Overview

This trial is active, not recruiting.

Condition sleep disorders
Treatments escitalopram, zolpidem, placebo
Phase phase 4
Sponsor National Institute of Mental Health (NIMH)
Start date February 2002
End date May 2008
Trial size 99 participants
Trial identifier NCT00177216, 010807, DATR A2-AID, R01 MH24652

Summary

This study will compare the symptoms, experiences, and laboratory sleep characteristics of young adults with and without insomnia.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Participants receiving an enzodiazepine receptor agonist (BzRA), zolpidem
zolpidem
Benzodiazepine receptor agonist (BzRA), zolpidem, treatment for insomnia
(Experimental)
Participants receiving an antidepressant, escitalopram
escitalopram
Antidepressant, escitalopram, treatment for insomnia
(Placebo Comparator)
Participants receiving a placebo
placebo
Placebo control

Primary Outcomes

Measure
Pittsburgh Sleep Quality Index score, Sleep Diary data, and polysomnographic sleep studies
time frame: Measured at baseline and Week 9

Secondary Outcomes

Measure
Self-report sleep diaries, improvement scales, Pittsburgh Insomnia Rating Scale, Arousal Predisposition Scale, and the Inventory of Depressive Symptomatology
time frame: Measured weekly for 9 weeks

Eligibility Criteria

Male or female participants from 20 years up to 50 years old.

Inclusion Criteria: - Physically healthy - Meets DSM-IV criteria for primary insomnia - For subjects interested in PET study only: right-handedness Exclusion Criteria: - Currently taking antidepressants, antianxiety medications or medications for sleep disorders - Currently experiencing symptoms of psychiatric disorders such as major depressive disorder, bipolar disorder, generalized anxiety disorder - Significant or unstable acute or chronic medical conditions, such as seizure disorder, tumor, liver disease, active peptic ulcer disease, arthritis, irritable bowel disease - Meets DSM-IV criteria for sleep apnea or periodic limb movement disorder

Additional Information

Official title Psychobiology and Treatment Response in Primary Insomnia
Principal investigator Daniel J. Buysse, MD
Description The overall aim of this research study is to compare the symptoms, experiences and laboratory sleep characteristics of young adults with and without insomnia. Insomnia is a pattern of difficulty falling asleep, staying asleep or feeling poorly rested despite an adequate amount of time for sleep, which occurs nearly every night for one month or longer. For those with insomnia, we will look at the effects of an intervention with one of two medications (escitalopram or zolpidem) or an inactive pill (placebo). This intervention will be followed by re-evaluation of symptoms, experiences and laboratory sleep characteristics. The three hypotheses being investigated are: compared to control subjects, those with insomnia will demonstrate affective disturbance and heightened arousal; the different medications will have different degrees of effect on the two dimensions being measured (affective disturbance and heightened arousal); and PET scans will reveal different patterns of activity in the brains of groups of people with insomnia. We will specifically focus on the syndrome of Primary Insomnia (PI), defined by DSM-IV as insomnia that lasts for at least one month and causes significant impairment or distress. PI excludes insomnia that occurs exclusively during the course of another sleep, mental, substance-induced, or medical disorder. Insomnia is a significant public health problem because of its prevalence, morbidity, and the risk it poses for the development of subsequent mental disorders, particularly depressive and anxiety disorders. Understanding the psychobiology of primary insomnia is a critical step toward addressing questions regarding its relationships with mood and anxiety disorders. Our model of insomnia builds on two major concepts running through previous insomnia research, affective disturbance and heightened arousal, as driving factors for the sleep-wake disturbances that define PI. Implicit in this model is that individuals with PI have different degrees of each dysfunction, which accounts for their heterogeneity of clinical symptoms. Contemporary theories of affect structure suggest that these two dimensions may be orthogonal in pure form, but are nevertheless related in clinical conditions characterized by mixed anxiety-depression, such as PI. Measures of affective disturbance and arousal in this study will include questionnaires, diary-based assessments, and physiological measures. Pharmacological treatment probes may help to further distinguish the roles of affective disturbance and heightened arousal in insomnia. We will use a benzodiazepine receptor agonist (BzRA), zolpidem, and an antidepressant, escitalopram. BzRA potentiate the effects of GABA (1), but have minimal direct activity at any other receptor types. They are efficacious treatments for insomnia (2-4), but have little effect on mood. We chose zolpidem because it is relatively specific for hypnotic versus anxiolytic or other actions (5), because it is the most widely-prescribed BzRA hypnotic, and because it is well-tolerated (6). Clinically-effective doses of even "nonsedating" antidepressants can also improve symptoms in PI (7), suggesting that direct sedation is not their only mechanism for improving insomnia. We chose escitalopram because it is neither strongly alerting nor sedating in clinical and polysomnographic studies. This "sleep-neutral" profile will allow us to use it for its effects on affective disturbance, rather than its nonspecific sedating properties. Escitalopram's specific effect on serotonin reuptake blockade and its lack of affinity for Bz receptors distinguish it from zolpidem as a pharmacologic probe. Functional neuroimaging studies in wakefulness and sleep may also help to identify the substrate of affective disturbance and heightened arousal in insomnia. Affective disturbance in the form of MDD is associated with alterations in both regional deactivation patterns during NREM sleep, and regional activation patterns during REM sleep. These observations suggest that a sleep-wake functional neuroimaging paradigm in insomnia patients, in conjunction with behavioral measures, may help to identify which brain systems mediate heightened arousal and affective disturbance, and how these systems interact.
Trial information was received from ClinicalTrials.gov and was last updated in April 2009.
Information provided to ClinicalTrials.gov by National Institute of Mental Health (NIMH).