Background. The majority of those suffering from anxiety or related disorders are outpatients, and presumably involved in daily activities such as driving a car. However, anxiolytic drugs may possess sedative properties that reduce alertness and produce sleepiness. Therefore, it must be questioned whether it is safe to drive a car when treated with these drugs. Methods.A MEDLINE literature search (keywords driving and anxiety) and cross-references identified 14 placebo-controlled, double-blind studies that examined the effects of anxiolytic drugs on driving ability by conducting the on-the-road driving test during normal traffic. Primary parameter of the driving test is the Standard Deviation of Lateral Position (SDLP), the weaving of the car. Data from epidemiological studies was summarized as supportive evidence.Results. After single dose administration of benzodiazepines and related GABAergic compounds (diazepam, lorazepam, alprazolam, oxazepam, alpidem, suriclone, zolpidem) driving performance was significantly impaired. Further, although tolerance develops, driving studies show that the impairing effects of benzodiazepines and related GABAergic compounds may still be present after on week of daily treatment (demonstrated for diazepam, lorazepam, alpidem, suriclone). Driving performance was also significantly impaired after single dose administration of TCAs (imipramine, amitriptyline), but after repeated use of TCAs tolerance developed to the impairing effects on driving ability. In contrast, SSRIs (paroxetine, fluoxetine), venlafaxine, ondansetron) and buspirone produced no significant impairment on the driving test after both acute and repeated administration. These findings were in line with epidemiological evidence.Conclusions. Patients treated with benzodiazepines, GABAergic compounds, or TCAs should be cautioned when driving a car. Driving a car when treated with buspirone, venlafaxine, 5HT-antagonists, and SSRIs seems relatively safe.

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Placebo effects, positive treatment outcomes that go beyond treatment processes, can alter sensations through learning mechanisms. Understanding how methodological factors contribute to the magnitude of placebo effects will help define the mechanisms by which these effects occur. We conducted a systematic review and meta-analysis of experimental placebo studies in cutaneous pain and itch in healthy samples, focused on how differences in methodology contribute to the resulting placebo effect magnitude. We conducted meta-analyses by learning mechanism and sensation, namely, for classical conditioning with verbal suggestion, verbal suggestion alone, and observational learning, separately for pain and itch. We conducted subgroup analyses and meta-regression on the type of sensory stimuli, placebo treatment, number of acquisition and evocation trials, differences in calibrated intensities for placebo and control stimuli during acquisition, age, and sex. We replicated findings showing that a combination of classical conditioning with verbal suggestion induced larger placebo effects on pain (k 5 68, g 5 0.59) than verbal suggestion alone (k 5 39, g 5 0.38) and found a smaller effect for itch with verbal suggestion alone (k 5 7, g 5 0.14). Using sham electrodes as placebo treatments corresponded with larger placebo effects on pain than when topical gels were used. Other methodological and demographic factors did not significantly affect placebo magnitudes. Placebo effects on pain and itch reliably occur in experimental settings with varied methods, and conditioning with verbal suggestion produced the strongest effects. Although methods may shape the placebo effect to some extent, these effects appear robust overall, and their underlying learning mechanisms may be harnessed for applications outside the laboratory.