Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis.

BACKGROUND: Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms has not been quantified. An estimate of antidepressant discontinuation symptoms incidence could inform patients and clinicians in the discontinuation of treatment, and provide useful information to researchers in antidepressant treatments. We aimed to assess the incidence of antidepressant discontinuation symptoms in patients discontinuing both antidepressants and placebo in the published literature. METHODS: We systematically searched Medline, EMBASE, and CENTRAL from database inception until Oct 13, 2022 for randomised controlled trials (RCTs), other controlled trials, and observational studies assessing the incidence of antidepressant discontinuation symptoms. To be included, studies must have investigated cessation or tapering of an established antidepressant drug (excluding antipsychotics, lithium, or thyroxine) or placebo in participants with any mental, behavioural, or neurodevelopmental disorder. We excluded studies in neonates, and those using antidepressants for physical conditions such as pain syndromes due to organic disease. After study selection, summary data extraction, and risk of bias evaluation, data were pooled in random-effects meta-analyses. The main outcome was the incidence of antidepressant discontinuation symptoms after discontinuation of antidepressants or placebo. We also analysed the incidence of severe discontinuation symptoms. Sensitivity and meta-regression analyses tested a selection of methodological variables. FINDINGS: From 6095 articles screened, 79 studies (44 RCTs and 35 observational studies) covering 21 002 patients were selected (72% female, 28% male, mean age 45 years [range 19·6-64·5]). Data on ethnicity were not consistently reported. 16 532 patients discontinued from an antidepressant, and 4470 patients discontinued from placebo. Incidence of at least one antidepressant discontinuation symptom was 0·31 (95% CI 0·27-0·35) in 62 study groups after discontinuation of antidepressants, and 0·17 (0·14-0·21) in 22 study groups after discontinuation of placebo. Between antidepressant and placebo groups of included RCTs, the summary difference in incidence was 0·08 [0·04-0·12]. The incidence of severe antidepressant discontinuation symptoms after discontinuation of an antidepressant was 0·028 (0·014-0·057) compared with 0·006 (0·002-0·013) after discontinuation of placebo. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms. Heterogeneity of results was substantial. INTERPRETATION: Considering non-specific effects, as evidenced in placebo groups, the incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication. Subgroup analyses and heterogeneity figures point to factors not accounted for by diagnosis, medication, or trial-related characteristics, and might indicate subjective factors on the part of investigators, patients, or both. Residual or re-emerging psychopathology needs to be considered when interpreting the results, but our findings can inform clinicians and patients about the probable extent of antidepressant discontinuation symptoms without causing undue alarm. FUNDING: None.

Alcohol Use Disorder and Chronic Pain: An Overlooked Epidemic.

Alcohol use disorder (AUD) and chronic pain disorders are pervasive, multifaceted medical conditions that often co-occur. However, their comorbidity is often overlooked, despite its prevalence and clinical relevance. Individuals with AUD are more likely to experience chronic pain than the general population. Conversely, individuals with chronic pain commonly alleviate their pain with alcohol, which may escalate into AUD. This narrative review discusses the intricate relationship between AUD and chronic pain. Based on the literature available, the authors present a theoretical model explaining the reciprocal relationship between AUD and chronic pain across alcohol intoxication and withdrawal. They propose that the use of alcohol for analgesia rapidly gives way to acute tolerance, triggering the need for higher levels of alcohol consumption. Attempts at abstinence lead to alcohol withdrawal syndrome and hyperalgesia, increasing the risk of relapse. Chronic neurobiological changes lead to preoccupation with pain and cravings for alcohol, further entrenching both conditions. To stimulate research in this area, the authors review methodologies to improve the assessment of pain in AUD studies, including self-report and psychophysical methods. Further, they discuss pharmacotherapies and psychotherapies that may target both conditions, potentially improving both AUD and chronic pain outcomes simultaneously. Finally, the authors emphasize the need to manage both conditions concurrently, and encourage both the scientific community and clinicians to ensure that these intertwined conditions are not overlooked given their clinical significance.

Estimate the prevalence of daily caffeine consumption, caffeine use disorder, caffeine withdrawal and perceived harm in Iran: a cross-sectional study.

One of the informal diagnoses in DSM-5 is Caffeine Use Disorder (CUD). CUD and high levels of caffeine consumption could impact mental health conditions. This study aimed to estimate the prevalence of CUD, caffeine consumption, caffeine-related harms, and related psychiatric symptoms in Iran. A cross-sectional survey with a convenience sample of 1228 adults were conducted in Iran. Caffeine consumption was assessed across 20 products in Iran. Caffeine Use Disorder Questionnaire (CUDQ), Caffeine Withdrawal Symptoms Questionnaire (CWSQ), 14-item Caffeine-related Harm Screening (CHS), and Symptom Checklist-25 (SCL-25) were used in the present study. We used SPSS (desktop version 26.0) to analyze the data using descriptive statistics, chi-square, and the least significant difference (LSD) post hoc test. The daily average caffeine consumption was 146.67 mg. The prevalence of CUD and caffeine withdrawal (C.W.) were estimated at 19.5% and 46.62%, respectively. Also, 12.9% of responders received CUD and C.W.s simultaneously. The prevalence of CUD was higher in men than females (25.08% vs. 13.93%). 95% of participants (n = 1166) reported using at least one caffeine product yesterday. Moreover, the most reported caffeine-related harms were the desire for sugar (42.9%), insomnia (39.3%), and caffeine dependence (38.3%). Age significantly correlates with CUD (- 0.07) and daily caffeine intake (0.08). Moreover, all SCL-90 subscales had a significant correlation with daily caffeine intake. Finally, responders at younger ages reported higher levels of CUD and caffeine consumption than older adults(P < 0.05). High rates of C.W. and CUD in the Iranian population suggest that it is necessary to develop evidence-based treatments.

Study on Risk Factors and Receiver Operator Characteristic Curve of Iatrogenic Withdrawal Syndrome in Pediatric Intensive Care Units: A Retrospective Study.

INTRODUCTION: The aims of this study were to investigate the independent risk factors associated with iatrogenic withdrawal syndrome in pediatric intensive care units (PICUs) and to establish receiver operator characteristic (ROC) curve to facilitate the diagnosis of iatrogenic withdrawal syndrome in clinical settings. METHODS: Pediatric patients who received analgesic and sedative medication at a tertiary hospital in the southern Zhejiang region of China between January 2016 and December 2022 were selected for the study. Clinical case data were retrospectively analyzed to gather information including age, gender, weight, total dose of analgesic and sedative medication, total treatment duration, average maintenance dose, and other relevant parameters. Medically induced withdrawal symptom scores were assessed using the Sophia Observation Scale for Withdrawal Symptoms (SOS). Univariate and multivariate logistic regression analyses were conducted on the above indicators to identify the risk factors for iatrogenic withdrawal, and an ROC curve was constructed. RESULTS: The study encompassed a total of 104 pediatric patients, comprising 47 patients in the SOS score ≥4 group and 57 patients in the SOS score ≤3 group. The incidence of iatrogenic withdrawal was 45.19%. Univariate analysis identified cumulative total dose of fentanyl, average daily dose of fentanyl, average daily dose of midazolam, and patient weight (p < 0.05) as factors associated with iatrogenic withdrawal syndrome. The logistic multiple regression analysis revealed that the average daily dose of fentanyl was an independent risk factor for the occurrence of iatrogenic withdrawal syndrome in critically ill children (p < 0.05). ROC curve analysis indicated an area under the curve of 0.711 (95% CI: 0.610-0.811) with sensitivity and specificity of 73.7% and 61.7%, respectively. CONCLUSION: The average daily maintenance dose of fentanyl holds significant clinical value in diagnosing and evaluating the prognosis of iatrogenic withdrawal syndrome and can provide a scientific foundation for enhancing sedative and analgesic management in clinical practice.

Withdrawal syndrome after antipsychotics discontinuation: an analysis of the WHO database of spontaneous reports (Vigibase) between 2000 and 2022.

RATIONALE: Withdrawal syndrome (WDS) has been described after discontinuation of antipsychotics. WDS could be the consequence of an over-activation of the dopaminergic pathway. Antipsychotics with a higher affinity for dopamine D2 receptors could be associated with a higher risk of WDS. This study aims to address this statement and evaluate the risk difference for withdrawal syndrome between antipsychotics based on pharmacovigilance data. METHODS: We collected individual reports registered in Vigibase® between 01/01/2000 and 31/12/2022 of patients treated with antipsychotics and who had presented WDS. A disproportionality analysis was performed to evaluate the risk of reporting WDS with each antipsychotic compared to all other antipsychotics. We performed a correlation analysis to assess the correlation between the risk of reporting WDS for each antipsychotic in relation with their pKi for D2 and 5HT2A receptors. RESULTS: The most frequent psychiatric withdrawal symptoms after antipsychotic discontinuation were insomnia, anxiety and depression. Tremor, headache and dizziness were among the most frequently reported neurologic withdrawal symptoms. Tiotixene had the highest risk of reporting WDS (ROR 7.08; 95%CI 3.49 - 14.35) followed by pimozide (ROR 4.35; 95%CI 1.93 - 9.77), quetiapine (ROR 4.24; 95%CI 3.87 - 4.64), thioridazine (ROR 4.17; 95%CI 2.50-6.98) and ziprasidone (ROR 2.98; 95%CI 2.41-3.67). We found a poor correlation between D2/5HT2A binding affinity and the risk of reporting withdrawal syndrome (R2 = 0,094). CONCLUSION: Our results suggest that there might be a risk difference for WDS between antipsychotics. Tiotixene, pimozide and quetiapine were associated with a higher risk of reporting a WDS whereas this risk was lower with chlorpromazine, clozapine and fluphenazine. We could not address the issue of withdrawal psychosis, withdrawal dyskinesia, rebound psychosis or supersensitivity psychosis due to the lack of specific WHO medDRA coded terms to identify potential cases.

The caffeine dilemma: unraveling the intricate relationship between caffeine use disorder, caffeine withdrawal symptoms and mental well-being in adults.

OBJECTIVE: This study aimed to explore the relationship between caffeine use disorder (CUD), caffeine withdrawal symptoms and the prevalence of depression, anxiety and stress (DASS) in adults. DESIGN: The study utilised a cross-sectional design to assess the relationships between CUD, caffeine withdrawal symptoms and DASS. SETTING: Participants' CUD was evaluated through the Caffeine Use Disorder Questionnaire (CUDQ), while the Depression Anxiety Stress Scale-21 (DASS-21) measured DASS levels. Caffeine withdrawal symptoms and total caffeine intake were calculated based on self-reported consumption of caffeine-rich products. PARTICIPANTS: The study involved 618 participants with an average age of 27·8 (sd 7·8) years. RESULTS: Participants consumed an average of 461·21 (sd 11·09) mg/d of caffeine, showing a positive correlation between CUD and total caffeine intake. The risk of CUD increased alongside levels of DASS. Individuals with caffeine withdrawal symptoms had higher CUDQ and DASS scores. A multiple linear regression model revealed significant associations between total caffeine intake (P < 0·001) and DASS-21 score (P < 0·001) with CUDQ score. CONCLUSIONS: The study concluded that caffeine, while recognised for its potential health benefits, also exhibits properties that may lead to addiction. The development of caffeine use disorder and cessation of caffeine intake can increase DASS levels in adults, indicating the need for awareness and appropriate interventions in public health nutrition.

Intersectional Risk and the Significant Gap in Care for Persons With Co-occurring Chronic Pain and Opioid Withdrawal.

OBJECTIVES: Persons with chronic pain and women tend to enter treatment for opioid use disorder with greater opioid withdrawal severity than persons without chronic pain and men, respectively. This study examined characteristics of facilities with opioid withdrawal treatment, including gender-based services, as a function of whether they reported having a tailored pain management program. METHODS: The National Survey of Substance Abuse Treatment Services 2020 was used to examine 3942 facilities with opioid withdrawal treatment in the United States. Using a multivariable binary logistic regression model, facilities were examined for the presence of a tailored program for individuals with co-occurring pain. Regional location of the facility, ownership status, and availability of tailored gender programs, nonhospital residential services, and outpatient services served as independent variables in the analysis. RESULTS: A slight majority of the sample had a program for both adult men and adult women ( n = 2010, 51.0%). Most facilities had outpatient services ( n = 3289, 83.4%) and did not have a tailored program for addressing co-occurring pain ( n = 2756, 69.9%). Binary logistic regression analysis showed that among opioid withdrawal facilities, programs with nonhospital residential services, government or private nonprofit funding, or tailored gender programming had higher odds of reporting having a tailored program for pain and substance use disorder. Facilities in the Western United States were most likely to have tailored programs for pain and substance use disorder. CONCLUSIONS: Future research should investigate what support patients may receive and how to better scale access to pain management during opioid withdrawal treatment.

Characterization of alcohol-related seizures in withdrawal syndrome.

OBJECTIVE: Alcohol-related seizures (ARS) are one of the most important consequences of alcohol withdrawal syndrome (AWS). However, demographic and clinical characteristics, and furthermore, the relationship of ARS with delirium tremens (DT), have not yet been evaluated in detail. Therefore, the aim of the present study was to reveal the correlates of ARS and examine the interaction of ARS with the occurrence of DT and with the severity of AWS. METHODS: In the retrospective study (Study 1) 2851 medical charts of inpatient admissions characterized by AWS and DT were listed. Demographic and clinical variables of ARS were assessed. In the follow-up study (Study 2), patients admitted with AWS without (N = 28) and with (N = 18) ARS were enrolled. Study 1 was performed between 2008 and 2023, and Study 2 was performed in 2019 in Hungary. To determine the severity of AWS, the Clinical Institute Withdrawal Assessment Scale for Alcohol, Revised (CIWA-Ar) was used. ARS is a provoked, occasional seizure; therefore, patients with epilepsy syndrome were excluded from the two studies. Statistical analyses were performed by the means of chi-square tests, multinomial logistic regressions, mixed ANOVA, and derivation. RESULTS: The occurrence of DT, the history of ARS, and somatic co-morbidities were found to be risk factors for the appearance of ARS. ARS was proved to be a risk factor for the development of DT. In the follow-up study, there was no difference in the decrease of CIWA-Ar scores between the groups. SIGNIFICANCE: Our present findings support the likelihood of kindling, which is one of the most important mechanisms underlying the development of ARS, but do not directly prove its presence. Additionally, our results revealed that the severity of AWS is not influenced by the presence of ARS. PLAIN LANGUAGE SUMMARY: Provoked, occasional seizures during AWS are defined as ARS. In the present study, predictors and interactions of these seizures with DT-the most severe form of withdrawal-and with the severity of withdrawal were examined in retrospective and follow-up studies. The present study shows that a history of withdrawal seizures, the occurrence of DT, and somatic comorbidities are predictors of the development of seizures. Furthermore, our findings suggest that the presence of seizures does not influence the severity of withdrawal.

Dexmedetomidine Withdrawal Syndrome in Children in the PICU: Systematic Review and Meta-Analysis.

OBJECTIVES: To systematically review literature describing the clinical presentation, risk factors, and treatment for dexmedetomidine withdrawal in the PICU (PROSPERO: CRD42022307178). DATA SOURCES: MEDLINE/PubMed, Cochrane, Web of Science, and Scopus databases were searched. STUDY SELECTION: Eligible studies were published from January 2000 to January 2022 and reported clinical data for patients younger than 21 years old following discontinuation of dexmedetomidine after greater than or equal to 24 hours of infusion. DATA EXTRACTION: Abstracts identified during an initial search were screened and data were manually abstracted after full-text review of eligible articles. The Newcastle-Ottawa Scale was used to assess study quality. Summary statistics were provided and Spearman rank correlation coefficient was used to identify relationships between covariates and withdrawal signs. A weighted prevalence for each withdrawal sign was generated using a random-effects model. DATA SYNTHESIS: Twenty-three studies (22 of which were retrospective cohort studies) containing 28 distinct cohorts were included. Median cumulative dexmedetomidine exposure by dose was 105.95 µg/kg (range, 30-232.7 µg/kg), median dexmedetomidine infusion duration was 131.75 hours (range, 20.5-525.6 hr). Weighted estimates for proportion (95% CI) of subjects experiencing withdrawal signs across all cohorts were: hypertension 0.34 (range, 0.0-0.92), tachycardia 0.26 (range, 0.0-0.87), and agitation 0.26 (range, 0.09-0.77). Meta-analysis revealed no correlation between dexmedetomidine exposure variables and withdrawal signs. A moderate negative monotonic relationship existed between the proportion of patients who had undergone cardiac surgery and the proportion experiencing hypertension (correlation coefficient, -0.47; p = 0.048) and tachycardia (correlation coefficient, -0.57; p = 0.008), indicating that in cohorts with a higher proportion of patients who were postcardiac surgery, there were fewer occurrences of hypertension and or tachycardia. CONCLUSIONS: On review of the 2000-2022 literature, dexmedetomidine withdrawal may be characterized by tachycardia, hypertension, or agitation, particularly with higher cumulative doses or prolonged durations. Since most studies included in the review were retrospective, prospective studies are needed to further clarify risk factors, establish diagnostic criteria, and identify optimal management strategies.

Examining Adult Patients' Success with Discontinuing Long-term Benzodiazepine Use: a Qualitative Study.

BACKGROUND: Little is known about patients' experiences with benzodiazepine (BZD) discontinuation, which is thought to be challenging given the physiological and psychological dependence and accompanying potential for significant withdrawal symptoms. The marked decline in BZD prescribing over the past decade in the US Department of Veterans Affairs healthcare system presents an important opportunity to examine the experience of BZD discontinuation among long-term users. OBJECTIVE: Examine the experience of BZD discontinuation among individuals prescribed long-term BZD treatment to identify factors that contributed to successful discontinuation. DESIGN: Descriptive qualitative analysis of semi-structured interviews conducted between April and December of 2020. PARTICIPANTS: A total of 21 Veterans who had been prescribed long-term BZD pharmacotherapy (i.e., > 120 days of exposure in a 12-month period) and had their BZD discontinued. APPROACH: We conducted semi-structured interviews with Veteran participants to learn about their BZD use and the process of discontinuation, with interviews recorded and transcribed verbatim. Data were deductively and inductively coded and coded text entered into a matrix to identify factors that contributed to successful BZD discontinuation. KEY RESULTS: The mean age of interview participants was 63.0 years (standard deviation 3.9); 94.2% were male and 76.2% were white. Of 21 participants, only 1 had resumed BZD treatment (prescribed by a non-VA clinician). Three main factors influenced success with discontinuation: (1) participants' attitudes toward BZDs (e.g., risks of long-term use, perceived lack of efficacy, potential for dependence); (2) limited withdrawal symptoms; and (3) effective alternatives, either from their clinician (e.g., medication, psychotherapy) or identified by participants. CONCLUSIONS: BZD discontinuation after long-term use is relatively well tolerated, and participants appreciated reducing their medication exposure, particularly to one associated with physical dependence. These findings may help reduce both patient and clinician anxiety related to BZD discontinuation.

Establishing the safety of phenobarbital treatment of alcohol withdrawal syndrome on general medical wards: A retrospective cohort study.

INTRODUCTION: Concern about adverse effects from phenobarbital limits its use in treating alcohol withdrawal syndrome (AWS) on general medical wards. Benzodiazepines are the recommended treatment for inpatient management of AWS, yet a subset of patients have an inadequate response or experience complications of AWS despite treatment with benzodiazepines. Data supporting an alternative treatment are needed. We set out to estimate the rate of serious adverse events (SAEs) of phenobarbital treatment for AWS on general medical wards. METHODS: Retrospective cohort study of all general medical ward patients hospitalized at a single tertiary urban VA Medical Center from October 2018-May 2021 who received phenobarbital for treatment of AWS. Primary outcomes were SAEs attributed to phenobarbital and treatment failure. SAEs were defined as ICU transfer or intubation for over-sedation, pneumonia, and death. Treatment failure was defined as progression of withdrawal resulting in seizure, ICU transfer, behavioral emergencies, or death. RESULTS: During the study period, phenobarbital was administered in 29% (244) of all AWS hospitalizations. Among them, 93% had a history of AWS hospitalization and 68% had a history of complicated AWS. Fifty-three percent of patients met criteria for moderate, severe, or complicated withdrawal prior to phenobarbital initiation. The mean cumulative dose of phenobarbital per patient was 966.5 mg (13.6 mg/kg). SAEs occurred in 1 of 244 hospitalizations (0.4%): there were no intubations, ICU transfers for oversedation, or deaths due to phenobarbital or AWS. One case of pneumonia was possibly attributable to phenobarbital. Treatment failures (6 ICU transfers, 9 behavioral emergencies) were identified during 12 of 244 hospitalizations (4.9%). CONCLUSIONS: SAEs and treatment failures were infrequent among 148 patients treated with phenobarbital across 244 hospitalizations with a mean cumulative dose of 966.5 mg per patient. Our findings suggest that phenobarbital is a safe alternative treatment of AWS in general medical ward patients.

Prevalence, Characteristics, and Reasons for Kratom Use among Psychiatrically Ill Inpatients Who Use Substances.

OBJECTIVE: Despite kratom impacting neurobiological systems involved in psychiatric disorders, little is known about the prevalence of use among patients with severe psychopathologies. Here, we investigated the prevalence of kratom use, motives for use, and the clinical associations among inpatients with severe psychiatric disorders. METHODS: A total of 578 patients, aged 18 to 65, were evaluated by New Hampshire Hospital's Addiction Services from January 1, 2020, to February 28, 2022. The study collected demographic information and used chi-square tests, multivariable logistic regression, and subgroup analyses with 95% confidence intervals to examine trends among kratom users. A receiver operating characteristic curve analysis was also conducted. All statistical tests were performed using IBM SPSS Version 28.0.1. RESULTS: Of the patients assessed, 2.2% (n = 13) reported using kratom. The reasons for kratom use were managing withdrawal symptoms (15.4%), maintaining sobriety and reducing cravings for opioids (53.8%), improving focus and concentration (30.8%), alleviating low moods (38.5%), and managing pain (15.4%). Compared to non-kratom users, the only factor with a fair to good association with kratom use is postsecondary education (Area Under Curve, AUC = 0.77). CONCLUSIONS: Prevalence of kratom use among patients with serious mental illness at our site aligns with that reported in the general population. Users often cite self-management of cravings and sobriety from opioids, as well as treatment of low mood states, as motivations for consumption. While observations suggest a possible association between kratom use and individuals with post-secondary education, multiple substance use, and experience of substance-induced psychosis or mood disorders, it is essential to interpret these links cautiously until further rigorous studies are carried out to substantiate these findings.

Evaluation of phenobarbital dosing strategies for hospitalized patients with alcohol withdrawal syndrome.

OBJECTIVE: Alcohol remains the fourth­leading preventable cause of death in the U.S. The objective of this study was to compare the incidence of phenobarbital (PHB)-resistant withdrawal and determine risk factors for PHB-resistant alcohol withdrawal syndrome (AWS). METHODS: This retrospective cohort study included adults admitted to an academic center with AWS who received PHB as part of an institution-specific treatment protocol. The primary outcome was incidence of AWS resistant to initial protocolized PHB load across two cohorts (standard-dose, 10 mg/kg vs. low-dose, 6 mg/kg). RESULTS: Among 176 included patients, there was no difference in the incidence of PHB-resistant AWS based on initial PHB load [low-dose load, 21 (18.3%) vs. standard-dose load, 12 (19.7%), p = 0.82]. There were also no differences in observed PHB-related ADEs between the groups. Total benzodiazepine dose received (mg) in the 24 h prior to initial PHB load was the only risk factor significantly associated with AWS resistant to initial protocolized PHB load [adjusted OR 1.79 (95% CI 1.24, 2.60)]. PHB-resistant withdrawal occurred in 33 (18.8%) patients with a median cumulative PHB dose of approximately 20 mg/kg during hospitalization. CONCLUSION(S): There were no differences in the incidence of PHB-resistant AWS or PHB-related ADEs based on initial PHB loading dose.

Prevalence and correlates of DSM-5 opioid withdrawal syndrome in U.S. adults with non-medical use of prescription opioids: results from a national sample.

Background: In the U.S. non-medical use of prescription opioids (NMOU) is prevalent and often accompanied by opioid withdrawal syndrome (OWS). OWS has not been studied using nationally representative data.Objectives: We examined the prevalence and clinical correlates of OWS among U.S. adults with NMOU.Methods: We used data from 36,309 U.S. adult participants in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III, 1,527 of whom reported past 12-month NMOU. Adjusted linear and logistic regression models examined associations between OWS and its clinical correlates, including psychiatric disorders, opioid use disorder (OUD; excluding the withdrawal criterion), medical conditions, and healthcare utilization among people with regular (i.e. ≥3 days/week) NMOU (n = 534).Results: Over half (50.4%) of the sample was male. Approximately 9% of people with NMOU met criteria for DSM-5 OWS, with greater prevalence of OWS (∼20%) among people with regular NMOU. Individuals with bipolar disorder, dysthymia, panic disorder, and borderline personality disorder had greater odds of OWS (aOR range = 2.71-4.63). People with OWS had lower mental health-related quality of life (ß=-8.32, p < .001). Individuals with OUD also had greater odds of OWS (aOR range = 26.02-27.77), an association that increased with more severe OUD. People using substance use-related healthcare services also had greater odds of OWS (aOR range = 6.93-7.69).Conclusion: OWS was prevalent among people with OUD and some psychiatric disorders. These findings support screening for OWS in people with NMOU and suggest that providing medication- assisted treatments and behavioral interventions could help to reduce the burden of withdrawal in this patient population.

Factors associated with discharge against medical advice in alcohol withdrawal patients.

This study aimed to examine characteristics associated with discharge against medical advice from the hospital in alcohol withdrawal patients, supporting the work of hospital staff and Alcohol Care Teams and identifying characteristics that may help target patients most likely to discharge against medical advice. We used Hospital Episode Statistics Data to identify demographic and clinical variables and compare these in alcohol withdrawal patients who discharged against medical advice from hospital, compared with those who were discharged by the clinical team. Factors significantly associated with alcohol withdrawal patients discharging against medical advice from hospital were: being admitted as an emergency; discharged on a weekend; living with no fixed abode; being male; being younger and having a shorter length of stay. This study identifies characteristics that can be used to support acute hospitals and Alcohol Care Teams, particularly in the allocation of resources to reduce discharges against medical advice and subsequent readmissions to the hospital. Particular consideration should be given to clinical provision in hospitals in emergency departments and on weekends, and also those patients who are admitted and are of no fixed abode.

Opioid, sedative, preadmission medication and iatrogenic withdrawal risk in UK adult critically ill patients: a point prevalence study.

BACKGROUND: Iatrogenic withdrawal syndrome, after exposure medication known to cause withdrawal is recognised, yet under described in adult intensive care. AIM: To investigate, opioid, sedation, and preadmission medication practice in critically ill adults with focus on aspects associated with iatrogenic withdrawal syndrome. METHOD: One-day point prevalence study in UK intensive care units (ICUs). We collected ICU admission medication and/or substances with withdrawal potential, sedation policy, opioid and sedative use, dose, and duration. RESULTS: Thirty-seven from 39 participating ICUs contributed data from 386 patients. The prevalence rate for parenteral opioid and sedative medication was 56.1% (212 patients). Twenty-three ICUs (59%) had no sedation/analgesia policy, and no ICUs screened for iatrogenic withdrawal. Patient admission medications with withdrawal-potential included antidepressants or antipsychotics (43, 20.3%) and nicotine (41, 19.3%). Of 212 patients, 202 (95.3%) received opioids, 163 (76.9%) sedatives and 153 (72.2%) both. Two hundred and two (95.3%) patients received opioids: 167 (82.7%) by continuous infusions and 90 (44.6%) patients for longer than 96-h. One hundred and sixty-three (76.9%) patients received sedatives: 157 (77.7%) by continuous infusions and 74 (45.4%) patients for longer than 96-h. CONCLUSION: Opioid sedative and admission medication with iatrogenic withdrawal syndrome potential prevalence rates were high, and a high proportion of ICUs had no sedative/analgesic policies. Nearly half of patients received continuous opioids and sedatives for longer than 96-h placing them at high risk of iatrogenic withdrawal. No participating unit reported using a validated tool for iatrogenic withdrawal assessment.

Phenobarbital versus benzodiazepines in alcohol withdrawal syndrome.

AIM: Phenobarbital, a long-acting barbiturate, presents an alternative to conventional benzodiazepine treatment for alcohol withdrawal syndrome (AWS). Currently, existing research offers only modest guidance on the safety and effectiveness of phenobarbital in managing AWS in hospital settings. The study objective was to assess if a phenobarbital protocol for the treatment of AWS reduces respiratory complications when compared to a more traditionally used benzodiazepine protocol. METHODS: A retrospective cohort study analyzing adults who received either phenobarbital or benzodiazepine-based treatment for AWS over a 4-year period, 2015-2019, in a community teaching hospital in a large academic medical system. RESULTS: A total of 147 patient encounters were included (76 phenobarbital and 71 benzodiazepine). Phenobarbital was associated with a significantly decreased risk of respiratory complications, defined by the occurrence of intubation (15/76 phenobarbital [20%] vs. 36/71 benzodiazepine [51%]) and decreased incidence of the requirement of six or greater liters of oxygen when compared with benzodiazepines (10/76 [13%] vs. 28/71 [39%]). There was a significantly higher incidence of pneumonia in benzodiazepine patients (15/76 [20%] vs. 33/71 [47%]). Mode Richmond Agitation Sedation Scale (RASS) scores were more frequently at goal (0 to -1) between 9 and 48 h after the loading dose of study medication for phenobarbital patients. Median hospital and ICU length of stay were significantly shorter for phenobarbital patients when compared with benzodiazepine patients (5 vs. 10 days and 2 vs. 4 days, respectively). CONCLUSION: Parenteral phenobarbital loading doses with an oral phenobarbital tapered protocol for AWS resulted in decreased risk of respiratory complications when compared to standard treatment with benzodiazepines.

International Analgesia and Sedation Weaning and Withdrawal Practices in Critically Ill Adults: The Adult Iatrogenic Withdrawal Study in the ICU.

OBJECTIVES: Iatrogenic withdrawal syndrome (IWS) associated with opioid and sedative use for medical purposes has a reported high prevalence and associated morbidity. This study aimed to determine the prevalence, utilization, and characteristics of opioid and sedative weaning and IWS policies/protocols in the adult ICU population. DESIGN: International, multicenter, observational, point prevalence study. SETTING: Adult ICUs. PATIENTS: All patients aged 18 years and older in the ICU on the date of data collection who received parenteral opioids or sedatives in the previous 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICUs selected 1 day for data collection between June 1 and September 30, 2021. Patient demographic data, opioid and sedative medication use, and weaning and IWS assessment data were collected for the previous 24 hours. The primary outcome was the proportion of patients weaned from opioids and sedatives using an institutional policy/protocol on the data collection day. There were 2,402 patients in 229 ICUs from 11 countries screened for opioid and sedative use; 1,506 (63%) patients received parenteral opioids, and/or sedatives in the previous 24 hours. There were 90 (39%) ICUs with a weaning policy/protocol which was used in 176 (12%) patients, and 23 (10%) ICUs with an IWS policy/protocol which was used in 9 (0.6%) patients. The weaning policy/protocol for 47 (52%) ICUs did not define when to initiate weaning, and the policy/protocol for 24 (27%) ICUs did not specify the degree of weaning. A weaning policy/protocol was used in 34% (176/521) and IWS policy/protocol in 9% (9/97) of patients admitted to an ICU with such a policy/protocol. Among 485 patients eligible for weaning policy/protocol utilization based on duration of opioid/sedative use initiation criterion within individual ICU policies/protocols 176 (36%) had it used, and among 54 patients on opioids and/or sedatives ≥ 72 hours, 9 (17%) had an IWS policy/protocol used by the data collection day. CONCLUSIONS: This international observational study found that a small proportion of ICUs use policies/protocols for opioid and sedative weaning or IWS, and even when these policies/protocols are in place, they are implemented in a small percentage of patients.

The Health Impact of Long-Term Kratom (Mitragyna Speciosa) Use in Southern Thailand.

BACKGROUND: Mitragyna speciosa or Kratom has been used in Thailand traditionally for its medicinal value. Despite case reports of kratom consumption causing adverse effects, research on its long-term health impact is limited. This study examines the long-term health impact of kratom use among people in Southern Thailand. METHODS: Three community-based surveys were conducted from 2011 to 2015. In the first and second surveys (2011 and 2012) a total of 1,118 male respondents comprising 355 regular kratom users, 171 occasional kratom users, 66 ex-users, and 592 non-users aged 25 or above, were recruited from 40 villages. All respondents were followed up in this study. However, not all respondents were successfully followed up throughout the entire set of studies. RESULTS: Common health complaints were no more common among kratom users than ex- and non-users, but more regular than occasional users claimed kratom to be addictive. Those with high kratom dependence scores were more likely to experience intense withdrawal symptoms, which developed 1-12 h after the last kratom intake. Over half (57.9%) of regular users had experienced intoxication effects compared to only 29.3% of occasional users. Kratom users were less likely to have a history of chronic diseases such as diabetes, hypertension, dyslipidemia than ex- and non-users. CONCLUSION: Regular long-term chewing of fresh kratom leaves was not related to an increase in common health complaints, but may pose a drug dependence risk. Severe kratom dependents were more likely to suffer from intense withdrawal symptoms. Medical records revealed no death due to traditional kratom use, but the high prevalence of tobacco or/and hand rolled cigarette smoking among kratom users should be of concern.

Establishing Core Symptoms of Acute Serotonin Reuptake Inhibitor Withdrawal: Results from an International Survey of Online Peer-Support Communities.

BACKGROUND: Serotonin reuptake inhibitor (SRI) antidepressants are commonly associated with withdrawal reactions. The Discontinuation Emergent Signs and Symptoms (DESS) checklist has been considered the gold standard research and screening tool for SRI withdrawal but has several limitations, including its length, lack of specificity, and omission of baseline symptom and symptom severity scores, making it impractical for use in clinical or research settings. We investigated the prevalence and severity of common SRI withdrawal symptoms to determine whether a very small subset of symptoms can capture most occurrences of SRI withdrawal. METHODS: We surveyed 344 members of online peer-support communities aged 18-65, reporting withdrawal symptoms after chronic SRI treatment. The severity of nine common withdrawal symptoms was evaluated at baseline and during the withdrawal period. RESULTS: Dizziness, brain zaps, irritability/agitation, and anxiety/nervousness demonstrated the largest increase in severity during withdrawal relative to baseline. Nearly all (97.7%) of the 344 subjects and all (100%) 153 subjects with relatively low baseline symptom scores (total<5) reported a worsening of one of these four symptoms. The presence of a baseline anxiety disorder did not affect rates of withdrawal-emergent anxiety/nervousness. CONCLUSION: Nearly all surveyed subjects reported worsening either of dizziness, brain zaps, irritability/agitation, or anxiety/nervousness in acute withdrawal. A screening test incorporating these four core symptoms may be sufficiently sensitive to rule out SRI withdrawal and may be valuable in clinical and research settings. Incorporating withdrawal symptom severity may further enhance specificity.