Effects of Eszopiclone on Sleep and Memory in Schizophrenia

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.

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.