A Retrospective Evaluation of Adjunctive Phenobarbital vs. Benzodiazepine Alone for the Treatment of Moderate Alcohol Withdrawal in the Emergency Department.

BACKGROUND: Phenobarbital has been used in the emergency department (ED) as both a primary and adjunctive medication for alcohol withdrawal, but previous studies evaluating its impact on patient outcomes are limited by heterogenous symptom severity. OBJECTIVES: We compared the clinical outcomes of ED patients with moderate alcohol withdrawal who received phenobarbital, with or without benzodiazepines, with patients who received benzodiazepine treatment alone. METHODS: This is a retrospective cohort study conducted at a single academic medical center utilizing chart review of ED patients with moderate alcohol withdrawal between 2015 and 2020. Patient encounters were classified into two treatment categories based on medication treatment: phenobarbital alone or in combination with benzodiazepines vs. benzodiazepines alone. Chi-square test or Fisher's exact was used to analyze categorical variables and the Student's t-test for continuous data. RESULTS: Among the 287 encounters that met inclusion criteria, 100 received phenobarbital, compared with 187 that received benzodiazepines alone. Patients who received phenobarbital were provided significantly more lorazepam equivalents. There was a significant difference in the percentage of patient encounters that required admission to the hospital in the phenobarbital cohort compared with the benzodiazepine cohort (75% vs. 43.3%, p < 0.001). However, there was no difference in admission level of care to the floor (51.2% vs. 52.0%), stepdown (33.8% vs. 28%), or intensive care unit (15% vs. 20%), respectively. CONCLUSIONS: Patients who received phenobarbital for moderate alcohol withdrawal were more likely to be admitted to the hospital, but there was no difference in admission level of care when compared with patients who received benzodiazepines alone. Patients who received phenobarbital were provided greater lorazepam equivalents in the ED.

Risk of suicide attempts and intentional self-harm on alprazolam.

BACKGROUND: From 2000-2021, U.S. suicide deaths have risen 36 %. Identification of pharmacological agents associated with increased suicide risk and safer alternatives may help reduce this trend. METHODS: An exposure-only within-subject time-to-event pharmacoepidemiologic study of the dynamic association between alprazolam treatment and suicide attempts over 2-years. Parallel analyses were conducted for diazepam, lorazepam and buspirone. Data for 2,495,520 patients were obtained from U.S. private insurance medical claims MarketScan from 2010 to 2019. FINDINGS: Alprazolam was associated with over a doubling of risk of suicide attempts (HR=2.21, 95 % CI=2.06,2.38). A duration-response analysis for the modal dose (0.5 mg) revealed a 5 % increase in suicidal events per additional month of treatment (HR=1.05, 95 % CI=1.04,1.07). Parallel analyses with long-acting (diazepam) and short-acting (lorazepam), found similar associations (diazepam HR=2.87, 95 % CI=2.56,3.21; lorazepam HR=1.83, 95 % CI=1.69,2.00), whereas the non-benzodiazepine anxiolytic, buspirone, showed significantly less risk (HR=1.25, 95 % CI=1.13,1.38), and no increased risk in patients with an attempt history (HR=1.05, 95 % CI=0.70,1.59). INTERPRETATION: This study confirmed an earlier signal linking alprazolam to increased suicide attempt risk. The increased risk extends to benzodiazepines in general, regardless of half-life and risk of withdrawal seizure. Buspirone appears to be a safer treatment than benzodiazepines, particularly in patients at increased risk for suicide.

The role of benzodiazepines in common conditions: a narrative review focusing on lormetazepam.

This review aimed to examine the place of benzodiazepines, specifically lormetazepam, in the treatment of insomnia, including during pregnancy or in patients with psychodermatoses. PubMed was searched for the term "lormetazepam" in association with MeSH terms encompassing anxiety, insomnia/sleep disorders, pregnancy/gestation, and psychodermatoses/skin disorders. English-language articles up to 31 July 2022 were identified. Ad hoc searches for relevant literature were performed at later stages of review development. Multiple randomized, placebo-controlled studies have demonstrated that lormetazepam dose-dependently increases total sleep time, decreases wakefulness over a dosing range of 0.5-2.0 mg, and improves subjective assessments of sleep quality. Lormetazepam is as effective as other benzodiazepines in improving sleep duration and quality, but is better tolerated than the long-acting agents with minimal next-day effects. Benzodiazepines can be used as short-term monotherapy at the lowest effective dose during the second or third trimesters of pregnancy; lormetazepam is also a reasonable choice due to its limited transplacental passage. Insomnia associated with skin disorders or pregnancy can be managed by effective symptom control (especially itching), sleep hygiene, treatment of anxiety/depression, and a short course of hypnotics.

Negative emotionality downregulation affects moral choice but not moral judgement of harm: a pharmacological study.

Previous neuroscientific research has expounded on the fundamental role played by emotion during moral decision-making. Negative emotionality has been observed to exert a general inhibitory effect towards harmful behaviors against others. Nevertheless, the downregulation of negative affects at different levels of moral processing (e.g. impersonal versus personal moral dilemmas) alongside its possible interactions with other factors (e.g. perspective taking) hasn't been directly assessed; both of which can assist in predicting future moral decision-making. In the present research, we empirically test (Study 1, N = 41) whether downregulating negative emotionality through pharmacological interventions using lorazepam (a GABA receptor agonist), modulate the permissibility of harm to others -i.e. if participants find it more morally permissible to harm others when harm is unavoidable (inevitable harm moral dilemmas), than when it may be avoided (evitable harm moral dilemmas). Furthermore, using another sample (Study 2, N = 31), we assess whether lorazepam's effect is modulated by different perspective-taking conditions during a moral dilemma task -e.g. "is it morally permissible for you to […]?" (1st person perspective), relative to "is it morally permissible for [x individual] to […]?" (3rd person perspective)-, where the outcome of the different scenarios is controlled. The results of both studies converge, revealing an emotion-dependent, rather than an outcome-dependent, pharmacological modulation. Lorazepam only influenced interpersonal moral judgments when not modulated by the evitable/inevitable condition. Furthermore, there was a significant interaction between perspective-taking and drug administration, as lorazepam exerted a larger effect in modulating moral choices rather than moral judgements.

Trace analysis of 47 psychotropic medications in environmental samples by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).

Psychotropic medications are one of the most prescribed pharmaceuticals in the world. Given their frequent detection and ecotoxicity to the no-target organism, the emission of these medications into environments has gradually draw attention. The study developed a sensitive and reliable analytic method to simultaneously investigate 47 psychotropic medications in four matrices: wastewater, surface water, activated sludge, and sediment by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). These 47 target analytes include 24 antidepressants, 17 antianxiety drugs, 5 anticonvulsants, and 1 relevant hormone. Solid phase extraction (SPE) was employed to extract analytes from water-phase samples. Ultrasonic Solvent Extraction method with Enhanced Matrix Removal clean-up (USE-EMR) was utilized to extract target compounds from solid-phase samples, which requires more straightforward and convenient procedures than previous methods. The extraction recoveries of all analytes ranged from 80 % to 120 % in these four sample matrices. In this study, The limit of quantitation for 47 psychotropic medications were 0.15 ng/L (estazolam) to 2.27 ng/L (lorazepam), 0.08 ng/L (desvenlafaxine) to 2 ng/L (mianserin), 0.22 ng/g (dry weight, dw) (nordiazepam) to 3.65 ng/g (dw) (lorazepam), and 0.07 ng/g (dw) (carbamazepine) to 2.85 ng/g (lorazepam), in wastewater, surface water, sludge, and sediment, respectively. In addition, the developed method was employed to analyse actual samples in two wastewater treatment plants and their receiving rivers. Carbamazepine, escitalopram, clozapine, desvenlafaxine, diazepam, lamotrigine, sertraline, temazepam, and venlafaxine were nearly ubiquitous in all matrices. Moreover, this study indicated that the inadequate removal efficiencies of psychotropic medications in wastewater treatment plants (WWTPs) had resulted in a persistent discharge of these contaminants from human sources into environments.

Thought Blocking as a Manifestation of Catatonia: A Case Report.

ABSTRACT: Catatonia is an underrecognized disorder that has been widely described as a psychomotor syndrome, with little emphasis on its thought and cognitive dimensions. The current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision describes only motor and behavioral presentations, whereas a few catatonia scales describe only one form of thought disorders, which is thought perseveration. Thought blocking, a disorder of the thought process, is characterized by regular interruptions in the thought stream. It was described by several scholars as a sign of schizophrenia, with few reports describing thought blocking in association with catatonia. In this article, we describe the course of a patient with bipolar I disorder who presented with catatonia and demonstrated thought blocking. Her catatonic symptoms and thought blocking improved with the addition of lorazepam, recurred upon lorazepam discontinuation, and improved with resumption of lorazepam, demonstrating a clear on/off phenomenon. This report highlights the importance of recognizing thought and cognitive manifestations of catatonia, as it can enhance recognition and improve treatment.

Lorazepam in catatonia - Past, present and future of a clinical success story.

The effect of lorazepam in the treatment of catatonia is outstanding and almost immediate. Clinicians are familiar with its effects: mute patients can speak again, akinetic patients can move again and patients with negativism can eat and drink again within usually a short duration of about 10 min to 1-2 h. Fear is often gone after lorazepam administration. While not always effective, the introduction of lorazepam into clinical practice represented a breakthrough and was often life-saving for many patients suffering from catatonia. It is rare to observe such rapid therapeutic effects in other domains of psychiatry. In this narrative review we will briefly look at the past, present and future of lorazepam in the treatment of catatonia. It is gratifying to reflect on the fact that clinicians using the age-old medical practice of observation and empirical treatment succeeded in advancing the management of catatonia 40 years ago. The present evidence shows that the clinical effect of lorazepam in catatonia treatment is excellent and more or less immediate although it remains to be explicitly tested against other substances such as diazepam, zolpidem, clozapine, quetiapine, amantadine, memantine, valproate and dantrolene in randomized clinical trials. In addition, future studies need to answer the question how long lorazepam should be given to patients with catatonia, months or even years? This narrative review promotes the rapid use of lorazepam in the treatment of acute catatonic patients and stipulates further scientific examination of its often impressive clinical effects.

Eliminating the benzos: A benzodiazepine-sparing approach to preventing and treating alcohol withdrawal syndrome.

BACKGROUND: Alcohol withdrawal syndrome (AWS) represents significant cost to the hospitalized trauma population from a clinical and financial perspective. Historically, AWS has been managed with benzodiazepines. Despite their efficacy, benzodiazepines carry a heavy adverse effect profile. Recently, benzodiazepine-sparing protocols for the prophylaxis and treatment of AWS have been used in medical patient populations. Most existing benzodiazepine-sparing protocols use phenobarbital, while ours primarily uses gabapentin and clonidine, and no such protocol has been developed and examined for safety and efficacy specifically within a trauma population. METHODS: In December of 2019, we implemented our benzodiazepine-sparing protocol for trauma patients identified at risk for alcohol withdrawal on admission. Trauma patients at risk for AWS admitted to an academic Level 1 trauma center before (conventional) and after (benzodiazepine-sparing [BS]) protocol implementation were compared. Outcomes examined include morphine milligram equivalent dosing rates and lorazepam equivalent dosing rates as well as the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) scores, hospital length of stay, intensive care unit length of stay, and ventilator days. RESULTS: A total of 387 conventional and 134 benzodiazepine sparing patients were compared. Injury Severity Score (13 vs. 16, p = 0.10) and admission alcohol levels (99 vs. 149, p = 0.06) were similar. Patients in the BS pathway had a lower maximum daily CIWA-Ar (2.7 vs. 1.5, p = 0.04). While mean morphine milligram equivalent per day was not different between groups (31.5 vs. 33.6, p = 0.49), mean lorazepam equivalents per day was significantly lower in the BS group (1.1 vs. 0.2, p < 0.01). Length of stay and vent days were not different between the groups. CONCLUSION: Implementation of a benzodiazepine-sparing pathway that uses primarily clonidine and gabapentin to prevent and treat alcohol withdrawal syndrome in trauma patients is safe, reduces the daily maximum CIWA-Ar, and significantly decreases the need for benzodiazepines. Future studies will focus on outcomes affected by avoiding AWS and benzodiazepines in the trauma population. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Catatonia as the Presentation of Encephalopathy Associated With Autoimmune Thyroiditis: A Case Report and Literature Review.

Encephalopathy can be associated with autoimmune disorders such as autoimmune thyroiditis, and it can present with a wide range of neuropsychiatric manifestations. However, it rarely presents with catatonia. We present the case of a middle-aged female with Hashimoto's thyroiditis presenting with catatonia. A literature review of previous similar cases highlighting significant points is also included. A 48-year-old female presented to the emergency department with catatonic symptoms that had worsened over the previous 5 days. A similar condition was reported to have occurred and resolved spontaneously 3 months earlier. On examination, the patient appeared uncooperative and unresponsive. She showed typical symptoms of catatonia, with a score of 21 points on the Bush-Francis Catatonia Rating Scale. Routine tests were within normal ranges except for an elevated level of C-reactive protein and an elevated erythrocyte sedimentation rate. Computed tomography, magnetic resonance imaging, and cerebrospinal fluid analysis were all normal. An electroencephalogram showed diffuse delta-theta range slowing with no epileptiform discharges. Lorazepam was initiated but did not control the catatonic symptoms. Re-evaluation revealed thyroid swelling and elevated levels of thyroperoxidase antibodies. IV methylprednisolone was therefore initiated and produced complete resolution of the catatonic symptoms in 4 hours. The patient was discharged and prescribed prednisone 1 mg/kg daily. At follow-up, the patient continued to show complete resolution of the catatonic symptoms. It is noteworthy that the patient developed hypothyroidism 6 months after this catatonic episode for which levothyroxine 50 mcg/d was prescribed. Encephalopathy associated with autoimmune thyroiditis can initially present with catatonic symptoms in euthyroid cases. The mainstay of treatment is steroids which result in complete resolution of the catatonic symptoms.

Surge of Midazolam Use in the Midst of Lorazepam Shortage.

BACKGROUND: Lorazepam is a widely prescribed benzodiazepine that is used to manage anxiety, insomnia, and status epilepticus and is used for pre-anesthetic care as well as several off-label indications including aggression, alcohol withdrawal, panic disorder, chemotherapy-associated anticipatory nausea, and catatonia. Recent increases in demand, manufacturing changes, and quality control issues have resulted in a shortage of injectable and oral lorazepam, prompting clinicians to use alternatives. One such alternative is midazolam, a drug that has been used primarily in the intensive care unit and anesthesia settings. PROCEDURES: This article examines the significant pharmacologic differences between lorazepam and midazolam. In addition, this article provides dosage guidelines based on the current scientific knowledge and recommendations for conversion equivalencies. RESULTS: The clinical preference for lorazepam can be attributed to its simpler metabolism with no active metabolites, better suitability for patients with less severe hepatic and renal impairment, less risk of adverse reactions, fewer drug-drug interactions, and greater desirability for special populations. In periods of shortages, midazolam has been shown to be effective for a number of off-label uses. To manage conditions that have not been extensively studied, clinicians may opt to use conversion equivalencies, with the caveat that guidelines may vary greatly between institutions and online sources; therefore, it would be best to start low and titrate slowly. CONCLUSIONS: Our goal is to aid clinicians in safely and effectively prescribing midazolam during the shortage of injectable lorazepam so that patients are provided the same effects and benefits.

Using Interdisciplinary Teams to Mitigate the Effects of Drug Shortages in Palliative Care: The Case of Lorazepam Injection.

Given the rising frequency of drug shortages in hospitals, interdisciplinary collaboration is necessary to manage medications, modify electronic medical records, and evaluate safety outcomes. One such shortage impacted lorazepam injection, a medication commonly used in palliative care to treat anxiety, agitation, and seizures. In anticipation of the lorazepam shortage in the summer of 2022, pharmacy staff collaborated with palliative care physicians to identify alternative treatment recommendations when providers were prohibited from ordering lorazepam injection. Before the shortage, lorazepam was used an average of 95 times per month on the palliative care unit. The overall use of benzodiazepines decreased substantially following the recommendation for the therapeutic alternative, midazolam, during the shortage. Once the shortage ended, use roughly returned to pre-shortage baselines. During this time, there were no patient safety events documented on the palliative care unit. Moreover, no changes to the care experience were reported by patients, family/caregivers, providers, or staff. The collaborative effort between pharmacy and palliative care specialists resulted in alternative treatments for palliative care patients during the drug shortage. This preserved the hospital's supply of lorazepam injection for a patient population with no suitable alternatives while still allowing for management of palliative patients.

Anxiolytics cause anxiety in pancreatic cancer.

Benzodiazepines (BZDs) are commonly prescribed for pancreatic cancer patients. To investigate the correlation between BZDs and survival outcomes a recent study by Cornwell et al. found that lorazepam (LOR) correlates with poor survival. The mechanistic study shows that LOR increases interleukin 6 (IL6) expression in cancer-associated fibroblasts via GPR68.

Acute Treatment of Adolescent Cannabinoid Hyperemesis Syndrome With Haloperidol, Lorazepam, and/or Capsaicin: A Single Institution Case Series.

Cannabinoid hyperemesis syndrome (CHS), an under-recognized and seemingly paradoxical condition, arises in some adolescents and adults who chronically use cannabis. It presents acutely with intractable nausea, vomiting, and abdominal pain but standard antiemetic therapy leads to improvement for only a minority of patients. Randomized controlled trial evidence in adults indicates the superiority of haloperidol over ondansetron in alleviating the acute symptoms of CHS, but safe and effective treatment for adolescents with the disorder is currently unknown. The successful use of topical capsaicin has also been reported. We report a case series of 6 adolescent patients with CHS who presented to Johns Hopkins All Children's Hospital and were treated with haloperidol, lorazepam, and/or capsaicin. Four patients given 5 mg intravenous (IV) haloperidol and 2 mg IV lorazepam and 1 patient treated with 5 mg IV haloperidol and peri-umbilical topical capsaicin (0.025%) experienced full acute symptomatic relief. One patient, treated only with topical capsaicin, reported improvement of symptoms with some persistent nausea. Haloperidol/lorazepam, haloperidol/capsaicin, and topical capsaicin alone appear safe and effective in adolescents, but larger studies are required to confirm our findings.

Prescribing Practices for Agitation Medication in Obese Patients Admitted to the Emergency Department.

INTRODUCTION: Weight is a factor that influences the dosages of many medications, although no clinical studies have evaluated this factor in the use of agitation medications in the obese population. The objectives of this study were to assess the need for weight considerations in dosing antipsychotics and benzodiazepines for patients with agitation and to assess prescribing patterns in agitated patients. METHODS: This retrospective cohort study compared outcomes between obese and nonobese adult patients who received at least one parenteral administration of an antipsychotic or benzodiazepine for agitation in the emergency department. The primary outcomes were total antipsychotic and benzodiazepine doses within 24 hours (in chlorpromazine equivalents and lorazepam equivalents, respectively). Key secondary outcomes included antipsychotic and benzodiazepine doses used for first administration, incidence of repeat emergency medication administration within 24 hours, time to next administration, and number of repeat administrations within 24 hours. RESULTS: The study examined 115 patient encounters in each cohort of patients in the study. The baseline characteristics of the 2 study cohorts were similar. Both groups had similar mean 24-hour antipsychotic usage [272.7 chlorpromazine equivalents (nonobese cohort), 313.5 chlorpromazine equivalents (obese cohort); P=0.157] and mean 24-hour benzodiazepine usage [0.9 lorazepam equivalents (both cohorts); P=0.750]. Differences between the study cohorts on all of the secondary outcomes were also not statistically significant (P>0.05). DISCUSSION: This study did not find the use of higher dosages of agitation medication in the obese compared with the nonobese population. Future prospective trials, with possible emphasis on individual medications, specific etiologies of agitation, or morbid obesity, are required to confirm this finding or to elucidate potential differences in optimal medication dosages for the obese population.

Percutaneous absorption and Skin accumulation of Lorazepam-Diphenhydramine- Haloperidol Carbopol gel in Porcine Ear Skin.

This study presents the formulation and evaluation of an ABH Carbopol gel containing lorazepam (Ativan®), diphenhydramine hydrochloride (Benadryl®), and haloperidol (Haldol®) for treating chemotherapy-induced nausea and vomiting (CINV) in hospice patients. ABH PLO gel is widely used for this purpose due to its low cost and presumed efficacy. However, previous studies, including one conducted by the authors, have reported insufficient drug absorption from the ABH PLO gel. Here we hypothesized that the ABH Carbopol gel would provide superior percutaneous absorption of the drugs. ABH Carbopol gel was characterized for pH, viscosity, thermal properties, and infrared spectroscopy. The percutaneous absorption and skin retention of the gel was evaluated across porcine ear skin using Franz diffusion cells, and the drug concentrations were determined by high-performance liquid chromatography. The pH of the ABH Carbopol gel was found to be 6.80 ± 0.33, and the retention time of diphenhydramine, haloperidol, and lorazepam were 4.73, 7.11, and 18.69 minutes, respectively. The thermogram of the ABH Carbopol gel indicates the drugs were present in the dissolved state. Based on the flux data, the estimated steady-state concentration (Css) of diphenhydramine, haloperidol, and lorazepam were found to be 44.64 ng/ml, 2.58 ng/ml, and 20.1 ng/ml, respectively. These values were significantly higher than those obtained from the ABH PLO gel. In conclusion, the ABH Carbopol gel provides a promising alternative to the ABH PLO gel for treating CINV in hospice patients. Further studies are required to validate these findings in clinical settings.

Lorazepam Stimulates IL6 Production and Is Associated with Poor Survival Outcomes in Pancreatic Cancer.

PURPOSE: This research investigates the association between benzodiazepines (BZD) and cancer patient survival outcomes, the pancreatic cancer tumor microenvironment, and cancer-associated fibroblast (CAF) signaling. EXPERIMENTAL DESIGN: Multivariate Cox regression modeling was used to retrospectively measure associations between Roswell Park cancer patient survival outcomes and BZD prescription records. IHC, H&E, Masson's trichrome, RNAscope, and RNA sequencing were used to evaluate the impact of lorazepam (LOR) on the murine PDAC tumor microenvironment. ELISA and qPCR were used to determine the impact of BZDs on IL6 expression or secretion by human-immortalized pancreatic CAFs. PRESTO-Tango assays, reanalysis of PDAC single-cell sequencing/TCGA data sets, and GPR68 CRISPRi knockdown CAFs were used to determine the impact of BZDs on GPR68 signaling. RESULTS: LOR is associated with worse progression-free survival (PFS), whereas alprazolam (ALP) is associated with improved PFS, in pancreatic cancer patients receiving chemotherapy. LOR promotes desmoplasia (fibrosis and extracellular matrix protein deposition), inflammatory signaling, and ischemic necrosis. GPR68 is preferentially expressed on human PDAC CAFs, and n-unsubstituted BZDs, such as LOR, significantly increase IL6 expression and secretion in CAFs in a pH and GPR68-dependent manner. Conversely, ALP and other GPR68 n-substituted BZDs decrease IL6 in human CAFs in a pH and GPR68-independent manner. Across many cancer types, LOR is associated with worse survival outcomes relative to ALP and patients not receiving BZDs. CONCLUSIONS: We demonstrate that LOR stimulates fibrosis and inflammatory signaling, promotes desmoplasia and ischemic necrosis, and is associated with decreased pancreatic cancer patient survival.

Efficacy and Safety of Anxiolytics in Mohs Micrographic Surgery: A Randomized, Double-Blinded, Placebo-Controlled Trial.

BACKGROUND: Patient anxiety can complicate surgical outcomes by elevating blood pressure, increasing the need for postoperative pain management, and reducing overall patient satisfaction. Despite the use of anxiolytic medications in outpatient procedures, there is limited comparative evidence on the efficacy and safety of these agents in Mohs micrographic surgery. OBJECTIVE: To compare the effectiveness and safety of different preprocedural anxiolytic agents in Mohs surgery on perioperative patient anxiety and patient satisfaction. MATERIALS AND METHODS: A double-blinded, randomized, placebo-controlled trial was conducted of 6 different preprocedural anxiolytic agents (lorazepam, diazepam, alprazolam, gabapentin, pregabalin, and melatonin) in 350 patients undergoing Mohs surgery. Anxiety and vital signs were recorded. RESULTS: Diazepam demonstrated a statistically significant, sustained reduction in anxiety levels compared with placebo ( p = .03). Gabapentin significantly reduced early anxiety ( p = .02). Alprazolam showed a trend to early anxiety reduction ( p = .08). Lorazepam ( p = .73), pregabalin ( p = .53), and melatonin ( p = .24) failed to reduce patient anxiety compared with placebo at any time point. No anxiolytic significantly impacted any patient vital sign or cognition. CONCLUSION: Although short-acting benzodiazepines and gamma-aminobutyric acid medications may have transient anxiolytic effects, a single oral dose of 5 mg of diazepam can provide a sustained anxiolytic effect in Mohs surgery, with excellent patient safety.