Abuse Liability of Pregabalin and Its Effects on Benzodiazepine Withdrawal Symptoms

Evaluation of Pregabalin's Abuse Liability and Its Effects on Benzodiazepine Withdrawal Symptoms in Inpatients Undergoing Medically Assisted Benzodiazepine Withdrawal

The purpose of this study is to determine if a single dose of pregabalin 300mg in patients receiving medications for sedative-hypnotic withdrawal symptoms will produce meaningful differences in measures of "drug liking" and "drug high" as compared to placebo.

Pregabalin is currently being explored as a pharmacotherapy for substance use disorders. Open-labeled, uncontrolled studies indicate modest efficacy of pregabalin in benzodiazepine withdrawal symptom management and as a long-term benzodiazepine dependence treatment. Concurrently, there is increasing information from case reports and adverse drug event registries regarding pregabalin abuse in patients with substance use disorders. Given that the abuse liability of pregabalin has not been clearly established, nor its effects on benzodiazepine withdrawal symptoms in inpatients, this study is a randomized, double-blind, placebo-controlled, cross-over, abuse liability study of a single dose of pregabalin 300mg, nested within a randomized,double-blind placebo-controlled, feasibility study evaluating pregabalin's effects on withdrawal symptoms in inpatients undergoing medically-assisted withdrawal from benzodiazepine, zopiclone or zolpidem.

In replacement of their morning 75mg pregabalin or placebo dose on Days 6 and 8, all participants will receive either a single dose of 300mg of pregabalin or placebo, in a randomized, double-blind, crossover manner. This is when steady state concentrations of pregabalin occur.

In replacement of their morning 75mg pregabalin or placebo dose on Days 6 and 8, all participants will receive either a single dose of 300mg of pregabalin or placebo, in a randomized, double-blind, crossover manner. This is when steady state concentrations of pregabalin occur.

Change from baseline on Visual Analogue Scale for "Drug Liking" over 5 hours post-dose administration

Change in score on the six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI)

Inclusion Criteria: Admitted to the Medical Withdrawal Unit at the Centre for Addiction and Mental Health for medically assisted withdrawal from benzodiazepines, zopiclone and/or zolpidem Willing and capable to give written informed consent Exclusion Criteria: Patients who are hypersensitive to pregabalin or to any ingredient in the formulation or component of the container. Pregnant or nursing women Renal impairment (creatinine clearance less than 60ml/min) History of angioedema, or taking drugs associated with angioedema (e.g., ACE-inhibitors). Currently taking pregabalin or gabapentin Currently taking thiazolidinedione antidiabetic agents (e.g., rosiglitazone, pioglitazone) Previous history of pregabalin or gabapentin abuse

The Centre for Addiction and Mental Health (CAMH) is the leading mental health and addictions research facility in Canada, and one of the largest in the world.