Precipitated opioid withdrawal in a patient started on olanzapine/samidorphan.

BACKGROUND: Olanzapine/Samidorphan (Lybalvi®) is a novel oral agent for the treatment of schizophrenia and bipolar I disorder. It was designed to reduce weight gain associated with olanzapine. Samidorphan is an analog of naltrexone, initially intended to treat substance use disorders by antagonizing mu, delta, and kappa opioid receptors. CASE REPORT: We present the case of a 36-year-old who took their first dose of olanzapine/samidorphan shortly before calling for emergency services. The patient took diphenhydramine and an epinephrine autoinjector for what they thought was an allergic reaction but continued to have symptoms. EMS reported involuntary muscle movements thought to be due to dystonia from olanzapine. In the ED, they experienced generalized muscle spasms lasting for several seconds and diaphoresis. Initially, the staff treated for a presumed dystonic reaction to olanzapine and administered diphenhydramine 25 mg IV, diazepam 2 mg IV, midazolam 5 mg IV, and benztropine 1 mg IV without improvement. It was later determined that the patient took 16 mg of buprenorphine SL daily. With this information, precipitated opioid withdrawal was felt to be the likely cause of symptoms. The patient received 16 mg of buprenorphine for an initial Clinical Opiate Withdrawal Scale (COWS) score of 11 with repeat COWS of 6. Why should an emergency physician be aware of this? Initiating olanzapine/samidorphan in the setting of chronic opioid therapy may result in precipitated opioid withdrawal. Additional SL buprenorphine may be a reasonable treatment modality.

Suicide attempt in a dopamine agonist withdrawal syndrome in Parkinson's disease.

Dopamine agonist withdrawal syndrome (DAWS) results from the reduction or suspension of dopamine agonist medications; it encompasses mainly psychiatric symptoms, including suicidal behaviors. In patients with Parkinson's disease (PD), the impact of DAWS can be significant in terms of distress and disability; however, we must take this syndrome into account as a threatening condition because suicidal behaviors could be developing in the context of DAWS. Here we present a brief case of DAWS affecting a young man with PD, whom abruptly discontinued DA treatment and developed psychiatric symptoms within two weeks which led to a suicidal attempt.

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.

Behavioral characterization of early nicotine withdrawal in the mouse: a potential model of acute dependence.

BACKGROUND: Clinical and preclinical research have demonstrated that short-term exposure to nicotine during the initial experimentation stage can lead to early manifestation of withdrawal-like signs, indicating the state of "acute dependence". As drug withdrawal is a major factor driving the progression toward regular drug intake, characterizing and understanding the features of early nicotine withdrawal may be important for the prevention and treatment of drug addiction. In this study, we corroborate the previous studies by showing that withdrawal-like signs can be precipitated after short-term nicotine exposure in mice, providing a potential animal model of acute dependence on nicotine. RESULTS: To model nicotine exposure from light tobacco use during the initial experimentation stage, mice were treated with 0.5 mg/kg (-)-nicotine ditartrate once daily for 3 days. On the following day, the behavioral tests were conducted after implementing spontaneous or mecamylamine-precipitated withdrawal. In the open field test, precipitated nicotine withdrawal reduced locomotor activity and time spent in the center zone. In the elevated plus maze test, the mecamylamine challenge increased the time spent in the closed arm and reduced the number of entries irrespective of nicotine experience. In the examination of the somatic aspect, precipitated nicotine withdrawal enhanced the number of somatic signs. Finally, nicotine withdrawal did not affect cognitive functioning or social behavior in the passive avoidance, spatial object recognition, or social interaction test. CONCLUSIONS: Collectively, our data demonstrate that early nicotine withdrawal-like signs could be precipitated by the nicotinic antagonist mecamylamine in mice, and that early withdrawal from nicotine primarily causes physical symptoms.

Early antiseizure medication withdrawal and risk of seizure recurrence in children after epilepsy surgery: A retrospective study.

OBJECTIVE: The timing of antiseizure medication (ASM) withdrawal in children after epilepsy surgery remains controversial and lacks recognized standards. Given the various negative effects of ASM on development in children, this study aimed to evaluate the safety and feasibility of early ASM withdrawal after epileptic resection surgery. METHODS: We retrospectively assessed the seizure outcomes and ASM profiles of children who had undergone epileptic resection surgery between August 2015 and August 2020 and attempted ASM reduction in the early postoperative phase. Tapering the dose of ASM was attempted when children were seizure-free with no interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) for at least 6 months postoperatively. RESULTS: This study included 145 children with a median follow-up duration of 40 months. Early ASM tapering was attempted postoperatively in 99 (68.3 %) children. Postoperative ASM discontinuation was attempted in 87 (60.0 %) children. Nine (9.1 %) children experienced seizure recurrence during the ASM reduction stage, and 10 (11.5 %) experienced recurrence after ASM discontinuation. Incomplete resection (P = 0.003) and postoperative seizures before ASM tapering (P = 0.003) were independent predictors of seizure recurrence during and after early ASM withdrawal. SIGNIFICANCE: ASM withdrawal is viable and safe to be initiated in children who are seizure-free postoperatively and have no IEDs on the scalp EEG for at least 6 months. Children with incomplete resection and postoperative seizures before ASM withdrawal are at a higher risk of seizure recurrence and may need to continue ASM for a longer period.

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.

Effects of Bundling Medication for Opioid Use Disorder With an mHealth Intervention Targeting Addiction: A Randomized Clinical Trial.

OBJECTIVE: Medication for opioid use disorder (MOUD) improves treatment retention and reduces illicit opioid use. A-CHESS is an evidence-based smartphone intervention shown to improve addiction-related behaviors. The authors tested the efficacy of MOUD alone versus MOUD plus A-CHESS to determine whether the combination further improved outcomes. METHODS: In an unblinded parallel-group randomized controlled trial, 414 participants recruited from outpatient programs were assigned in a 1:1 ratio to receive either MOUD alone or MOUD+A-CHESS for 16 months and were followed for an additional 8 months. All participants were on methadone, buprenorphine, or injectable naltrexone. The primary outcome was abstinence from illicit opioid use; secondary outcomes were treatment retention, health services use, other substance use, and quality of life; moderators were MOUD type, gender, withdrawal symptom severity, pain severity, and loneliness. Data sources were surveys comprising multiple validated scales, as well as urine screens, every 4 months. RESULTS: There was no difference in abstinence between participants in the MOUD+A-CHESS and MOUD-alone arms across time (odds ratio=1.10, 95% CI=0.90-1.33). However, abstinence was moderated by withdrawal symptom severity (odds ratio=0.95, 95% CI=0.91-1.00) and MOUD type (odds ratio=0.57, 95% CI=0.34-0.97). Among participants without withdrawal symptoms, abstinence rates were higher over time for those in the MOUD+A-CHESS arm than for those in the MOUD-alone arm (odds ratio=1.30, 95% CI=1.01-1.67). Among participants taking methadone, those in the MOUD+A-CHESS arm were more likely to be abstinent over time (b=0.28, SE=0.09) than those in the MOUD-alone arm (b=0.06, SE=0.08), although the two groups did not differ significantly from each other (∆b=0.22, SE=0.11). MOUD+A-CHESS was also associated with greater meeting attendance (odds ratio=1.25, 95% CI=1.05-1.49) and decreased emergency department and urgent care use (odds ratio=0.88, 95% CI=0.78-0.99). CONCLUSIONS: Overall, MOUD+A-CHESS did not improve abstinence relative to MOUD alone. However, MOUD+A-CHESS may provide benefits for subsets of patients and may impact treatment utilization.

Management of Cholinergic Rebound After Abrupt Withdrawal of Clozapine: A Case Report and Systematic Literature Review.

BACKGROUND: Cholinergic discontinuation symptoms, also known as "cholinergic rebound," from abrupt clozapine discontinuation are characterized by a range of somatic and psychiatric symptoms. OBJECTIVE: The objective of this study was to describe the clinical features and management options for clozapine withdrawal-associated cholinergic rebound syndrome (henceforth referred to as CWCRS) and present an illustrative case report. METHODS: Based on a literature search of the databases PubMed, OVID Medline, and Embase as well as reviewing reference lists of relevant past reviews, we carried out a systematic review of case reports on the management of CWCRS from 1946 to 2023. RESULTS: We identified 10 previously published articles on the clinical management of CWCRS, with a total of 18 patients (6 female, 12 male) with an average age of 43 years (standard deviation 14). Half of the patients had a history of tardive dyskinesia. The mean dose of clozapine before discontinuation was 351 mg/day, with duration of clozapine treatment ranging from 3 weeks to 9 years. Clozapine was the most effective treatment, followed by benztropine. CONCLUSIONS: Given the small number of cases and the nonexperimental nature of the available studies, this review could not provide reliable data to guide management of CWCRS. The findings, however, suggest that clozapine may be more effective than other commonly used treatment options. With the high rates of discontinuation among patients on clozapine, there is a pressing need for further research into the epidemiology, natural history, and management of clozapine withdrawal syndromes.

A systematic review of phenibut withdrawal focusing on complications, therapeutic approaches, and single substance versus polysubstance withdrawal.

INTRODUCTION: Phenibut is an unregulated supplement that acts primarily as a gamma-aminobutyric acid type B receptor agonist. Use of phenibut can lead to dependence and subsequent withdrawal when use is stopped. Phenibut withdrawal can cause severe symptoms such as delirium, hallucinations, and seizures. The purpose of this systematic review is to characterize the natural history of phenibut withdrawal and summarize treatment strategies published in the literature. METHODS: A systematic review was conducted using the preferred reporting items for systematic reviews and meta-analyses checklist. English language peer-reviewed articles or conference abstracts in humans describing phenibut withdrawal after cessation of use were included. Databases (Ovid/MEDLINE, Web of Science, and Science Direct) and references of included articles were searched. Case reports were appraised using the Joanna Briggs Institute critical appraisal checklist for case reports. Patient demographics and key outcomes, including withdrawal characteristics and treatment characteristics, were collected into a predefined data collection sheet by six independent reviewers. RESULTS: Search results yielded 515 articles of which 25 were included. All articles were case reports or published conference abstracts. All of the cases (100 percent) involved male patients and the median age was 30 years, (interquartile range 23.5-34 years, range 4 days-68 years). The median daily phenibut dose prior to experiencing withdrawal was 10 g (interquartile range 4.75-21.5 g, range 1-200 g). The shortest duration of phenibut use (2-3 g daily) prior to withdrawal was one week. Withdrawal symptoms occurred as quickly as two hours after the last phenibut dose. Sixteen patients (64 percent) reported progression of withdrawal severity within the first 24 hours of healthcare contact. Seizures were reported in two patients (8 percent), intubation in six patients (24 percent), and intensive care unit admission in 11 patients (44 percent). Withdrawal patterns and outcomes were similar in those using phenibut alone and those with comorbid polysubstance use. Withdrawal treatment strategies varied widely. Only three cases (12 percent) were managed outpatient and all three utilized a phenibut tapering strategy. All patients undergoing medication-assisted abstinence were admitted inpatient for symptom management and received a drug that acts on gamma-aminobutyric acid receptors. The most commonly used medication was a benzodiazepine, reported in 17 cases (68 percent). Nineteen patients (76 percent) required at least two drug therapies to manage symptoms. Baclofen was used in 15 cases (60 percent), primarily in conjunction with gamma-aminobutyric acid type A agonists (12 of 15 cases) or as monotherapy during a phenibut taper (two of 15 cases). Two patients using baclofen monotherapy outpatient, after initial stabilization with multiple drug classes, reported adverse effects. One patient had a seizure and the other experienced recurrent withdrawal symptoms, returned to using phenibut, and was admitted to a hospital for withdrawal symptom management with benzodiazepines. LIMITATIONS: This review is subject to several limitations. Due to the manual nature of article selection, it is possible relevant articles may not have been included. As the entire data set is comprised of case reports it may suffer from publications bias. Outcomes and meaningful conclusions from specific treatment strategies were rarely available because of the heterogeneous nature of case reports. It is possible those reporting only phenibut use were actually using multiple substances. The doses of phenibut a user believed they were taking may be different from what was present in the unregulated product. CONCLUSIONS: Phenibut withdrawal appears to have a range of severity. It is important to recognize that patients undergoing phenibut abstinence may have progressive symptom worsening during early withdrawal. All published cases of abrupt phenibut abstinence were admitted inpatients for symptom management. Benzodiazepines or barbiturates with adjunctive baclofen appear to be the most commonly used drugs for moderate to severe withdrawal. Outpatient management via slow phenibut tapers with or without adjunctive gamma-aminobutyric acid agonist therapy may be successful. However, there is no standard treatment, and consultation with experts (e.g., toxicologists, addiction specialists) experienced in managing withdrawal syndromes is recommended. Significant study is warranted to develop methods of triaging phenibut withdrawal (e.g., severity scoring, inpatient versus outpatient management) and creating optimal treatment regimens.

Severe Alprazolam Withdrawal With Delirium and Psychosis: A Case Report and Literature Review.

ABSTRACT: In our report, and review of the literature, we present an important clinical lesson for the recognition and treatment of alprazolam withdrawal with complicated delirium and psychosis, and present a strong case for future treatment algorithms. Our case is unique due to the severity of behavioral disturbance associated with acute psychosis secondary to alprazolam withdrawal and the significant quantity of alprazolam consumed. The use of high cumulative doses of longer-acting benzodiazepines resulted in rapid improvement in symptoms with full resolution of psychosis. Within 4 days of treatment in hospital, delirium and psychosis had fully resolved. Detoxification continued in the community and the patient was followed up in clinic for monitoring of mental state. There was no recurrence of psychotic symptoms.

A Case of Acute Opioid Withdrawal after Liposuction Surgery in a Patient on Extended-release Buprenorphine.

BACKGROUND: The US Food and Drug Administration approved the once-monthly injectable extended-release buprenorphine product to treat moderate-to-severe opioid use disorders. The patient in our case report had a liposuction procedure and immediately started having opioid withdrawal symptoms after the procedure. CASE DESCRIPTION: The patient is a 27-year-old African-American woman who injects drugs and has morbid obesity. She enrolled in a medications for addiction treatment program and opted to get treated with extended-release buprenorphine monthly injections. She tolerated them well for a span of 6 months. In one clinic visit, she reported opioid withdrawal symptoms and started purchasing and using sublingual buprenorphine from her acquaintances. On review of history, she underwent liposuction surgery and this triggered the opioid withdrawal symptoms. Examining her abdomen revealed surgical scars at the site of the buprenorphine injection and the residual buprenorphine depot was not palpable.A subcutaneous injection of 300-mg extended release buprenorphine was administered in the right periumbilical area in this clinic visit. The following week, she was doing well and denied any withdrawal symptoms. DISCUSSION: This is a unique case of "iatrogenic opioid withdrawal" after a fairly common surgical procedure. The extended-release buprenorphine formulation solidifies when it comes into contact with bodily fluids forming a depot. The depot and surrounding adipose tissue may have been removed during the patient's liposuction procedure, causing an immediate drop in buprenorphine levels leading to acute opioid withdrawal.This case report highlights the precautions that need to be taken before patients go for a surgical procedure like liposuction.

Atypical Withdrawal Symptoms after Abrupt Tramadol Discontinuation: A Case Report.

Tramadol is a commonly utilized analgesic in the United States. One common misconception is that tramadol is safer than other opioid medications, or less likely to cause physical dependence. Given these misconceptions, the likelihood of patients experiencing withdrawal after discontinuation may be commonly overlooked as well. A 68-year old female patient with fibromyalgia was referred to a clinical pharmacy pain clinic for medication management. The patient was evaluated one month after abrupt discontinuation of tramadol 50 mg every 6 h for at least 10 years of use. She reports concerning symptoms of significant mucus production, fullness in chest and soreness in neck. Although tramadol is a Schedule IV Controlled Substance the risk of physical dependence and likelihood of patients experiencing withdrawal symptoms after abrupt cessation should not be diminished. Tramadol should not be considered a "safer" opioid therapy without potential of classic or atypical withdrawal symptoms, as well as risk of abuse, misuse or addiction.

The gut microbiome contributes to somatic morphine withdrawal behavior and implicates a TLR2 mediated mechanism.

The ongoing opioid epidemic has left millions of people suffering from opioid use disorder due to the over-prescription of highly addictive substances. Chronic opioid exposure leads to dependence, where the absence of the drug results in negative symptoms of withdrawal, often driving patients to continue drug use; however, few therapeutic strategies are currently available to combat the cycle of addiction and the severity of morphine withdrawal. This study investigates the microbiome as a potential therapeutic target for morphine withdrawal, as gut dysbiosis caused by morphine use has been proven to contribute to other aspects of opioid use disorders, such as tolerance. Results show that although the microbiome during morphine withdrawal trends toward recovery from morphine-induced dysbiosis, there continues to be a disruption in the alpha and beta diversity as well as the abundance of gram-positive bacteria that may still contribute to the severity of morphine withdrawal symptoms. Germ-free mice lacking the microbiome did not develop somatic withdrawal symptoms, indicating that the microbiome is necessary for the development of somatic withdrawal behavior. Notably, only TLR2 but not TLR4 whole-body knockout models display less withdrawal severity, implicating that the microbiome, through a gram-positive, TLR2 mediated mechanism, drives opioid-induced somatic withdrawal behavior.

Non-Psychosis Symptoms of Clozapine Withdrawal: a Systematic Review.

OBJECTIVE: Clozapine is a potent antipsychotic medication with a complex receptor profile. It is reserved for treatment-resistant schizophrenia. We systematically reviewed studies of non-psychosis symptoms of clozapine withdrawal. METHODS: CINAHL, Medline, PsycINFO, PubMed, and the Cochrane Database of Systematic Reviews were searched using the keywords 'clozapine,' and 'withdrawal,' or 'supersensitivity,' 'cessation,' 'rebound,' or 'discontinuation'. Studies related to non-psychosis symptoms after clozapine withdrawal were included. RESULTS: Five original studies and 63 case reports / series were included in analysis. In 195 patients included in the five original studies, approximately 20% experienced non-psychosis symptoms following discontinuation of clozapine. In 89 patients in four of the studies, 27 experienced cholinergic rebound, 13 exhibited extrapyramidal symptoms (including tardive dyskinesia), and three had catatonia. In 63 case reports / series included, 72 patients with non-psychosis symptoms were reported, which were catatonia (n=30), dystonia or dyskinesia (n=17), cholinergic rebound (n=11), serotonin syndrome (n=4), mania (n=3), insomnia (n=3), neuroleptic malignant syndrome (NMS) [n=3, one of them had both catatonia and NMS], and de novo obsessive compulsive symptoms (n=2). Restarting clozapine appeared to be the most effective treatment. CONCLUSIONS: Non-psychosis symptoms following clozapine withdrawal have important clinical implications. Clinicians should be aware of the possible presentations of symptoms to ensure early recognition and management. Further research is warranted to better characterise the prevalence, risk factors, prognosis, and optimal drug dosing for each withdrawal symptom.

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.

Evaluation of phenobarbital for prevention of alcohol withdrawal in trauma patients.

BACKGROUND: Up to 30% of trauma patients experience alcohol withdrawal syndrome (AWS) during their hospital admission, which is associated with worse outcomes. While benzodiazepines and phenobarbital are the mainstay of AWS management, there are limited data on the prevention of AWS. The objective was to evaluate the safety and efficacy of phenobarbital for the prevention of AWS. METHODS: Adult patients admitted to a level 1 trauma center who received at least one dose of phenobarbital for the prevention of AWS between January 2019 and August 2021 were included. Patients were case matched to a control group managed with symptom-triggered therapy based on risk of AWS. Risk factors included sex, age, history of AWS/delirium tremens or withdrawal seizures, selected laboratory values, and screening questionnaires. The primary endpoint was the need for rescue therapy. Secondary endpoints included the time to rescue therapy, intensive care unit (ICU) length of stay (LOS), and hospital LOS. RESULTS: Overall, 110 patients were included with 55 patients in each group. The phenobarbital group had higher baseline Injury Severity Scores ( p = 0.03) and were more likely to be admitted to the ICU (44% vs. 24%; p = 0.03). The phenobarbital group required less rescue therapy (16% vs. 62%; p < 0.001) with a longer time to rescue therapy administration (26 vs. 11 hours; p = 0.01). The phenobarbital group had a longer hospital LOS (216 vs. 87 hours; p = 0.0001) but no difference in ICU LOS ( p = 0.36). There was no incidence of delirium tremens or seizures and no difference in intubation rates ( p = 0.68). There was no incidence of hypotension associated with phenobarbital. CONCLUSION: Patients managed with phenobarbital had a lower need for rescue therapy for AWS with no increased adverse effects. Further studies should evaluate a protocol to prevent alcohol withdrawal in the trauma population. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.