Hypnotic Medications and Memory: Effect of Drug Exposure During the Night

Hypnotic Medications and Sleep-dependent Memory Consolidation: the Effect of Variable Drug Exposure During the Night

The purpose of this study is to determine the effect of two hypnotic medications, zolpidem extended release and zaleplon, on memory. It is expected that a hypnotic with shorter drug duration will allow greater memory consolidation than a hypnotic with longer drug duration.

Study Overview

• Status: Completed
• Conditions: Sleep; Memory
• Intervention / Treatment: Drug: bedtime placebo; Drug: middle of the night placebo; Drug: zolpidem extended release; Drug: zaleplon

Detailed Description

A growing body of evidence has demonstrated that sleep promotes memory consolidation in healthy individuals. However, little research has been conducted regarding the effect of hypnotics on sleep-dependent memory. One study found that zopiclone (7.5 mg), but not brotizolam (0.25 mg), impaired sleep-dependent memory consolidation in normal sleepers. Another study reported significant impairment of sleep-dependent memory on a motor task with triazolam (0.375 mg), but not with zolpidem immediate release (10 mg). These studies provide some evidence that sedative-hypnotic drugs may impair sleep-dependent memory consolidation, but further investigation is clearly needed in this area. Because hypnotics are commonly prescribed for insomnia, it is important to determine if there is a significant risk of impairment in sleep-dependent memory consolidation associated with these medications. Further, investigation of alternative doses and drug regimens upon memory consolidation appears warranted.

The purpose of the current study is to determine the effect of two hypnotic medications on sleep-dependent memory consolidation in normal sleepers. Zolpidem extended release, which will be active for most of the sleep period when administered at bedtime, will be compared to zaleplon, which will be active for half of the sleep period when administered in the middle of the night. This comparison allows us to address the question of whether a few hours of drug-free sleep results in better memory consolidation than sleep with drug throughout the night.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • St. Luke's Hospital Sleep Medicine and Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 to 50 years of age
• no sleep complaints or problems
• good sleep quality per questionnaire
• sufficient time in bed each night

Exclusion Criteria:

• any clinically significant unstable medical condition
• recent psychiatric disorder
• prior diagnosis or symptoms of a sleep disorder
• recent history of substance abuse
• recent use of prescription hypnotic medication or over-the-counter sleep aid
• recent use of psychotropic medication
• history of adverse reaction to benzodiazepines
• body mass index > 36
• currently pregnant or nursing
• currently working rotating or night shift
• consumption of > 700 mg per day of xanthine-containing food or beverages
• consumption of > 14 units of alcohol per week
• smoke > 1 pack of cigarettes per day, use of chewing tobacco more than 3 times per day, or unable to refrain from smoking or chewing without distress or discomfort while in the sleep laboratory

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Bedtime Placebo	Drug: bedtime placebo; placebo
Placebo Comparator: Middle of the Night Placebo	Drug: middle of the night placebo; placebo
Experimental: Zolpidem	Drug: zolpidem extended release; 12.5 mg; Other Names: Ambien CR
Experimental: Zaleplon	Drug: zaleplon; 10 mg; Other Names: Sonata

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Memory	Two memory tasks will be used to assess memory.	8 timepoints: 4 evenings and 4 mornings

Collaborators and Investigators

• Sponsor: St. Luke's Hospital, Chesterfield, Missouri
• Collaborators: American Academy of Sleep Medicine
• Investigators: Principal Investigator: Janine M Hall-Porter, PhD, St. Luke's Hospital

Publications and helpful links

General Publications

• Greenblatt DJ, Harmatz JS, von Moltke LL, Ehrenberg BL, Harrel L, Corbett K, Counihan M, Graf JA, Darwish M, Mertzanis P, Martin PT, Cevallos WH, Shader RI. Comparative kinetics and dynamics of zaleplon, zolpidem, and placebo. Clin Pharmacol Ther. 1998 Nov;64(5):553-61. doi: 10.1016/S0009-9236(98)90139-4.
• Weinling E, McDougall S, Andre F, Bianchetti G, Dubruc C. Pharmacokinetic profile of a new modified release formulation of zolpidem designed to improve sleep maintenance. Fundam Clin Pharmacol. 2006 Aug;20(4):397-403. doi: 10.1111/j.1472-8206.2006.00415.x.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: July 8, 2010
• First Submitted That Met QC Criteria: July 8, 2010
• First Posted (Estimate): July 9, 2010

Study Record Updates

• Last Update Posted (Estimate): August 26, 2014
• Last Update Submitted That Met QC Criteria: August 25, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: memory; sleep; Polysomnography; hypnotics; Hypnotics and Sedatives; zaleplon; zolpidem; Sonata; Ambien; Monitoring, sleep
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; GABA Modulators; GABA Agents; Anticonvulsants; Sleep Aids, Pharmaceutical; GABA-A Receptor Agonists; GABA Agonists; Zolpidem; Zaleplon
• Other Study ID Numbers: 63-SR-10