Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial.

OBJECTIVE: This study was undertaken to describe patterns of benzodiazepine use as first-line treatment of status epilepticus (SE) and test the association of benzodiazepine doses with response to second-line agents in patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT). METHODS: Patients refractory to an adequate dose of benzodiazepines for the treatment of SE were enrolled in ESETT. Choice of benzodiazepine, doses given prior to administration of second-line agent, route of administration, setting, and patient weight were characterized. These were compared with guideline-recommended dosing. Logistic regression was used to determine the association of the first dose of benzodiazepine and the cumulative benzodiazepine dose with the response to second-line agent. RESULTS: Four hundred sixty patients were administered 1170 doses of benzodiazepines (669 lorazepam, 398 midazolam, 103 diazepam). Lorazepam was most frequently administered intravenously in the emergency department, midazolam intramuscularly or intravenously by the emergency medical services personnel, and diazepam rectally prior to ambulance arrival. The first dose of the first benzodiazepine (N = 460) was lower than guideline recommendations in 76% of midazolam administrations and 81% of lorazepam administrations. Among all administrations, >85% of midazolam and >76% of lorazepam administrations were lower than recommended. Higher first or cumulative benzodiazepine doses were not associated with better outcomes or clinical seizure cessation in response to second-line medications in these benzodiazepine-refractory seizures. SIGNIFICANCE: Benzodiazepines as first-line treatment of SE, particularly midazolam and lorazepam, are frequently underdosed throughout the United States. This broad and generalizable cohort confirms prior single site reports that underdosing is both pervasive and difficult to remediate. (ESETT ClinicalTrials.gov identifier: NCT01960075.).

Intramuscular midazolam versus intravenous lorazepam for the prehospital treatment of status epilepticus in the pediatric population.

OBJECTIVE: To examine the effectiveness of intramuscular (IM) midazolam versus intravenous (IV) lorazepam for the treatment of pediatric patients with status epilepticus (SE) in the prehospital care setting. METHODS: This multicenter clinical trial randomized patients diagnosed with SE to receive either IM midazolam or IV lorazepam administered by paramedics in the prehospital care setting. Included in this secondary analysis were only patients younger than 18 years of age. Evaluated were the associations of the treatment group (IM vs. IV) with the primary outcome, defined as seizure cessation prior to emergency department (ED) arrival, and with patient characteristics, time to important events, and adverse events. Descriptive statistics and 99% confidence intervals (CIs) were used for the analysis. RESULTS: Of 893 primary study subjects, 120 met criteria for this study (60 in each treatment group). There were no differences in important baseline characteristics or seizure etiologies between groups. The primary outcome was met in 41 (68.3%) and 43 (71.7%) of subjects in the IM and IV groups, respectively (risk difference [RD] -3.3%, 99% CI -24.9% to 18.2%). Similar results were noted for those younger than 11 years (RD -1.3%, 99% CI -25.7% to 23.1%). Time from initiating the treatment protocol was shorter for children who received IM midazolam, mainly due to the shorter time to administer the active treatment. Safety profiles were similar. SIGNIFICANCE: IM midazolam can be rapidly administered and appears to be safe and effective for the management of children with SE treated in the prehospital setting. The results must be interpreted in the context of the secondary analysis design and sample size of the study.

Seeing the unseen: Charles Bonnet syndrome revisited.

Charles Bonnet syndrome (CBS) is a rare condition that encompasses three clinical features: complex visual hallucinations, ocular pathology causing visual deterioration, and preserved cognitive status. Common associated ocular pathologies include age-related macular degeneration, glaucoma, and cataracts. Several theories have been proposed to try to explain the visual hallucinations. However, the pathophysiology remains poorly understood, and treatment is largely based on anecdotal data. The lack of awareness of CBS among medical professionals often leads to inappropriate diagnosis and medication. In a country like India, where awareness of mental health is not widespread, cultural myths and stigma prevent patients from seeking professional help. Here we describe two cases of CBS and revisit different ocular morbidities that have been reported to occur in conjunction with CBS. Psychiatrists and ophthalmologists alike must be sensitive to this clinical condition to ensure prompt diagnosis and treatment.

A comparative study of fixed tapering dose regimen versus symptom-triggered regimen of lorazepam for alcohol detoxification.

AIMS: The study aimed at comparing the fixed tapering dose and the symptom-triggered regimens of lorazepam for alcohol detoxification. METHODS: We carried out a prospective, randomized, double blind controlled trial involving 63 consecutive consenting male patients admitted with diagnosis of uncomplicated alcohol withdrawal. The patients were randomized into two groups based on the type of lorazepam dosage: symptom-triggered (n = 33) and fixed tapering dose regimens (n = 30). Alcohol withdrawal symptoms were rated on CIWA-Ar (Clinical Institute Withdrawal Assessment - Alcohol revised). The main outcome measures were the total amount and duration of lorazepam treatment and the incidence of adverse events or complications. RESULTS: The mean lorazepam dose administered in the symptom-triggered group was significantly lower than in the fixed tapering dose group (9.5 versus 19.9 mg, P < 0.001) and for a significantly shorter duration of time (47.8 versus 146 h, P < 0.001) with more significant results for higher initial CIWA-Ar scores. There were no significant differences between both the groups in terms of the incidence of complications like seizures or delirium tremens. CONCLUSION: Symptom-triggered lorazepam treatment for alcohol withdrawal resulted in administration of lower total doses of medication for a shorter duration of treatment and was as safe as the fixed tapering dose.

Lorazepam-diazepam protocol for catatonia in schizophrenia: a 21-case analysis.

OBJECTIVES: Catatonia is a unique clinical phenomenon characterized by concurrent motor, emotional, vegetative and behavioral signs. Benzodiazepines (BZD) and electroconvulsive therapy (ECT) can rapidly relieve catatonic signs. The lorazepam-diazepam protocol presented here has been proven to relieve catatonia in schizophrenia within a day. METHODS: From July 2002 to August 2011, schizophrenic patients requiring psychiatric intervention for catatonia in Kaohsiung Chang Gung Memorial Hospital were studied by medical chart review. The study used the Bush-Francis Catatonia Rating Scale (BFCRS). Patients receiving the lorazepam-diazepam protocol were identified. RESULTS: The survey included 21 patients (eight males and 13 females) with a mean age of 30.3 ± 12.6 years. Mean duration of schizophrenia was 4.7 ± 5.6 years. Thirteen (61.9%) patients responded within 2 h, 18 (85.7%) responded within one day, and all became catatonia-free within a week. Mean BFCRS score was 9.9 ± 3.0 before treatment. Patients that responded with a single intramuscular lorazepam injection had mean BFCRS score of 8.9 ± 2.8, significantly lower than the mean score (11.6 ± 2.5) of the rest of the patients (p = 0.034). CONCLUSIONS: The lorazepam-diazepam protocol can rapidly relieve retarded catatonia in schizophrenia. Most patients became catatonia-free within one day but some may require up to a week. ECT should be considered if the protocol fails.

RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): a double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics.

Early treatment of prolonged seizures with benzodiazepines given intravenously by paramedics in the prehospital setting has been shown to be associated with improved outcomes. However, an increasing number of Emergency Medical System (EMS) protocols use an intramuscular (IM) route because it is faster and consistently achievable. RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial) is a double-blind randomized clinical trial to determine if the efficacy of IM midazolam is noninferior by a margin of 10% to that of intravenous (IV) lorazepam in patients treated by paramedics for status epilepticus (SE). Children and adults with >5 min of convulsions who are still seizing after paramedic arrival are administered study medication by IM autoinjector or IV infusion. The primary efficacy outcome is absence of seizures at emergency department (ED) arrival, without EMS rescue therapy. Safety outcomes include acute endotracheal intubation and recurrent seizures. Secondary outcomes include timing of treatment and initial seizure cessation. At the time of writing this communication, enrollment of all subjects is near completion and the study data will soon be analyzed.

Neuropsychiatric manifestations in adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is an uncommon inflammatory condition characterised by a triad of fevers, arthralgias and a salmon-coloured rash. It is also strongly associated with high ferritin levels, whose role in its pathogenesis is not entirely clear. Central nervous system (CNS) manifestations are exceedingly rare in this disease, accounting for only a handful of reported cases. Herein, we describe a case of a 63-year-old woman who developed new-onset psychiatric symptoms in the months preceding her diagnosis. 2 months after her diagnosis, she experienced an exacerbation of psychiatric symptoms followed by new-onset seizures in conjunction with an acute lung infection. In addition, we discuss two other previously reported cases of AOSD patients with psychiatric symptoms as their initial presentation.

CADASIL presenting as status migrainosus and persisting aura without infarction.

Different types of migraine have been reported in 20-40% of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We describe a novel migrainous manifestation of CADASIL consisting in status migrainosus and persistent aura without infarction. The symptoms resolved after i.v. treatment with lorazepam and mannitol.

Catatonia in patients with dementia: a case report.

Catatonia occurring as part of a clinical picture of dementia has been reported with almost all types of dementia. It remains under-diagnosed in older adults and those with dementia. We review a case of a young patient admitted in our psychiatric department for catatonia and after efficient treatment with Lorazepam, assessment revealed a dementia. Catatonia is a severe neuropsychiatric syndrome with an excellent prognosis if recognized and treated without delay.

Case of acute psychosis from herbal supplements.

A recent study estimates that 15.2 percent of American adults use nonprescription dietary supplements for weight loss. Sale of ephedrine- and ephedrine-alkaloid-containing products was prohibited by the Food and Drug Administration in February 2004 after research demonstrated an increased risk of arrhythmia, mortality and hypertension following use of products containing these sympathomimetics. Subsequently, nutritional supplement manufacturers have turned to other products to promote weight loss. The following paper reports a case study of a 28-year-old woman with no prior psychiatric history who was hospitalized secondary to an acute psychotic episode. The patient reported starting several weight-loss and nutritional sports supplements approximately one week prior to admission. The relationship between the onset of psychosis and the initiation of the dietary supplements strongly suggests a correlation exists. Heightened consumer education regarding the contents of dietary supplements, along with their potential for causing adverse effects when used alone or in combination with other medications, is warranted. Patients who choose to take dietary supplements should be encouraged to inform their health care providers about the supplements they are taking.

Efficacy and safety of intranasal lorazepam versus intramuscular paraldehyde for protracted convulsions in children: an open randomised trial.

BACKGROUND: In sub-Saharan Africa, rectal diazepam or intramuscular paraldehyde are commonly used as first-line anticonvulsant agents in the emergency treatment of seizures in children. These treatments can be expensive and sometimes toxic. We aimed to assess a drug and delivery system that is potentially more effective, safer, and easier to administer than those presently in use. METHODS: We did an open randomised trial in a paediatric emergency department of a tertiary hospital in Malawi. 160 children aged over 2 months with seizures persisting for more than 5 min were randomly assigned to receive either intranasal lorazepam (100 microg/kg, n=80) or intramuscular paraldehyde (0.2 mL/kg, n=80). The primary outcome measure was whether the presenting seizure stopped with one dose of assigned anticonvulsant agent within 10 min of administration. The primary analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00116064. FINDINGS: Intranasal lorazepam stopped convulsions within 10 min in 60 (75%) episodes treated (absolute risk 0.75, 95% CI 0.64-0.84), and intramuscular paraldehyde in 49 (61.3%; absolute risk 0.61, 95% CI 0.49-0.72). No clinically important cardiorespiratory events were seen in either group (95% binomial exact CI 0-4.5%), and all children finished the trial. INTERPRETATION: Intranasal lorazepam is effective, safe, and provides a less invasive alternative to intramuscular paraldehyde in children with protracted convulsions. The ease of use of this drug makes it an attractive and preferable prehospital treatment option.

Adult oral sedation in California: what can a dentist do without a special permit or certificate from the Dental Board of California?

A significant percentage of patients are fearful of dental procedures, and this has not changed significantly over the past 50 years. Apprehensive patients tend to avoid necessary dental treatment, and their quality of life is compromised in the long term. This article discusses the use of zaleplon, triazolam, and lorazepam to provide oral sedation for apprehensive adult dental patients. Patient evaluation, pharmacology, and selection based on duration of the ental procedure are discussed. Dentists can use the practical protocols and sample prescriptions provided in this article without obtaining special permits r certificates from the Dental Board.

Sedation in the critically ill ventilated patient: possible role of enteral drugs.

OBJECTIVE: Sedation by the enteral route is unusual in intensive medicine. We analysed the feasibility/efficacy of long-term enteral sedation in ventilated critically ill patients. DESIGN: Prospective interventional cohort study. SETTING: General ICU. PATIENTS AND PARTICIPANTS: Forty-two patients needing ventilation and sedation for at least 4 days. INTERVENTIONS: At admission, sedation was induced with propofol or midazolam. Enteral hydroxyzine (+/- enteral lorazepam) was added in all patients within the second day. Intravenous drugs were gradually withdrawn, trying to maintain only enteral sedation after the initial 48 h. Analgesia was provided with continuous IV fentanyl. MEASUREMENTS AND RESULTS: Sedation level was assessed evaluating, on a daily basis, patients' compliance to the invasive care and comparing observed vs planned Ramsay scores three times a day. Excluding the first 2 days of patient-stabilisation and fast titration of sedation level, 577 days with ventilatory support were analysed. In 460 days (79.7%) total enteral sedation was given. This percentage rose to 94.2% when the requested Ramsay was 2 (347 days). Daily sedation was judged as adequate in 82.8% of days of total enteral sedation. Thirty-one patients had total enteral as the exclusive route of sedation. CONCLUSIONS: After 24-48 h, enteral sedation may replace, totally/in part, IV sedation in ventilated patients. Total enteral sedation easily fits the target when a Ramsay score 2 is planned. When a deeper sedation is needed, a mixed regimen is effective and lowers IV drug dosages. No side effects were reported.

Risperidone liquid concentrate and oral lorazepam versus intramuscular haloperidol and intramuscular lorazepam for treatment of psychotic agitation.

BACKGROUND: Although agitation associated with psychosis is a common presentation in the psychiatric emergency service, there is no consensus concerning the best treatment. Standard treatment often consists of intramuscular (i.m.) injection of high-potency neuroleptics, sometimes combined with benzodiazepines. The objective of this study was to determine the relative efficacy, safety, and tolerability of oral risperidone versus intramuscular haloperidol, both in combination with lorazepam, for the emergency treatment of psychotic agitation in patients who are able to accept oral medications. METHOD: A convenience sample of psychotic patients admitted to a large psychiatric emergency service who required emergency medication for the control of agitation and/or violence was offered risperidone (2 mg liquid concentrate) and oral lorazepam (2 mg) as an alternative to standard care at the institution, haloperidol (5 mg i.m.) and lorazepam (2 mg i.m.). Subjects who refused the oral medications were given the intramuscular treatment as a component of routine care. RESULTS: Thirty patients were enrolled in each treatment group. Although men were significantly more likely to choose oral medication (chi2 = 5.165, p < .023), other demographic characteristics did not differ significantly between the 2 treatment groups. Both groups showed similar improvement in agitation as measured by 5 agitation subscales of the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scale, and time to sedation. No patients receiving risperidone demonstrated any side effects or adverse events, while 1 patient receiving intramuscular treatment with haloperidol developed acute dystonia. One subject receiving risperidone required subsequent treatment with haloperidol for ongoing agitation. CONCLUSION: Oral treatment with risperidone and lorazepam appears to be a tolerable and comparable alternative to intramuscular haloperidol and lorazepam for short-term treatment of agitated psychosis in patients who accept oral medications.

Total control of chemotherapy induced emesis.

A combination of lorazepam, prochlorperazine, dexamethasone, scopolamine and ondansetron was used to prevent and diminish the occurrence of nausea and vomiting during administration of emetogenic chemotherapy. Immediately prior to administering chemotherapy a cutaneous scopolamine patch was applied to the retroaural area, prochlorperazine 5 mg was given orally, and intravenous (IV) lorazepam 0.5 mg, ondansetron 10 mg and dexamethasone 10 mg were given. The last two were repeated after 4 hours twice, and lorazepam at 6 hour intervals for four doses. A chemotherapy course consisted of mitoxantrone 20 mg/m2 i.v., followed by thiotepa 60 mg/m2 followed by 3 grams/m2 of cyclophosphamide as a constant infusion over 48 hours. There were 80 courses given to 30 women and one man with a median age of 42 years (29-58). Complete protection from vomiting in all 80 courses resulted. Minor nausea occurred in 25 courses. The antiemetic regimen was well tolerated and all patients received all the doses as prescribed.

Oral risperidone plus oral lorazepam versus standard care with intramuscular conventional neuroleptics in the initial phase of treating individuals with acute psychosis.

Although atypical antipsychotics are now considered first line treatments for schizophrenia, intramuscular (i.m.) conventional neuroleptics are often still considered necessary in emergency treatment of acute psychoses. This European, multicentre, open-label, active-controlled trial compared oral risperidone plus oral lorazepam to standard care with i.m. conventional neuroleptics with or without lorazepam in the emergency treatment of acutely psychotic patients. Patients were allowed to choose either oral risperidone (a single dose of 2 mg and 2.0-2.5 mg lorazepam; 121 patients) or standard i.m. treatment (conventional neuroleptic with or without lorazepam; 105 patients). No additional treatment was allowed for 2 h. Primary outcome was the percentage of patients with treatment success (asleep or at least much improved on Clinical Global Impression-global improvement scale) 2 h after treatment initiation. Baseline characteristics were similar in both treatment groups. Oral risperidone plus oral lorazepam was more successful at 2 h (66.9%) and significantly non-inferior compared to standard i.m. care (54.3%; P=0.0003), and the incidence of extrapyramidal symptoms (EPS) was lower (1.7%) compared to standard i.m. care (9.5%). In acutely psychotic patients requiring emergency treatment, oral risperidone/oral lorazepam was at least as effective as i.m. conventional neuroleptic treatment with or without lorazepam. Oral risperidone plus lorazepam rapidly reduces symptoms, including aggression, and causes fewer EPS.

Comparative audit of intravenous lorazepam and diazepam in the emergency treatment of convulsive status epilepticus in children.

There is little evidence on which to judge the optimal treatment for convulsive status epilepticus (CSE) in children. This study compares the effect of intravenous (iv) lorazepam with iv diazepam as the first line of treatment of CSE. We studied all children with prolonged seizures arriving in the Accident and Emergency (A&E) Department in two separate periods. In the first 6-month period iv diazepam was used as standard treatment, in the second 1-year period iv lorazepam was used. We measured latency to stopping of seizure and any adverse events. A successful treatment was defined as one in which the seizure clinically ceased within 15 minutes after siting the iv cannula, requiring no further treatment.Intravenous diazepam (0.32 mg kg (-1)) was used in 17 of 26 patients, whilst iv lorazepam (0.13 mg kg (-1)) was used in 31 of 59. There were no differences between the two groups regarding age, sex and seizure type.The seizure was successfully controlled 15 minutes after siting the iv cannula in 11 (65%) patients treated with diazepam (median time of 3 minutes) and in 20 (65%) patients treated with lorazepam (median time of 5 minutes). These preliminary results suggest that iv lorazepam may be as effective as iv diazepam.