Characteristics of Sleep Patterns in Young Adults With and Without Insomnia
Condition: Sleep Disorders
MeSH terms: Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders
Study type: Interventional
Phase: Phase 4

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

Detailed 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.
    

Intervention name(s): Zolpidem; Escitalopram; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): The benzodiazepine receptor agonist (BzRA), zolpidem was given in an initial dose of 5 mg by mouth every night, 30 minutes prior to bedtime. The dose was increased to a maximum of 10 mg after the first week if there was no improvement in overall symptoms (CGI score of 4 or >). The dose was decreased to 5 mg if side effects occurred.; The antidepressant, escitalopram was initiated at 5 mg by mouth every night, 30 minutes prior to bedtime. If there were no side effects, the dose was increased every four days until the target dose of 20 mg (maximum dose) was reached by day 13. If significant side effects appeared, the highest tolerated dose was used.; A placebo capsule was given with instructions to take it every night by mouth, 30 minutes prior to bedtime.
Other intervention name(s): Ambien; Celexa; Placebo control
Intervention MeSH terms: Zolpidem; Escitalopram
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Primary Insomnia; Insomnia; Placebo-Controlled; Double-Blind; Polysomnography; PET Studies; Escitalopram; Zolpidem