RESUMEN
INTRODUCTION: First-generation antihistamines taken for relief of allergic rhinitis are sedating and pose potential risks for those driving a car or operating machinery. Desloratadine is a potent, selective, histamine H(1)-receptor antagonist that does not easily cross the blood-brain barrier. It is nonsedating at therapeutic doses and should not affect driving or psychomotor performance. OBJECTIVE: This study compared the acute effects of desloratadine with diphenhydramine (active control) and placebo on the performance of healthy subjects evaluated with standard over-the-road driving tests (primary objective). The subjects' performances were also evaluated (secondary objective) with the use of conventional performance tests. METHODS: Eighteen men and women received a single dose of desloratadine 5 mg, diphenhydramine 50 mg, or placebo during each period of this randomized, double-blind, three-way, crossover study. Two hours post-dosing, subjects operated a specially instrumented vehicle in a 90-min test designed to measure their ability (1) to maintain constant speed and lateral position while following another vehicle at a constant distance and (2) to respond to brake signals. Additionally, a full battery of performance tests was administered. RESULTS: No significant differences were noted between desloratadine and placebo in standard deviation of lateral position (SDLP), whereas diphenhydramine treatment significantly increased SDLP ( P< 0.001 for both comparisons). Brake reaction time was significantly faster following treatment with desloratadine than diphenhydramine (473.72 ms vs 541.22 ms; P< 0.001) or placebo (512.06 ms; P=0.033). No differences were seen among treatments in deviation of speed or distance to the lead car. The majority of performance tests showed no significant differences among groups. CONCLUSION: Desloratadine at a therapeutic dose does not impair driving performance.
Asunto(s)
Conducción de Automóvil , Difenhidramina/farmacología , Antagonistas de los Receptores Histamínicos H1 no Sedantes/farmacología , Loratadina/análogos & derivados , Loratadina/farmacología , Desempeño Psicomotor/efectos de los fármacos , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , MasculinoRESUMEN
Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition, psychomotor performance and driving-related task performance. Twelve healthy recreational ecstasy users participated in an experimental study conducted according to a double-blind, double-dummy, placebo-controlled three-way cross-over design. MDMA improved psychomotor performance, such as movement speed and tracking performance in a single task, as well as in a divided attention task. MDMA impaired the ability to predict object movement under divided attention. However, the inability to accurately predict object movement after MDMA may indicate impairment of particular performance skills relevant to driving. There was no effect of MDMA on visual search, planning or retrieval from semantic memory.
Asunto(s)
Atención/efectos de los fármacos , Alucinógenos/efectos adversos , N-Metil-3,4-metilenodioxianfetamina/efectos adversos , Desempeño Psicomotor/efectos de los fármacos , Adulto , Conducción de Automóvil/psicología , Estudios Cruzados , Método Doble Ciego , Interacciones Farmacológicas , Etanol/efectos adversos , Alucinógenos/sangre , Humanos , N-Metil-3,4-metilenodioxianfetamina/sangre , Factores de TiempoRESUMEN
The primary objective of this study was to compare the objective and subjective effects of amisulpride with those of a classic antipsychotic, haloperidol, when both were given to healthy volunteers in representative therapeutic doses over 5 days. The secondary objective was to compare the effects of relatively low and high doses of amisulpride to confirm the suspected duality of its pharmacologic activity. Twenty-one subjects participated in the four-way, randomized, double-blind, crossover study with repeated daily doses of amisulpride 50 mg, amisulpride 400 mg, haloperidol 4 mg, and placebo. Subjects were institutionalized during treatment periods and were under 24-hour medical supervision. They underwent a series of psychomotor and cognitive tests 1 hour before and 3 and 6 hours after dosing on days 1 and 5. Their extrapyramidal disturbances and drug-related feelings were assessed at the end of each replication. Psychiatric interviews and ratings of depression, subjective well-being, and negative symptoms occurred on day 4. Amisulpride 50 mg had no significant effect on any parameter. Amisulpride 400 mg had several adverse effects on psychomotor and, although less severe, on cognitive performance on the fifth day only. Amisulpride 400 mg produced no significant extrapyramidal disturbances in the group as a whole, although it may have in some individual subjects. Also, it produced no signs of mental disturbances on clinical rating scales or during a structured psychiatric interview. Haloperidol ubiquitously impaired psychomotor and cognitive performance in a similar fashion after the first and the final doses. It produced extrapyramidal disturbances in nearly every subject, the most common being akathisia and the most severe, in the case of one individual, being acute dystonia. Unlike amisulpride, haloperidol produced a number of mental disturbances, the most noteworthy being negative symptoms. Amisulpride seems to be a well-tolerated drug. Its side effects should be much less troublesome to patients using the drug on a long-term basis than those of classic antipsychotics, like haloperidol.
Asunto(s)
Antipsicóticos/farmacología , Enfermedades de los Ganglios Basales/inducido químicamente , Cognición/efectos de los fármacos , Haloperidol/farmacología , Desempeño Psicomotor/efectos de los fármacos , Sulpirida/análogos & derivados , Adulto , Trastornos Psicóticos Afectivos/inducido químicamente , Amisulprida , Antipsicóticos/efectos adversos , Estudios Cruzados , Método Doble Ciego , Femenino , Haloperidol/efectos adversos , Humanos , Masculino , Sulpirida/efectos adversos , Sulpirida/farmacologíaRESUMEN
Parallel groups of depressed (DSM III-R) outpatients received moclobemide (n = 22) and fluoxetine (n = 19), double blind, for 6 weeks. Respective starting doses were 150 mg twice a day and 20 mg q.a.m. These could be doubled after 3 weeks for greater efficacy. Chronic users of benzodiazepine anxiolytics continued taking them as comedication. Therapeutic and side effects were assessed using conventional rating scales. Actual driving performance was assessed during the week before therapy and at 1, 3 and 6 weeks thereafter using a standardized test that measures standard deviation of lateral position (SDLP). Similar remissions in depressive symptoms and side effects occurred in both groups. Patients drove with normal and reliable (r = 0.87) SDLPs before treatments. Most continued to do so but a few drove with progressively rising SDLPs and the overall trends were significant in both groups (p < 0.03). A post-hoc multiple regression analysis was applied for identifying factors that correlated with SDLP in separate tests after the beginning of therapy. At 3 and 6 weeks there were significant (p < 0.03) relationships involving the same factor; patients who drove with progressively higher SDLPs appeared to be those using benzodiazepines that are metabolized by a P450 isozyme subject to inhibition by their particular antidepressant.
Asunto(s)
Ansiolíticos/efectos adversos , Antidepresivos/efectos adversos , Conducción de Automóvil/psicología , Sistema Enzimático del Citocromo P-450/metabolismo , Trastorno Depresivo/enzimología , Trastorno Depresivo/psicología , Desempeño Psicomotor/efectos de los fármacos , Adolescente , Adulto , Anciano , Ansiolíticos/sangre , Ansiolíticos/uso terapéutico , Antidepresivos/uso terapéutico , Benzamidas/efectos adversos , Benzamidas/uso terapéutico , Benzodiazepinas , Método Doble Ciego , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Fluvoxamina/efectos adversos , Fluvoxamina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Moclobemida , Inhibidores de la Monoaminooxidasa/efectos adversos , Inhibidores de la Monoaminooxidasa/uso terapéutico , Escalas de Valoración Psiquiátrica , Factores de TiempoRESUMEN
OBJECTIVES: The purpose of this study was to test the hypothesis that learning ability is impaired in patients with seasonal allergic rhinitis relative to untreated individuals and to evaluate a combination compound (acrivastine 8 mg + pseudoephedrine 60 mg) for attenuation of the learning impairment in these patients. BACKGROUND: In a previous study employing the same method it was shown that young children (10 to 12 yrs) suffering from seasonal allergic rhinitis performed significantly worse on tests of learning and using knowledge after acute treatment with a sedating antihistamine (diphenhydramine 50 mg) or placebo as compared with nontreated healthy controls. This effect was partially reversed by treatment with loratadine. METHODS: Sixty-seven young adults suffering from seasonal allergic rhinitis and 28 matched controls were trained on didactic simulation for three consecutive days. Atopic subjects were treated differentially during training according to a double-blind, randomized, parallel group design with either diphenhydramine hydrochloride 50 mg, a combination compound (acrivastine 8 mg + pseudoephedrine 60 mg, A + P), or placebo, administered qd. After training, all atopic subjects were maintained on A + P treatment for 14 days at which time all groups returned for examination. RESULTS: Mean performance at the end of training was worse for all atopic subjects combined compared with normal subjects. Subjects treated with diphenhydramine performed significantly worse than either normals (P < .001) or those treated with A + P (P < .001). At the examination, the diphenhydramine group's performance differed significantly from those of the normal (P < .001) and A + P groups (P < .001). CONCLUSION: The study supports our previous finding that allergy symptoms reduce learning ability which is further reduced learning ability which is further reduced by diphenhydramine. Atopic subjects with allergies treated with acrivastine + pseudoephedrine learned as well as normal subjects.
Asunto(s)
Difenhidramina/efectos adversos , Efedrina/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Discapacidades para el Aprendizaje/etiología , Rinitis Alérgica Estacional/complicaciones , Triprolidina/análogos & derivados , Adolescente , Adulto , Método Doble Ciego , Combinación de Medicamentos , Femenino , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Humanos , Aprendizaje/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Rinitis Alérgica Estacional/tratamiento farmacológico , Triprolidina/administración & dosificaciónRESUMEN
OBJECTIVE: To determine whether mefloquine, a quinoline antimalarial drug, affects psychomotor and actual driving performance when given in prophylactic regimen, alone or in combination with alcohol. METHODS: Forty male and female volunteers were randomly assigned in equal numbers to two groups, and were treated double-blind for one month with mefloquine and placebo. The medication was taken in a 250 mg dose on the evenings of Days 1, 2, 3, 8, 15, 22 and 29. Testing was done on Days 4, 23 and 30, the latter after repeated doses of alcohol sufficient to sustain a blood concentration of about 0.35 mg.ml-1. Two real driving tests were used to measure prolonged (1 h) road tracking and car following performance. Critical Flicker/Fusion Frequency (CFF), critical instability tracking and body sway were also measured in the laboratory. RESULTS: Mefloquine caused no significant impairment in any test at any time relative to placebo. It significantly improved road tracking performance on Day 4. A significant interaction between prior treatment and alcohol was found in the body sway test, as the alcohol-induced change was less after mefloquine than placebo. The sensitivity of the driving test and the CFF test were shown by the significant overall effect of alcohol which did not discriminate between the two prior treatments. CONCLUSION: Mefloquine did not impair driving performance but rather improved it in the longer test, suggesting that the drug may possess psychostimulating properties.
Asunto(s)
Antimaláricos/efectos adversos , Depresores del Sistema Nervioso Central/efectos adversos , Etanol/efectos adversos , Mefloquina/efectos adversos , Desempeño Psicomotor/efectos de los fármacos , Adulto , Método Doble Ciego , Interacciones Farmacológicas , Etanol/sangre , Femenino , Humanos , Masculino , Mefloquina/sangre , Persona de Mediana EdadRESUMEN
The effects of befloxatone (20 mg o.d. for 10 days) alone and in combination with ethanol on psychomotor performance, memory and mood were assessed in a randomized, double-blind, placebo controlled study. On treatment days 6, 8 and 10, subjects received 0.5 and 0.8 g/kg ethanol and ethanol placebo in randomly assigned, balanced orders, 2 h post-drug. Critical fusion frequency, choice reaction time, postural instability, critical tracking and mood were measured 1h before ethanol and 1, 3 and 5 h afterwards. Divided attention, sustained attention and memory (immediate and delayed recall) were also measured in single tests, 2.5-5 h post-ethanol.Ethanol's effects were generally significant when blood alcohol concentrations (BAC) after both doses were the highest; i.e. 0.48-0.67 and 0.96-1.10 mg/ml. Those effects were virtually gone after the subjects' mean BACs fell below 0.40 mg/ml. Befloxatone alone had no significant impairing effect in any test. Neither did it significantly interact with ethanol to cause any greater impairment than the latter alone. It was concluded that befloxatone does not potentiate the sedating and impairing effects of ethanol.
RESUMEN
1. The acute and subchronic effects of dothiepin 75-150 mg and fluoxetine 20 mg on critical fusion frequency (CFF), sustained attention and actual driving performance were compared with those of placebo in a double-blind, cross-over study involving 18 healthy volunteers. Drugs and placebo were administered for 22 days in evening doses. Fluoxetine doses were constant but dothiepin doses increased on the evening of day 8. Performance was assessed on days 1, 8 and 22 of each treatment series. Subjective sleep parameters and possible side effects were recorded on visual analogue scales on alternate treatment days. 2. Dothiepin reduced sustained attention on day 1 by 6.7% (95% confidence interval (C1): -12.0 to -1.3%) and CFF on day 22 by 1.1 (CI: -2.2 to -0.1) Hz. Fluoxetine reduced sustained attention days 1, 8 and 22 of treatment by 7.4, 6.7 and 6.5% respectively (CI: -11.3 to -3.6; -14.3 to -1.5 and -9.5 to -3.4). CFF decreased linearly over days during fluoxetine treatment and significantly differed from placebo on day 22 with 1.2 Hz (CI: -2.3 to -0.2). Neither drug significantly affected driving performance. Whilst receiving dothiepin, subjects complained of drowsiness on days 1-3 of treatment (mean rank 5.6; CI: 2.0 to 9.2) and slept 43 min longer (CI: 8.2 to 76.2).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Conducción de Automóvil , Dotiepina/farmacología , Fluoxetina/farmacología , Desempeño Psicomotor/efectos de los fármacos , Adulto , Atención/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Dotiepina/efectos adversos , Dotiepina/sangre , Método Doble Ciego , Femenino , Fluoxetina/efectos adversos , Fluoxetina/sangre , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Sueño/efectos de los fármacos , Encuestas y CuestionariosRESUMEN
This study was designed to confirm the hypothetical dose-dependent effect of alprazolam on memory and to compare its effects on tests measuring different aspects of cognitive and psychomotor functioning. A secondary purpose was to compare the sensitivity of newly developed telephone tests with a standard laboratory test of memory. Twenty healthy male volunteers (aged 18-35 years) participated in a five-way double-blind crossover design. Treatments were single oral doses of alprazolam (0.25, 0.5 and 1.0 mg), placebo and lorazepam 2.0 mg. The latter was included as an internal control for demonstrating sensitivity of the method. Lorazepam significantly impaired all performance measures except two: verbal fluency and accuracy of music recognition were insensitive to drug effects. Alprazolam had clear dose-dependent effects on different aspects of memory: 0.25 mg did not affect any parameter; 0.5 mg impaired performance in a Word Learning Test and a Spatial Memory Test and also psychomotor performance; 1.0 mg additionally impaired Syntactic Reasoning, Semantic Verification, and Critical Flicker Fusion performance. Alprazolam's effects were not selective for any of the cognitive functions as measured in this study. The telephone tests were clearly less sensitive than the standard test, though sufficient for showing significant effects of alprazolam 1 mg and lorazepam 2 mg.