Sleep Dysfunction in Women Medication
- Author: Gila Hertz, PhD, ABSM; Chief Editor: Selim R Benbadis, MD more...
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.
These agents are used for the treatment of acute and short-term insomnia.
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 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 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 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.
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.
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.
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 is effective for the treatment of clinical depression in women. It is also indicated for panic disorders and obsessive-compulsive disorders.
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 has been approved for the treatment of PMDD. It is indicated for the treatment of premenstrual insomnia associated with PMDD.
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 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.
These agents may be effective in narcolepsy.
Modafinil's mechanism or mechanisms of action in wakefulness are unknown. It has wake-promoting actions like sympathomimetic agents.
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.
Dopamine agonists may be effective for the treatment of RLS.
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.
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, a short-acting agent, is good for use in sleep-onset insomnia. It has no significant residual effects in the morning.
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 is indicated for sleep-onset and maintenance insomnia. It should be taken at bedtime to prevent daytime aftereffects.
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 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.
Antiparkinson Agents, Dopamine Agonist
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 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.
Lyytikäinen P, Rahkonen O, Lahelma E, Lallukka T. Association of sleep duration with weight and weight gain: a prospective follow-up study. J Sleep Res. 2011 Jun. 20(2):298-302. [Medline].
Mork PJ, Nilsen TI. Sleep problems and risk of fibromyalgia: longitudinal data on an adult female population in Norway. Arthritis Rheum. 2012 Jan. 64(1):281-4. [Medline].
Suarez EC. Self-reported symptoms of sleep disturbance and inflammation, coagulation, insulin resistance and psychosocial distress: evidence for gender disparity. Brain Behav Immun. 2008 Aug. 22(6):960-8. [Medline]. [Full Text].
Moe KE. Reproductive hormones, aging, and sleep. Semin Reprod Endocrinol. 1999. 17(4):339-48. [Medline].
Driver HS, McLean H, Kumar DV, et al. The influence of the menstrual cycle on upper airway resistance and breathing during sleep. Sleep. 2005 Apr 1. 28(4):449-56. [Medline].
Owens JF, Matthews KA. Sleep disturbance in healthy middle-aged women. Maturitas. 1998 Sep 20. 30(1):41-50. [Medline].
Bamford CR. Menstrual-associated sleep disorder: an unusual hypersomniac variant associated with both menstruation and amenorrhea with a possible link to prolactin and metoclopramide. Sleep. 1993 Aug. 16(5):484-6. [Medline].
Ancoli-Israel S, Kripke DF, Klauber MR, et al. Periodic limb movements in sleep in community-dwelling elderly. Sleep. 1991 Dec. 14(6):496-500. [Medline].
Ekbom KA. Restless legs syndrome. Neurology. 1960 Sep. 10:868-73. [Medline].
Arnulf I. REM sleep behavior disorder: Motor manifestations and pathophysiology. Mov Disord. 2012 May. 27(6):677-89. [Medline].
Bodkin CL, Schenck CH. Rapid eye movement sleep behavior disorder in women: relevance to general and specialty medical practice. J Womens Health (Larchmt). 2009 Dec. 18(12):1955-63. [Medline].
Boeve BF. REM sleep behavior disorder: Updated review of the core features, the REM sleep behavior disorder-neurodegenerative disease association, evolving concepts, controversies, and future directions. Ann N Y Acad Sci. 2010 Jan. 1184:15-54. [Medline]. [Full Text].
Koo BB, Dostal J, Ioachimescu O, Budur K. The effects of gender and age on REM-related sleep-disordered breathing. Sleep Breath. 2008 Aug. 12(3):259-64. [Medline].
Manber R, Armitage R. Sex, steroids, and sleep: a review. Sleep. 1999 Aug 1. 22(5):540-55. [Medline].
Parry BL, LeVeau B, Mostofi N, et al. Temperature circadian rhythms during the menstrual cycle and sleep deprivation in premenstrual dysphoric disorder and normal comparison subjects. J Biol Rhythms. 1997 Feb. 12(1):34-46. [Medline].
Kronenberg F. Hot flashes: epidemiology and physiology. Ann N Y Acad Sci. 1990. 592:52-86; discussion 123-33. [Medline].
Brownell LG, West P, Kryger MH. Breathing during sleep in normal pregnant women. Am Rev Respir Dis. 1986 Jan. 133(1):38-41. [Medline].
Popovic RM, White DP. Upper airway muscle activity in normal women: influence of hormonal status. J Appl Physiol. 1998 Mar. 84(3):1055-62. [Medline].
Block AJ, Boysen PG, Wynne JW, Hunt LA. Sleep apnea, hypopnea and oxygen desaturation in normal subjects. A strong male predominance. N Engl J Med. 1979 Mar 8. 300(10):513-7. [Medline].
Feinsilver SH, Hertz G. Respiration during sleep in pregnancy. Clin Chest Med. 1992 Dec. 13(4):637-44. [Medline].
Kripke DF, Jean-Louis G, Elliott JA, et al. Ethnicity, sleep, mood, and illumination in postmenopausal women. BMC Psychiatry. 2004 Apr 7. 4(1):8. [Medline].
Paul KN, Turek FW, Kryger MH. Influence of sex on sleep regulatory mechanisms. J Womens Health (Larchmt). 2008 Sep. 17(7):1201-8. [Medline].
Phillips BA, Collop NA, Drake C, Consens F, Vgontzas AN, Weaver TE. Sleep disorders and medical conditions in women. Proceedings of the Women & Sleep Workshop, National Sleep Foundation, Washington, DC, March 5-6, 2007. J Womens Health (Larchmt). 2008 Sep. 17(7):1191-9. [Medline].
Manconi M, Ulfberg J, Berger K, Ghorayeb I, Wesström J, Fulda S, et al. When gender matters: Restless legs syndrome. Report of the "RLS and woman" workshop endorsed by the European RLS Study Group. Sleep Med Rev. 2011 Nov 8. [Medline].
Beaudreau SA, Spira AP, Stewart A, Kezirian EJ, Lui LY, Ensrud K, et al. Validation of the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale in older black and white women. Sleep Med. 2011 Oct 25. [Medline].
Ameratunga D, Goldin J, Hickey M. Sleep disturbance in menopause. Intern Med J. 2012 Jan 31. [Medline].
Moline ML, Broch L, Zak R. Sleep in women across the life cycle from adulthood through menopause. Med Clin North Am. 2004 May. 88(3):705-36, ix. [Medline].
Ekholm EM, Polo O, Rauhala ER, Ekblad UU. Sleep quality in preeclampsia. Am J Obstet Gynecol. 1992 Nov. 167(5):1262-6. [Medline].
Newman AB, Enright PL, Manolio TA, et al. Sleep disturbance, psychosocial correlates, and cardiovascular disease in 5201 older adults: the Cardiovascular Health Study. J Am Geriatr Soc. 1997 Jan. 45(1):1-7. [Medline].
Suarez EC. Self-reported symptoms of sleep disturbance and inflammation, coagulation, insulin resistance and psychosocial distress: evidence for gender disparity. Brain Behav Immun. 2008 Aug. 22(6):960-8. [Medline].
Chen JC, Brunner RL, Ren H, Wassertheil-Smoller S, Larson JC, Levine DW, et al. Sleep duration and risk of ischemic stroke in postmenopausal women. Stroke. 2008 Dec. 39(12):3185-92. [Medline].
Diagnostic Classification Steering Committee. International Classification of Sleep Disorders: Diagnostic and Coding Manual of Sleep Disorders. American Sleep Disorders Association. 1990.
Miró E, Martínez MP, Sánchez AI, Prados G, Medina A. When is pain related to emotional distress and daily functioning in fibromyalgia syndrome? The mediating roles of self-efficacy and sleep quality. Br J Health Psychol. 2011 Nov. 16(4):799-814. [Medline].
Lee KA, Shaver JF, Giblin EC, Woods NF. Sleep patterns related to menstrual cycle phase and premenstrual affective symptoms. Sleep. 1990 Oct. 13(5):403-9. [Medline].
Manber R, Bootzin RR. Sleep and the menstrual cycle. Health Psychol. 1997 May. 16(3):209-14. [Medline].
Patkai P, Johannson G, Post B. Mood, alertness and sympathetic-adrenal medullary activity during the menstrual cycle. Psychosom Med. 1974 Nov-Dec. 36(6):503-12. [Medline].
Fast A, Hertz G. Nocturnal low back pain in pregnancy: polysomnographic correlates. Am J Reprod Immunol. 1992 Oct-Dec. 28(3-4):251-3. [Medline].
Hertz G, Fast A, Feinsilver SH, et al. Sleep in normal late pregnancy. Sleep. 1992 Jun. 15(3):246-51. [Medline].
Schweiger MS. Sleep disturbance in pregnancy. A subjective survey. Am J Obstet Gynecol. 1972 Dec 1. 114(7):879-82. [Medline].
Woodward S, Freedman RR. The thermoregulatory effects of menopausal hot flashes on sleep. Sleep. 1994 Sep. 17(6):497-501. [Medline].
Lee KA. Self-reported sleep disturbances in employed women. Sleep. 1992 Dec. 15(6):493-8. [Medline].
Bourjeily G, Ankner G, Mohsenin V. Sleep-disordered breathing in pregnancy. Clin Chest Med. 2011 Mar. 32(1):175-89, x. [Medline].
Santiago JR, Nolledo MS, Kinzler W, Santiago TV. Sleep and sleep disorders in pregnancy. Ann Intern Med. 2001 Mar 6. 134(5):396-408. [Medline].
Frank E, Kupfer DJ, Jacob M, et al. Pregnancy-related affective episodes among women with recurrent depression. Am J Psychiatry. 1987 Mar. 144(3):288-93. [Medline].
Driver HS, Shapiro CM. A longitudinal study of sleep stages in young women during pregnancy and postpartum. Sleep. 1992 Oct. 15(5):449-53. [Medline].
Keefe DL, Watson R, Naftolin F. Hormone replacement therapy may alleviate sleep apnea in menopausal women: a pilot study. Menopause. 1999. 6(3):196-200. [Medline].
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17. 288(3):321-33. [Medline].