Lorazepam is a benzodiazepine medication developed by DJ Richards. It went on the market in the United States in 1977. Lorazepam is commonly used as the sedative and anxiolytic of choice in the inpatient setting owing to its fast (1 to 3 minute) onset of action when administered intravenously.[1] Lorazepam is also one of the few sedative-hypnotics with a relatively clean side effect profile. Lorazepam is FDA approved for short-term (4 months) relief of anxiety symptoms related to anxiety disorders, anxiety-associated insomnia, anesthesia premedication in adults to relieve anxiety or to produce sedation/amnesia, and treatment of status epilepticus.[2] Off-label (non-FDA-approved) uses for Lorazepam include rapid tranquilization of the agitated patient, alcohol withdrawal delirium, alcohol withdrawal syndrome, insomnia, panic disorder, delirium, chemotherapy-associated anticipatory nausea and vomiting (adjunct or breakthrough), as well as psychogenic catatonia.[3]

The consumption of psychoactive pharmaceuticals has increased worldwide, and wastewater treatment plants are not able to eliminate them from the effluent. An extensive review was carried out to assess the environmental risk (ERA model) based on secondary data about potential impacts on non-target organisms of seven psychoactive drugs consumed worldwide (alprazolam, bromazepam, citalopram, clonazepam, diazepam, lorazepam, and oxazepam). Risk quotients (RQs) were calculated according to the European Medicines Agency (EMA) on ERA of Medicinal Products For Human Use based on (i) the predicted and measured environmental concentrations (PEC and MEC, respectively) of the psychoactive drug in surface water, groundwater, and wastewater effluent and (ii) the predicted no-effect concentration (PNEC) derived from ecotoxicological assays or ECOSAR software. Furthermore, this study reviews and discusses non-standardized ecotoxicity assays, such as sublethal and behavioral effects on different organisms. In total, 903 MEC entries of psychoactive drugs and 162 data on ecotoxicological assays were gathered from the literature survey addressing behavioral effects (115), acute/chronic effects (35), and sublethal effects (12). Citalopram and diazepam were the only substances that are likely to pose an environmental risk (RQ > 1) to surface waters. Even though there is considerable amount of data on behavioral effects of psychoactive drugs to aquatic species, results are currently not integrated into the EMA risk assessment framework. The large amount of data on psychoactive drug concentrations and effects on non-target organisms collected, interpreted, and discussed in the present study should be used as a baseline for future improvement of ERA strategies.

Catatonia has been increasingly recognized in people with autism spectrum disorders (ASD). Assessment, diagnosis, and treatments are reviewed and illustrated with 2 new case vignettes. The use of electroconvulsive treatment (ECT) is recommended in patients who fail to respond to medical treatments, including a trial of lorazepam or another benzodiazepine. The importance of maintenance ECT is discussed. There is an urgent need for prospective studies of catatonia in ASD and for controlled treatment trials.

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.

The objective of this study is to describe the pharmacokinetics of lacosamide in a critically ill adult during continuous venovenous hemofiltration (CVVH). A 78-year-old male developed sepsis and acute kidney injury following cardiac surgery. He was initially treated with intermittent hemodialysis but developed nonconvulsive status epilepticus at the end of the first session and was subsequently initiated on CVVH. In addition to lorazepam boluses, levetiracetam, and midazolam infusion, he was loaded with lacosamide 400 mg intravenously and started on 200 mg intravenously twice daily as maintenance therapy. Noncompartmental modeling of lacosamide pharmacokinetics revealed significant extracorporeal removal, a volume of distribution of 0.69 L/kg, elimination half-life of 13.6 hours, and peak and trough concentrations of 7.4 and 3.7 mg/L, respectively (goal trough, 5-10 mg/L). We found significant extracorporeal removal of serum lacosamide during CVVH, which was higher than previously reported. This led to subtherapeutic concentrations and decreased overall antiepileptic drug exposure. The relationship between serum lacosamide concentrations and clinical efficacy is not well understood; thus, therapeutic drug monitoring is not routinely recommended. Yet, we demonstrated that measuring serum lacosamide concentrations in the critically ill population during continuous renal replacement therapy may be useful to individualize dosing programs. Further pharmacokinetic studies of lacosamide may be necessary to generate widespread dosing recommendations.

A young man previously diagnosed with Kleine-Levin syndrome (KLS) presented with abnormal behaviour over the last 8 days. This included decreased sleeping hours and appetite, hypersexuality, aggressiveness and visual hallucinations. All blood tests and investigations in the emergency department yielded normal results. A preliminary diagnosis of a KLS episode with psychosis was made and the patient was started on a regimen of aripiprazole 10 mg once daily along with lorazepam 2 mg intravenously in two divided doses in the event of agitation or insomnia. On discharge 5 days later, the patient had returned to his premorbid level of functioning and was willing to follow up in the neurology clinic. He was discharged on aripiprazole 10 mg once daily and lorazepam 2 mg two times daily as needed for 2 weeks to help with his agitation and insomnia, as well as lithium carbonate 400 mg at night.