Event-related potentials and secondary task performance during simulated driving.

Inattention and distraction account for a substantial number of traffic accidents. Therefore, we examined the impact of secondary task performance (an auditory oddball task) on a primary driving task (lane keeping). Twenty healthy participants performed two 20-min tests in the Divided Attention Steering Simulator (DASS). The visual secondary task of the DASS was replaced by an auditory oddball task to allow recording of brain activity. The driving task and the secondary (distracting) oddball task were presented in isolation and simultaneously, to assess their mutual interference. In addition to performance measures (lane keeping in the primary driving task and reaction speed in the secondary oddball task), brain activity, i.e. event-related potentials (ERPs), was recorded. Performance parameters on the driving test and the secondary oddball task did not differ between performance in isolation and simultaneous performance. However, when both tasks were performed simultaneously, reaction time variability increased in the secondary oddball task. Analysis of brain activity indicated that ERP amplitude (P3a amplitude) related to the secondary task, was significantly reduced when the task was performed simultaneously with the driving test. This study shows that when performing a simple secondary task during driving, performance of the driving task and this secondary task are both unaffected. However, analysis of brain activity shows reduced cortical processing of irrelevant, potentially distracting stimuli from the secondary task during driving.

The impact of chronic pain patients' psychotropic drug knowledge and warning labels on the decision whether to drive a car or not.

OBJECTIVE: The attitudes of patients towards driving a car while taking medication with psychotropic side effects is unclear. A growing number of patients use these psychotropic medicines on a daily basis, and this may interfere with their ability to drive a car. METHODS: By means of a survey, we examined attitudes towards driving while using psychotropic medicinal drugs and the effect of warning labels on the decision whether to drive a car or not in patients with chronic pain. RESULTS: Fifty-eight of 100 patients possessing a driver's license used psychotropic medication. Despite warning labels affixed on the packages that these drugs might impair driving ability, the majority (71%) of these patients continued driving a car. A point of concern is that 40% of these patients reported not to be more cautious in traffic after taking psychotropic drugs. CONCLUSION: The results of this survey indicate that drug warning labels applied by Dutch pharmacies do not significantly change attitudes towards driving a car in patients taking medicinal drugs with psychotropic side effects. Future road-safety campaigns should pay more attention to the impairing effects of psychotropic drugs on driving.

Processing capacity in chronic pain patients: a visual event-related potentials study.

Chronic pain may impair performance on attentional processing capacity tasks. In the present study, event-related potentials were recorded to examine whether pain patients show performance decrements on attentional processing capacity tasks due to shared resources by pain and attention or, alternatively, due to deficits in allocating attentional resources during pain. Fourteen chronic pain patients and thirty age and education matched healthy controls were investigated. An attentional capacity probe task was used in which the difficulty level was manipulated, resulting in an easy and a difficult condition, while task-irrelevant visual probes were presented. These probe-elicited P3 amplitudes were assumed to provide the most pure estimate of processing capacity since they are relatively free from target-related processes. Event-related potentials were recorded from the midline electrodes Fz, Cz, Pz, and Oz. For the behavioral measures, it was found that pain patients maintained a different speed-accuracy tradeoff. Pain patients showed faster reaction time responses and higher error rates compared to controls. No significant differences were found between pain patients and controls on the primary task. Pain patients differed from controls with respect to amplitudes elicited by task-irrelevant probe stimuli. For healthy controls, the expected decreased amplitude was found for probe stimuli in the difficult compared to the easy task. In contrast, the pain patients did not show decreased probe amplitudes with increasing task load. The data may imply that allocation of attentional resources is deficient in pain patients, instead of attentional capacity.

Effect of chronic nonmalignant pain on highway driving performance.

Most pain patients are treated in an outpatient setting and are engaged in daily activities including driving. Since several studies showed that cognitive functioning may be impaired in chronic nonmalignant pain, the question arises whether or not chronic nonmalignant pain affects driving performance. Therefore, the objective of the present study was to determine the effects of chronic nonmalignant pain on actual highway driving performance during normal traffic. Fourteen patients with chronic nonmalignant pain and 14 healthy controls, matched on age, educational level, and driving experience, participated in the study. Participants performed a standardized on-the-road driving test during normal traffic, on a primary highway. The primary parameter of the driving test is the Standard Deviation of Lateral Position (SDLP). In addition, driving-related skills (tracking, divided attention, and memory) were examined in the laboratory. Subjective assessments, such as pain intensity, and subjective driving quality, were rated on visual analogue scales. The results demonstrated that a subset of chronic nonmalignant pain patients had SDLPs that were higher than the matched healthy controls, indicating worse highway driving performance. Overall, there was a statistically significant difference in highway driving performance between the groups. Further, chronic nonmalignant pain patients rated their subjective driving quality to be normal, although their ratings were significantly lower than those of the healthy controls. No significant effects were found on the laboratory tests.

Acute and subchronic effects of amitriptyline on processing capacity in neuropathic pain patients using visual event-related potentials: preliminary findings.

RATIONALE: Little is known about the effects of low doses of amitriptyline, prescribed in the treatment of neuropathic pain, on attentional processing capacity. OBJECTIVES: Changes due to amitriptyline treatment on attentional processing capacity were investigated on behavioral measures and event-related brain potentials (ERPs) in six patients with neuropathic pain. MATERIALS AND METHODS: Patients were treated for 15 consecutive days with 25 mg nocturnally administered amitriptyline or placebo in a double-blind crossover randomized design. Measurements were carried out on day 1 and day 15 of each treatment period. An attentional capacity probe task was used in which the difficulty level was manipulated, resulting in an easy and a hard condition, while task-irrelevant visual probes were presented. During task performance, ERPs were measured from the midline electrodes Fz, Cz, Pz, and Oz. RESULTS: Amitriptyline increased reaction times (RTs) after acute but not after subchronic administration. ERP analyses showed that P3 amplitudes to the task stimuli were not affected by amitriptyline in either treatment phase. Moreover, P3 amplitudes to the probes were increased in the easy compared to the hard task condition after subchronic amitriptyline treatment, indicating beneficial effects of repeated amitriptyline administration. In contrast, acute amitriptyline administration did reduce an earlier visual evoked potential, N1, preceding the P3 component. CONCLUSIONS: The results suggest that amitriptyline, even at low dosages of 25 mg, affects performance after acute administration in chronic neuropathic pain patients. After 2 weeks of treatment, performance appears to be unaffected. No deficits in processing capacity due to amitriptyline treatment were found.

Differential effects of amitriptyline, nefazodone and paroxetine on performance and brain indices of visual selective attention and working memory.

RATIONALE: Antidepressants may vary widely in their potential to impair cognitive and psychomotor functions. Little is known about their effects on event-related brain potentials (ERPs).OBJECTIVES. To compare the effects of three pharmacologically different antidepressants on performance and ERPs in tasks of selective attention and working memory. METHODS: Subjects were treated for 8 days with amitriptyline (sedative/anticholinergic TCA), nefazodone (5-HT(2) receptor antagonist), paroxetine (SSRI) and placebo, in a double-blind, crossover design. Measurements were carried out on day 1 and 8 of each treatment period. A task was used in which memory load (two and four items) and attention (focused, divided) were orthogonally varied. RESULTS: On day 1 amitriptyline increased reaction times (focused attention) and the percentage of misses (load 4>load 2) and false alarms. Sensitivity (A') was reduced as a function of memory load. Effects were greatly diminished on day 8. The ERP analysis yielded a reduced early frontal positive difference wave related to memory load (day 1). Attention-related search negativity was slightly prolonged. P3 latency (stimulus evaluation time) was prolonged. P3 amplitude was reduced (mainly on day 8) suggesting diminished attention capacity. Nefazodone increased reaction times and miss rates and reduced sensitivity (A') on day 8 only. Paroxetine speeded responses on day 1 and slightly increased miss rates on day 8. Performance effects of nefazodone and paroxetine did not interact with the task factors. Search negativity and P3 measures were not affected. CONCLUSIONS: The results suggest that the pharmacologically selective serotonergic antidepressants lack the specific memory and attention deficits seen with amitriptyline. Both performance and ERP data suggest that paroxetine and nefazodone may influence response-related processes, while for nefazodone an effect on other processes cannot be excluded.

Subchronic effects of the GABA-agonist lorazepam and the 5-HT2A/2C antagonist ritanserin on driving performance, slow wave sleep and daytime sleepiness in healthy volunteers.

RATIONALE: Lorazepam, a benzodiazepine anxiolytic, may increase daytime sleepiness and impair psychomotor performance, which is hazardous for patients engaging in daily activities such as car driving. Given current prescription practice, information on the repeated dose effects is required. The 5-HT2A/2C antagonist ritanserin was originally developed as a safer alternative to the benzodiazepines, yet having limited clinical efficacy. 5HT2A/2C receptors have been implicated in regulating slow-wave sleep but little is known about their role in human performance. OBJECTIVE: The present study investigated the subchronic effects of the benzodiazepine anxiolytic lorazepam and the 5-HT2A/2C antagonist ritanserin on actual driving performance, objective and subjective sleepiness, and nocturnal slow wave sleep. METHODS: Eighteen healthy volunteers were treated twice daily for 7 days with ritanserin 5 mg, lorazepam 1.5 mg or placebo. Treatments were administered according to a double-blind, cross-over design. Tests were performed on day 7 of each treatment week. Sleep EEG was recorded during the preceding night. RESULTS: Lorazepam had a pronounced impairing effect on lateral position control and induced daytime sleepiness, while having no effect on other parameters. In contrast, ritanserin did not impair driving performance or affect objectively measured daytime sleepiness, while subjects reported to feel more alert during daytime. Moreover, consistent with its effects on 5-HT2 receptors, ritanserin increased the amount of nocturnal slow wave sleep. There were no relationships between changes in slow wave sleep and performance parameters. CONCLUSIONS: Lorazepam administered for 7 consecutive days may be hazardous for patients who engage in driving activities. Antagonism of 5-HT2A/2C receptors, as accomplished by ritanserin, increases slow wave sleep and is devoid of effects on objective sleepiness and driving behaviour. Whether this extends to other cognitive and psychomotor domains remains to be established.

Acute and subchronic effects of nefazodone and imipramine on highway driving, cognitive functions, and daytime sleepiness in healthy adult and elderly subjects.

The acute and subchronic effects of two dosages of a new serotonergic antidepressant, nefazodone, and those of the tricyclic imipramine were examined in a double-blind, crossover, placebo-controlled study. Twenty-four healthy subjects from two age groups (12 adults and 12 elderly from both sexes) received the four treatments (nefazodone, 100 and 200 mg twice daily; imipramine, 50 mg twice daily; and placebo) for 7 days with a 7-day washout period. Measurements were performed after the morning doses on day 1 and day 7. These included a standard over-the-road highway driving test, a psychomotor test battery, and sleep latency tests. Blood samples were taken on both days and analyzed to determine concentrations of parent drugs and their major metabolites. The main results showed that the reference drug, imipramine, had a detrimental effect after a single dose on lateral position control in the driving test, primarily in the adult group, that diminished after repeated dosing. Minor impairment on psychomotor test performance was found with both days. On the other hand, a single administration of both doses of nefazodone did not impair highway driving performance (even showed some improvement) and had no or only minor effects on psychomotor performance. After repeated dosing, nefazodone 200 mg twice daily (but not the 100-mg dose) produced slight impairment of lateral position control; dose-related impairment of cognitive and memory functions was found. The effects of nefazodone were generally in the same direction in both age groups. Significant correlations were found between steady-state concentrations of nefazodone in plasma (200-mg, twice-daily condition) as well as imipramine, and reaction time changes in a memory scanning task. Neither drug appeared to induce daytime sleepiness as measured by the sleep latency tests.

A cetirizina pertence à nova geraçåo de anti-histamínicos?: uma investigaçåo de seus efeitos agudos e subcrônicos sobre a conduçåo de veículo em rodovia, o desempenho em testes psicométricos e a sonolência diurna / Does cetirizine belong to the new generation of antihistamines?: an investigation into its acute and subchronic effects on highway driving, psychometric test performance and daytime sleepiness

Vinte e sete voluntários saudáveis do sexo masculino participam deste ensaio duplo-cego cruzado em cinco etapas, que foi realizado para comparar um novo antagonista seletivo dos receptores de H1 - a cetirizina (10 mg q.d.) - e a terfenadina (60 mg b.i.d. e 120 mg q.d.) a um antagonista dos receptores de H1 mais tradicional, a tripolidina (5 mg b.i.d.), e a placebo. Os medicamentos foram administrados durante quatro dias consecutivos e os participantes foram testados no 1§ e no 4§ dias. No teste, os participantes já dirigiram um veículo equipado com instrumentos de mediçåo em uma rodovia de 100 Km, tentando manter uma velocidade constante (90 km/h) e um posionamento lateral estável na faixa de trafégo da direita. A seguir, foram submetidos a três testes computadorizados da memória. No 4§ dia de tratamento, a latência do sono foi medida antes e após o teste de direçåo. Em ambos os dias, a triprolidina comprometeu significativamente o desempenho dos participantes nos testes de direçåo e psicométricos, além de reduzir a latência, em comparaçåo com placebo, no 4§ dia de tratamento. A administraçåo de 60 m g b.i.d. de terfenadina comprometeu o desempenho psicométrico após o tratamento subcronico. Conclui-se que a cetirizina, com a terfenadina, pertence å classe mais recente de antihistamínicos e pode ser administrada com segurança a pacientes que continuam suas atitudes diárias

Therapeutic effects and effects on actual driving performance of chronically administered buspirone and diazepam in anxious outpatients.

Two groups of 12 outpatients each (six men and six women) with generalized anxiety disorder, participated in this study. Each patient was treated single-blind with placebo during the first 7 days (baseline), followed by a double-blind drug treatment period of 4 consecutive weeks (active) and ending again with 7 days single-blind placebo treatment (washout). One group received buspirone 5 mg three times a day in the first week and continued with 10 mg in the morning, 5 mg in the afternoon, and 5 mg in the evening during the second, third, and fourth weeks. The other group received diazepam 5 mg three times a day in all 4 weeks. On the evening of the seventh day of each treatment week the Hamilton Rating Scale for Anxiety and the Symptom Check List (90 items) were applied to assess the therapeutic effects, followed by an on-the-road driving test that started 1.5 hours after the last drug or placebo intake. The test consisted of operating an instrumented vehicle over a 100 kilometer highway circuit while attempting to maintain a constant speed and a steady lateral position within the right traffic lane. Two patients in the diazepam group were unable to complete their test after the first and second treatment week, respectively, because of serious sedative reactions. Both buspirone and diazepam were equally effective in reducing overall anxiety symptoms. The specific profiles showed that buspirone also reduced concomitant depressive symptoms and symptoms of interpersonal sensitivity and anger-hostility. In contrast, diazepam was found to be slightly more effective in reducing somatic symptoms and to positively affect sleep disturbances. Moreover, abrupt discontinuation of diazepam resulted in a relapse of psychic anxiety symptoms comparable with the placebo-baseline level and a partial relapse of somatic anxiety symptoms. Chronic treatment with buspirone had no significant effects on lateral position and speed control. In contrast, diazepam significantly impaired control of lateral position in the first 3 weeks of treatment. There was no significant impairment in the fourth treatment week and the placebo-washout week. Speed control was significantly impaired only in the first week. The relevance of the trend toward decreasing performance impairment during chronic treatment remains to be established.

Repeated dose effects of lormetazepam and flurazepam upon driving performance.

The residual effects of lormetazepam 1 mg and 2 mg in soft gelatine capsules on driving performance were assessed and compared to those of flurazepam 30 mg, which is also a powerful hypnotic, but possesses a far less favourable pharmacokinetic profile with a long-acting sedative metabolite. Driving performance was tested 10 to 11 h and 16 to 17 h post administration, after 2 days on placebo (baseline), and 2, 4 and 7 days of drug treatment (active), and after 1 and 3 days following the resumption of placebo (washout). The driving test consisted of operating an instrumented motor-vehicle over a 72 km highway circuit in light traffic. Flurazepam 30 mg significantly impaired the ability to control the lateral position of the vehicle compared to placebo baseline measurements. The degree of impairment was substantial in the female subjects and was greater in the morning than in the afternoon. Lormetazepam 1 mg showed no residual effect on driving performance. Lormetazepam 2 mg impaired driving performance to some extent on the following morning, 10 to 11 h post administration, but no residual effect was found in the afternoon. All drugs improved sleep quality and prolonged sleep duration to more or less the same extent.

Hypnotics and actual driving performance.

Several related studies of the residual effects of hypnotic drugs on actual driving performance have been conducted using a standard approach and the most recent is described in detail. In it, 12 female formerly diagnosed insomniacs and hypnotic users acted as subjects. They were treated in two separate series with placebo for 2 nights, then hypnotic medication for 8 nights followed by placebo again for 3 nights. In one series, the medication was nitrazepam (10 mg nocte) and in the other, temazepam (20 mg nocte). Eleven subjects completed both series in a double-blind, cross-over (with respect to drugs) design. Their driving performance was repeatedly tested on a 100 km primary highway circuit, in normal traffic, during both the morning and afternoon (10-11 hours and 16-17 hours after drug and placebo ingestion, respectively). Nitrazepam but not temazepam significantly impaired driving performance, the difference lasting throughout the active medication period. These results along with those obtained in the earlier studies are compared to show degrees of driving impairment which follow the use of various hypnotics.