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Sleep Dysfunction in Women Medication

  • Author: Gila Hertz, PhD, ABSM; Chief Editor: Selim R Benbadis, MD  more...
 
Updated: May 13, 2014
 

Medication Summary

Underlying disease can be treated with HRT, hypnotics, antidepressants, and behavioral therapy. Estrogen replacement can improve sleep in menopausal women, primarily through the reduction of vasomotor symptoms that disturb sleep. It may also improve sleep-related breathing disorders. Moreover, studies indicate that estrogen, either alone or combined with progestin (but not progestin alone), markedly reduces OSA in menopausal women.

Antidepressants are indicated for PMDD, postpartum depression, and clinical depression in patients of any age. Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressive agents.

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Nonbenzodiazepine Hypnotics

Class Summary

These agents are used for the treatment of acute and short-term insomnia.

Zolpidem (Ambien, Ambien CR, Edluar)

 

Zolpidem is the drug of choice (DOC) for the treatment of primary insomnia (ie, sleep-onset insomnia). It is indicated for acute, short-term insomnia for a duration that does not exceed a few weeks. The extended-release product (Ambien CR) consists of a coated, 2-layer tablet and is useful for insomnia characterized by difficulties with sleep onset and/or sleep maintenance. The first layer releases the drug content immediately to induce sleep; the second layer gradually releases additional drug to provide continuous sleep..

Zaleplon (Sonata)

 

Zaleplon is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class. It has a chemical structure unrelated to benzodiazepines, barbiturates, or other hypnotic drugs but interacts with the GABA-benzodiazepine receptor complex. It binds selectively to the omega-1 receptor situated on the alpha subunit of the GABAA receptor complex in the brain. Zaleplon potentiates t-butyl-bicyclophosphorothionate (TBPS) binding and has preferential binding to the omega-1 receptor of the GABA receptor family. It is indicated for short term treatment of insomnia. It should be used for 7-10 days. Zaleplon has been shown to cause minimal daytime grogginess

Eszopiclone (Lunesta)

 

Eszopiclone is a nonbenzodiazepine hypnotic pyrrolopyrazine derivative of the cyclopyrrolone class. The precise mechanism of action is unknown, but the drug is believed to interact with the GABA receptor at binding domains close to or allosterically coupled with benzodiazepine receptors.

Eszopiclone is indicated for insomnia to decrease sleep latency and improve sleep maintenance. It has a short half-life of 6 hours. Higher doses (ie, 2 mg for elderly adults and 3 mg for nonelderly adults) are more effective for sleep maintenance, whereas lower doses (ie, 1 mg for elderly adults and 2 mg for nonelderly adults) are suitable for difficulty in falling asleep.

Ramelteon (Rozerem)

 

Ramelteon is a melatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep and to be involved in the maintenance of circadian rhythm and the normal sleep-wake cycle.

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Estrogens/Progestins-HRT

Class Summary

Estrogen replacement has been shown to improve sleep in menopausal women, primarily by reducing vasomotor symptoms that disturb sleep. In addition, it may improve sleep-related breathing disorders. Studies found that estrogen, either alone or combined with progestin (but not progestin alone), markedly reduced OSA in menopausal women. Oral Premarin is an example of an oral estrogen replacement. The choice of HRT should be made on an individual basis in consultation with a gynecologist.[47]

Conjugated estrogens (Premarin)

 

Multiple aspects of menopause respond to estrogen replacement therapy, including vasomotor symptoms and atrophic vaginitis. However, such therapy has not been shown to be effective in treating depression associated with menopause. Decisions for HRT should be made on an individual basis in consultation with a gynecologist. Dosing may need to be titrated individually, with each patient monitored for risks and adverse effects. Premarin is available in tablet form for oral administration in strengths of 0.3 mg, 0.625 mg, 0.9 mg, 1.25 mg, and 2.5 mg.

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Antidepressants, SSRIs

Class Summary

SSRIs are generally well tolerated and are currently the most frequently prescribed drugs for the treatment of depression. Pharmacologic treatment with antidepressants is indicated for PMDD, postpartum depression, and clinical depression in patients of any age.

Serotonin noradrenaline reuptake inhibitors (SNRIs) are also used. These agents exhibit noradrenergic and serotonergic effects in patients with depression.

Sertraline (Zoloft)

 

Sertraline is effective for the treatment of clinical depression in women. It is also indicated for panic disorders and obsessive-compulsive disorders.

Escitalopram oxalate (Lexapro)

 

Escitalopram oxalate is prescribed for insomnia associated with depression. A selective serotonin reuptake inhibitor (SSRI) and an S-enantiomer of citalopram, it is used for the treatment of depression. Its mechanism of action is thought to be the potentiation of serotonergic activity in the central nervous system (CNS) resulting from the inhibition of the CNS neuronal reuptake of serotonin. The onset of depression relief may be obtained after 1-2 weeks, which is sooner than for other antidepressants.

Fluoxetine hydrochloride (Sarafem)

 

Fluoxetine hydrochloride has been approved for the treatment of PMDD. It is indicated for the treatment of premenstrual insomnia associated with PMDD.

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Antidepressants, Other

Class Summary

Alpha2-adrenergic antagonists increase the release of norepinephrine and serotonin but do not inhibit the reuptake of norepinephrine or serotonin. These agents exhibit noradrenergic and serotonergic effects in patients with depression.

Mirtazapine (Remeron)

 

Mirtazapine is a relatively new antidepressant and is not as widely used as sertraline. It exhibits noradrenergic and serotonergic activity. It has been shown to be superior to other SSRI drugs in cases of depression associated with severe insomnia and anxiety.

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Stimulants

Class Summary

These agents may be effective in narcolepsy.

Modafinil (Provigil)

 

Modafinil's mechanism or mechanisms of action in wakefulness are unknown. It has wake-promoting actions like sympathomimetic agents.

Armodafinil (Nuvigil)

 

Armodafinil is an R-enantiomer of modafinil (mixture of R- and S-enantiomers). It elicits wake-promoting actions similar to those of sympathomimetic agents, although its pharmacologic profile is not identical to sympathomimetic amines. In vitro, armodafinil binds to the dopamine transporter and inhibits dopamine reuptake. It is not a direct- or indirect-acting dopamine receptor agonist. Armodafinil is indicated for the improvement of wakefulness in individuals with excessive sleepiness associated with narcolepsy, obstructive sleep apnea-hypopnea syndrome (OSAHS), or shift-work sleep disorder.

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Dopamine agonists

Class Summary

Dopamine agonists may be effective for the treatment of RLS.

Pramipexole (Mirapex)

 

Pramipexole is a nonergot dopamine agonist with specificity for the D2 dopamine receptor, but it also has been shown to bind to D3 and D4 receptors and may stimulate dopamine activity on nerves of the striatum and substantia nigra.

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Benzodiazepines

Class Summary

These agents have been the hypnotics of choice for many years because of their relative safety compared with barbiturates. By binding to specific receptor sites, benzodiazepines appear to potentiate the effects of GABA and to facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.

Benzodiazepines are used when additional anxiolytic effects are desired in addition to hypnotic effects. Intermediate and long-acting benzodiazepines are used for sleep-maintenance insomnia.

Triazolam (Halcion)

 

Triazolam, a short-acting agent, is good for use in sleep-onset insomnia. It has no significant residual effects in the morning.

Estazolam

 

Estazolam is an intermediate-acting agent with a slow onset of action and a long duration. It is a good agent for sleep-maintenance insomnia.

Temazepam (Restoril)

 

Temazepam is indicated for sleep-onset and maintenance insomnia. It should be taken at bedtime to prevent daytime aftereffects.

Quazepam (Doral)

 

Quazepam is used for sleep-maintenance insomnia. It enhances the inhibitory effects of the GABA neurotransmitter on neuronal excitability that results by increased neuronal permeability to chloride ions. The shift in chloride ions results in hyperpolarization and stabilization of the neuronal membrane.

Flurazepam

 

Flurazepam is frequently chosen as a short-term treatment of insomnia. It enhances the inhibitory effects of the GABA neurotransmitter on neuronal excitability that results by increased neuronal permeability to chloride ions. The shift in chloride ions results in hyperpolarization and stabilization of the neuronal membrane.

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Antiparkinson Agents, Dopamine Agonist

Class Summary

These agents may be effective for moderate to severe primary RLS. Neuropharmacologic evidence suggests that they have primary dopaminergic system involvement in RLS.

Ropinirole hydrochloride (Requip)

 

Ropinirole hydrochloride is a second-generation, nonergoline dopamine agonist that directly stimulates dopamine receptors in the brain. It has high specificity for the D3 receptor subtype. Ropinirole hydrochloride is taken at bedtime and is indicated for moderate to severe RLS.

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Contributor Information and Disclosures
Author

Gila Hertz, PhD, ABSM Director, Center for Insomnia and Sleep Disorders, Clinical Associate Professor of Psychiatry and Behavioral Sciences, State University of New York at Stony Brook

Gila Hertz, PhD, ABSM is a member of the following medical societies: American Academy of Sleep Medicine, American Psychological Association

Disclosure: Nothing to disclose.

Coauthor(s)

Mary E Cataletto, MD Professor of Clinical Pediatrics, State University of New York at Stony Brook

Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cyberonics; Eisai; Lundbeck; Sunovion; UCB; Upsher-Smith<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cyberonics; Eisai; Glaxo Smith Kline; Lundbeck; Sunovion; UCB<br/>Received research grant from: Cyberonics; Lundbeck; Sepracor; Sunovion; UCB; Upsher-Smith.

Acknowledgements

Norberto Alvarez, MD Assistant Professor, Department of Neurology, Harvard Medical School; Consulting Staff, Department of Neurology, Boston Children's Hospital; Medical Director, Wrentham Developmental Center

Norberto Alvarez, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and Child Neurology Society

Disclosure: Nothing to disclose.

Carmel Armon, MD, MSc, MHS Professor of Neurology, Tufts University School of Medicine; Chief, Division of Neurology, Baystate Medical Center

Carmel Armon, MD, MSc, MHS is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American College of Physicians, American Epilepsy Society, American Medical Association, American Neurological Association, American Stroke Association, Massachusetts Medical Society, Movement Disorders Society, and Sigma Xi

Disclosure: Avanir Pharmaceuticals Consulting fee Consulting

Gabriele M Barthlen, MD Assistant Professor, Department of Neurology, Cornell University; Director of Sleep-Wake Disorders Center, Department of Neurology, New York Presbyterian Hospital

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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