Effects of Eszopiclone on Sleep and Memory in Schizophrenia

Not Applicable

Completed

Conditions: Schizophrenia

Interventions: Drug: eszopiclone
Drug: placebo

Registration Number: NCT01641900

Lead Sponsor: Massachusetts General Hospital

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 59

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Schizophrenia	placebo	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.
Healthy Controls	placebo	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.
Schizophrenia	eszopiclone	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.
Healthy Controls	eszopiclone	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.

Primary Outcome Measures

Name	Time	Method
Sleep Spindle Density	Spindles will be averaged for the Baseline (Night 1) and Experimental Nights (Night 2)	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.

Secondary Outcome Measures

Name	Time	Method
Motor Procedural Memory Performance	Experimental Night (Night 2)	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.