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Acute and subchronic effects of amitriptyline 25mg on actual driving in chronic neuropathic pain patients

Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Department of Psychopharmacology, Utrecht University, Utrecht, The Netherlands. Pain Clinic, Department of Anaesthesiology, University Medical Centre Utrecht, Utrecht, The Netherlands

Albert J.M. van Wijck

Pain Clinic, Department of Anaesthesiology, University Medical Centre Utrecht, Utrecht, The Netherlands

Joris C. Verster

Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Department of Psychopharmacology, Utrecht University, Utrecht, The Netherlands

J. Leon Kenemans

Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Department of Psychopharmacology, Utrecht University, Utrecht, The Netherlands; Helmholtz Research Institute, Department of Psychonomics, Utrecht University, Utrecht, The Netherlands

Cor J. Kalkman

Pain Clinic, Department of Anaesthesiology, University Medical Centre Utrecht, Utrecht, The Netherlands

Berend Olivier

Edmund R. Volkerts

Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Department of Psychopharmacology, Utrecht University, Utrecht, The Netherlands

The acute and subchronic effects of low doses nocturnally administered amitriptyline were compared to placebo in a double-blind crossover randomized study on driving ability and driving-related skills involving seven chronic neuropathic pain patients. Performance testing occurred at the first and last day of each 15-day drug administration period, which was preceded by a 6-day washout phase. A standardized method of measuring driving ability, the on-the-road driving test, was performed on all visits. Patients were instructed to drive with a steady lateral position while maintaining a constant speed of 95km/h. The primary outcome of the driving test is the Standard Deviation of Lateral Position (SDLP, cm), which is an index of weaving of the car. At the first treatment day, driving performance was significantly impaired in patients after nocturnal administration of 25mg amitriptyline compared to placebo. The increase in SDLP of 3cm was higher than the increment generally observed with a blood alcohol concentration of 0.5mg/ml or higher, the legal limit for driving in many countries. Also, reaction times on a memory test were significantly increased, indicating worse performance after acute treatment of amitriptyline compared to placebo. In contrast, after 2 weeks of treatment, no significant differences were found between amitriptyline and placebo, suggesting that tolerance had developed to the impairing effects of amitriptyline.

Key Words: amitriptyline • driving • SDLP • neuropathic pain • psychomotor performance • cognition

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