Insomnia, Schizoaffective Disorder, Schizophrenia, Sleep Disorders
Conditions
Brief summary
The major goal of this project is to investigate established insomnia treatments in a schizophrenia population to see if the improved sleep leads to overall better quality of life. In addition, we hypothesize that the insomnia treatment may also lead to observed improvements in other symptoms associated with schizophrenia such as cognitive impairments, obesity, and negative symptoms.
Detailed description
The primary aim of this study is to investigate the clinical efficacy of eszopiclone for the treatment of schizophrenia-related insomnia over 8 weeks. A two-week, single-blind placebo phase followed the double-blind phase to evaluate rebound and withdrawal effects after abrupt discontinuation.
Interventions
DRUGEszopiclone
Eszopiclone 2mg each night for the first week then Eszopiclone 3mg each night for the remaining weeks.
DRUGPlacebo
Placebo or inactive substance (sugar pill)taken each night for all weeks of the study
Sponsors
Sumitomo Pharma America, Inc.
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Be between the ages of 18 to 64 * Meet DSM-IV criteria for schizophrenia or schizoaffective disorder * Sleep difficulties at least 2x per week in the preceding month * Be on a stable dose of antipsychotic medication * Symptomatically stable in the last 2 months * English speaking.
Exclusion criteria
* Meet criteria for current alcohol or other substance dependence * A history of dementia, mental retardation or other neurological disorder * Not capable of giving informed consent for participation in this study. * Ongoing pregnancy * Known sensitivity to zopiclone. * Insomnia associated with medical disorders likely to impair sleep. * Use of any medication that affects sleep/wake function (other than antipsychotic medication), within the past 2 weeks or within a time period that is less than 7 half-lives since last use of the medication. * Lack of sleep benefit from previous adequate eszopiclone treatment * History of clinically significant hepatic impairment. * Subject is taking a potent cytochrome p450 3A4 inhibitor medication (ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole) and is unwilling or it is clinically contraindicated to stop the medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Insomnia Severity Index From Baseline. | 8 Weeks | The Insomnia Severity Index (ISI) is a 7-item self-report questionnaire that provides a global measure of insomnia severity based on several indicators (e.g., difficulty falling or staying asleep, satisfaction with sleep, degree of impairment with daytime functioning). It has adequate internal consistency (Cronbach's alpha=0.91) and temporal stability (r=0.80), has been validated against sleep diary and polysomnography data and was sensitive to change in several insomnia treatment studies. The ISI scale range is: minimum = 0, maximum = 28. The interpretation is that lower is 'better sleep', while higher is considered 'worse sleep/more insomnia'. |
Countries
United States
Participant flow
Recruitment details
The study was conducted between May 2008 and February 2011 at a community mental health center. Following screening and baseline assessment, eligible patients who continued to meet inclusion criteria were randomly assigned to either placebo or eszopiclone in a 1:1 ratio using a randomization procedure blind to both research team and subjects.
Pre-assignment details
179 outpatients were screened, 44 met initial eligibility criteria. Forty-three consented to participate and 4 were withdrawn prior to randomization. Of the remaining 39, 19 were randomized to placebo and 20 to eszopiclone 3mg. Two participants in the placebo arm and 1 participant in the eszopiclone arm withdrew before receiving study medication
Participants by arm
| Arm | Count |
|---|---|
| Eszopiclone Group Participants assigned to this arm will receive Eszopiclone 2mg each night for the first week then Eszopiclone 3mg each night for the remaining weeks.
Eszopiclone: Eszopiclone 2mg each night for the first week then Eszopiclone 3mg each night for the remaining weeks. | 19 |
| Placebo Group Participants assigned to this arm will receive placebo (an inactive substance or a sugar pill) to be taken each night for all weeks of the study.
Placebo: Placebo or inactive substance (sugar pill)taken each night for all weeks of the study | 17 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomized | Withdrawal by Subject | 1 | 2 |
| Received Medication | Adverse Event | 2 | 1 |
| Received Medication | Lost to Follow-up | 1 | 0 |
| Received Medication | Protocol Violation | 2 | 1 |
| Received Medication | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Eszopiclone Group | Placebo Group | Total |
|---|---|---|---|
| Age, Continuous | 45.7 years STANDARD_DEVIATION 7.4 | 47.5 years STANDARD_DEVIATION 10.2 | 46.5 years STANDARD_DEVIATION 12.9 |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 19 | 13 / 17 |
| serious Total, serious adverse events | 3 / 19 | 1 / 17 |
Outcome results
Primary
Change in Insomnia Severity Index From Baseline.
The Insomnia Severity Index (ISI) is a 7-item self-report questionnaire that provides a global measure of insomnia severity based on several indicators (e.g., difficulty falling or staying asleep, satisfaction with sleep, degree of impairment with daytime functioning). It has adequate internal consistency (Cronbach's alpha=0.91) and temporal stability (r=0.80), has been validated against sleep diary and polysomnography data and was sensitive to change in several insomnia treatment studies. The ISI scale range is: minimum = 0, maximum = 28. The interpretation is that lower is 'better sleep', while higher is considered 'worse sleep/more insomnia'.
Time frame: 8 Weeks
Population: Of 39 eligible participants, 19 were randomized to placebo and 20 to eszopiclone 3mg. Two participants in the placebo arm and 1 participant in the eszopiclone arm withdrew before receiving study medication. 36 participants were included in the modified ITT analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Eszopiclone Group | Change in Insomnia Severity Index From Baseline. | -10.7 units on a scale |
| Placebo Group | Change in Insomnia Severity Index From Baseline. | -6.9 units on a scale |
p-value: 0.03995% CI: [-7.5, -0.2]Mixed Models Analysis