Sleep Initiation and Maintenance Disorders
Conditions
Brief summary
Sleeping medications, called hypnotics, are often prescribed for insomnia and are associated with adverse health outcomes in older adults. Response rates to hypnotic discontinuation programs are often inadequate, and many patients eventually resume use of hypnotics, suggesting that other mechanisms need to be targeted to achieve and sustain high rates of non-use. Current programs focus on the tapering of hypnotics and/or the treatment of insomnia symptoms. These programs employ strategies such as supervised gradual taper, cognitive behavioral therapy targeting hypnotic withdrawal, and/or cognitive behavioral therapy for insomnia. Evidence suggests that another mechanism involving "placebo" effects may be a viable target for achieving and sustaining higher discontinuation rates. Cognitive expectancies play a key role in producing placebo effects, which are characterized as real improvements in sleep arising from psychosocial aspects of treatment rather than drug effects alone. In this study, investigators are comparing two programs for discontinuing hypnotic medications-a program that addresses placebo effects associated with hypnotic use and a program that does not address these effects.
Detailed description
Investigators will complete a 5-year randomized trial, recruiting participants from two healthcare systems using a three-step screening process that minimizes time and travel burden to participants. Step 1 (identification of participants): Investigators will identify participants aged \>= 55 years who have current prescriptions for lorazepam, temazepam, alprazolam, and/or zolpidem for \>= 3 months. Investigators will use three sources to identify these patients: medication lists from electronic health records/administrative data, consults to insomnia clinic, and referrals from providers. The research team will mail a recruitment letter (with opt-out card) to patients identified from these sources. Step 2 (phone screening for current or prior insomnia and current hypnotic use); Patients who endorse a history of insomnia symptoms and current hypnotic use will be invited for an in-person screening. Step 3 (in-person screening for remaining eligibility criteria (and baseline assessments): After written consent, the in-person screening visit consists of a comprehensive sleep, mental health, and brief physical health assessment. Individuals who meet study criteria and agree to continue will be randomized to receive either the Program A (N=94) or Program B (N=94). The interventions are approximately 2 months. Following intention-to-treat principles, all randomized participants will complete an assessment immediately after the intervention ends and 6 months after completing treatment. Participants will be compensated monetarily for assessment visits. Investigators will measure hypnotic expectancies, hypnotic discontinuation, and insomnia severity post-treatment and at 6-months follow-up.
Interventions
Sponsors
University of California, Los Angeles
US Department of Veterans Affairs
Virginia Commonwealth University
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>= 55 years * Use of lorazepam, alprazolam, temazepam,and/or zolpidem for current or prior insomnia symptoms 2 or more nights per week for at least 3 months * Current or prior insomnia symptoms * Available to attend weekly in-person sessions over 9 weeks
Exclusion criteria
High risk for complications in outpatient hypnotic discontinuation program: * Seizure disorder * Supratherapeutic or high baseline hypnotic dose (\> diazepam-equivalent of 8 mg/night). * High baseline risk of complicated withdrawal;benzodiazepine intoxication or current or past symptoms of complicated benzodiazepine/alcohol withdrawal (e.g.,seizure, delirium at baseline (prior to taper)) * Polydrug use (e.g., chronic high dose opioids) * Unable to keep study medications in secure location * Evidence of prescription fraud (e.g., multiple prescriptions for same drug filled at multiple pharmacies during overlapping time periods, diversion) Discontinuation of hypnotic not appropriate: •Study-targeted hypnotic used to treat another clinical condition (e.g., panic disorder) Poor candidate for cognitive behavioral therapy for insomnia: * Presence of bipolar disorder * Cognitive impairment (e.g., Mini-Mental State Examination \< 24) * Sleep/wake difficulty is better explained by another sleep disorder such as restless legs syndrome, narcolepsy, insufficient sleep syndrome, or circadian rhythm sleep-wake disorders * Untreated sleep-disordered breathing (respiratory event index \>= 15 and \< 30 plus excessive daytime sleepiness, or REI \>=30) * Medically/psychiatrically unstable (e.g., planned major surgery during the study period;psychosis, suicidal, active alcohol/substance abuse based on history and medical records) * Unstable housing situation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Hypnotic Discontinuation | 6 months after treatment ends (which is an average of 8 months from randomization) | The percentage of participants who had stopped taking a benzodiazepine or z-drug at follow-up. This outcome was measured with 7-day self-reported medication logs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insomnia Severity Index | One week post intervention (which is an average of 9 weeks from randomization) | Mean score on Insomnia Severity Index. This 7-item scale measures self-reported severity of insomnia symptoms. Total score ranges from 0 to 28, with higher scores indicating greater insomnia severity. |
| Dysfunctional Beliefs and Attitudes About Sleep - Medication Subscale | One week post intervention (which is an average of 9 weeks from randomization) | These 3-items were used to measure hypnotic expectancies. Items ranged from 0 (strongly disagree/least expectancy) to 10 (strongly agree/most expectancy). The scale score is the average of the 3 items and ranged from 0-10 with higher scores indicating greater hypnotic expectancy. Higher hypnotic expectancies are worse outcomes, lower hypnotic expectancies are better outcomes. |
| Rates of Hypnotic Discontinuation | One week post intervention (which is an average of 9 weeks from randomization) | The percentage of participants who had stopped taking a benzodiazepine or z-drug one week after the end of treatment . This outcome was measured with 7-day self-reported medication logs. |
| Hypnotic Dose | One week post intervention (which is an average of 9 weeks from randomization) | The mean daily dose based on self-reported 7-day medication log (in diazepam-equivalent milligrams). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORConstance Fung, MD, MSHS
UCLA, VA Greater Los Angeles
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Program A Cognitive behavioral therapy type A plus medications in packaging type A
Program A: Cognitive behavioral therapy type A plus medications prepared in packaging type A. | 92 |
| Program B Cognitive behavioral therapy type B plus medications in packaging type B
Program B: Cognitive behavioral therapy type B plus medications in packaging type B. | 96 |
| Total | 188 |
Baseline characteristics
| Characteristic | Program A | Program B | Total |
|---|---|---|---|
| Age, Continuous | 69.0 years STANDARD_DEVIATION 8.8 | 69.4 years STANDARD_DEVIATION 7.8 | 69.2 years STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 7 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 79 Participants | 89 Participants | 168 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Insomnia Severity Index | 13.8 units on a scale STANDARD_DEVIATION 6.9 | 14.3 units on a scale STANDARD_DEVIATION 5.7 | 14.0 units on a scale STANDARD_DEVIATION 6.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 7 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) White | 72 Participants | 76 Participants | 148 Participants |
| Region of Enrollment United States | 92 Participants | 96 Participants | 188 Participants |
| Sex: Female, Male Female | 31 Participants | 34 Participants | 65 Participants |
| Sex: Female, Male Male | 61 Participants | 62 Participants | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 92 | 0 / 96 |
| other Total, other adverse events | 5 / 92 | 6 / 96 |
| serious Total, serious adverse events | 4 / 92 | 0 / 96 |
Outcome results
Primary
Rates of Hypnotic Discontinuation
The percentage of participants who had stopped taking a benzodiazepine or z-drug at follow-up. This outcome was measured with 7-day self-reported medication logs.
Time frame: 6 months after treatment ends (which is an average of 8 months from randomization)
Population: For this outcome, the analysis is performed only on those participants who completed the 6-month follow-up assessment and provided data on medication usage. As a result, there were 87 in program A and 89 in program B who met these criteria.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Program A | Rates of Hypnotic Discontinuation | 64 Participants |
| Program B | Rates of Hypnotic Discontinuation | 52 Participants |
p-value: 0.03995% CI: [1.03, 3.7]Regression, Logistic
Secondary
Dysfunctional Beliefs and Attitudes About Sleep - Medication Subscale
These 3-items were used to measure hypnotic expectancies. Items ranged from 0 (strongly disagree/least expectancy) to 10 (strongly agree/most expectancy).The scale score is the average of the 3 items and ranged from 0-10 with higher scores indicating greater hypnotic expectancy. Higher hypnotic expectancies are worse outcomes, lower hypnotic expectancies are better outcomes.
Time frame: 6 months after treatment ends (which is an average of 8 months from randomization)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Program A | Dysfunctional Beliefs and Attitudes About Sleep - Medication Subscale | 3.37 score on a scale | Standard Error 0.3 |
| Program B | Dysfunctional Beliefs and Attitudes About Sleep - Medication Subscale | 3.33 score on a scale | Standard Error 0.3 |
p-value: 0.84395% CI: [-0.96, 0.78]Mixed Models Analysis
Secondary
Dysfunctional Beliefs and Attitudes About Sleep - Medication Subscale
These 3-items were used to measure hypnotic expectancies. Items ranged from 0 (strongly disagree/least expectancy) to 10 (strongly agree/most expectancy). The scale score is the average of the 3 items and ranged from 0-10 with higher scores indicating greater hypnotic expectancy. Higher hypnotic expectancies are worse outcomes, lower hypnotic expectancies are better outcomes.
Time frame: One week post intervention (which is an average of 9 weeks from randomization)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Program A | Dysfunctional Beliefs and Attitudes About Sleep - Medication Subscale | 2.38 score on a scale | Standard Error 0.25 |
| Program B | Dysfunctional Beliefs and Attitudes About Sleep - Medication Subscale | 2.72 score on a scale | Standard Error 0.24 |
p-value: 0.22895% CI: [-1.25, 0.3]Mixed Models Analysis
Secondary
Hypnotic Dose
The mean daily dose based on self-reported 7-day medication log (in diazepam-equivalent milligrams).
Time frame: 6 months after treatment ends (which is an average of 8 months from randomization)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Program A | Hypnotic Dose | 1.05 diazepam-equivalent milligrams | Standard Error 0.32 |
| Program B | Hypnotic Dose | 1.32 diazepam-equivalent milligrams | Standard Error 0.32 |
p-value: 0.40995% CI: [-1.41, 0.58]Mixed Models Analysis
Secondary
Hypnotic Dose
The mean daily dose based on self-reported 7-day medication log (in diazepam-equivalent milligrams).
Time frame: One week post intervention (which is an average of 9 weeks from randomization)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Program A | Hypnotic Dose | 0.40 diazepam-equivalent milligrams | Standard Error 0.16 |
| Program B | Hypnotic Dose | 0.57 diazepam-equivalent milligrams | Standard Error 0.16 |
p-value: 0.44395% CI: [-1.14, 0.5]Mixed Models Analysis
Secondary
Insomnia Severity Index
Mean score on Insomnia Severity Index. This 7-item scale measures self-reported severity of insomnia symptoms. Total score ranges from 0 to 28, with higher scores indicating greater insomnia severity.
Time frame: One week post intervention (which is an average of 9 weeks from randomization)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Program A | Insomnia Severity Index | 7.35 score on a scale | Standard Error 0.58 |
| Program B | Insomnia Severity Index | 6.47 score on a scale | Standard Error 0.57 |
p-value: 0.15595% CI: [-0.52, 3.29]Mixed Models Analysis
Secondary
Insomnia Severity Index
Mean score on Insomnia Severity Index. This 7-item scale measures self-reported severity of insomnia symptoms. Total score ranges from 0 to 28, with higher scores indicating greater insomnia severity.
Time frame: 6 months after treatment ends (which is an average of 8 months from randomization)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Program A | Insomnia Severity Index | 7.36 score on a scale | Standard Error 0.69 |
| Program B | Insomnia Severity Index | 7.71 score on a scale | Standard Error 0.68 |
p-value: 0.8895% CI: [-1.88, 2.2]Mixed Models Analysis
Secondary
Rates of Hypnotic Discontinuation
The percentage of participants who had stopped taking a benzodiazepine or z-drug one week after the end of treatment . This outcome was measured with 7-day self-reported medication logs.
Time frame: One week post intervention (which is an average of 9 weeks from randomization)
Population: For this outcome, the analysis is performed only on those participants who completed the post-intervention assessment and provided data on medication usage. As a result, there were 86 in program A and 92 in program B who met these criteria.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Program A | Rates of Hypnotic Discontinuation | 76 Participants |
| Program B | Rates of Hypnotic Discontinuation | 62 Participants |
p-value: 0.00195% CI: [1.67, 8.12]Regression, Logistic
Other Pre-specified
Digit Symbol Substitution
This test measures processing speed, working memory, visuospatial processing, and attention. It is sensitive to cognitive impairment and change in cognition. The score is based on the number of symbols that the person correctly substitutes in 90 seconds. Total score can range from 0 to 135, with higher scores indicating better cognitive performance.
Time frame: One week post intervention (which is an average of 9 weeks from randomization)
Other Pre-specified
Digit Symbol Substitution
This test measures processing speed, working memory, visuospatial processing, and attention. It is sensitive to cognitive impairment and change in cognition. The score is based on the number of symbols that the person correctly substitutes in 90 seconds. Total score can range from 0 to 135, with higher scores indicating better cognitive performance.
Time frame: 6 months after treatment ends (which is an average of 8 months from randomization)
Other Pre-specified
Mini-Mental State Examination
This is a 30-item test of cognitive function. Scores range from 0-30, with higher scores indicating better cognitive function.
Time frame: One week post intervention (which is an average of 9 weeks from randomization)
Other Pre-specified
Mini-Mental State Examination
This is a 30-item test of cognitive function. Scores range from 0-30, with higher scores indicating better cognitive function.
Time frame: 6 months after treatment ends (which is an average of 8 months from randomization)
Other Pre-specified
One-leg Balance Test
Objective measure of balance. Participants are timed while they stand on one-leg for up to 60 seconds. Score is the number of seconds able to stand on one-leg. Higher scores indicate better balance.
Time frame: One week post intervention (which is an average of 9 weeks from randomization)
Other Pre-specified
One-leg Balance Test
Objective measure of balance. Participants are timed while they stand on one-leg for up to 60 seconds. Score is the number of seconds able to stand on one-leg. Higher scores indicate better balance.
Time frame: 6 months after treatment ends (which is an average of 8 months from randomization)
Other Pre-specified
Trail Making Test A and B
Objective measure of cognitive executive functioning. The scores is the number of seconds it takes to complete the test. Lower scores indicate better cognitive functioning.
Time frame: One week post intervention (which is an average of 9 weeks from randomization)
Other Pre-specified
Trail Making Test A and B
Objective measure of cognitive executive functioning. The scores is the number of seconds it takes to complete the test. Lower scores indicate better cognitive functioning.
Time frame: 6 months after treatment ends (which is an average of 8 months from randomization)