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At least 19 recordsLinked to original sources

PubMed1999

Continuous infusion of lorazepam versus medazolam in patients in the intensive care unit: sedation with lorazepam is easier to manage and is more cost-effective.

OBJECTIVE: To evaluate the effectiveness of lorazepam and midazolam for long-term sedation of critically ill, mechanically ventilated patients. DESIGN: Double-blind, randomized, controlled study. SETTING: Medical intensive care unit in a university teaching hospital. PATIENTS: Sixty-four evaluable adult patients admitted to the intensive care department requiring mechanical ventilation for >3 days. INTERVENTIONS: Patients were randomized to receive blinded solutions of either lorazepam or midazolam by continuous infusion. The lowest dose that achieved an adequate sedation was infused. The maximum dose allowed for each drug was 60 mg/hr for midazolam and 4 mg/hr for lorazepam. Sedation was assessed initially and at least every 8 hrs thereafter on a seven-point scale if the sedation was adequate and every 2 hrs if it was not. MEASUREMENTS AND MAIN RESULTS: Measurements included the score on the sedation scale, the time between determination of the desired level of sedation and the achievement of that level, and plasma concentrations. It is significantly easier to reach a desired level of sedation with lorazepam than with midazolam. No difference in recovery was found in the 24 hrs after discontinuation of therapy. The fact that there are many factors influencing midazolam pharmacokinetics may explain the more difficult management of desired sedation levels. The equipotent dose of 10 mg of midazolam proved to be 0.7 mg of lorazepam in long-term sedation. The average cost for therapy with midazolam was approximately ten times more than that with lorazepam. CONCLUSIONS: Lorazepam is a useful alternative to midazolam for the long-term sedation of patients in the medical intensive care unit and provides easier management of the sedation level. Sedation with lorazepam offers a significant cost-savings.

Adult↗

PubMed1993

Multiple-dose lorazepam kinetics: shuttling of lorazepam glucuronide between the circulation and the gut during day- and night-time dosing intervals in response to feeding.

Lorazepam kinetics were examined in seven healthy males age 18 to 30 years after single- and multiple-dose lorazepam administration and in the presence and absence of neomycin and cholestyramine to block the enterohepatic circulation of the drug. Methods used a simultaneous i.v./p.o. dosing regimen with provision to measure lorazepam clearance during day- and night-time dosing intervals. The day-time steady-state clearance of free lorazepam measured 7.55 +/- 1.95 ml/min/kg (mean +/- S.D.) and was identical to that observed after single-dose administration (7.68 +/- 3.19 ml/min/kg). Neomycin and cholestyramine increased lorazepam clearances 5 to 45% (P < or = .05) as would be expected for interruption of an enterohepatic circulation and in keeping with previous observations under nonsteady-state conditions. Lorazepam clearances were the same during the day as during the night, except in the presence of neomycin and cholestyramine, where night-time clearances were significantly greater (10.16 +/- 3.52 vs. 8.77 +/- 2.43 ml/min/kg, P < or = .05). Urinary recoveries of lorazepam glucuronide, on the other hand, were greater during the day than during the night (114 +/- 11 vs. 77 +/- 15%, P < or = .05) and in all cases were greater than 100% of the administered dose for that interval. Thus, there is a diurnal variation in lorazepam elimination consistent with a fasting-induced increase in hepatic glucuronidation during the night. This, combined with the relative inactivity of the gut during this period, serves to trap the glucuronide and delay its transfer back to the systemic circulation and urine.

Administration, Oral↗

PubMed1976

Clinical pharmacokinetics of lorazepam. I. Absorption and disposition of oral 14C-lorazepam.

Eight healthy male subjects received single 2-mg oral doses of lorazepam containing 24 muCi/mg of 2-14C-lorazepam. Multiple venous blood samples were drawn during the first 96 hr after the dose, and all urine and stool were collected for 120 hr after dosing. Concentrations of lorazepam and its metabolites in body fluids were determined by appropriate analytic techniques. Following a lag time, lorazepam was absorbed with an apparent first-order half-life of 15 min. The peak plasma concentration was 16.9 ng/ml, measured in the pooled sample drawn 2 hr after the dose, This corresponded to the time at which clinical effects appeared to be maximal. The apparent elimination half-life of lorazepam was about 12 hr. Biotransformation to a pharmacologically inactive glucuronide metabolite appeared to be the major mechanism of lorazepam clearance. A mean of 88% of administered radioactivity was recovered in urine, and 7% was recovered in stool. Lorazepam glucuronide comprised 86% of urinary reactivity; its renal clearance was 37 ml/min. Other identified metabolites included hydroxylorazepam, a quinazolinone derivative, and a quinazoline carboxylic acid; all of these were quantitatively minor.

Administration, Oral↗

PubMed1982

Pharmacokinetic comparison of sublingual lorazepam with intravenous, intramuscular, and oral lorazepam.

Ten healthy volunteers received single 2-mg doses of lorazepam on five occasions in random sequence. Modes of administration were: A, intravenous injection; B, deltoid intramuscular injection; C, oral tablets in the fasting state; D, sublingual dosage of oral tablets in the fasting state; and E, sublingual dosage of specially formulated tablets in the fasting state. Kinetic variables were determined from multiple plasma lorazepam concentrations measured during 48 hr postdose. After intravenous lorazepam, mean (+/- SE) values were: elimination half-life (t 1/2 beta), 12.9 (+/- 0.8) hr; volume of distribution, 1.3 (+/- 0.07) liters/kg; total clearance, 1.21 (+/- 0.1) ml/min/kg. Absorption of intramuscular lorazepam was rapid. Peak plasma levels were reached at 1.15 hr after dosage, with absorption half-life averaging 14.2 (+/- 4.7) min. Absorption or oral and sublingual lorazepam tended to be less rapid than intramuscular injection, although differences were not significant. Times of peak concentration were 2.37, 2.35, and 2.25 hr postdose for trials C,D, and E, respectively; values of absorption half-life were 32.5, 28.5, and 28.7 min. Absolute systemic availability for trials B, C, D, and E averaged 95.9, 99.8, 94.1, and 98.2%, respectively; none of these differed significantly from 100%. Values of t1/2 beta were highly replicable within individuals regardless of the administration route. Thus, sublingual lorazepam is completely absorbed and is a suitable administration route in clinical practice.

Administration, Oral↗

PubMed2004

Acute treatment of psychotic agitation: a randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam.

BACKGROUND: Standard treatment for acute psychotic agitation often involves intramuscular administration of the benzodiazepine lorazepam and the antipsychotic haloperidol. This study compared the efficacy and safety of oral treatment with the atypical antipsychotic risperidone plus lorazepam with those of standard intramuscular treatment. We hypothesized that the efficacy and speed of action of both treatments would be similar. METHOD: In a prospective, parallel-group, randomized, rater-blinded noninferiority study conducted at 24 sites in the United States, 162 patients exhibiting agitation associated with active psychosis were randomly assigned to receive either oral treatment with 2 mg of risperidone plus 2 mg of lorazepam (N = 83) or intramuscular treatment with 5 mg of haloperidol plus 2 mg of lorazepam (N = 79). The change scores on a 5-item acute-agitation cluster from the Positive and Negative Syndrome Scale (hallucinatory behavior, excitement, hostility, uncooperativeness, and poor impulse control) were the main outcome measure. The study was conducted from January 8 to August 8, 2001. RESULTS: Mean acute-agitation cluster scores were similar in the 2 groups at baseline. Mean score improvements at 30, 60, and 120 minutes after dosing were significant at each timepoint in both groups (p <.0001) and were similar in both groups (p >.05). Both treatments were well tolerated. CONCLUSION: A single oral dose of risperidone plus lorazepam was as effective as parenterally administered haloperidol plus lorazepam for the rapid control of agitation and psychosis. These findings suggest that this oral regimen is an acceptable alternative to the current intramuscular treatment for acute psychotic agitation.

Acute Disease↗

PubMed1997

Comparative studies on the effects of the combination drug lorazepam plus diphenhydramine (Somnium) versus lorazepam on the noopsyche, thymopsyche and psychophysiology in nonorganic insomnia related to generalized anxiety disorder.

In a double-blind, parallel-group design study on hypnotic and anxiolytic effects of the combination drug Somnium (lorazepam 1 mg + diphenhydramine 25 mg) (SOM) as compared with 1 mg lorazepam (LOR) alone, daytime behavioral effects were studied in 44 patients with nonorganic insomnia related to a mild generalized anxiety disorder. After a placebo run-in phase of 1 week, they received active treatment for 4 weeks. Psychometric evaluations included 6 thymopsychic variables (somatic complaints, state anxiety, trait anxiety, self-rating anxiety and depression scale and adjective mood scale), 6 noopsychic variables (general, associative, numerical and total verbal memory; correct reproductions and errors-Benton visual memory test), 4 pupillary measures (pupillary diameter, latency, relative change in % and half recovery time in pupillary response) and 6 skin conductance measures (baseline, latency, ascending time, time to peak, skin conductance response and skin conductance response maximum). Multivariate statistical analysis of the thymopsyche demonstrated significant improvement after both compounds, with the combination drug significantly superior to its single component lorazepam. Also regarding noopsychic measures, Somnium was significantly superior to the single component lorazepam, as specifically verbal memory was improved after Somnium, while opposite changes occurred after lorazepam alone. Pupillary measures revealed no significant overall inter-drug differences, whereas skin conductance findings demonstrated that the combination drug Somnium was superior to the single component lorazepam also in regard to the anxiolytic effect at the autonomic nervous system level.

Adult↗

PubMed1983

Lorazepam in children. A double-blind trial comparing lorazepam, diazepam, trimeprazine and placebo.

One hundred patients aged 5-13 yr were randomly allocated to four groups in a double-blind study of premedication. Drugs studied were lorazepam, diazepam and trimeprazine. A placebo group was included. All the drugs appeared satisfactory as premedicants. Lorazepam induced the most sedation immediately after surgery, but by 4 h lorazepam and diazepam appeared similar. Lorazepam produced better amnesia than the other drugs. There were no untoward side-effects and no cardiorespiratory depression in any group. Lorazepam appears a suitable premedicant for children.

Adolescent↗

PubMed2001

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.

Acute Disease↗

PubMed2001

Comparison of ondansetron-dexamethasone-lorazepam versus metoclopramide-dexamethasone-lorazepam in the control of cisplatin induced emesis.

The antiemetic effect of ondansetron-dexamethasone-lorazepam versus those of metoclopramide-dexamethasone-lorazepam were evaluated in 30 ovarian cancer patients undergoing treatment with the same chemotherapeutic regimen (cisplatin 60 mg/m2 and cyclophosphamide 700 mg/m2). Patients were randomly selected to receive either the ondansetron arm or the metoclopramide arm in their first cycle of chemotherapy, but were given an alternative combination in the second cycle. In the ondansetron arm, ondansetron was given 8 mg intravenously (i.v.) plus dexamethasone 20 mg i.v. and lorazepam 0.5 mg oral. For the metoclopramide arm, metoclopramide 10 mg was given i.v. plus dexamethasone 20 mg i.v. and lorazepam 0.5 mg oral. All antiemetics were given twice; 30 minutes before and 6 hours after chemotherapy. In the metoclopramide arm, metoclopramide 40 mg continuous infusion was also administered. During the acute phase, the ondansetron combination was significantly superior to the metoclopramide combination for all evaluation parameters. Complete control of emesis was 90 per cent vs 36.7 per cent, complete protection from nausea was 80 per cent vs 43.3 per cent, and complete protection from both nausea and vomiting was 73.3 per cent vs 30.0 per cent. Forty per cent of patients in the ondansetron arm did not complain of any adverse reaction compared to 13.4 per cent in the metoclopramide arm. It can be concluded, therefore, that a combination of ondansetron, dexamethasone and lorazepam appears to provide a significantly better emetic control with less adverse reaction than the metoclopramide combination in the acute nausea-vomiting phase after receiving cisplatin.

Adult↗

PubMed1978

Analysis of lorazepam and its glucuronide metabolite by electron-capture gas--liquid chromatography. Use in pharmacokinetic studies of lorazepam.

This paper describes a rapid and sensitive method for analysis of lorazepam and its glucuronide metabolite in plasma and urine following therapeutic doses of lorazepam in humans. After addition of the structurally related benzodiazepine derivative, oxazepam, as the internal standard, 1-ml samples of plasma or urine are extracted twice at neutral pH with benzene (containing 1.5% isoamyl alcohol). The combined extracts are evaporated to dryness, reconstituted, and subjected to gas chromatographic analysis using a 3% OV-17 column and an electron-capture detector. Lorazepam glucuronide in urine is similarly analyzed following enzymatic cleavage with Glusulase. The sensitivity limits are 1--3 ng of analyzed following enzymatic cleavage with Glusulase. The sensitivity limits are 1--3 ng of lorazepam per ml of original sample, and the variability of identical samples is 5% or less. The applicability of the method to pharmacokinetic studies of lorazepam is demonstrated.

Administration, Oral↗

PubMed1995

Prenatal lorazepam exposure: 4. Persistent alterations in pentylenetetrazole-induced seizure threshold and GABA-dependent chloride uptake after prenatal lorazepam exposure.

Prenatal benzodiazepine exposure is associated with behavioral and neurochemical alterations in the early postnatal period. To determine the persistence of these effects, we evaluated pentylenetetrazole-induced seizure threshold and GABA-dependent chloride uptake in mice at 6 and 12 months of age after prenatal lorazepam exposure. Seizure threshhold was reduced after acute lorazepam pretreatment in mice exposed to lorazepam prenatally, compared to control groups, at 6 and 12 months of age. Maximal GABA-dependent chloride uptake was also reduced in exposed mice at 6 and 12 months of age. These data indicate that behavioral and neurochemical alterations persist well into maturity after prenatal lorazepam exposure.

Animals↗

PubMed1991

High-dose metoclopramide + lorazepam versus low-dose metoclopramide + lorazepam + dehydrobenzperidol in the treatment of cisplatin-induced nausea and vomiting.

In a randomized double-blind, cross-over trial of 34 patients receiving cisplatin-based chemotherapy (20-100 mg/m2), the antiemetic effect of high-dose metoclopramide (HDM) (10 mg/kg iv. loading dose + 7 hours continuous infusion) + lorazepam (L) (2.5 mg x 4 po) was compared with low-dose metoclopramide (LDM) (70 mg) + L (2.5 mg x 2 po) + dehydrobenzperidol (5 mg x 2 im). Among the 29 patients who completed the cross-over, HDM significantly reduced the number of vomiting episodes (p = 0.002) and the degree of nausea (p = 0.004). Seventeen patients preferred the HDM and 4 the LDM regimen (p = 0.01). Sedation was seen in all but 1 patient, and was graded as severe in 6 patients receiving the HDM and in 2 patients receiving the LDM regimen. No extrapyramidal adverse reactions were seen. We conclude that high-dose metoclopramide + lorazepam is a safe antiemetic regimen and significantly superior to low-dose metoclopramide + lorazepam + dehydrobenzperidol. Owing to the severe sedation which occurs in some patients, the dose of lorazepam should be individually adjusted.

Adult↗

PubMed1997

Comparison of lorazepam alone vs lorazepam, morphine, and perphenazine for cardiac premedication.

PURPOSE: To compare the effects of two premedication regimens on cardiorespiratory variables, sedation, and anxiety in patients scheduled for coronary artery bypass graft (CABG) surgery. METHODS: This was a prospective randomized, double-blind clinical trial. Sixty-eight patients were monitored for 1.5 hr before and 2.0 hr after premedication with lorazepam (0.03 mg.kg-1 sl), morphine (0.15 mg.kg-1 im), and perphenazine (0.05 mg.kg-1 im) [Group 1], or with lorazepam (0.03 mg.kg-1 sl) and saline (1.5 ml im) [Group 2]. All were continuously monitored with a 12-lead ECG ST monitors, respiratory inductive plethysmography (RIP), digital pulse oximetry, intra-arterial blood pressure, and arterial blood gas analysis. Sedation and anxiety scores were also recorded. RESULTS: The incidence and duration of myocardial ischaemia was low and similar in Groups 1 and 2. Patients in Group 1, but not in Group 2, had a greater number of events (P < 0.04) and duration (P < 0.02) of O2 desaturation; higher PaCO2 (P < 0.001), and more haemodynamic events (P < 0.006) after premedication when compared with baseline. There was no difference in RIP or ECG variables between the two groups. Following premedication, both groups reported reduced anxiety scores and elevated sedation scores (P < 0.01), with sedation greater in Group 1 than in Group 2 (P < 0.01). CONCLUSION: In CABG patients, premedication with lorazepam provides adequate anxiolysis and sedation, and the addition of morphine and perphenazine results in elevated PaCO2, arterial haemoglobin desaturation, and potentially adverse haemodynamic changes.

Aged↗

PubMed2005

Oral risperidone with lorazepam versus oral zuclopenthixol with lorazepam in the treatment of acute psychosis in emergency psychiatry: a prospective, comparative, open-label study.

Acutely psychotic patients presenting as psychiatric emergencies with aggression or agitation are often administered conventional antipsychotics intramuscularly. However, patients view intramuscular administration as coercive, and conventional antipsychotics are often associated with adverse events. In this open study, consecutive adult patients presenting with an acute exacerbation of schizophrenia or other psychotic disorder were assigned to oral risperidone 2-6 mg/day (n = 48) or oral zuclopenthixol 20-50 mg/day (n = 27) for 7-14 days. Lorazepam (either oral or intramuscular) was administered to both groups as needed. Patients were assessed regularly until day 14 or discharge. Mean Positive And Negative Syndrome Scale (PANSS) aggression scores (sum of item scores on excitement, poor impulse control, hostility and uncooperativeness) decreased steadily and similarly in both groups; the mean changes from baseline were statistically significant at days 10 and 14 and at study end-point. The mean decrease at study end-point in the PANSS component score for hostility was statistically significant in the risperidone group, but not in the zuclopenthixol group. Social Dysfunction and Aggression Scale aggression scores and Clinical Global Impression scores decreased significantly and similarly in both groups. Overall, 18.7% of patients showed minor extrapyramidal symptoms during the study, but only 16.7% of risperidone-treated patients, compared to 59.3% of zuclopenthixol-treated patients, received anti-parkinsonian medication (p < 0.001). Lorazepam was administered to all of the patients assigned to risperidone and to 89% of those assigned to zuclopenthixol. Oral risperidone plus lorazepam is a convenient, effective and well-tolerated alternative to conventional antipsychotics for the treatment of acute psychosis in emergency psychiatry.

Adolescent↗

PubMed2004

Effects of word frequency on recall memory following lorazepam, alcohol, and lorazepam alcohol interaction in healthy volunteers.

Free recall of words has been extensively used in psychopharmacology to assess the effects of CNS-active drugs on memory functions. However, there is a relative lack of information on the impact of word frequency on the subsequent recall of words following the administration of psychoactive drugs. The present double-blind, placebo-controlled, repeated-measures experiment used lorazepam and alcohol to test the effects of word frequency on immediate and delayed word recall in 24 healthy volunteers. One half of the words contained in the lists had a high frequency (HF) of occurrence and the remainder were of low frequency (LF). The results showed that LF words were more sensitive to memory impairment than HF words. However, the more accurate recall of HF words (with respect to LF words) was eliminated when a combination of lorazepam with alcohol was administered. These findings indicate that word frequency has a significant impact on memory and, as such, is a factor to be taken into account when using memory recall tasks to assess the effects of psychoactive drugs on memory.

Adolescent↗

PubMed1991

Randomized trial for the control of acute vomiting in cisplatin-treated patients: high-dose metoclopramide with dexamethasone and lorazepam as adjuncts versus high-dose alizapride plus dexamethasone and lorazepam. Study of the incidence of delayed emesis.

This study investigated the antiemetic activity of two different acute antiemesis regimens in patients receiving cisplatin-based chemotherapy. Seventy-four patients were treated with high-dose metoclopramide, dexamethasone and lorazepam (MDL) and 71 patients received high-dose alizapride, dexamethasone and lorazepam (ADL). Complete protection from vomiting was 50% in MDL-treated patients as compared with 30% in the ADL arm (p = 0.04). Incidence of delayed emesis was assessed in the first 82 patients accrued for the 120 h postcisplatin, being 69 and 60% in MDL and ADL, respectively.

Antiemetics↗

PubMed1987

Randomized, double-blind, cross-over study comparing prochlorperazine and lorazepam with high-dose metoclopramide and lorazepam for the control of emesis in patients receiving cytotoxic chemotherapy.

To further define optimal combinations of antiemetics, high-dose metoclopramide and lorazepam (M+L) were compared with prochlorperazine and lorazepam (P+L) in a randomized, double-blind, cross-over study. Both patient and observer assessments were documented in 66 patients receiving cisplatin and noncisplatin chemotherapy. M+L significantly reduced the severity of vomiting (P = 0.01), duration of vomiting (P = 0.05), and number of vomiting episodes (P = 0.003). Comparing the severity or duration of nausea, M+L and P+L were not significantly different. M+L significantly reduced severity of vomiting (P = 0.005) and number of vomiting episodes (P = 0.03) in the cisplatin subset. The number of vomiting episodes was also reduced in the noncisplatin subset (P = 0.03). When asked to nominate a preferred regimen, 41% of patients preferred P+L, 35% preferred M+L, and 24% rated them equally. M+L was associated with significantly more anxiety and less sedation than P+L. Patient assessments produced similar results to observer assessments but gave a broader understanding of our patients' tolerance to chemotherapy. M+L is a superior regimen in controlling vomiting induced by chemotherapy.

Adult↗

PubMed1997

Nonorganic insomnia in generalized anxiety disorder. 2. Comparative studies on sleep, awakening, daytime vigilance and anxiety under lorazepam plus diphenhydramine (Somnium) versus lorazepam alone, utilizing clinical, polysomnographic and EEG mapping methods.

Previous human pharmacological and toxicological studies demonstrated advantages of the combination drug Somnium [SOM, lorazepam (LOR) 1 mg plus diphenhydramine 25 mg] over 1 mg LOR alone, as it showed synergistic effects in hypnotic properties and antagonistic effects in regard to toxicity. In the present double-blind, parallel-group study, hypnotic and anxiolytic effects of SOM were studied in 44 patients with non-organic insomnia related to mild generalized anxiety disorder (GAD), as compared with LOR alone. After a placebo run-in phase of 1 week, they received active treatment (1 tablet SOM or LOR 1 mg) for 4 weeks and thereafter placebo again for 1 week. Clinical evaluations included the physician's general assessment of efficacy, tolerance and adverse effects, the Hamilton anxiety rating scale (HAMA), the Zung self-rating anxiety scale (SAS) and depression scale, the withdrawal symptom scale (WSS), hematology and blood chemistry. Sleep laboratory evaluations included objective and subjective sleep and awakening quality, measured by polysomnography, self-rating of sleep and awakening quality (SSA) and a psychometric test battery in the morning, as well as measurement of daytime brain function, objectivated by EEG mapping. Physicians' global evaluation of insomnia demonstrated no changes in the pre-drug placebo period, moderate improvement under both drugs, with a marginal advantage of SOM over LOR in the first 2 weeks, and a return to pre-drug values in the post-drug placebo period. Anxiety improved in observer ratings (HAMA) under both drugs, in self-rating (SAS) under the combination drug only, with the scores returning to pre-drug placebo values after post-drug placebo substitution. There were no significant findings in the self-rating depression scale and the WSS, with the exception of an improvement in the WSS score 4 weeks after SOM, as compared with pre-drug placebo. There were no rebound phenomena. Both drugs were well tolerated-in regard to both adverse effects and laboratory findings. Confirmatory statistics on the polysomnographically recorded target variable latency to sleep onset stage 2 demonstrated a significant shortening of sleep latency after SOM and a significant superiority of the combination drug SOM over LOR after acute dosing, as compared with pre-drug placebo. Descriptive statistics demonstrated further a significant improvement of sleep efficiency and total sleep time after SOM and of wakefulness time and number of awakenings during the total sleep period after both drugs, but no interdrug differences. Sleep architecture remained unchanged. Subjective sleep quality improved with both drugs, morning drowsiness and the total SSA score only with SOM, while LOR was superior to SOM regarding morning somatic complaints. There were neither changes nor interdrug differences in the morning noopsyche. In psychophysiology, critical flicker frequency decreased more under SOM than LOR. After 4 weeks therapy, no significant findings in polysomnography and subjective sleep and awakening were seen, except for an increase in movement time under LOR (tolerance development). In objective awakening quality, psychometry revealed an improvement of reaction time under SOM and a decrease of attention variability and an increase in fine-motor activity under LOR, with an interdrug comparison showing a significant superiority of SOM over LOR in regard to reaction time, reaction time variability and reaction time performance. After placebo substitution, rebound phenomena were seen in polysomnography and subjective sleep and awakening in the 1st night of the SOM group only, which were gone in the 7th placebo night, however. Noopsychic performance remained improved in both groups, with a superiority of SOM to LOR in regard to reaction time and reaction time variability. (ABSTRACT TRUNCATED)

Adult↗