Insomniacs driving after use of sleeping medication

Rationale: To date, most experimental studies investigating the next-day residual effects of hypnotics on actual driving performance have been conducted in healthy young volunteers after evening administration of a single dose. This group of subjects differs, however, on two important aspects with the target population, i.e. insomniacs. First, insomniacs have sleeping problems and may therefore benefit from the therapeutic effects of hypnotics. The disturbed sleep in insomniacs may cause significant impairment in daytime performance. Daytime performance after a hypnotic-induced night would be improved compared to performance after a medication-free night. Secondly, a large number of patients are using hypnotics for prolonged periods, which may result in tolerance towards the residual effects. No study has directly compared the residual effects of hypnotics on driving performance between medication-naïve healthy volunteers and insomniacs using hypnotics for prolonged periods.

Objective: The primary objective of the study is to determine whether the residual effects of zopiclone 7.5 mg on highway driving performance differ between patients complaining of insomnia and frequently using hypnotics, insomnia patients not frequently using hypnotics, and healthy controls, using a one-hour standardized highway driving test in normal traffic.

Study design: A 2x3, double-blind, crossover design comparing the residual effects of zopiclone 7.5 mg and placebo on actual driving performance and cognitive and psychomotor performance in three groups.

Study population: Participants will be a total of 48 participants in this study, divided in three groups:

- 16 individuals complaining of insomnia and frequently using hypnotics (‘users’), defined as an average use of hypnotics of at least four nights per week for more than 3 months

- 16 individuals complaining of insomnia and not using hypnotics (‘non-users’), defined as an average use of hypnotics of less or equal to two nights per week for more than 3 months

- 16 self-defined good sleepers (matched for age, sex, education and driving experience (‘controls’)

Intervention: Subjects receive a single oral dose of zopiclone 7.5 mg or placebo. Balancing of treatments will be accomplished by randomly assigning subjects to one of two treatment sequences (placebo – zopiclone or vice versa).

Main study parameters/endpoints: The main study parameter is Standard Deviation of Lateral Position (SDLP in cm) in the highway driving test.

Driving performance after administration of zopiclone 7.5 mg is not different between patients complaining of insomnia and frequently using hypnotics, insomnia patients not frequently using hypnotics and matched healthy controls.

Activity Day 1 Actual Time(h:m)

Arrival and check-in: 20:00

Adverse events

Concomitant medication: 20:00 – 20:30

Attachment Polysomnography electrodes: 20:30

Reminder to make ready for bed: 23:00

Instruction to sleep (drug intake ‘users’): 23:30




Activity Day 2

Wake up subject: 07:30

Standard breakfast

- Sleep Quality Scale [2 min] 08:00–9:00

- Bond and Lader VAS [3 min]

- Cognitive Performance Tests [57 min]

- Word Learning Test Immediate Recall [8 min]

- Critical Tracking Task [3 min]

- Divided Attention Task [12 min]

- Psychomotor Vigilance Task [11 min]

- Stop Signal Task [16 min]

- Digit Span Forward & Backward [5 min]

- Word Learning Test Delayed Recall and Recognition Task [5 min]

Serum concentration: 09:00

Highway Driving Test: 09:30 – 10:45
Car Following Test:

Subjective Driving Quality: 10:45 – 11:10

Subjects receive a single oral dose of zopiclone 7.5 mg or placebo. Balancing of treatments will be accomplished by randomly assigning subjects to one of two treatment sequences (placebo – zopiclone or vice versa).