Lorazepam Group Research Articles

Adequate Information to Patients on Lorazepam and Its Expected Actions Enhances the Antianxiety Effect of This Drug During Dental Treatment

Background: Antianxiety agents can be used to pretreat dental outpatients with anxiety or fear of painful dental procedures. No studies, however, have focused on the effects of providing adequate predose information on a drug and its expected actions in reducing dental anxiety.Methods: One-hundred and four dental outpatients aged 20-65 years were randomly assigned to four groups in a double-blinded comparison study to evaluate the antianxiety effects of lorazepam. Groups were given either the drug or a placebo, and were provided either detailed information about the drug and its actions or minimal information prior to dosing. The four groups were as follows: 1) well informed and treated with 0.5 mg of lorazepam; 2) minimally informed and treated with 0.5 mg of lorazepam; 3) well informed and treated with placebo and 4) minimally informed and treated with the placebo. Anxiety levels in patients were scored at baseline and at 35 min and 1 hr after dosing according to the following scales: state anxiety scale of state-trait anxiety inventory (STAI-S), visual analog scale (VAS), and face scale (FS). At the same timepoints, heart rate (HR) was determined as an additional parameter for evaluating anxiety level.Results: Comparison between the lorazepam groups revealed significantly lower anxiety levels in the well informed patients than in the minimally informed patients, as evidenced by significantly decreased STAI-S, VAS, and FS scores at 35 min. The antianxiety effect of lorazepam was more prominent in the well informed group than in the minimally informed group, as evaluated by STAI-S and VAS scores at 1 hr after dosing. Similarly, comparison between the placebo groups showed significantly lower anxiety levels in the well informed patients than in the minimally informed patients, as evidenced by significantly decreased STAI-S and VAS scores at 35 min after dosing. In the placebo groups, HR was significantly lower at 35 min and 1 hr after dosing in the well informed patients than in the minimally informed patients.Conclusion: In the treatment of dental anxiety with lorazepam, providing predose information on the drug and its expected actions to patients enhances the anxiety reducing effects of the drug in dental outpatients.

Scopolamine but Not Lorazepam Modulates Face Repetition Priming: A Psychopharmacological fMRI Study

Repetition priming is a basic form of learning associated with decreased neuronal responses following stimulus repetition. In this experiment, we address cholinergic and GABAergic modulation of repetition priming in a face recognition paradigm. In experiment 1, we used event-related functional magnetic resonance imaging (fMRI) in combination with pharmacological challenge where participants were given placebo, lorazepam (2mg po), or scopolamine (0.4mg IV) prior to study. Behavioral data showed intact priming for famous faces in the placebo and lorazepam group but impaired priming following scopolamine. In within-group analyses, a right fusiform region showed a fame by repetition interaction characterized by a response decrease to repetition of famous faces and a response enhancement to repetition of unfamous faces in the placebo group. In subjects treated with lorazepam, a main effect of repetition, driven by response decreases to repetition of famous faces, was seen in this right fusiform region. No significant repetition effects were found after scopolamine. In experiment 2, we further investigated behaviorally the cholinergic impairment of repetition priming. Participants were given either placebo or scopolamine (0.4mg IV) after study. Behavioral data showed intact priming for famous faces in the placebo and scopolamine group. The results suggest that scopolamine but not lorazepam impair repetition priming for famous faces in a face recognition paradigm. These cholinergic impairments are likely to reflect interference with acquisition processes during study that may co-occur with a modulation of right fusiform decreases to repetition of famous faces.

The Effects of Carbamazepine and Lorazepam on Single versus Multiple Previous Alcohol Withdrawals in an Outpatient Randomized Trial

Benzodiazepines are the mainstay of treatment for mild-to-moderate alcohol withdrawal in outpatient settings, but they can interact with alcohol, cause motor incoordination, or be abused. This study compared the therapeutic responses of the benzodiazepine lorazepam and the anticonvulsant carbamazepine for the outpatient treatment of acute alcohol withdrawal in terms of patients' previous detoxification histories, and compared the effects of these 2 medications on drinking behaviors in the immediate postdetoxification period. This was a randomized double-blind trial comparing patient responses to carbamazepine and lorazepam across 2 levels of detoxification histories (0-1 or >or=2 previous medicated detoxifications). A university medical center substance abuse clinic in Charleston, SC. One hundred thirty-six patients in moderate alcohol withdrawal were randomized. Major exclusions were significant hepatic or hematologic abnormalities and use of medications that could alter withdrawal symptoms. Patients received 600-800 mg of carbamazepine or 6-8 mg of lorazepam in divided doses on day 1 tapering to 200 mg of carbamazepine or 2 mg of lorazepam. The Clinical Institute Withdrawal Assessment for Alcohol-Revised was used to assess alcohol withdrawal symptoms on days 1 through 5 and postmedication at days 7 and 12. Daily drinking was measured by patient report using a daily drinking log and a breath alcohol level with each visit. Side effects were recorded daily. Carbamazepine and lorazepam were equally effective at decreasing the symptoms of alcohol withdrawal. In the post-treatment period, 89 patients drank on at least 1 day; on average, carbamazepine patients drank less than 1 drink per drinking day and lorazepam patients drank almost 3 drinks per drinking day (P =.003). Among those with multiple past detoxifications, the carbamazepine group drank less than 1 drink per day on average and the lorazepam group drank about 5 drinks per day on average (P =.033). Lorazepam-treated patients had a significant rebound of alcohol withdrawal symptoms post-treatment (P =.007) and the risk of having a first drink was 3 times greater (P =.04) than for carbamazepine-treated patients. Twenty percent of lorazepam-treated patients had dizziness, motor incoordination, or ataxia and did not recognize their impairment. Twenty percent of carbamazepine-treated patients reported pruritus but no rash. Carbamazepine and lorazepam were both effective in decreasing the symptoms of alcohol withdrawal in relatively healthy, middle-aged outpatients. Carbamazepine, however, was superior to lorazepam in preventing rebound withdrawal symptoms and reducing post-treatment drinking, especially for those with a history of multiple treated withdrawals.

Treatment of Out-of-Hospital Status Epilepticus.

A Comparison of Lorazepam, Diazepam, and Placebo for the Treatment of Out-of-Hospital Status Epilepticus Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, Gottwald MD, O'Neil N, Neuhaus JM, Segal MR, Lowenstein DH N Engl J Med 2001;345:631–637 Background It is uncertain whether the administration of benzodiazepines by paramedics is an effective and safe treatment for out-of-hospital status epilepticus. Methods We conducted a randomized, double-blind trial to evaluate intravenous benzodiazepines administered by paramedics for the treatment of out-of-hospital status epilepticus. Adults with prolonged (lasting five minutes or more) or repetitive generalized convulsive seizures received intravenous diazepam (5 mg), lorazepam (2 mg), or placebo. An identical second injection was given if needed. Results Of the 205 patients enrolled, 66 received lorazepam, 68 received diazepam, and 71 received placebo. Status epilepticus had been terminated on arrival at the emergency department in more patients treated with lorazepam (59.1 percent) or diazepam (42.6 percent) than patients given placebo (21.1 percent) (P=0.001). After adjustment for covariates, the odds ratio for termination of status epilepticus by the time of arrival in the lorazepam group as compared with the placebo group was 4.8 (95 percent confidence interval, 1.9 to 13.0). The odds ratio was 1.9 (95 percent confidence interval, 0.8 to 4.4) in the lorazepam group as compared with the diazepam group and 2.3 (95 percent confidence interval, 1.0 to 5.9) in the diazepam group as compared with the placebo group. The rates of respiratory or circulatory complications (indicated by bag valve-mask ventilation or an attempt at intubation, hypotension, or cardiac dysrhythmia) after the study treatment was administered were 10.6 percent for the lorazepam group, 10.3 percent for the diazepam group, and 22.5 percent for the placebo group (P=0.08). Conclusions Benzodiazepines are safe and effective when administered by paramedics for out-of-hospital status epilepticus in adults. Lorazepam is likely to be a better therapy than diazepam.

Intravenous lorazepam versus dimenhydrinate for treatment of vertigo in the emergency department: A randomized clinical trial

Study Objective: To determine whether lorazepam is more effective than dimenhydrinate in relieving the symptom of vertigo in the emergency department setting. Methods: A prospective, randomized, double-blind trial of intravenous lorazepam versus dimenhydrinate therapy was conducted in the ED of a county-owned, university-affiliated hospital. All adult patients who presented between January 24, 1998, and May 23, 1999, with the symptom of vertigo were eligible for inclusion. The intervention was varying the intravenous treatment between lorazepam, 2 mg, and dimenhydrinate, 50 mg. All patients received intravenous infusion of Ringer’s lactate solution at a rate of 100 mL/h. Adequacy of randomization to the 2 treatment groups was assessed by comparing the patients’ relevant baseline history, physical examination, and symptoms. The predetermined primary outcome measurement was the patient’s sensation of “vertigo with ambulation” 1 and 2 hours after treatment. Secondary outcome measurements included vertigo while lying, sitting, and turning the head, ability to ambulate as judged by the enrolling physician, and sensation of nausea and drowsiness 1 and 2 hours after treatment, and whether the patient was “ready to go home” per patient report or physician assessment 2 hours after treatment. All patient symptoms were reported on 10-point scales. Outcome measurements were compared between the 2 treatment groups with a 2-way repeated-measures analysis of variance, Student’s t test, Mann-Whitney U, and χ2 test as appropriate. Results: Ten patients refused entry into the study, 16 were excluded, and 74 were enrolled, treated, and included in the analysis. One enrolled patient had evidence of vertigo of central origin. The pretreatment values of vertigo with ambulation were strongly correlated with the patient’s ability to ambulate (P <.001), suggesting good internal validity. The patients randomly assigned to the lorazepam group were sicker based on their pretreatment symptoms and ability to ambulate, and this may have biased the study results. The patients’ symptom of “vertigo with ambulation” decreased 1.5 units more (95% confidence interval [CI] 0 to 3.0) on average on a 10-point scale 2 hours after treatment in the dimenhydrinate group. All other measures of vertigo also decreased more in the dimenhydrinate group, although the differences were not statistically significant. At 2 hours after treatment, the patients’ ability to ambulate was better in the dimenhydrinate group (P <.001), and 17% (95% CI –2 to 36) more patients in this group were “ready to go home.” Patients in the lorazepam group experienced a 1.8-unit (95% CI 0.2 to 3.4) greater increase in drowsiness 2 hours after treatment. Conclusion: Our results suggest that dimenhydrinate was more effective in relieving vertigo and less sedating than lorazepam at the intravenous doses administered in this study. Dimenhydrinate appears to be the preferred medicine for patients who present to the ED with vertigo likely to be of peripheral origin. [Marill KA, Walsh MJ, Nelson BK. Intravenous lorazepam versus dimenhydrinate for treatment of vertigo in the emergency department: a randomized clinical trial. Ann Emerg Med. October 2000;36:310-319.]

Divalproex in the Treatment of Alcohol Withdrawal

The present study represents an open-label clinical trial comparing treatment with a benzodiazepine (lorazepam) to divalproex in 11 inpatients with uncomplicated alcohol withdrawal syndrome. The trial used the Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA-Ar) scale. There were no significant differences in demographics or substance use parameters between the divalproex group (n = 6) or the lorazepam group (n = 5). A significant Group × CIWA-Ar score interaction [F(8,72) = 2.57, p ≤. 01] was confirmed and further substantiated by a quadratic trend component for the interaction [F(1,9) = 24.9, p ≤. 001]. This preliminary study supports further investigation of divalproex in the treatment of alcohol withdrawal.

Combined sedation and topical anesthesia for cataract surgery

PurposeTo determine whether lidocaine jelly is as efficacious as tetracaine drops for obtaining ocular anesthesia and to evaluate sublingual lorazepam as premedication for sedation in cataract surgery. SettingAn ambulatory surgical center dedicated to ophthalmic surgery. MethodsThe study was divided into 2 phases. In the first, 100 patients were divided into 2 groups of 50 each. The first group received tetracaine 0.5% drops for anesthesia. The second group received lidocaine 2% jelly for topical anesthesia. In the second stage, 100 patients were divided into 2 groups of 50 each. The first 50 patients were given 1 mg of sublingual lorazepam before surgery. The second group had cataract surgery without sublingual lorazepam. All patients were operated on by the same surgeon in an ambulatory surgical center. The technique was temporal clear corneal cataract surgery with foldable intraocular lens implantation. Exclusions from the study were the need to convert to peribulbar or retrobulbar anesthesia, intraocular complications, and altered mental status. ResultsIn the first phase of the study, lidocaine 2% jelly was as efficacious as tetracaine 0.5% drops for topical anesthesia in cataract surgery. In the second phase of the study, overall, patients in the lorazepam group had less anxiety, greater amnesia, and lower blood pressure than those not receiving lorazepam as sedation for topical anesthesia. ConclusionsLidocaine 2% jelly combined with sublingual lorazepam provided excellent cost-effective anesthesia and sedation for topical anesthesia in cataract surgery and enhanced patient satisfaction with the procedure.

Sublingual lorazepam as premedication in peribulbar anesthesia

Purpose: To assess the efficacy of sublingual lorazepam in inducing amnesia when used as a premedication for peribulbar anesthesia.Setting: Department of Ophthalmology in a large district general hospital.Methods: Following local ethical committee approval, a prospective, randomized, placebo-controlled, double-blind study of patients having routine cataract or glaucoma surgery under local anesthetic was undertaken. Patients older than 90 years of age or who were frail, confused, or unfit for surgery were excluded, as were those who weighed less than 50 kg, swallowed the tablet, or had missing data. Sixty volunteer patients were randomly given 1 mg of lorazepam or a placebo tablet by sublingual route 1 hour preoperatively. All patients were assessed for sedation, akinesia, intraoperative analgesia, and patient response including amnesia.Results: There was no significant difference between groups in sedation, analgesia, or akinesia. Overall patient response was better in the lorazepam group (P = .05). Patient-reported incidence of amnesia was significantly higher in the lorazepam than in the placebo group (P < .05).Conclusions: Sublingual lorazepam improved patient comfort by inducing amnesia, and in the low dose used in this study, did not adversely affect surgery by undue heavy sedation.

A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients

The purpose of this study was to examine the efficacy and side effects of haloperidol, chlorpromazine, and lorazepam for the treatment of the symptoms of delirium in adult AIDS patients in a randomized, double-blind, comparison trial. Nondelirious, medically hospitalized AIDS patients (N = 244) consented to participate in the study and were monitored prospectively for the development of delirium. Patients entered the treatment phase of the study if they met DSM-III-R criteria for delirium and scored 13 or greater on the Delirium Rating Scale. Thirty patients were randomly assigned to treatment with haloperidol (N = 11), chlorpromazine (N = 13), or lorazepam (N = 6). Efficacy and side effects associated with the treatment were measured with repeated assessments using the Delirium Rating Scale, the Mini-Mental State, and the Extrapyramidal Symptom Rating Scale. Treatment with either haloperidol or chlorpromazine in relatively low doses resulted in significant improvement in the symptoms of delirium as measured by the Delirium Rating Scale. No improvement in the symptoms of delirium was found in the lorazepam group. Cognitive function, as measured by the Mini-Mental State, improved significantly from baseline to day 2 for patients receiving chlorpromazine. Treatment with haloperidol or chlorpromazine was associated with an extremely low prevalence of extrapyramidal side effects. All patients receiving lorazepam, however, developed treatment-limiting adverse effects. Although only a small number of patients had been treated with lorazepam, the authors became sufficiently concerned with the adverse effects to terminate that arm of the protocol early. Symptoms of delirium in medically hospitalized AIDS patients may be treated efficaciously with few side effects by using low-dose neuroleptics (haloperidol or chlorpromazine). Lorazepam alone appears to be ineffective and associated with treatment-limiting adverse effects.

The Effect of Midazolam and Lorazepam on Postoperative Recovery After Cardiac Surgery

The Effect of Midazolam and Lorazepam on Postoperative Recovery After Cardiac Surgery

Lorazepam 0.25 mg twice a day improves aspects of psychometric performance in healthy volunteers

The effects of lorazepam (0.25 mg) twice a day on several cognitive and performance tasks, pictures test, digit-symbol substitution test (DSST), choice reaction time (CRT) and critical flicker fusion (CFF), were investigated in healthy students. A double-blind independent group design was used to compare placebo and lorazepam (30 volunteers in each group). After randomisation, all subjects received placebo for 3 days (D), followed by 14 days of treatment, with either lorazepam or placebo. Subjects completed a battery of tests at Do, then D(3), D(7) , D(10) and D(14). D(3) performance was poorer in the lorazepam group except for CFF (ascending values and total values), yet the only significant improvement was in total reaction time on the CRT test. However, a significant improvement of performance was shown at D(7), D(10) and D(14) in the lorazepam group compared with the control group (except in recognition reaction time). The current study shows that low repeated doses of lorazepam are able to produce small improvements in some aspects of psychomotor and cognitive functions in healthy volunteers. Different points are discussed to explain the performance improvement: training effect, tolerance effect, partial inverse agonist effect and the possible release of cholecystokinin.

Cardiac dysrhythmias associated with intravenous lorazepam, diazepam, and midazolam during oral surgery

The incidence and nature of cardiac dysrhythmias occurring during intravenous sedation with lorazepam, diazepam, and midazolam for oral surgery were studied. Sixty American Society of Anesthesiologists (ASA) I patients of both sexes between the ages 17 and 32 years were randomly allocated to three groups. Groups received either intravenous lorazepam (.05 mg/kg), diazepam (.25 mg/kg), or midazolam (.1 mg/kg) prior to the oral surgical procedure. Electrocardiograms were made before medication and thereafter throughout the entire procedure. Of the 60 patients studied, 16 (26.7%) exhibited dysrhythmias during the surgical procedure. If sinus dysrhythmias were excluded as a cause of abnormal rhythms, only six patients (10%) exhibited dysrhythmias during surgery. No atrial or ventricular premature beats were recorded for the lorazepam group. In the diazepam group five of the patients (25%) exhibited dysrhythmias; 15% were mainly unifocal ventricular premature beats. Only one patient in the midazolam group exhibited unifocal ventricular premature beats.

Depression in the course of treatment of generalized anxiety disorder with lorazepam, ipsapirone, and placebo: Results from a multicenter trial

AbstractThe present report addresses the occurrence of depression during a multicenter, double‐blind, randomized, placebo‐controlled trial investigating the comparative anxiolytic efficacy of ipsapirone and lorazepam versus placebo in generalized anxiety disorder (GAD). Patients who entered the study scored ≥18 on the HAM‐A, scored ≥ 8 on the Covi anxiety scale, and scored ⩽ 7 on the Raskin depression scale. Patients were randomized to lorazepam (2–6 mg/day), ipsapirone (10–30 mg), or placebotid for 4 weeks acute treatment. Efficacy of ipsapirone versus lorazepam and placebo in GAD was assessed with weekly HAM‐A and CGI ratings. Worsening or emergence of depression was assessed with HAM‐D ratings performed at baseline and weeks 2 and 4. Adverse events were assessed weekly. Ninety‐six males and 161 females (age range 18–78 years) were valid for efficacy after a 4‐week acute treatment period. HAM‐A and CGI scores were significantly reduced with lorazepam and ipsapirone compared with placebo. HAM‐D scores were also reduced significantly from baseline in the lorazepam, ipsapirone, and placebo groups; HAM‐D core items significantly decreased in the ipsapirone but not in the lorazepam and placebo groups. Individual incidents of depression showed significantly (p &lt; 0.05) higher frequency in the lorazepam group (10/104; 9.6%) compared with ipsapirone (2/106; 1.9%), but only a trend (p &lt; 0.10) compared with placebo (4/105; 3.8%). There was an increased severity of the depressive incidents in the lorazepam group compared with the other two treatment groups. This report confirms an earlier study reporting that depression is a potential side effect of lorazepam treatment in GAD patients. Depression 1:172–176 (1993). © 1993 Wiley‐Liss, Inc.

Alpidem and lorazepam in the treatment of patients with anxiety disorders: Comparison of efficacy and rebound

AbstractAlpidem, a novel imidazo‐pyridine anxiolytic, was compared with lorazepam for efficacy and withdrawal effects in 23 (17 male) anxious psychiatric out‐patients of mean age 35.3 years with a mean Hamilton Anxiety Rating Scale (HAM‐A) total score of 26.4. Treatment was double blind for 4 weeks with doses built up to a mean of 112.5 mg alpidem and 3.5 mg lorazepam per day. Assessment were made for a further 2 weeks after abrupt withdrawal.There were no differences in scores between the groups before treatment. The HAM‐A, Hospital Anxiety and Depression Scale, Sleep Rating Scale and other measures showed both drugs to be equally effective for psychic and somatic anxiety, depression and insomnia. Despite the small numbers, lorazepam produced greater improvement in the anxious mood, fear and insomnia items of the HAM‐A. After stopping treatment serious rebound in mood and somatic scores was experienced by the lorazepam group in contrast to those patients on alpidem who maintained their improvement. Neither group was troubled by side effects; dropouts were few and due to inefficacy (1 alpidem) or withdrawal problems (2 lorazepam). Alpidem seemed to offer effective anxiolysis without the risk of rebound associated with lorazepam use.

Comparison of various physiologic and psychomotor parameters in patients sedated with intravenous lorazepam, diazepam, or midazolam during oral surgery

Intravenously administered lorazepam (0.05 mg/kg), diazepam (0.25 mg/kg), and midazolam (0.1 mg/kg) were compared for sedation during oral surgery under local anesthesia. Sixty patients were randomly allocated into three groups in this double-blind, parallel study. The results from this trial show that all three drugs provide satisfactory sedation. Average mean arterial pressures, however, decreased significantly with midazolam and diazepam. Statistically significantly higher heart rates during the entire procedure were also found for lorazepam when compared with diazepam and midazolam. At the postblock stage, the midazolam group had respiratory rates that were significantly higher than those of the other two drug groups. Patients in the diazepam and midazolam groups took significantly longer to complete the pegboard test at the preblock stage than those in the lorzepam group. At 1, 1.5, and 2 hours after arrival in the recovery room, an inversion of groups took place, with the lorazepam group taking significantly longer for their tests than the other two groups. Significantly more improvement in anxiety levels was found at 10 minutes postdrug for the patients who had received diazepam and this tended to remain so on arrival in the recovery room. When compared with the other two groups, significantly more patients in the lorazepam group reported giddiness/dizziness and significantly more in the diazepam group reported pain on injection.

A Double-Blind Comparison of the Effects of Gradual Withdrawal of Lorazepam, Diazepam and Bromazepam in Benzodiazepine Dependence

Using a double-blind procedure, 68 patients with putative benzodiazepine dependence were randomly allocated to one of three groups given lorazepam (n = 22), diazepam (n = 23) or bromazepam (n = 23) in doses equivalent to those of the patients' original benzodiazepine. After four weeks the dosage was reduced in 25% quantities until no further benzodiazepines were taken. A total of 23 patients dropped out during the study, ten on lorazepam (one of whom committed suicide), seven on diazepam and six on bromazepam. There were few differences in withdrawal symptoms between the three groups but, despite the higher dropout rate, these symptoms were somewhat less marked in the lorazepam group. Withdrawal symptoms were greater in patients who had taken a benzodiazepine for greater than 5 years and were most marked in those with personality disorders, predominantly dependent ones.

Lorazepam as night sedation and premedication: a comparison with diazepam

Fifty healthy female patients scheduled for surgery were randonly allocated into two groups in a double-blind study. One group received lorazepam 2.5 mg orally at 2200 h on the evening before surgery as night sedation, and again at 0800 h on the morning before surgery as premedication. The second group received diazepam 10 mg orally at the samte times. The quality of sleep the night before surgery was superior in the lorazepam group (p less than 0.02). The frequency of effective sedation produced pre-operatively was similar in both groups. Although the incidence of amnesia for visual stimuli following lorazapam was higher (p less than 0.05) than with diazepam, there was no difference in the recall of auditory and painful stimuli. The overall incidence of side effects was similar for each drug and at the dosage used no difference was found in the time to awaken from anaesthesia.