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A double-blind, placebo- and positive-internal-controlled (alprazolam) investigation of the cognitive and psychomotor profile of pregabalin in healthy volunteers

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Abstract

Rationale

Pregabalin potently and selectively binds to the alpha2-delta subunit of voltage-dependent calcium channels, reducing calcium influx and modulating release of downstream excitatory neurotransmitters, such as glutamate. Pregabalin has demonstrated robust efficacy for several disease states, but its neuropharmacology is still being elucidated.

Objective

This study was conducted to evaluate the cognitive and psychomotor effects of oral pregabalin (150 mg t.i.d.) using alprazolam (1 mg t.i.d.) as a positive internal control and placebo.

Methods

Twenty-four healthy volunteers were randomised to a double-blind, three-way crossover study. Each period consisted of 3-day double-blind treatment followed by 1 day of single-blind placebo. Psychometrics included tests of Choice Reaction Time (CRT), CNS arousal (Critical Flicker Fusion, CFF), vigilance (Rapid Visual Information Processing, RVIP), serial memory scanning (Sternberg Short-Term Memory Scanning Test, STM), divided attention (Compensatory Tracking Task, CTT), Brake Reaction Time (BRT) in an on-the-road vehicle, and subjective Line Analogue Rating Scales (LARS) for sedation.

Results

Pregabalin showed no significant effects on the objective psychometrics—CRT, BRT, RVIP, STM—compared with placebo. Pregabalin produced a limited, significant decrement on CFF and CTT and a significant effect on the LARS. Pregabalin was associated with improvement relative to placebo in BRT. The positive control, alprazolam, produced significant impairment on all objective measures and significant impairment on the LARS, thus establishing the sensitivity of the test battery used in the study.

Conclusions

Pregabalin did not differ on most assessments from placebo, producing only minor, transient impairment on some objective cognitive and psychomotor measures, suggesting a relatively benign CNS side-effect profile.

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Acknowledgements

This study was supported by an unrestricted research grant to the HPRU Medical Research Centre, University of Surrey, from Pfizer, Inc.

The authors would like to thank Drs. Neil Stanley, Richard Kavoussi, Gail Farfel, and Mark Versavel for their support and valuable comments.

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Authors and Affiliations

  1. HPRU Medical Research Centre, School of Biomedical and Molecular Sciences, University of Surrey, Egerton Road, Guildford, Surrey, GU2 7XP, UK

    Ian Hindmarch, Leanne Trick & Fran Ridout

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  1. Ian Hindmarch
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  2. Leanne Trick
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  3. Fran Ridout
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Correspondence to Ian Hindmarch.

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Hindmarch, I., Trick, L. & Ridout, F. A double-blind, placebo- and positive-internal-controlled (alprazolam) investigation of the cognitive and psychomotor profile of pregabalin in healthy volunteers. Psychopharmacology 183, 133–143 (2005). https://doi.org/10.1007/s00213-005-0172-7

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