications for the future study and treatment of OUD.

Withdrawal interference scale: a novel measure of withdrawal-related life disruption in opioid use disorder and alcohol use disorder.

Background: Hyperkatifeia describes amplified emotional and motivational withdrawal due to addiction-related sensitization of brain-stress-systems. Hyperkatifeia has been proposed as a target for addiction treatment development. However, translation of basic research in this area will require new tools designed to measure hyperkatifeia and related phenomena outside of laboratory settings.Objectives: We define a novel concept, withdrawal interference, and introduce a new tool - the Withdrawal Interference Scale (WIS) - which measures the impact of withdrawal on daily life among individuals with OUD or AUD.Methods: Described are the combined results of three separate cross-sectional studies. The structural validity, convergent validity, construct validity, trans-diagnostic (AUD/OUD) configural, metric, and scalar invariance, internal consistency, and composite reliability of WIS was tested among three independent samples of 1) treatment-seeking adults with OUD (n = 132), 2) treatment-seeking adults with AUD (n = 123), and 3) non-treatment-seeking adults with OUD (n = 140). Males numbered 218 and females were 163.Results: WIS exhibited structural validity (1 factor), convergent validity (average variance extracted .670-.676), construct validity, trans-diagnostic configural (χ2/df = 2.10), metric (Δχ2 = 5.70, p = .681), and scalar invariance (Δχ2 = 12.34, p = .338), internal consistency (α .882-928), and composite reliability (.924-.925).Conclusion: These results suggest WIS is a valid and reliable instrument for measuring withdrawal-related life disruption in AUD and OUD. Further, given our findings of transdiagnostic measurement invariance, WIS scores of individuals with AUD and OUD can be meaningfully compared in future statistical analyses.

The Perceived Role of Withdrawal in Maintaining Opioid Addiction among Adults with Untreated Opioid Use Disorder: A Survey of Syringe Exchange Program Participants.

Background: Withdrawal is believed to play a central role in the brain disease model of addiction. However, little research describes withdrawal-motives among untreated individuals in community settings. Methods: This cross-sectional study surveyed syringe exchange program participants (n = 139) with untreated opioid use disorder (OUD) in Columbus, Ohio from January 10th to March 25th, 2023, to assess their perceptions of the role of withdrawal in OUD maintenance, treatment delay, and OUD's refractoriness to buprenorphine. Participants responded to a survey including DSM-5 OUD criteria, demographics, and questions about substance use and opioid withdrawal. Participant ages ranged from 21 to 65 years with a mean age of 37.5 years and standard deviation of 8.1. The racial distribution of the sample was as follows: 81% White/Caucasian, 12% Black/African American, 3% Native American or Alaskan Native. Results: Sixty-six percent of participants agreed, or strongly agreed that opioid withdrawal was "the most important reason" they had been unable to stop using opioids. Almost seventy-one percent agreed, or strongly agreed that worry about opioid withdrawal had caused them to "put off or delay" OUD treatment. Although all participants had active, untreated OUD at the time of recruitment, most (85%) had previously tried buprenorphine, and the majority (78%) reported having experienced buprenorphine-precipitated withdrawal. Conclusions: Among this community sample of individuals with untreated OUD, withdrawal was perceived to have an important role in maintaining OUD, including by motivating OUD treatment delay. Prior buprenorphine-precipitated withdrawal was common, suggesting aversion to withdrawal might possibly be associated with OUD's refractoriness to buprenorphine.

Deprescribing in older people.

Deprescribing is the process of discontinuing drugs that are either potentially harmful or no longer required. It can be achieved in older people and may be associated with improved health outcomes without long-term adverse effects. The risk of drug withdrawal effects can often be mitigated by carefully monitoring and gradually tapering the dose. Deprescribing should ideally be a shared decision-making process between the patient and the prescriber.

High doses of benzodiazepine predict analgesic and sedative drug withdrawal syndrome in paediatric intensive care patients.

AIM: Critically ill children can develop withdrawal syndrome after prolonged analgesia and sedation in a paediatric intensive care unit (PICU), when treatment is stopped abruptly or reduced quickly. The aim of this study was to evaluate the incidence of withdrawal syndrome in patients after three or more days of analgesic or sedative drug therapy, using a validated scale. We also analysed the association between withdrawal syndrome and the patients' outcome and factors related to analgesia and sedation treatment. METHODS: This prospective observational study analysed 89 periods of weaning from analgesia and sedation in 60 children between October 2010 and October 2011. Of these, 65% were less than six months old and 45% were admitted to the PICU after heart surgery. Withdrawal syndrome was assessed using the Withdrawal Assessment Tool-1 (WAT-1) scale. RESULTS: The incidence of withdrawal syndrome was 37%, and the only variable that predicted its presence was the highest administered dose of benzodiazepine. The duration of weaning, Sophia Observational Withdrawal Symptom scale score and nurse judgment were also associated with positive WAT-1 scores. CONCLUSION: Withdrawal syndrome should be considered after three or more days of analgesic or sedative treatment. A high dose of benzodiazepine increases the risk of developing withdrawal symptoms.

A Rare Phenomenon, Recurrent Acute Dystonia after Withdrawal of 'Methylphenidate-immediate Release Form': A Pediatric Case with ADHD.

Drug-induced acute dystonia is usually associated with combination therapies of neuroleptics, but rarely with the withdrawal or rebound effect of various psychotrops. Very sparse reports have described acute dystonia as a methylphenidate withdrawal (rebound effect), particularly in combination modalities. However, there is no case report or research regarding acute dystonia related to the withdrawal of the short-acting methylphenidate-immediate release form (MPH-IR) in the case of monotherapy of MPH-IR or a combination with guanfacine. Herein, a pediatric case of recurrent acute dystonia with two separate phenomena, locating orolingual and oromandibular/lower extremities, is presented as a withdrawal adverse reaction occurring after abrupt discontinuation of MPH-IR when under a combination therapy with guanfacine. Various options such as anticholinergic agents, re-administrating MPH, or turning to monotherapy from combination modalities, can be suggested in treatment, as well as only hydration may also have the benefit of resolving the symptoms, as in the current case. Practitioners should be aware of all possible adverse effects of MPH, even the rebound effect of short-acting forms.

Treatment of Opioid Withdrawal Syndrome Triggered by Oxycodone/Naloxone with Dexmedetomidine.

The combination of oxycodone and naloxone is useful for cancer pain management. Naloxone, as a pure opioid antagonist, cannot be used simultaneously with opioids. However, owing to its low bioavailability, it can be used in an oral composite formulation. We present the case of a 55-year-old man with gastric cancer who experienced severe opioid withdrawal syndrome (OWS) triggered by oxycodone/naloxone that was successfully managed with dexmedetomidine. He had been in a stable condition on intravenous morphine to alleviate cancer pain. Intravenous morphine was switched to oral oxycodone/naloxone for discharge from the hospital. The patient suddenly developed restlessness, heartburn, and violent behavior 30 minutes after taking oxycodone/naloxone. We attempted sedation with midazolam and propofol, but paradoxical agitation and desaturation occurred. Next, we tried dexmedetomidine and the patient showed a decreased heart rate and reduced agitation. The patient was eventually stabilized by increasing the dose of dexmedetomidine. This report informs clinicians of the possibility of OWS when switching from opioids to oxycodone/naloxone, which can be overcome with the appropriate use of sedatives and dexmedetomidine depending on the patient's condition.

Outcomes of hyperbolic tapering of antidepressants.

Background: In patients attempting to discontinue their antidepressant medication, there have been no prospective studies on patterns of withdrawal as a function of the rate of antidepressant reduction during the tapering trajectory, and moderators thereof. Objective: To investigate withdrawal as a function of gradual dose reduction. Design: Prospective cohort study. Methods: The sampling frame consisted of 3956 individuals in the Netherlands who received an antidepressant tapering strip between 19 May 2019 and 22 March 2022 in routine clinical practice. Of these, 608 patients, majorly with previous unsuccessful attempts to stop, provided daily ratings of withdrawal in the context of reducing their antidepressant medications (mostly venlafaxine or paroxetine), using hyperbolic tapering strips offering daily tiny reductions in dose. Results: Withdrawal in daily-step hyperbolic tapering trajectories was limited, and inverse to the rate of taper. Female sex, younger age, presence of one or more risk factors and faster rate of reduction over shorter tapering trajectories were associated with more withdrawal and differential course over time. Thus, sex and age differences were less marked early in the course of the trajectory, whereas differences associated with risk factors and shorter trajectories tended to peak early in the trajectory. There was evidence that tapering in weekly larger steps (mean per-week dose reduction: 33.4% of previous dose), in comparison with daily tiny steps (mean per-day dose reduction: 4.5% of previous dose or 25.3% per week), was associated with more withdrawal in trajectories of 1, 2 or 3 months, particularly for paroxetine and the group of other (non-paroxetine, non-venlafaxine) antidepressants. Conclusion: Antidepressant hyperbolic tapering is associated with limited, rate-dependent withdrawal that is inverse to the rate of taper. The demonstration of multiple demographic, risk and complex temporal moderators in time series of withdrawal data indicates that antidepressant tapering in clinical practice requires a personalised process of shared decision making over the entire course of the tapering period.

Effect of Enteral Guanfacine on Dexmedetomidine Use in the ICU.

Describe the efficacy and safety of guanfacine for dexmedetomidine weaning in critically ill patients. DESIGN: Retrospective descriptive analysis. SETTING: Six hundred thirteen-bed academic medical center from October 2020 to October 2021. PATIENT/SUBJECTS: All Adult patients on IV dexmedetomidine who received at least one dose of guanfacine for sedation or agitation were included. INTERVENTIONS: Enteral guanfacine. MEASUREMENTS AND MAIN RESULTS: The primary outcome was discontinuation of dexmedetomidine therapy within 48 hours after guanfacine initiation. Secondary outcomes assessed included adjunctive medication use, rate of dexmedetomidine reinitiation, and safety outcomes. One hundred five patients were included in the analysis. Median age was 59 years old, 66% were male, and median daily dose of guanfacine was 1.5 mg. Dexmedetomidine was discontinued within 48 hours in 58% of patients (n = 61) and within 72 hours in 71% of patients (n = 75). Fifty-five percent of patients (n = 58) required rescue medications for poorly controlled agitation, sedation, or pain while on guanfacine. Dexmedetomidine withdrawal occurred in 2% of patients (n = 2) while on guanfacine. Adverse effects attributed to guanfacine occurred in 8% of patients (n = 8), all experiencing hypotension leading to medication discontinuation. CONCLUSION: Dexmedetomidine was successfully weaned within 48 hours of guanfacine initiation in 58% of patients with minimal withdrawal or adverse effects. Guanfacine may be an effective and safe enteral option for dexmedetomidine weaning in critically ill patients.

Delirium After Pregabalin Withdrawal.

Pregabalin is a γ-amino butyric acid analogue drug that is used in fibromyalgia, neuropathic pain associated with diabetic peripheral neuropathy, spinal cord injury, and postherpetic neuralgia. Symptoms reported in association with pregabalin withdrawal include insomnia, gastrointestinal distress, tachycardia, and headache. This case report describes a 68-year-old patient who developed delirium after experiencing pregabalin withdrawal. Clinicians should be aware of the possibility of pregabalin withdrawal delirium.

A Retrospective Review of Morbidity and Mortality Associated with Acute Benzodiazepine Withdrawal at a Midwestern Academic Medical Center.

INTRODUCTION: There is concern that acute benzodiazepine (BZD) withdrawal may result in morbidity and mortality. However, there is a paucity of medical literature regarding clinical characteristics and outcomes of acute BZD withdrawal. We sought to characterize acute BZD withdrawal and its associated clinical outcomes and treatment at a midwestern academic medical center. METHODS: This was a retrospective study. The medical records of the University of Kansas Hospital, a tertiary academic medical center, were queried for patients with a diagnosis of BZD withdrawal, drug withdrawal, sedative-hypnotic withdrawal, or withdrawal-NOS from January 1, 2009 to January 1, 2016. Data collected included age, sex, month/year of encounter, initial vital signs, type of drug withdrawal (alcohol, opioid, BZD, or other), type of BZD withdrawing from, disposition, duration of hospitalization, seizures, endotracheal intubation, mortality, and pharmacological treatment. RESULTS: Eighty-two cases were identified. Cases per year increased over the study period. Thirty-one (38%) cases involved concurrent drug withdrawal with opioids most common (n = 25). Alprazolam (n = 32) was the most common BZD implicated in BZD withdrawal. Thirty-nine cases (47%) were admitted including seven to the ICU. Seizures were reported in 8 (10%) cases. Endotracheal intubation occurred in three (3.6%). Sixty-seven patients (81%) were treated with a BZD, with lorazepam (n = 42) most used. There were no deaths. Upon discharge, 40 (49%) patients received a prescription for a benzodiazepine. CONCLUSIONS: Cases of acute BZD withdrawal increased over the study period but were associated with only occasional morbidity and no mortality. Further multi-center studies are warranted to characterize the incidence and characteristics of acute BZD withdrawal better.

Successful use of tapering strips for hyperbolic reduction of antidepressant dose: a cohort study.

BACKGROUND: Tapering strips facilitate antidepressant discontinuation, allowing for personalised titration of discontinuation to the intensity of withdrawal. A tapering strip consists of antidepressant or other medication, packaged in a 28-day roll of daily pouches, each with the same or slightly lower dose than the one before. Previous studies demonstrated 70% real-world effectiveness of tapering strips. Here, we present a third, questionnaire-based retrospective cohort study in a large sample. METHODS: Patients whose doctor had prescribed tapering strips between October 2015 and December 2018 were sent a questionnaire for participation after completion of tapering between December 2015 and January 2020. Of 1240 individuals who returned a questionnaire (response rate: 59%), 987 (80%) used an antidepressant, of whom 824 (83%) had wished to discontinue their antidepressant. RESULTS: The sample was demographically representative of antidepressant users in the Netherlands. Less than 40% of participants had heard of tapering strips through their clinicians - Internet was the most frequent source. Of the 824 individuals, 341 (41%) had used strips for tapering venlafaxine, 206 (25%) for paroxetine and 277 (34%) for other antidepressants. Median duration of antidepressant use was 5-10 years, and most (71%) had tried to come off without tapering strips at least once. Most patients (72%) were able to discontinue their antidepressant, using a median of two strips to taper over a median period of 56 days. Females and individuals with (1) more severe experience of withdrawal during the use of tapering strips, (2) more years of use of antidepressant medication and (3) more previous attempts at discontinuation were less likely to be able to discontinue their antidepressant medication with tapering strips. CONCLUSION: The results of this study validate, for the third time, the observation that tapering strips can address the problem of antidepressant withdrawal symptoms in individuals attempting to discontinue antidepressants.

Maternal Exposure and Neonatal Effects of Drugs of Abuse.

The public health crisis of pregnant women being exposed to drugs of abuse and of its impact on their unborn children continues to grow at an alarming rate globally. The state of pregnancy is unique, with physiological changes that can lead to changes in the way drugs are handled by the body in both pharmacokinetics and response. These changes place the pregnant woman, fetus, and newborn infant at risk, as many of these drugs can cross the placenta and into breast milk. The substances most commonly linked to harmful effects include alcohol, tobacco, cannabis, stimulants, and opioids. The pharmacological and toxicological changes caused by in utero exposure or breastfeeding exposure are difficult to study, and the full extent of the mechanisms involved are not fully understood. However, these changes can significantly affect the risks of substance abuse and influence optimal treatment of pregnant women with a substance use disorder. In addition, newborns who were exposed to drugs of abuse in utero can experience withdrawal syndromes. Pharmacological management in infants is used to guide and treat withdrawal symptoms, with the goal being to improve the infant's sleep, eating, and comfort. Several barriers may prevent pregnant women from seeking help for substance use, including stigma and interactions with the legal system. Understanding changes in pharmacology, including pharmacokinetic changes that happen during pregnancy, is essential for anticipating the extent of maternal exposure and neonatal adverse effects.

Outcome of antidepressant drug discontinuation with taperingstrips after 1-5 years.

BACKGROUND: Stopping antidepressants is often difficult due to withdrawal. Taperingstrips were developed to facilitate antidepressant discontinuation according to the recently described Horowitz-Taylor method, allowing for personalised titration of discontinuation to the intensity of withdrawal. A taperingstrip consists of antidepressant or other medication, packaged in a 28-day roll of small daily pouches, each with the same or slightly lower dose than the one before it. We previously reported that the short-term success rate of antidepressant taperingstrips was 71%. Here, we examine longer-term outcome after 1-5 years. METHODS: Patients whose doctor had ordered taperingstrips between January 2015 and December 2019 were sent a questionnaire for participation in anonymised research in January 2020. Of 1012, 483 participated, of whom 408 (85%) had attempted antidepressant tapering. RESULTS: Of the 408 patients included, 192 (47%) had used strips for tapering venlafaxine, 142 (35%) for paroxetine and 74 (18%) for other antidepressants. Median length of antidepressant use was 4 years, and most (61%) had tried to come off without taperingstrips at least once. After 1-5 years, 270 patients (66%) remained off antidepressants after tapering their antidepressant, 6 (2%) had successfully reduced their medication, 87 (21%) had restarted due to (self-reported) relapse, 35 had restarted for another indication (9%), and 10 (3%) reported another outcome. People with more severe experience of withdrawal prior to tapering, and people who had been on antidepressants for a shorter period of time, were more likely to remain off medication after 1-5 years. CONCLUSION: The previously reported 71% short-term success rate of taperingstrips in the most severely affected group, was matched by a 68% rate after 1-5 years. The evidence-based approach of personal tapering to counter withdrawal, as used for drugs causing withdrawal, for example, benzodiazepines, may represent a simple solution for an important antidepressant-related public health problem, without extra costs.

Base on concept of traditional Chinese medicine: Experimental studies on efficacy of BIOCERAMIC Resonance to alleviate drug withdrawal symptoms.

Those who are challenged by dependency on prescription drugs or suffer drug addictions have few options available to them for recovery, such as psychotherapy and physiotherapy. Here we present a new approach with clinical examples involving stimulant addiction or overdose of hypnotic drugs that were received BIOCERAMIC Resonance, which was developed based on concept of 12 meridian channels of traditional Chinese medicine, and has successful withdrawal or dose reduction benefits. We describe the whole process and the clinical outcome. And by help of our previous publication on functional MRI, we discuss the possible brain locations response to BIOCERAMIC Resonance that may be corresponding to the beneficial effects of relief of depression, sleep deprivation and other mental symptoms that associate with substance abuse and withdrawal effects. We suggest this could be potentially widely application on substances abuse.

Relief of cannabis withdrawal symptoms and cannabis quitting strategies in people with schizophrenia.

This study examined the response to cannabis withdrawal symptoms and use of quitting strategies to maintain abstinence in people with schizophrenia. A convenience sample of 120 participants with schizophrenia who had at least weekly cannabis use and a previous quit attempt without formal treatment were administered the 176-item Marijuana Quit Questionnaire to characterize their "most serious" (self-defined) quit attempt. One hundred thirteen participants had withdrawal symptoms, of whom 104 (92.0%) took some action to relieve a symptom, most commonly nicotine use (75%). 90% of withdrawal symptoms evoked an action for relief in a majority of participants experiencing them, most frequently anxiety (95.2% of participants) and cannabis craving (94.4%). 96% of participants used one or more quitting strategies to maintain abstinence during their quit attempt, most commonly getting rid of cannabis (72%) and cannabis paraphernalia (67%). Religious support or prayer was the quitting strategy most often deemed "most helpful" (15%). Use of a self-identified most helpful quitting strategy was associated with significantly higher one-month (80.8% vs. 73.6%) and one-year (54.9% vs. 41.3%) abstinence rates. Actions to relieve cannabis withdrawal symptoms in people with schizophrenia are common. Promotion of effective quitting strategies may aid relapse prevention.