Cognitive effects of pregabalin in the treatment of long-term benzodiazepine-use and dependence

Hum Psychopharmacol. 2014 May;29(3):224-9. doi: 10.1002/hup.2391. Epub 2014 Feb 17.


Objective: Long-term benzodiazepine (BDZ) use and dependence affect cognitive functioning adversely and partly irreversibly. Emerging evidence suggests that pregabalin (PGB) might be a safe and efficacious treatment of long-term BDZ use. The aim of the present study was to investigate the changes in several core cognitive functions after successful treatment of long-term BDZ use and dependence with PGB.

Methods: Fourteen patients with long-term BDZ use (mean duration >15 years) underwent neuropsychological assessment with the mini-mental state examination and four tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) battery before the initiation of PGB treatment and at a two months follow-up after the cessation of BDZs. Patients' CANTAB percentile score distributions were compared with normative CANTAB data.

Results: Patients improved on cognitive measures of global cognitive functioning, time orientation, psychomotor speed, and visuospatial memory and learning with strong effect sizes. By contrast, they failed to improve on measures of attentional flexibility. Despite their significant improvement, patients' scores on most tests remained still at the lower percentiles of CANTAB normative scores.

Conclusions: Although preliminary, our findings suggest that successful treatment of long-term BDZ use with PGB is associated with a substantial, though only partial, recovery of BDZ-compromised neuropsychological functioning, at least at a 2-month follow-up.

Keywords: benzodiazepine dependence; cognition; pregabalin.

MeSH terms

  • Benzodiazepines / adverse effects*
  • Central Nervous System Agents / therapeutic use*
  • Cognition / drug effects
  • Cognition Disorders / chemically induced
  • Cognition Disorders / drug therapy*
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neuropsychological Tests
  • Pregabalin
  • Psychotropic Drugs / adverse effects*
  • Substance-Related Disorders / drug therapy*
  • Time Factors
  • Treatment Outcome
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / therapeutic use


  • Central Nervous System Agents
  • Psychotropic Drugs
  • Benzodiazepines
  • Pregabalin
  • gamma-Aminobutyric Acid