Effects of Eszopiclone on Sleep and Memory in Schizophrenia

Sleep-dependent Memory Processing in Schizophrenia

The investigators will test the hypothesis that the sleep medication, eszopiclone, can normalize brain activity during sleep and improve memory in patients with schizophrenia. The investigators will do this by measuring sleep and memory performance on two conditions separated by one week: taking 3 mg of eszopiclone and taking placebo. The investigators will study healthy subjects and chronic, medicated outpatients with schizophrenia.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: eszopiclone; Drug: placebo

Detailed Description

Sleep spindles, a defining oscillation of stage 2 non-rapid eye movement sleep (N2), are strongly linked to memory and IQ in healthy individuals. Schizophrenia is characterized by a spindle deficit that correlates with deficient sleep-dependent memory consolidation, symptom severity, IQ and executive function. In a small pilot study of schizophrenia patients, eszopiclone , significantly increased sleep spindles but its effect on memory was not significant. Here, in a larger double-blind, placebo-controlled, cross-over design study, we investigated whether eszopiclone can both increase spindle density and improve memory consolidation. Chronic, medicated schizophrenia outpatients and demographically-matched healthy control participants were randomly assigned to receive either placebo first or 3mg of eszopiclone first for two consecutive nights with high density polysomnography. Placebo and eszopiclone visits were one week apart. Participants were trained on the Motor Sequence Task (MST) at bedtime of the second night of each visit and tested the following morning to probe sleep-dependent motor memory consolidation.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• clinically stable outpatients with schizophrenia,
• proficient in English,
• able to give informed consent,
• maintained on a stable dose of atypical antipsychotic medications for at least 6 weeks prior to enrollment.
• healthy Control participants matched as a group to the patients for age, sex, and parental socioeconomic status.

Exclusion Criteria:

• Substance abuse or dependence within the past six months;
• other chronic medical conditions that affect sleep; (- pregnancy/breast feeding;
• hepatic impairment;
• treatment with inhibitors or inducers of CYP 3A4 or 2E1 enzymes (which metabolize eszopiclone);
• a history of head injury resulting in prolonged loss of consciousness or other neurological sequelae; (- mental retardation; (- a diagnosed sleep disorder other than insomnia,
• neurological disorder; sleep disorder, other than insomnia, identified in a clinical sleep evaluation.

Patients on conventional agents, benzodiazepines, or other sleep agents will be excluded. Potential controls will be excluded for a personal history of mental illness, a family history of schizophrenia spectrum disorder or psychosis, and treatment with medications known to affect sleep or cognition.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Schizophrenia; Outpatients with a Structural Clinical Interview confirmed DSM-IV diagnosis of schizophrenia. All participants receive two interventions: 3 mg eszopiclone and Placebo Intervention conditions are separated by 1 week.	Drug: eszopiclone; 3 mg of eszopiclone for two consecutive nights (Baseline Night and Experimental Night). Sleep spindle density (primary outcome) is measured for both nights. Memory consolidation (secondary outcome) is measured over Experimental Night.; Other Names: Lunesta; Drug: placebo; placebo capsule for two consecutive nights. (Baseline Night and Experimental Night). Sleep spindle density (primary outcome) is measured for both nights. Memory consolidation (secondary outcome) is measured over Experimental Night.
Experimental: Healthy Controls; Adult participants screened to exclude a personal history of mental illness, family history of schizophrenia spectrum disorder, and psychoactive medication use. All participants receive two interventions: 3 mg eszopiclone and Placebo Intervention conditions are separated by 1 week.	Drug: eszopiclone; 3 mg of eszopiclone for two consecutive nights (Baseline Night and Experimental Night). Sleep spindle density (primary outcome) is measured for both nights. Memory consolidation (secondary outcome) is measured over Experimental Night.; Other Names: Lunesta; Drug: placebo; placebo capsule for two consecutive nights. (Baseline Night and Experimental Night). Sleep spindle density (primary outcome) is measured for both nights. Memory consolidation (secondary outcome) is measured over Experimental Night.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep Spindle Density	This measure is averaged for Baseline and Experimental nights. Sleep spindle density (number/minute) for non-Rapid Eye Movement Stage 2 sleep (N2) detected at channel Cz based on polysomnographic recordings.	Spindles will be averaged for the Baseline (Night 1) and Experimental Nights (Night 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor Procedural Memory Performance	Overnight performance improvement on the finger tapping motor sequence task (MST).The MST involves pressing four numerically labeled keys on a standard keyboard with the fingers of the left hand, repeating a 5 digit sequence as quickly and accurately as possible for 12 trials at 30 seconds each separated by 30 sec rest periods. Different sequences were employed for the Placebo and Drug visits in a counter-balanced order. MST performance is measured as the number of correctly typed sequences in each trial. The primary outcome measure is overnight improvement calculated as the percent increase in average of correct sequences from the last three training trials to the average of first three test trials. Since the outcome measure is calculated as percent improvement from training to test for each participant, there is no highest or lowest possible score.	Experimental Night (Night 2)

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Beth Israel Deaconess Medical Center; Mclean Hospital
• Investigators: Principal Investigator: Dara S Manoach, Ph.D., Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: January 25, 2012
• First Submitted That Met QC Criteria: July 12, 2012
• First Posted (Estimate): July 17, 2012

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: May 16, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: memory; sleep; schizophrenia; eszopiclone
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Eszopiclone
• Other Study ID Numbers: R01MH092638 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no plan to share IPD data.