Effects of Eszopiclone on Sleep and Memory in Schizophrenia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Sleep-dependent Memory Processing in Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: eszopiclone
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Schizophrenia<br>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<br>* 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.<br>* Other names: Lunesta;Drug: placebo<br>* 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.<br>|
| Experimental: Healthy Controls<br>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<br>* 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.<br>* Other names: Lunesta;Drug: placebo<br>* 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.<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sleep, memory, schizophrenia, eszopiclone