Specific Inhibition of Interpeduncular Nucleus GABAergic Neurons Alleviates Anxiety-Like Behaviors in Male Mice after Prolonged Abstinence from Methamphetamine.

Anxiety is one of the most common withdrawal symptoms of methamphetamine (METH) abuse, which further drives relapse to drugs. Interpeduncular nucleus (IPN) has been implicated in anxiety-like behaviors and addiction, yet its role in METH-abstinence-induced anxiety remains unknown. Here, we found that prolonged abstinence from METH enhanced anxiety-like behaviors in male mice, accompanied by more excited IPN GABAergic neurons, as indicated by the increased c-fos expression and the enhanced neuronal excitability by electrophysiological recording in the GABAergic neurons. Using the designer receptors exclusively activated by designer drugs method, specific inhibition of IPN GABAergic neurons rescued the aberrant neuronal excitation of IPN GABAergic neurons and efficiently reduced anxiety-like behaviors, whereas it did not induce depression-like behaviors in male mice after prolonged abstinence from METH. These findings reveal that IPN GABAergic neurons should be a promising brain target to alleviate late withdrawal symptoms from METH with few side effects.SIGNIFICANCE STATEMENT Prolonged abstinence from METH triggers IPN GABAergic neurons and ultimately increases anxiety in male mice. Suppressing IPN GABAergic neurons rescues METH abstinence-induced aberrant neuronal excitation of IPN GABAergic neurons and efficiently reduces anxiety in mice.

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.

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.

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.

The Independent Contribution of Positive and Negative Metacognitions About Smoking to Urge to Smoke, Withdrawal Symptoms and Dependence in Smoking-Dependent Men.

Previous research has indicated that various factors, such as psychological distress, distress intolerance, anhedonia, impulsivity and smoking metacognitions, have been individually linked to the urge to smoke, withdrawal symptoms and dependence. However, these factors have not been collectively examined to determine whether smoking metacognitions independently and significantly contribute to these outcomes. Therefore, the aim of this study was to investigate the impact of distress intolerance, anhedonia, impulsivity and smoking metacognitions on the urge to smoke, withdrawal symptoms and dependency in men who are dependent on smoking. A total of 300 smoking-dependent men completed psychological scales and smoking-related measures. The findings of the study indicated that positive metacognitions about emotion regulation significantly predicted the urge to smoke, even when accounting for other significant predictors such as the number of daily cigarettes smoked, psychological distress, anhedonia and impulsivity. Furthermore, positive metacognitions about cognitive regulation were found to be a significant predictor of withdrawal symptoms, independent of other significant predictors such as psychological distress and the urge to smoke. Smoking dependence was predicted by negative metacognitions about uncontrollability beyond other significant predictors, including the number of daily cigarettes smoked and distress intolerance. These results highlight the role of metacognitions about smoking in both short- and long-term clinical outcomes related to smoking. Consequently, addressing such beliefs during treatment for smoking dependence should be an important therapeutic goal.

Prospective validation of Sophia observation withdrawal symptoms: A paediatric delirium scale in critically ill children in Denmark.

BACKGROUND: Paediatric delirium (PD) is increasingly recognised as a common disorder in critically ill children with a reported prevalence ranging from 9% to 66%. We validated the PD component of the Sophia Observation withdrawal Symptoms-Paediatric Delirium (SOS-PD) scale in a Danish setting to provide increased awareness and reliable identification of this critical condition, thereby paving the way for improved pathways to targeted delirium care. OBJECTIVE: The objectives of this study were to criterion validate the PD component of the SOS-PD screening tool by comparing blinded psychiatric and nurse assessments and to estimate the prevalence of delirium in critically ill children in a Danish context. METHODS: A prospective observational study was performed on critically ill children aged between 3 m and 18 y, admitted to an intensive care unit, with a hospital stay of 48 h or more. Assessments took place on a fixed weekday over an 18-month period. To test accuracy and criterion validity, bedside nurses' SOS-PD assessments were compared to the reference standard, a diagnostic assessment performed by a child psychiatrist according to the Diagnostic and Statistical Manual-V criteria by use of the Vanderbilt Assessment of Delirium in Infants and Children. RESULTS: We included 141 children in the study, 30 (21%) of whom were diagnosed with delirium by the child psychiatrist. The accuracy of the delirium diagnosis was 93.6% (95% confidence interval [CI]: 88.3-97.1) among the nurses' SOS-PD assessments compared to the reference standard. The SOS-PD demonstrated a high sensitivity of 83.3% (95% CI: 65.3-94.4) and a high specificity of 96.4% (95% CI: 91.0-99.0) with five false-negative and four false-positive cases. CONCLUSION: The PD component of the SOS-PD tool has good accuracy and validity for assessments performed by nurses compared to a child psychiatrist's diagnosis in critically ill children in a Danish setting. We recommend the use of the SOS-PD instrument in clinical practice.

Minnesota Tobacco Withdrawal Scale revision 2020, validated Czech translation.

Most smokers are addicted to tobacco or nicotine not only psychosocially but also physically, what results in withdrawal symptoms after they miss their dose. These are one of the major barriers to quitting. In the treatment of tobacco dependence, the evaluation of the degree of withdrawal symptoms helps to guide psychobehavioral intervention and, above all, the choice of the type, dose, and duration of pharmacotherapy. The Minnesota Withdrawal Symptoms Scale is one of the most widely used for this purpose, revised in 2020. We present a validated translation of this update.

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.

Delayed crises following benzodiazepine withdrawal: deficient adaptive mechanisms or simple pharmacokinetics? Detoxification assisted by serum-benzodiazepine elimination tracking.

OBJECTIVE: Rapid relapses after successful withdrawal occur even in apparently motivated benzodiazepine (BZD)-dependent patients. Regardless of known personality or biological (re-adaptation) issues, the aim of this open-label, single-arm, seminaturalistic study was to search for any detoxification errors contributing to failures. METHODS: The data came from 350 inpatients. Based on serum-BZD evolution criteria, the procedure was divided into four stages: substitution, accumulation, elimination and post-elimination observation. After switching the patients to a long-acting substitute (diazepam), to prevent data falsification due to unwanted overaccumulation, the doses were expeditiously reduced under laboratory feedback until accumulation stopped. With the start of effective elimination, the tapering rate slowed and was individually adjusted to the patient's current clinical state. The tracking of both serum-BZD concentration and the corresponding intensity of withdrawal symptoms was continued throughout the entire elimination phase, also following successful drug withdrawal. Detoxification was concluded only after the patient's post-elimination stabilization. RESULTS: Regardless of various initial serum-BZD concentration levels and the customized dose-reduction rate, and despite the novel lab-driven actions preventing initial overaccumulation, elimination was systematically proven to be protracted and varied within the 2- to 95-day range after the final dose. Within this period, withdrawal syndrome culminated several times, with varying combinations of symptoms. The last crisis occurrence (typically 2-3 weeks after withdrawal) correlated with the final serum-BZD elimination. The factors that prolonged elimination and delayed the final crisis were patient age, duration of addiction, adjunct valproate medication and elimination stage start parameters growing with former overaccumulation. CONCLUSIONS: The low-concentration detoxification stage is critical for patients' confrontations with recurring withdrawal symptoms. Underestimated elimination time following drug withdrawal and premature conclusions of detoxification expose patients to unassisted withdrawal crises. Concentration tracking defines proper limits for medical assistance, preventing early relapses.

Discontinuation of chronic benzodiazepine use in primary care: a nonrandomized intervention.

BACKGROUND: Chronic benzodiazepine use is a challenge in primary care practice. Protocols to support safe discontinuation are still needed, especially in countries with high utilization rates. OBJECTIVES: To evaluate the feasibility, effectiveness, and safety of a benzodiazepine discontinuation protocol in primary care setting. METHODS: Nonrandomized, single-arm interventional study, at primary care units. Family physicians (FPs) recruited patients (18-85 years-old) with benzodiazepine dependence and chronic daily use ≥3 months. Patients with daily dosages ≥30 mg diazepam-equivalent, taking zolpidem, with a history of other substance abuse or major psychiatric disease were excluded. After the switch to diazepam, the dosage was gradually tapered according to a standardized protocol. Primary endpoint was the percentage of patients who stopped benzodiazepine at the intervention last visit. Dosage reduction, withdrawal symptoms, patients' and FPs' satisfaction with the protocol were evaluated. RESULTS: From 66 enrolled patients (74% female; 66.7% aged >64 years; median time of benzodiazepine use was 120 months), 2 withdrew due to medical reasons and 3 presented protocol deviations. Overall, 59.4% of participants successfully stopped benzodiazepine (60.7% when excluding protocol deviations). Men had higher probability of success (relative risk = 0.51, P = 0.001). A total of 31 patients reported at least 1 withdrawal symptom, most frequently insomnia and anxiety. Most of participating FP considered the clinical protocol useful and feasible in daily practice. Among patients completing the protocol, 77% were satisfied. For the patients who reduced dosage, 85% kept without benzodiazepines after 12 months. CONCLUSION: The discontinuation protocol with standardized dosage reduction was feasible at primary care and showed long-term effectiveness.

Effectiveness of non-opioid interventions to reduce opioid withdrawal symptoms in patients with chronic pain: a systematic review.

BACKGROUND: Dealing with the opioid crisis, medical doctors are keen to learn how to best treat opioid dependency in patients with chronic non-cancer pain. Opioid replacement therapy is commonly used, but success rates vary widely. Since many patients still experience severe withdrawal symptoms, additional interventions are necessary. OBJECTIVE: To review the effectiveness of interventions in the treatment of withdrawal symptoms during opioid tapering or acute withdrawal in patients with long-term non-cancer pain. METHODS: A systematic review was conducted in Embase.com, MEDLINE, Web of Science, PsycINFO, and Cochrane CENTRAL register of trials. Studies eligible for inclusion were (non-)randomized controlled trials in adults with long-term opioid prescriptions for non-cancer pain. Included trials had to compare a non-opioid intervention to placebo, usual care, no treatment, or non-opioid drug and had to report on withdrawal symptoms as an outcome. Study quality was assessed with the 2.0 Cochrane risk of bias (RoB) tool. Evidence quality was rated following the GRADE approach. RESULTS: One trial (n = 21, some concerns regarding RoB) compared Varenicline to placebo. There was no statistically significant between-group reduction of withdrawal symptoms (moderate-quality evidence). CONCLUSIONS: Evidence from clinical trials on interventions reducing withdrawal symptoms is scarce. Based on one trial with a small sample size, no firm conclusion can be drawn. Meanwhile, doctors are in dire need for therapeutic options to tackle withdrawal symptoms while tapering patients with prescription opioid dependence. We hope this review draws attention to this unfortunate research gap so that future research can provide doctors with answers.

There is a global increase of patients depended on opioids prescribed by a doctor for chronic non-cancer pain. Tapering these drugs is challenging, especially since treatment options for withdrawal symptoms are lacking. We conducted a systematic review of controlled studies on interventions aimed at reducing withdrawal symptoms during opioid tapering in patients with long term opioid treatment for chronic non-cancer pain. One trial could be included. No firm conclusions can be drawn from this one trial. Hence, this review demonstrates that to improve care for patients depended on opioids for chronic non-cancer pain, more high-quality research in this field is necessary.

Benzodiazepine withdrawal in older people: what is the prevalence, what are the signs, and which patients?

PURPOSE: Benzodiazepines (BZDs) and related drugs (Z-drugs) are mainly taken chronically, and older people are much more likely to take them on a chronic basis despite recommendations. Withdrawal symptoms could be an obstacle to stopping BZD/Z-drug administration. The main objective of this study is to estimate the prevalence of withdrawal symptoms in patients aged 65 years and older who have experience a stop of BZD/Z-drug. The secondary objectives are to describe the withdrawal symptoms and identify factors associated. METHOD: This ancillary study was based on a national observational study in patients with chronic BZD/Z-drug consumption. Patients who made at least one BZD/Z-drug stop experience were selected. Withdrawal symptoms are described, and a logistic regression was carried out to identify the variables most associated with withdrawal symptoms. RESULTS: In total, 697 patients were selected: 78% experienced at least one withdrawal symptom after a stop administering BZDs or Z-drugs; most of the withdrawal symptoms were psychological disorders. CONCLUSION: Our study identifies a specific population experiencing withdrawal symptoms and who cannot stop administering BZD/Z-drug. We assume that withdrawal symptoms in patients with chronic use play an essential role in the nonstop use of BZD/Z-drugs.

Prevalence of and factors associated with acute withdrawal symptoms after 24 weeks of eszopiclone treatment in patients with chronic insomnia: a prospective, interventional study.

BACKGROUND: Although long-term use of benzodiazepines and benzodiazepine receptor agonists (BZDs) has been associated with an increased risk of dependence, the incidence, details of clinical manifestations, and triggering factors of withdrawal symptoms associated with long-term BZD use at common clinical doses remain unclear. METHODS: In a multicenter, open-label study of 123 Japanese patients with insomnia, patients were given a common clinical dose of eszopiclone (2 mg) for 24 weeks, and then treatment was abruptly discontinued. Withdrawal symptoms were evaluated using the Benzodiazepine Hypnotics Withdrawal Symptom Scale (BHWSS). The Insomnia Severity Index (ISI) was used to rate insomnia severity during treatment and 2 weeks after discontinuation. Dependence and poor compliance during treatment without strict medication controls were evaluated with the Benzodiazepine Dependence Self Report Questionnaire short version (Bendep-SRQ SV) subscale sum scores for problematic use, preoccupation, and lack of compliance. Associations between the presence of clinically relevant withdrawal symptoms (BHWSS≥7) and demographic measures, ISI scores at Week 24, and Bendep-SRQ SV subscale sum scores were evaluated by multivariable stepwise logistic regression analyses. RESULTS: Seventy-six patients completed treatment and 2 weeks of withdrawal; eight (10.5%) had clinically relevant withdrawal symptoms. On multiple logistic regression analysis, Bendep-SRQ SV subscale sum scores were correlated with withdrawal symptoms (odds ratio, 1.650; 95% confidence interval, 1.105-2.464; p = 0.014). Exacerbation of post-discontinuation insomnia was not significantly different between patients who showed clinically relevant withdrawal symptoms and those who did not (p = 0.245). CONCLUSIONS: Dependence and poor compliance may contribute to withdrawal symptoms with long-term BZD use. Providing guidance to ensure proper compliance is thought to be the best way to mitigate withdrawal symptoms. TRIAL REGISTRATION: UMIN000024462 (18/10/2016).

The Era of E-Cigarettes: A Cross-Sectional Study of Vaping Preferences, Reasons for Use and Withdrawal Symptoms Among Current E-Cigarette Users in the United Arab Emirates.

Electronic cigarette (E-cig) use has increased substantially among the young population, who adopt using E-cig for various reasons. Our present study aimed to explore vaping preferences and reasons for using E-cig among current users in the United Arab Emirates (UAE) and to assess physical and psychological symptoms experienced while using E-cig during intermittent fasting. A cross-sectional study was conducted from April 23 to May 22, 2020, to solicit responses from current E-cig users in the UAE. Data were collected about sociodemographic profile, tobacco cigarette smoking, vaping preferences, reasons for use, and withdrawal symptoms during fasting in Ramadan. A convenience sample of 591 adult E-cig users were initially recruited, of whom 392 participants with complete responses were included in our analysis. The majority of participants were males (n = 275, 70.2%) and around 28.6% (n = 112) were dual users. Vape tank/Box-mod was the most used type of E-cig (50.3%). Most of the participants (n = 317; 80.9%) believed that E-cigs are less harmful than tobacco cigarettes. During fasting time, around 46.2% (n = 181) of E-cig users have experienced various physical symptoms, while 51.0% (n = 200) of users have experienced various psychological symptoms. E-cig use is gaining popularity within the UAE after the recent legalization as these devices are commonly advertised and claimed by manufacturers to aid smoking cessation. The effectiveness of E-cig in aiding smoking cessation should be investigated with a higher level of evidence, especially in a new context of usage as the UAE, considering various types of devices, hundreds of E-liquid brands, and the influence of concurrent poly-tobacco use.

Effects of Multiple Detoxifications on Withdrawal Symptoms, Psychiatric Distress and Alcohol-Craving in Patients with an Alcohol Use Disorder.

Previous studies have shown an association between the number of withdrawal attempts and increased severity of withdrawal symptoms in patients with an alcohol use disorder (AUD). An underlying allostatic neuroadaptive response may negatively affect the withdrawal pathology after alcohol discontinuation. The objective of the present research is to examine the intensification of psychiatric distress, craving, and post-detoxification drinking outcomes, which may result from these neurobehavioral alternations. Fifty-two AUD inpatients were divided into two groups: <2 previous detoxifications and ≥2 previous detoxifications. Patients completed the Dutch version of the Severity of Withdrawal Scale (SWS), Depression Anxiety Stress Scales (DASS-21), VAS Craving, and Desires for Alcohol Questionnaire (DAQ). Linear mixed effects models were applied, controlling for the number of drinks consumed in the past 30 days and alcohol drinking history (years). Patients who had undergone ≥2 detoxifications reported statistically significantly higher scores on SWS withdrawal and DASS psychiatric symptoms. Also, craving patterns were different between groups, as shown by a statistically significant interaction effect for VAS craving for the time of day factor (morning vs. evening). No statistically significant group differences were found for DAQ scores and post-detoxification drinking outcomes. Due to relatively low 1-month follow-up rates our power was limited to detect such a difference. The present study contributes to the existing body of evidence that multiple detoxifications are associated with aggravated withdrawal/psychiatric pathology, and distinct diurnal patterns of VAS craving. Several clinical implications are discussed and alternative strategies are provided to manage repeated cycles of detoxifications.

Withdrawal Symptoms among Cigarette and Waterpipe Smokers: A Study in Natural Setting.

BACKGROUND: The rates of tobacco use, including cigarette and waterpipe smoking, are surging in the Eastern Mediterranean region. The use of these products causes nicotine dependence that makes even short-term tobacco abstinence difficult due to aversive symptoms. During the daytime fasting of the month of "Ramadan", people accept significant disruption in regular activities, including tobacco smoking. Thus, daytime during Ramadan (before sunset) is likely associated with abstinence symptoms emerging among tobacco smokers. We assessed this hypothesis by measuring tobacco/nicotine abstinence symptoms and craving among smokers of cigarettes or waterpipes during Ramadan. METHODS: A cross-sectional survey-based study was conducted on a convenience sample of adults. Participants were assessed for general information about tobacco smoking, dependence, and nicotine desire or craving, and withdrawal symptoms using the Minnesota Nicotine Withdrawal Scale (MNWS) and the Tiffany-Drobes Questionnaire on Smoking Urges. RESULTS: The study sample included 632 exclusive cigarette smokers and 161 exclusive waterpipe tobacco smokers. After fasting and abstaining from tobacco during the day, approximately 75% of cigarette smokers and 20% of waterpipe smokers reported smoking within the first 30 minutes. In addition, 10% of cigarette smokers and 30% of waterpipe smokers reported smoking within the first 60 minutes. Regarding smoking urge, no significant difference was found between cigarette and waterpipe smokers. For nicotine craving and withdrawal, significant differences between cigarette and waterpipe smokers were found when comparing mean scores for each of the following items: (i) urge to smoke, (ii) craving nicotine, (iii) hunger, (iv) desire for sweets, and (v) depression/feeling blue (P-values < 0.05). CONCLUSION: This study provided evidence from the month of Ramadan that waterpipe smoking is associated with abstinence-induced smoking urge and withdrawal symptoms that are comparable to cigarette smoking. More interdisciplinary research must be focused on developing interventions to reduce tobacco smoking, including waterpipe.

Opioid withdrawal symptoms, a consequence of chronic opioid use and opioid use disorder: Current understanding and approaches to management.

WHAT IS KNOWN AND OBJECTIVE: Opioid use in the United States has reached unprecedented-some would even say crisis-levels. Although many individuals use opioid drugs as part of legitimate pain management plans, a significant number misuse prescription or illicit opioids. With regular opioid use, individuals develop tolerance and physical dependence; both are predictable, physiologic responses to repeated opioid exposure. However, a substantial number of individuals who misuse opioids will develop opioid use disorder (OUD), a complex, primary, chronic, neurobiological disease rooted in genetic, environmental and psychosocial factors. This article discusses OUD, opioid receptor physiology, and opioid withdrawal symptomatology and pathophysiology, as well as current treatment options available to reduce opioid withdrawal symptoms in individuals with physical dependence and/or OUD. METHODS: The research articles regarding OUD and its management have been reviewed thoroughly based on a PubMed literature search using keywords related to opioid dependence, its pathophysiology and current treatment strategies. RESULTS AND DISCUSSION: Tolerance/physical dependence and the behavioural characteristics associated with OUD reflect complex neurobiologic adaptations in several major systems of the brain, including the locus ceruleus and mesolimbic systems. Physical dependence is responsible for the distressing withdrawal symptoms individuals experience upon abrupt cessation or rapid dose reduction of exogenous opioids. Opioid withdrawal symptoms are a key driver behind continued opioid use, and a barrier to opioid discontinuation. Several opioid-based medications are available to treat patients with OUD; these treatments can diminish opioid withdrawal symptoms and cravings as well as block opioid effects in the event of relapse. Additionally, non-opioid drugs may be used during acute detoxification to help alleviate opioid withdrawal symptoms. WHAT IS NEW AND CONCLUSION: The opioid crisis has produced many challenges for physicians, one being the need to determine which patients would benefit most from maintenance therapy and which may be candidates for opioid discontinuation. In addition to summarizing current understanding of OUD, we provide a new algorithm for determining the need for continued opioid use as well as examples of situations where management of opioid withdrawal symptoms is indicated.

Factors Predicting 6-Month Smoking Cessation in Korean Adults.

The purpose of this study was to identify factors predicting 6-month smoking cessation in Korean adult smokers. This descriptive correlation study assessed levels of urine cotinine, serum cotinine, serum serotonin, and 5-hydroxyindoleacetic acid; tobacco withdrawal symptoms; and resilience among 164 Korean adult smokers. Serum cotinine levels were negatively related to resilience at six months (r = -.42, p = .019), but were positively related to the amount of smoking (r = .32, p = .008) and with the Week 6 tobacco withdrawal symptoms score (r = .48, p = .001, n = 41). Higher resilience was associated with a higher 5-HIAA concentration. Greater therapy attendance, resilience, and withdrawal symptoms explained 35.3% of the variance in 6-month smoking cessation (Nagelkerke R2 = .35, p < .001, n = 76). Efforts to increase counseling attendance rates and resilience and decrease withdrawal symptoms could be useful ways to improve smoking cessation rates.

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.

Intensity of Withdrawal Symptoms During Opioid Taper in Patients with Chronic Pain-Individualized or Fixed Starting Dosage?

OBJECTIVE: Controlled opioid withdrawal is recommended for patients with chronic noncancer pain (CNCP) with insufficient pain reduction or intolerable side effects while on opioid treatment. Few studies have investigated the management of opioid withdrawal (OW). Most common are protocols with an individualized starting dosage (ISD), calculated from the last opioid intake. After two cases of overdose, we introduced a novel withdrawal protocol using a low fixed starting dosage (FSD) for safety reasons. The present study compares the intensity of withdrawal symptoms using the Subjective Opioid Withdrawal Scale (SOWS) and incidences of serious adverse events (SAE) and dropouts in each taper schedule in 195 CNCP patients with OW in an inpatient facility. METHODS: Two protocols were compared: FSD (2014-2016): N = 68, starting dose: 90 mg morphine/d; and ISD (2010-2014): N = 127, starting dose: 70% of the patient's daily morphine equivalent dose (MED). Outcome criteria: primary: mean daily SOWS score during the first 10 days (16 questions, daily score 0-64); secondary: change in pain intensity on a numeric rating scale (0-10), rate of dropouts and SAEs. Statistics: Student test, Mann-Whitney U test, chi-square test, analysis of variance, P < 0.05. RESULTS: The mean daily SOWS score was lower in the FSD group (14.9 ± 9.4 vs 16.1 ± 10, P < 0.05) due to a lower rate of high-intensity withdrawal symptoms (12.4% vs 17.6%, P < 0.01), particularly in patients on >180 mg MED (9.7% vs 18.4%, P < 0.01). Pain intensity decreased after withdrawal, and the incidence of SAEs and dropouts was low in both groups. CONCLUSIONS: The FSD protocol provides a lesser burden of withdrawal symptoms and equal patient safety. It can be recommended for OW in CNCP patients.