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Background: Pediatric catatonia is believed to be a rare condition, but challenges in recognition and variability in presentation may lead to underdiagnosis. Early identification and effective treatment of pediatric catatonia is critical given the significant morbidity and mortality associated with the condition. Given the widespread shortage of child and adolescent psychiatrists, at times consultation-liaison (C-L) psychiatrists without child training may be the frontline specialty providers asked to guide treatment of these pediatric patients., Objective: To review the literature on pediatric catatonia using clinical cases to illustrate unique aspects of its presentation, evaluation, and management., Methods: We describe the presentation and management of 6 adolescents with catatonia on an inpatient pediatric service at a general hospital and use these cases as a focal point for a review of the literature., Conclusion: Pediatric catatonia is a potentially lethal disease entity that can be effectively treated if accurately identified early in its course. Psychiatrists working in a C-L setting may encounter this syndrome and should be aware of its presentation, evaluation, and management., (Copyright © 2018. Published by Elsevier Inc.)

Context: Kambo cleanse is a purification, cleansing ritual traditionally performed by South American shaman to confer luck and health to hunters. Case details: We report a patient who presented to the emergency department with prolonged symptoms of vomiting, flushing, facial swelling, altered mental status, and agitation requiring chemical restraints, 22 h after a Kambo cleanse. The patient was found with four small, circular, superficial burns to the ankle at the site where the resin was introduced. Discussion: The cleanse consists of rubbing resin obtained from the secretions of the giant leaf frog ( Phyllomedusa bicolor ) into superficial wounds to produce intense gastrointestinal symptoms followed by a sensation of increased stamina and strength. The cleanse is now being increasingly performed in Europe and USA.

Diazepam is labeled for status epilepticus (SE) in children, but there are limited data characterizing its disposition in pediatric patients. We developed a population pharmacokinetic (PK) model of i.v. diazepam in children with SE. We evaluated relationships between PK parameters and both safety and efficacy, and simulated exposures using dosing regimens from the product label and clinical practice. The model was developed using prospective data from a pediatric clinical trial comparing diazepam to lorazepam for treatment of SE. Altogether, 87 patients aged ≥ 3 months to < 18 years contributed 162 diazepam concentrations. Diazepam PKs were well characterized by a two-compartment model scaled by body size. No significant or clinically important relationships were observed between diazepam PKs and safety or efficacy. Simulations demonstrated that, compared with label dosing, the study dose (0.2 mg/kg i.v., maximum 8 mg) resulted in greater frequency in rapidly achieving the target therapeutic range of 200-600 ng/mL., (© 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Catatonia is a rare, underdiagnosed syndrome in children. We report the case of a 4-year-old child admitted for recent social withdrawal alternating with psychomotor excitement, verbigeration, and a loss of toilet readiness. He had a history of neonatal seizures, had been stabilized with vigabatrin, and was seizure free without treatment for several months. The pediatric and psychiatric examination revealed motor stereotypes, mannerism, bilateral mydriasis, and visual hallucinations. Laboratory and brain imaging explorations were initially negative. Catatonic symptoms, as measured with the Pediatric Catatonia Rating Scale, significantly decreased after introducing lorazepam, the first-line recommended treatment of this condition. On the basis of the neonatal seizure history, complementary genetic investigations were performed and revealed a mutation in the SCN2A gene, which encodes the voltage-gated sodium channel Nav1.2. Catatonic symptoms progressively disappeared after reintroducing vigabatrin. At the syndromic level, catatonia in young children appears responsive to high-dose lorazepam and is well monitored by using the Pediatric Catatonia Rating Scale. This case reveals the need for wide-ranging explorations in early-onset catatonia because specific targeted treatments might be available., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Background: Catatonia is frequently associated with mood and psychotic disorders as well as with general medical conditions, especially with seizures. In the case of the latter, catatonia mostly resolves when the seizures respond to the anticonvulsive treatment. We report, to our knowledge, the first case of a patient without affective or psychotic disorder, who developed catatonia in the postictum and whose catatonia did not resolve with anticonvulsive treatment, but did so with lorazepam., Case Presentation: We describe a 36-year-old man, with no psychiatric history, except for a possible disorder in the use of cannabis, who developed catatonia after epileptic seizures. The catatonia did not respond to the anticonvulsant therapy, but did so to lorazepam 17 mg/d. Lorazepam could be tapered slowly and stopped without reemergence of catatonic signs., Conclusion: Catatonia should be part of the differential diagnosis in patients with bradyphrenia and/or remarkable postictal behavior. This report shows that lorazepam should be taken into consideration (before moving to ECT), in cases of unresolved catatonia, even if the seizures are reduced with anticonvulsants.

Eslicarbazepine is a novel anti-epileptic agent indicated for the treatment of partial-onset seizures. We present the case of an 18 year old female that presented to the Emergency Department four hours after a reported intentional ingestion of an estimated 5600 mg of eslicarbazepine. Although initially hemodynamically stable and neurologically normal, shortly after arrival she developed confusion, rigidity and clonus, followed by recurrent seizures, hypoxemia and cardiac arrest which responded to cardiopulmonary resuscitation and wide complex tachycardia requiring defibrillation. Treatment for refractory seizures included benzodiazepines and eventual intubation and sedation with propofol. Cardiac toxicity responded to sodium bicarbonate. In addition, empiric hemodialysis was performed. In this case report, we discuss the successful management of the first reported overdose of eslicarbazepine using supportive care and hemodialysis.

Introduction: Benzodiazepine (BZD)-resistant alcohol withdrawal remains a challenge for most institutions due to limited evidence with available agents. One published study currently exists utilizing the N-methyl-D-aspartate antagonist, ketamine, for alcohol withdrawal., Objective: The purpose of our study was to evaluate the effect of adjunctive ketamine continuous infusion on symptom control and lorazepam infusion requirements for BZD-resistant alcohol withdrawal patients in the intensive care unit., Methods: A retrospective review was conducted of patients receiving ketamine adjunctively with a lorazepam infusion for severe alcohol withdrawal between August 2012 and August 2014. Outcomes included time to symptom control, lorazepam infusion requirements, ketamine initial and maximum daily infusion rates, and adverse effects of ketamine., Results: Thirty patients were included in the analysis. Mean time to initiation of ketamine after the initiation of a lorazepam infusion was 41.4 h. All patients achieved initial symptom control within 1 h of ketamine initiation. Median initial ketamine infusion rate was 0.75 mg/kg/h and the average maximum daily rate was 1.6 mg/kg/h. Significant decreases in lorazepam infusion rates from baseline were observed at 24 h (- 4 mg/h; p = 0.01) after ketamine initiation. No patients experienced documented CNS adverse effects. Two patients experienced hypertension and no patients experienced tachycardia related to ketamine., Conclusion: Adjunctive ketamine could provide symptom control for BZD-refractory patients and may potentially reduce lorazepam infusion requirements. Future studies to determine optimal dosing, timing of initiation, and place in therapy for BZD-resistant alcohol withdrawal are needed. The mechanism of action via the NMDA receptor with ketamine may provide benefit for BZD-resistant alcohol withdrawal.

BACKGROUND Central nervous system complications after transplantation occur in up to 40% of recipients and these complications are associated with increased length of hospital stay and mortality. Catatonia is a neuropsychiatric clinical syndrome which has been described in case reports and in a small case series as occurring in the immediate post-solid organ transplantation (SOT) period, and it has been attributed to calcineurin inhibitor neurotoxicity, psychological vulnerability, and depression. Among transplant recipients, the incidence of catatonia is unknown; it may be under diagnosed in part due to a broad differential diagnosis in the post-transplantation setting, which includes hypoactive delirium, non-convulsive status epilepticus, drug toxicity, conversion disorder, and volitional uncooperativeness. CASE REPORT We present 2 cases of catatonia diagnosed in liver allograft recipients. We also reviewed current literature for cases of catatonia among SOT recipients. We provide provisional evaluation and management strategies of recipients with clinical concern for catatonia. Catatonia generally occurs within the few first days after liver transplantation, and presents with staring, immobility, or mutism, but is also associated with other neurological and psychiatric symptoms. Catatonia can be successfully treated with intravenous lorazepam, and thus, modifying immunosuppressive regimens may be avoidable. Medications to treat catatonia are generally tapered over weeks to months, and psychiatric follow-up is indicated. The early post-liver transplantation period may be a state of relative deficiency in GABA (gamma-aminobutyric acid) signaling, predisposing liver transplant recipients in particular to post-transplantation catatonia. CONCLUSIONS Despite difficulties in establishing the diagnosis, catatonia after liver transplantation was rapidly responsive to intravenous lorazepam, indicating that changing immunosuppressants may be avoidable.

Background and Objectives: While some case reports indicate that high doses of propylene glycol (PG) may result in metabolic acidosis, there has been no large-scale study that evaluated the risk of metabolic acidosis in patients receiving PG-containing benzodiazepines for acute alcohol withdrawal. This study was undertaken to evaluate the potential toxicity of PG in patients with acute alcohol withdrawal treated with intermittent intravenous bolus doses of diazepam and/or lorazepam., Methods: This is a retrospective case study using data collected from 18 randomly selected patients receiving one or both of these medications per a modified Clinical Institute Withdrawal Assessment for Alcohol (CIWA) Class 3 protocol. Plasma levels of PG were estimated using a one-compartment pharmacokinetic model., Results: Only two patients had an elevated anion gap compared to their baseline value with one also experiencing a significant increase in serum creatinine. No increases in serum osmolarity were noted. Analysis showed that the benzodiazepine dose received was a good predictor of the estimated PG concentration (r = 0.6), but was poorly correlated with the anion gap. No significant correlation was found with the creatinine clearance or serum creatinine. Patients receiving several daily doses were at higher risk of developing an anion gap (r = 0.33), but the estimated maximum PG concentration did not correlate with the anion gap or serum concentration., Conclusion: It does not appear that intermittent bolus administration of intravenous benzodiazepines for alcohol withdrawal influenced renal function or anion gap regardless of number of administered doses, amount of PG received, or the estimated PG concentration.

History:  The 43-year-old patient was admitted because of vomiting and abdominal pain. He had a history of depression and multiple discus prolapses. He reported the consumption of three beers per day., Findings:  The patient presented diffuse abdominal pain. The serume-kreatine was elevated (205 µmol/l), there was a leucocytosis (18,4^3/µl) and a mild elvation of y-GT (2,3µkat/l). Stool culture was negative. An abdominal ultrasound and a gastroscopy did not show groundbreaking findings., Therapy and Course:  The acute kidney injury was treated by administration of intravenous fluid. The vomiting persisted despite of administration of Metoclopramid and Dimenhydrinat. Just Lorazepam and hot showers brought relief of symptoms. A decided drug history revealed a marijuana abusus. After ceasing marijuana consumption and administration of Haloperidol the vomiting stopped., Conclusions:  The cannabinoid hyperemesis syndrome is characterized by vomiting, diffuse abdominal pain and taking hot showers. With typical combination of symptoms a drug history should be taken. The knowledge of this syndrome can help to avoid overdiagnostic., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The Richmond Agitation-Sedation Scale (RASS) is commonly used to assess psychomotor activity; however, to the authors' knowledge, its minimal clinically important difference (MCID) has not been determined to date. The objective of the current study was to identify the MCID for RASS using 2 anchor-based approaches., Methods: The current study was a secondary analysis of a randomized controlled trial to compare the effect of lorazepam versus placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium. The primary outcome was change in RASS (10-point numeric rating scale ranging from -5 [unarousable] to +4 [combative]) from baseline to 8 hours after treatment administration. The sensitivity-specificity and within-patient change methods were used to identify the MCID, with the anchor being patient comfort after the study intervention as perceived by caregivers and nurses., Results: A total of 90 patients were randomized and 58 (64%) received the study medication for restlessness/agitation (mean baseline RASS, 1.6). A total of 23 caregivers (61%) and 23 nurses (55%) perceived that the patient was more comfortable after treatment. Using the sensitivity-specificity method, the optimal RASS reduction was ≥4 points according to both caregivers (sensitivity of 61% and specificity of 80%; area under the curve, 0.71) and nurses (sensitivity of 73% and specificity of 84%; area under the curve, 0.78). The RASS cutoff value based on the within-patient change method was similar (-4.2 for caregivers and -4.0 for nurses)., Conclusions: For patients with persistent restlessness/agitation, a reduction of ≥4 points in RASS was considered to be the MCID for both nurses and caregivers. These preliminary findings may have implications for sample size calculation and the interpretation of treatment effect in future delirium trials. Cancer 2018;124:2246-52. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Background: Catatonia in medically ill patients is rare but often unrecognized. This monograph summarizes current knowledge on the diagnosis, epidemiology, etiology, and management of catatonia occurring in the medical setting., Methods: PubMed searches were used to identify relevant articles from 1962 to present., Results: More than 3,000 articles were obtained and reviewed for relevance, including references of articles identified by the initial search. Several areas were identified as important, including: (1) catatonia and delirium; (2) malignant catatonia; (3) pediatric catatonia; (4) catatonia associated with another medical condition (CAMC); (5) drug exposure and withdrawal syndromes associated with catatonia; and (6) treatment of catatonia in the medical setting., Conclusions: Catatonia in the medically ill appears to have numerous etiologies, although etiology does not seem to modify the general treatment approach of prompt administration of lorazepam. Delirium and catatonia are commonly comorbid in the medical setting and should not be viewed as mutually exclusive. Electroconvulsive therapy should be offered to patients who do not respond to benzodiazepines or have malignant features. Removing offending agents and treating the underlying medical condition is paramount when treating CAMC. Memantine or amantadine may be helpful adjunctive agents. There is not enough evidence to support the use of antipsychotics or stimulants in treating CAMC.

Exercise-associated hyponatraemia (EAH) always involves a component of overhydration relative to available exchangeable sodium stores. In the majority of cases, this is purely due to excessive consumption of fluids during exercise. In a lesser number of cases, it is apparent that excessive sodium loss through sweat may play a role by decreasing the amount of acutely available exchangeable sodium. Two cases demonstrating the latter, one in an individual with cystic fibrosis (CF) and another in an endurance athlete without CF, demonstrate how elevated dermal sweat losses may contribute to a relative dilutional EAH along a pathophysiological continuum., Competing Interests: Competing interests: Not required., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

An 82-year-old man was admitted to the emergency department following bizarre behaviour. Police had noticed him driving erratically through his village. He did not stop when instructed, drove slowly home and appeared 'vacant' on questioning. While in hospital, he had approximately 15 episodes of catatonia, involving rigidity, negativism, mutism except echolalia and perseveration, automatic obedience and utilisation phenomena, lasting 2-20 min each. Between episodes, he was amnestic but otherwise well. Electroencephalography demonstrated bifrontal slowing with left-sided emphasis, and captured two focal onset partial seizures with the clinical correlate of the syndrome described above. He improved rapidly on levetiracetam and lorazepam, was discharged and received a diagnosis of dementia by his community mental health team shortly afterwards, based on chronic short-term memory loss, functional decline and MRI changes. This case has implications for our understanding of the neural correlate of catatonia, specifically frontal lobe pathway dysfunction., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: Lorazepam and electroconvulsive therapy (ECT) are effective treatments for catatonia. However, systematic data on these treatments in catatonia are limited. In the present study, we aimed to investigate the clinical and treatment-related characteristics of patients with catatonia who underwent lorazepam and/or ECT., Methods: Between January 2012 and December 2016, we received 60 patients with catatonia hospitalized in the Gaziantep University Faculty of Medicine Clinic of Psychiatry. Lorazepam and/or ECT were used in the patients' treatment schedule. Treatment results were evaluated using the Bush-Francis Catatonia Rating Scale and Clinical Global Impression-Improvement., Results: Thirty-five patients (58.3%) in the sample were in their first catatonic episode. The most common comorbidity was mood disorder (n = 34, 56.7%), whereas the most frequent catatonic sign was mutism (n = 43, 71.7%). Moreover, 31 patients (51.7%) had some form of medical comorbidity. Cerebral abnormalities were detected in computed tomography/magnetic resonance imaging in 22 patients (36.7%). Furthermore, 95% of the patients (n = 57) fully recovered after administration of the treatment., Conclusions: Lorazepam is a reasonable initial choice in the treatment of catatonia, with rapid consideration for ECT if there is no rapid response to lorazepam.

Competing Interests: Competing interests: None declared.

Purpose: The purpose of this study was to compare the efficacy and safety of lacosamide (LCM) and sodium valproate (SVA) in lorazepam (LOR)-resistant SE., Methods: Patients with LOR-resistant SE were randomized to intravenous LCM 400mg at the rate of 60mg/kg/min or SVA 30mg/kg at the rate of 100mg/min. The SE severity score (STESS), duration of SE and its etiology, and MRI findings were noted. Primary outcome was seizure cessation for 1h, and secondary outcomes were 24h seizure remission, in-hospital death, and severe adverse events (SAE)., Results: Sixty-six patients were included, and their median age was 40 (range 18-90) years. Thirty-three patients each received LCM and SVA. Their demographic, clinical, STESS, etiology, and MRI findings were not significantly different. One-hour seizure remission was not significantly different between LCM and SVA groups (66.7% vs 69.7%; P=0.79). Twenty-four-hour seizure freedom was insignificantly higher in SVA (20, 66.6%) compared with LCM group (15, 45.5%). Death (10 vs 12) and composite side effects (4 vs 6) were also not significantly different in LCM and SVA groups. LCM was associated with hypotension and bradycardia (1 patient), and SVA with liver dysfunction (6)., Conclusion: In patients with LOR-resistant SE, both LCM and SVA have comparable efficacy and safety., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A young male with schizophrenia, dependence syndrome (multiple drug use) and a severe depressive episode develops a serotonin syndrome with Sertraline and Ziprasidone. Making the correct diagnosis, although potentially challenging, remains vital., Competing Interests: Interessenkonflikt: Die Autoren geben an, dass kein Interessenkonflikt besteht.Herr F. hat die finale Version des Manuskripts gelesen und ist mit der Veröffentlichung dieser Kasuistik einverstanden., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Rodent approach-avoidance conflict tests are common preclinical models of human anxiety disorder. Their translational validity mainly rests on the observation that anxiolytic drugs reduce rodent anxiety-like behavior. Here, we capitalized on a recently developed approach-avoidance conflict computer game to investigate the impact of benzodiazepines and of amygdala lesions on putative human anxiety-like behavior. In successive epochs of this game, participants collect monetary tokens on a spatial grid while under threat of virtual predation., Methods: In a preregistered, randomized, double-blind, placebo-controlled trial, we tested the effect of a single dose (1 mg) of lorazepam (n = 59). We then compared 2 patients with bilateral amygdala lesions due to Urbach-Wiethe syndrome with age- and gender-matched control participants (n = 17). Based on a previous report, the primary outcome measure was the effect of intra-epoch time (i.e., an adaptation to increasing potential loss) on presence in the safe quadrant of the spatial grid. We hypothesized reduced loss adaptation in this measure under lorazepam and in patients with amygdala lesions., Results: Lorazepam and amygdala lesions reduced loss adaptation in the primary outcome measure. We found similar results in several secondary outcome measures. The relative reduction of anxiety-like behavior in patients with amygdala lesions was qualitatively and quantitatively indistinguishable from an impact of anterior hippocampus lesions found in a previous report., Conclusions: Our results establish the translational validity of human approach-avoidance conflict tests in terms of anxiolytic drug action. We identified the amygdala, in addition to the hippocampus, as a critical structure in human anxiety-like behavior., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: A protocol was developed to achieve status epilepticus (SE) resolution: step 1, intramuscular (IM) lorazepam; step 2, repeat IM lorazepam; step 3, rectal diazepam., Objective: The primary objective was to identify the number of patients with SE resolution after step 1. Secondary objectives included categorization of mean number of IM doses per episode and patient factors associated with SE resolution., Methods: This was a retrospective study of patients <21 years old with complex medical and physical disabilities admitted over 5 years. For analysis, IM dosing was categorized as high dose (>0.05 mg/kg/dose) and low dose (≤0.05 mg/kg/dose). A generalized linear mixed-model regression was used to assess the relationship with SE resolution at step 1 and patient characteristics., Results: A total of 44 patients were included (n = 162 episodes). SE resolution was noted in 68.5% of episodes after step 1. Models were stratified by gender to present odds of SE resolution at step 1 versus step 2/3. For women, no covariate was significant. For men, the odds of SE resolution at step 1 were 14.9 times higher in those receiving 2 versus 4 maintenance antiepileptics, adjusting for covariates. Additionally, odds of resolution at step 1 was 3.1 times higher for high-dose versus low-dose lorazepam in males, adjusting for covariates, but was not statistically significant., Conclusions: SE resolution was noted in 68.5% after step 1. Unadjusted, females had a higher odds of SE resolution at step 1 than males. In males, high-dose lorazepam had higher odds of SE resolution at step 1 than low-dose lorazepam, though not significantly different.

Objective: The objective of the study was to compare nitrous oxide with oxygen (N 2 O/O 2 ) to oral hydrocodone/acetaminophen and lorazepam for analgesia during first-trimester surgical abortion., Study Design: This double-blind randomized trial assigned women undergoing first-trimester surgical abortion at<11 weeks' gestation to inhaled N 2 O/O 2 vs. oral sedation for pain management. The N 2 O/O 2 group received up to 70:30 ratio during the procedure and placebo pills preprocedure; the oral group received inhaled oxygen during the procedure and oral hydrocodone/acetaminophen 5 mg/325 mg and lorazepam 1 mg preprocedure. The primary outcome was maximum procedural pain, assessed on a 100-mm visual analog scale (VAS; anchors 0=no pain and 100=worst pain) at 2 min postprocedure. A difference of 13 mm on the VAS was considered clinically significant. Satisfaction with pain management was measured on a 100-mm VAS (anchors 0=very unsatisfied, 100=very satisfied)., Results: We randomized 140 women, 70 per study arm. Mean age of participants was 26±6.6 years; mean gestational age was 7.3±1.5 weeks. Mean maximum procedure pain scores were 52.5±26.7 and 60.8±24.4 for N 2 O/O 2 and oral groups, respectively (p=.09). Satisfaction with pain management was 69.3±28.4 and 61.5±30.4 for N 2 O/O 2 and oral groups. respectively (p=.15)., Conclusion: We found no difference in mean procedural pain scores between women assigned to N 2 O/O 2 vs. those assigned to oral sedation for first-trimester surgical abortion. Satisfaction with both options was high., Implications: Women undergoing early surgical abortion experienced no differences in pain and satisfaction between those who used inhaled nitrous oxide and oral sedation. Nitrous oxide, with side effects limited to the duration of inhalation and no need for a ride home, is a viable alternative to oral sedation for first-trimester abortion pain management., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Benzodiazepines are the first-line treatment of catatonia, but a substantial number of patients do not respond to them. Amisulpride is one of the atypical antipsychotic that has been effective for negative symptoms of schizophrenia. We examined the effect of augmentation of oral low doses of amisulpride with lorazepam on resolution of catatonic symptoms. Fifteen patients with catatonia were treated with a combination of oral lorazepam (2-4 mg) with amisulpride (100 mg). Catatonic symptoms were rated using the Bush Francis Catatonia Rating Scale at the baseline and daily thereafter. There was complete resolution of catatonic symptoms on the third day in all patients. There was significant reduction of the total Bush Francis Catatonia Rating Scale score over time (F = 181.38, P < 0.001) with a strong effect size (partial η = 0.96). Augmentation of lorazepam with low-dose amisulpride can be a reliable strategy for management of catatonia.

Benzodiazepines are commonly used for the treatment of acute agitation in a psychiatric setting.We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant publications. Randomized trials evaluating intramuscular (IM) midazolam or lorazepam given as monotherapy or as add-on treatment, with more than 10 patients aged 18-65 years, conducted in a psychiatric setting, and published between January 1, 1980, and February 3, 2016, were included. 16 studies from a search result of 5 516 studies were included. In total, 577 patients were treated with lorazepam IM 2-4 mg, and 329 patients were treated with midazolam IM 5-15 mg. It is unclear whether lorazepam IM or midazolam IM is as efficacious as an antipsychotic IM. It is a bit more certain that the combination of benzodiazepines IM and a low dose antipsychotic IM is more efficacious than the benzodiazepine and the antipsychotic alone. However, there is no doubt that benzodiazepines are less likely to be associated with treatment emergent side effects, as compared to antipsychotics., Competing Interests: Conflicts of Interest: SJ Kousgaard has nothing to declare. RW Licht has received consulting fees and honoraria for lecturing within the last 3 years from Astra-Zeneca, Bristol-Myers Squibb, Janssen Cilag, Lundbeck, Otsuka, Servier, and Sunovion. RE Nielsen has received research grants from H. Lundbeck for clinical trials, received speaking fees from Bristol-Myers Squibb, Astra Zeneca, Janssen & Cilag, Lundbeck, Servier, Otsuka Pharmaceuticals, and Eli Lilly, and has acted as advisor to Astra Zeneca, Eli Lilly, Lundbeck, Otsuka Pharmaceuticals, Takeda, and Medivir., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Intranasal (IN) medication delivery is a viable alternative to other routes of administration, including intravenous (IV) and intramuscular (IM) administration. The IN route bypasses the risk of needle-stick injuries and alleviates the emotional trauma that may arise from the insertion of an IV catheter., Objective: This review aims to evaluate published literature on medications administered via the IN route that are applicable to practice in emergency medicine., Discussion: The nasal mucosa is highly vascularized, and the olfactory tissues provide a direct conduit to the central nervous system, bypass first-pass metabolism, and lead to an onset of action similar to IV drug administration. This route of administration has also been shown to decrease delays in drug administration, which can have a profound impact in a variety of emergent scenarios, such as seizures, acutely agitated or combative patients, and trauma management. IN administration of midazolam, lorazepam, flumazenil, dexmedetomidine, ketamine, fentanyl, hydromorphone, butorphanol, naloxone, insulin, and haloperidol has been shown to be a safe, effective alternative to IM or IV administration. As the use of IN medications becomes a more common route of administration in the emergency department setting, and in prehospital and outpatient settings, it is increasingly important for providers to become more familiar with the nuances of this novel route of medication delivery., Conclusions: IN administration of the reviewed medications has been shown to be a safe and effective alternative to IM or IV administration. Use of IN is becoming more commonplace in the emergency department setting and in prehospital settings., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The present study illustrates the application of the concept of Quality by Design for development, optimization and evaluation of Lorazepam loaded microemulsion containing ion responsive In situ gelator gellan gum and carbopol 934. A novel approach involving interactions between surfactant and polymer was employed to achieve controlled drug release and reduced mucociliary clearance. Microemulsion formulated using preliminary solubility study and pseudo ternary phase diagrams showed significantly improved solubilization capacity of Lorazepam with 54.31±6.07nm droplets size. The effect of oil to surfactant/cosurfactant ratio and concentration of gelling agent on the drug release and viscosity of microemulsion gel (MEG) was evaluated using a 3 2 full factorial design. The gel of optimized formulation (MEG 1 ) showed a drug release up to 6h of 97.32±1.35% of total drug loaded. The change in shear-dependent viscosity for different formulations on interaction with Simulated Nasal Fluid depicts the crucial role of surfactant-polymer interactions on the gelation properties along with calcium ions binding on the polymer chains. It is proposed that the surfactant-polymer interactions in the form of a stoichiometric hydrogen bonding between oxyethylene and carboxylic groups of the polymers used, provides exceptional ME stability and adhesion properties. Compared with the marketed formulation, optimized MEG showed improved pharmacodynamic activity. Ex vivo diffusion studies revealed significantly higher release for MEG compared to microemulsion and drug solution. MEG showed higher flux and permeation across goat nasal mucosa. According to the study, it could be concluded that formulation would successfully provide the rapid onset of action, and decrease the mucociliary clearance due to formation of in situ gelling mucoadhesive system., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Carisoprodol, a centrally acting muscle relaxant with a high abuse potential, has barbiturate-like properties at the GABA-A receptor, leading to central nervous system depression and desired effects. Its tolerance and dependence has been previously demonstrated in an animal model, and withdrawal has been described in several recent case reports. Many cases can be effectively managed with a short course of benzodiazepines or antipsychotic agents. However, abrupt cessation in a patient with a history of long-term and high-dose carisoprodol abuse may result in symptoms that are more difficult for providers to treat., Case Report: We present a case of a 34-year-old man with a long history of carisoprodol abuse who was found unresponsive after having ingested 7.5 grams of carisoprodol. He was intubated and admitted to the intensive care unit. He was given propofol, dexmedetomidine, fentanyl, ketamine, lorazepam, midazolam, quetiapine, and haloperidol, some at high-dose infusions, before his agitation and ventilator asynchrony could be controlled. His improvement coincided with the addition of carisoprodol and phenobarbital to his treatment regimen. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Trends show increasing emergency department presentations for drug-related disorders and treatment. This case highlights an uncommon case of carisoprodol withdrawal that may be encountered by emergency physicians, and demonstrates that benzodiazepines may not be sufficient to suppress severe withdrawal symptoms. Treatment with carisoprodol and phenobarbital provided additional benefit and can be considered in cases of severe carisoprodol withdrawal., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Although commonly linked to psychiatric disorders, catatonia is frequently identified secondary to neurological and general medical conditions (GMCs). The present study aimed to characterize the diagnostic workup of cases of catatonia in a general hospital setting. The authors performed a retrospective chart review of 54 cases of catatonia, over 3 years. Clinical suspicion of comorbid delirium was the strongest predictor of a more thorough general medical workup. Attribution of catatonia to a psychiatric etiology was associated with significantly less diagnostic workup. Prospective studies should help clarify the relationship between catatonia and delirium and standardize the diagnostic approach to patients presenting with catatonia.

Pain management in the neonatal ICU remains challenging for many clinicians and in many complex care circumstances. The authors review general pain management principles and address the use of pain scales, non-pharmacologic management, and various agents that may be useful in general neonatal practice, procedurally, or at the end of life. Chronic pain and neonatal abstinence are also noted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The purpose was to describe the use of valproate therapy for agitation in critically ill patients, examine its safety, and describe its relationship with agitation and delirium., Materials and Methods: This retrospective cohort study evaluated critically ill adults treated with valproate for agitation from December 2012 through February 2015. Information on valproate prescribing practices and safety was collected. Incidence of agitation, delirium, and concomitant psychoactive medication use was compared between valproate day 1 and valproate day 3. Concomitant psychoactive medication use was analyzed using mixed models., Results: Fifty-three patients were evaluated. The median day of valproate therapy initiation was ICU day 7, and it was continued for a median of 7 days. The median maintenance dose was 1500 mg/d (23 mg/kg/d). The incidence of agitation (96% vs 61%, P < .0001) and delirium (68% vs 49%, P = .012) significantly decreased by valproate day 3. Treatment with opioids (77% vs 65%, P = .02) and dexmedetomidine (47% vs 24%, P = .004) also decreased. In mixed models analyses, valproate therapy was associated with reduced fentanyl equivalents (-185 μg/d, P = .0003) and lorazepam equivalents (-2.1 mg/d, P = .0004). Hyperammonemia (19%) and thrombocytopenia (13%) were the most commonly observed adverse effects., Conclusions: Valproate therapy was associated with a reduction in agitation, delirium, and concomitant psychoactive medication use within 48 hours of initiation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: There are limited data on the efficacy of symptom-triggered therapy for alcohol withdrawal syndrome (AWS) in the intensive care unit (ICU)., Objective: To evaluate the safety and efficacy of a symptom-triggered benzodiazepine protocol utilizing Riker Sedation Agitation Scale (SAS) scoring for the treatment of AWS in the ICU., Methods: We performed a before-and-after study in a medical ICU. A protocol incorporating SAS scoring and symptom-triggered benzodiazepine dosing was implemented in place of a protocol that utilized the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale and fixed benzodiazepine dosing., Results: We enrolled 167 patients (135 in the preintervention and 32 in the postintervention group). The median duration of AWS was shorter in the postintervention (5, interquartile range [IQR] = 4-8 days) than in the preintervention group (8, IQR = 5-12 days; P < 0.01). Need for mechanical ventilation (31% vs 57%, P = 0.01), median ICU length of stay (LOS; 4, IQR = 2-7, vs 7, IQR = 4-11 days, P = 0.02), and hospital LOS (9, IQR = 6-13, vs 13, IQR = 9-18 days; P = 0.01) were less in the postintervention group. There was a reduction in mean total benzodiazepine exposure (74 ± 159 vs 450 ± 701 mg lorazepam; P < 0.01) in the postintervention group., Conclusion: A symptom-triggered benzodiazepine protocol utilizing SAS in critically ill patients is associated with a reduction in the duration of AWS treatment, benzodiazepine exposure, need for mechanical ventilation, and ICU and hospital LOS compared with a CIWA-Ar-based protocol using fixed benzodiazepine dosing.

Objective: Kainic acid (KA) is a potent glutamate analog that is used to induce neurodegeneration and model temporal lobe epilepsy (TLE) in rodents. KA reliably induces severe, prolonged seizures, that is, convulsive status epilepticus (cSE), which is typically fatal without pharmacologic intervention. Although the use of KA to model human epilepsy has proven unquestionably valuable for >30 years, significant variability and mortality continue to confound results. These issues are probably the consequence of cSE, an all-or-nothing response that is inherently capricious and uncontrollable. The relevance of cSE to the human condition is dubious, however, as most patients with epilepsy never experienced it. We sought to develop a simple, KA-based animal model of TLE that avoids cSE and its confounds., Methods: Adult, male Sprague-Dawley rats received coincident subcutaneous injections of KA (5 mg) and lorazepam (0.25 mg), approximately 15.0 and 0.75 mg/kg, respectively. Continuous video-electroencephalography (EEG) was used to monitor acute seizure activity and detect spontaneous seizures. Immunocytochemistry, Fluoro-Jade B staining, and Timm staining were used to characterize both acute and chronic neuropathology., Results: Acutely, focal hippocampal seizures were induced, which began after about 30 min and were self-terminating after a few hours. Widespread hippocampal neurodegeneration was detected after 4 days. Spontaneous, focal hippocampal seizures began after an average of 12 days in all animals. Classic hippocampal sclerosis and mossy fiber sprouting characterized the long-term neuropathology. Morbidity and mortality rates were both 0%., Significance: We show here that the effects of systemic KA can be limited to the hippocampus simply with coadministration of a benzodiazepine at a low dose. This means that lorazepam can block convulsive seizures without truly stopping seizure activity. This novel, cSE-free animal model reliably mimics the defining characteristics of acquired mesial TLE: hippocampal sclerosis and spontaneous hippocampal-onset seizures after a prolonged seizure-free period, without significant morbidity, mortality, or nonresponders., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Objectives: Long QT syndrome (LQTS) is described as the development of sudden syncope attacks or death as a result of ventricular tachycardia (VT) episodes that might be observed as elongated QT interval in electrocardiography (ECG). Implantable Cardioverter Defibrillator (ICD) is recommended as first-line treatment for the condition in guidelines. We aimed to present an adolescent recently diagnosed with Bipolar Disorder (BD) who had LQTS that was treated with ICD, discussing her follow up and treatment along with relevant literature., Methods: Psychiatric assessment of the case that applied to our child psychiatry unit due to manic symptoms were carried out by using Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) criteria. Symptom severity was monitored via Young Mania Rating Scale scores (YMRSS)., Results: The case met criteria for Bipolar Disorder Type I (BD-I). She had improvement in her mood symptoms with treatment regimen as risperidone 3 mg/day, valproate 1000 mg/day and lorazepam 1 mg/dayi after her 2-week follow up as well as no reported ICD activity, reflecting fine cardiac functions and rhythm., Conclusions: LQTS is a serious health issue for children and adolescents diagnosed with BD. This condition should be kept in mind especially in cases where familial risk factors are present and precautions need to be maintained upon required assessments. These cases need to be closely monitored due to risk factors related to both BD and LQTS, in a multidisciplinary fashion, involving both psychiatry and cardiology divisions.