User login
How plasma donation can affect your patient’s pharmacotherapy
Discuss this article at www.facebook.com/CurrentPsychiatry
Many economically disadvantaged psychiatric patients donate plasma for financial incentive. However, plasmapheresis (PP)—separation of plasma and cellular components of blood—can increase drug clearance, which may affect how you manage patients who donate plasma frequently.
Donated plasma is used to help patients with hemophilia and other blood disorders and burn victims. It’s also valuable for medical research. Typically, donors cannot be taking lithium, experiencing active hallucinations, receiving ≥3 psychotropic medications, or have had a psychiatric hospitalization in the past 12 months. Patients can donate while taking antidepressants, mood stabilizers, antipsychotics, and anticonvulsants.1
Pharmacotherapeutic concerns
During PP, solutes in plasma such as drugs can be removed, increasing drug clearance by 30%.2,3 PP affects both protein-bound and free drug concentrations. PP effectively clears drugs that are highly protein bound and have a small volume of distribution. As a result, serum levels of psychotropics are lowered. Most psychotropics except lithium are bound to plasma protein. Because of high protein binding, plasma concentrations of psychotropics may rebound after PP. Antipsychotics are highly protein bound—85% to 90%—and highly lipophilic. For a list of protein binding percentages of commonly used psychotropics, see the Table.4
Table
Protein binding percentages of common psychotropics
| Drug(s) | Percentage of protein binding |
|---|---|
| Lamotrigine; topiramate | Minimal |
| Desvenlafaxine | 30% |
| Carbamazepine | 40% to 90% |
| Venlafaxine | 40% to 50% |
| Oxcarbazepine | 40% to 60% |
| Escitalopram | 56% |
| All other SSRIs | 75% |
| Bupropion | 84% |
| Mirtazapine | 85% |
| Duloxetine; divalproex | 90% |
| Tricyclic antidepressants | 98% |
| SSRIs: selective serotonin reuptake inhibitors Source: Reference 4 | |
Plasma is regenerated 24 to 48 hours after PP; therefore, the clinical effect on daily psychotropic dosing should be small unless the donations are frequent. Long-term and regular plasma donation may result in hypoalbuminemia and hypocholesterolemia5; however, the effects of hypoalbuminemia on psychotropics routinely bound to serum proteins are unknown. Patients with an acute infection or malnourishment could have further decreased albumin production or increased catabolism, resulting in a significant decrease in serum albumin concentration, which may affect psychotropic pharmacokinetics.5
Other concerns
Beware of financial incentives because economically disadvantaged psychiatric patients are vulnerable to coercion. Some plasma donor centers will pay donors a specific amount—ranging from $20 to $30— for their first 2 donations and offer monthly bonuses if a patient donates 8 times a month.
The amount of plasma a patient can donate is based on their weight; patients who weigh more get paid more. This may conflict with your attempts to motivate patients to lose weight.
Disclosures
Dr. Selvaraj receives an internal grant from Creighton University.
Drs. Gabel and Ramaswamy report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Acknowledgement
The authors would like to thank Darrel E. Willoughby, Librarian, Omaha Veterans Affairs Medical Center, Omaha, NE, for his assistance with this article.
1. American Red Cross. Eligibility criteria by topic. http://www.redcrossblood.org/donating-blood/eligibility-requirements/eligibility-criteria-topic#meds_vaccinations. Accessed April 11 2012.
2. Kale-Pradhan PB, Woo MH. A review of the effects of plasmapheresis on drug clearance. Pharmacotherapy. 1997;17(4):684-695.
3. Ibrahim RB, Liu C, Cronin SM, et al. Drug removal by plasmapheresis: an evidence-based review. Pharmacotherapy. 2007;27(11):1529-1549.
4. Clinical pharmacology online. http://www.clinicalpharmacology.com. Accessed April 11 2012.
5. Jones DK, Dunn MI. ‘Vampire syndrome’: serum protein and lipid abnormalities related to frequent sale of plasma. J Fam Pract. 1995;40(3):288-290.
Discuss this article at www.facebook.com/CurrentPsychiatry
Many economically disadvantaged psychiatric patients donate plasma for financial incentive. However, plasmapheresis (PP)—separation of plasma and cellular components of blood—can increase drug clearance, which may affect how you manage patients who donate plasma frequently.
Donated plasma is used to help patients with hemophilia and other blood disorders and burn victims. It’s also valuable for medical research. Typically, donors cannot be taking lithium, experiencing active hallucinations, receiving ≥3 psychotropic medications, or have had a psychiatric hospitalization in the past 12 months. Patients can donate while taking antidepressants, mood stabilizers, antipsychotics, and anticonvulsants.1
Pharmacotherapeutic concerns
During PP, solutes in plasma such as drugs can be removed, increasing drug clearance by 30%.2,3 PP affects both protein-bound and free drug concentrations. PP effectively clears drugs that are highly protein bound and have a small volume of distribution. As a result, serum levels of psychotropics are lowered. Most psychotropics except lithium are bound to plasma protein. Because of high protein binding, plasma concentrations of psychotropics may rebound after PP. Antipsychotics are highly protein bound—85% to 90%—and highly lipophilic. For a list of protein binding percentages of commonly used psychotropics, see the Table.4
Table
Protein binding percentages of common psychotropics
| Drug(s) | Percentage of protein binding |
|---|---|
| Lamotrigine; topiramate | Minimal |
| Desvenlafaxine | 30% |
| Carbamazepine | 40% to 90% |
| Venlafaxine | 40% to 50% |
| Oxcarbazepine | 40% to 60% |
| Escitalopram | 56% |
| All other SSRIs | 75% |
| Bupropion | 84% |
| Mirtazapine | 85% |
| Duloxetine; divalproex | 90% |
| Tricyclic antidepressants | 98% |
| SSRIs: selective serotonin reuptake inhibitors Source: Reference 4 | |
Plasma is regenerated 24 to 48 hours after PP; therefore, the clinical effect on daily psychotropic dosing should be small unless the donations are frequent. Long-term and regular plasma donation may result in hypoalbuminemia and hypocholesterolemia5; however, the effects of hypoalbuminemia on psychotropics routinely bound to serum proteins are unknown. Patients with an acute infection or malnourishment could have further decreased albumin production or increased catabolism, resulting in a significant decrease in serum albumin concentration, which may affect psychotropic pharmacokinetics.5
Other concerns
Beware of financial incentives because economically disadvantaged psychiatric patients are vulnerable to coercion. Some plasma donor centers will pay donors a specific amount—ranging from $20 to $30— for their first 2 donations and offer monthly bonuses if a patient donates 8 times a month.
The amount of plasma a patient can donate is based on their weight; patients who weigh more get paid more. This may conflict with your attempts to motivate patients to lose weight.
Disclosures
Dr. Selvaraj receives an internal grant from Creighton University.
Drs. Gabel and Ramaswamy report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Acknowledgement
The authors would like to thank Darrel E. Willoughby, Librarian, Omaha Veterans Affairs Medical Center, Omaha, NE, for his assistance with this article.
Discuss this article at www.facebook.com/CurrentPsychiatry
Many economically disadvantaged psychiatric patients donate plasma for financial incentive. However, plasmapheresis (PP)—separation of plasma and cellular components of blood—can increase drug clearance, which may affect how you manage patients who donate plasma frequently.
Donated plasma is used to help patients with hemophilia and other blood disorders and burn victims. It’s also valuable for medical research. Typically, donors cannot be taking lithium, experiencing active hallucinations, receiving ≥3 psychotropic medications, or have had a psychiatric hospitalization in the past 12 months. Patients can donate while taking antidepressants, mood stabilizers, antipsychotics, and anticonvulsants.1
Pharmacotherapeutic concerns
During PP, solutes in plasma such as drugs can be removed, increasing drug clearance by 30%.2,3 PP affects both protein-bound and free drug concentrations. PP effectively clears drugs that are highly protein bound and have a small volume of distribution. As a result, serum levels of psychotropics are lowered. Most psychotropics except lithium are bound to plasma protein. Because of high protein binding, plasma concentrations of psychotropics may rebound after PP. Antipsychotics are highly protein bound—85% to 90%—and highly lipophilic. For a list of protein binding percentages of commonly used psychotropics, see the Table.4
Table
Protein binding percentages of common psychotropics
| Drug(s) | Percentage of protein binding |
|---|---|
| Lamotrigine; topiramate | Minimal |
| Desvenlafaxine | 30% |
| Carbamazepine | 40% to 90% |
| Venlafaxine | 40% to 50% |
| Oxcarbazepine | 40% to 60% |
| Escitalopram | 56% |
| All other SSRIs | 75% |
| Bupropion | 84% |
| Mirtazapine | 85% |
| Duloxetine; divalproex | 90% |
| Tricyclic antidepressants | 98% |
| SSRIs: selective serotonin reuptake inhibitors Source: Reference 4 | |
Plasma is regenerated 24 to 48 hours after PP; therefore, the clinical effect on daily psychotropic dosing should be small unless the donations are frequent. Long-term and regular plasma donation may result in hypoalbuminemia and hypocholesterolemia5; however, the effects of hypoalbuminemia on psychotropics routinely bound to serum proteins are unknown. Patients with an acute infection or malnourishment could have further decreased albumin production or increased catabolism, resulting in a significant decrease in serum albumin concentration, which may affect psychotropic pharmacokinetics.5
Other concerns
Beware of financial incentives because economically disadvantaged psychiatric patients are vulnerable to coercion. Some plasma donor centers will pay donors a specific amount—ranging from $20 to $30— for their first 2 donations and offer monthly bonuses if a patient donates 8 times a month.
The amount of plasma a patient can donate is based on their weight; patients who weigh more get paid more. This may conflict with your attempts to motivate patients to lose weight.
Disclosures
Dr. Selvaraj receives an internal grant from Creighton University.
Drs. Gabel and Ramaswamy report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Acknowledgement
The authors would like to thank Darrel E. Willoughby, Librarian, Omaha Veterans Affairs Medical Center, Omaha, NE, for his assistance with this article.
1. American Red Cross. Eligibility criteria by topic. http://www.redcrossblood.org/donating-blood/eligibility-requirements/eligibility-criteria-topic#meds_vaccinations. Accessed April 11 2012.
2. Kale-Pradhan PB, Woo MH. A review of the effects of plasmapheresis on drug clearance. Pharmacotherapy. 1997;17(4):684-695.
3. Ibrahim RB, Liu C, Cronin SM, et al. Drug removal by plasmapheresis: an evidence-based review. Pharmacotherapy. 2007;27(11):1529-1549.
4. Clinical pharmacology online. http://www.clinicalpharmacology.com. Accessed April 11 2012.
5. Jones DK, Dunn MI. ‘Vampire syndrome’: serum protein and lipid abnormalities related to frequent sale of plasma. J Fam Pract. 1995;40(3):288-290.
1. American Red Cross. Eligibility criteria by topic. http://www.redcrossblood.org/donating-blood/eligibility-requirements/eligibility-criteria-topic#meds_vaccinations. Accessed April 11 2012.
2. Kale-Pradhan PB, Woo MH. A review of the effects of plasmapheresis on drug clearance. Pharmacotherapy. 1997;17(4):684-695.
3. Ibrahim RB, Liu C, Cronin SM, et al. Drug removal by plasmapheresis: an evidence-based review. Pharmacotherapy. 2007;27(11):1529-1549.
4. Clinical pharmacology online. http://www.clinicalpharmacology.com. Accessed April 11 2012.
5. Jones DK, Dunn MI. ‘Vampire syndrome’: serum protein and lipid abnormalities related to frequent sale of plasma. J Fam Pract. 1995;40(3):288-290.
Treating insomnia across women’s life stages
Discuss this article at http://currentpsychiatry.blogspot.com/2010/07/treating-insomnia-in-women.html#comments
Ms. A, age 44, reports a 3-month history of forgetfulness, difficulty concentrating, and insomnia. She says she can fall asleep but wakes up multiple times during the night and feels tired during the day. She has no history of a mood or anxiety disorder or medications that might be responsible for her symptoms.
Before her current insomnia began, Ms. A could sleep for 7 to 8 hours at night. Her husband suffers from obstructive sleep apnea (OSA), and his snoring occasionally would awaken her, but she slept well overall. Ms. A cannot identify anything that could be causing her sleep complaints. She states “The weird thing is that sometimes I am not sure if I’m cold or hot” and “I sometimes wake up drenched in sweat.” She also reports recent changes in the timing of her otherwise regular menstrual flow.
Ms. A attributes her memory problems to her poor sleep. A recent audit at her company held her responsible for several accounting errors, and Ms. A is worried that she might lose her job. She denies symptoms that would suggest major depression. You are unable to elicit a history of limb movements or excessive snoring.
Compared with men, women have a 1.3- to 1.8-fold greater risk for developing insomnia.Improve sleep with group CBT for insomnia,” Current Psychiatry, April 2009.) Pharmacotherapy during pregnancy and for breast-feeding mothers is guided by evaluating the risk/benefit ratio and safety considerations.
Maintain a high index of suspicion for breathing-related sleep disorders, such as OSA,21 and RLS.22 Atypical presentations of OSA are common in pregnant or postpartum women; compared with men, women with OSA are more likely to report fatigue and less likely than to report sleepiness. Refer patients whom you think may have OSA for polysomnography.
If you suspect RLS, check for low ferritin and folate levels. Nutritional supplements may be necessary for women in high-risk groups, including those who are pregnant or have varicose veins, venous reflux, folate deficiency, uremia, diabetes, thyroid problems, peripheral neuropathy, Parkinson’s disease, or certain autoimmune disorders, such as Sjögren’s syndrome, celiac disease, and rheumatoid arthritis.23 Advise these patients to avoid caffeine.
Although indicated for treating RLS, ropinirole and pramipexole are FDA Pregnancy Category C, which means animal studies have shown adverse effects on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite risks. Opioids, carbamazepine, or gabapentin may be safer for pregnant patients.24
Insomnia during menopause
The prevalence of insomnia increases from 33% to 36% in premenopausal women to 44% to 61% in postmenopausal women.14 Hot flashes, comorbid mood disturbances, sleep-disordered breathing, and RLS contribute to increased insomnia risk in postmenopausal women (Table 3).4,14,25,26
Treatment strategy. Always inquire about sleep in perimenopausal/postmenopausal women, even when her presenting complaint is related to menstrual cycle changes or vasomotor symptoms such as hot flashes.16 Assess patients for OSA, RLS, and mood, anxiety, and cognitive symptoms.26 In addition to pharmacotherapy and behavioral therapy, treatment options include hormone replacement therapy (HRT) and herbal and dietary supplements (Table 4).27-32
Table 3
Sleep difficulties during menopause: Differential diagnoses
| Condition | Features | Findings | Other considerations |
|---|---|---|---|
| Hot flashes (prevalence: 75% to 85%)14 | Vasomotor phenomenon characterized by feelings such as ‘spreading warmth,’ diaphoresis, palpitations, nausea, and insomnia Mediated through the preoptic area of the anterior hypothalamus, which regulates temperature and sleep Increased brain norepinephrine metabolism | Discrepancies between objective (PSG) and subjective measures (surveys)4 Discrepancies between self-reported and laboratory reported sleep data might be explained by thermoregulatory differences between NREM and REM sleep24 | Nocturnal hot flashes trigger awakenings and insomnia14 Hot flashes can follow arousals and awakenings HRT is highly effective in treating hot flashes; however, data on its direct effects on sleep complaints are inconsistent |
| Primary menopausal insomnia25 | Menopausal symptoms (eg, hot flashes) trigger insomnia that persists secondary to behavioral conditioning | Increase in nocturnal skin temperature coincides with decrease in skin resistance and waking episodes in PSG | Behavioral insomnia therapies are useful adjuncts to treatment of menopause symptoms |
| Sleep-disordered breathing (OSA) | Menopause increases risk for OSA independent of body weight Redistribution of body fat with an increase in the waist-to-hip circumference ratio occurs in menopause Loss of ventilatory drive because of diminished progesterone levels | Sleep fragmentation and daytime sleepiness are common, as opposed to apneic episodes or oxygen desaturation in men | Maintain a high index of suspicion and promptly refer patients to a sleep center |
| Restless legs syndrome | Related to iron deficiency | Low ferritin and folate levels | Advise patients to avoid caffeine |
| HRT: hormone replacement therapy; NREM: non-rapid eye movement; OSA: obstructive sleep apnea; PSG: polysomnography; REM: rapid eye movement | |||
Table 4
Treating insomnia in menopausal women
| Therapy | Comments |
|---|---|
| Hormone replacement therapy (HRT) | Effective for hot flashes, insomnia,26-28 and sleep apnea29 Long-term safety is questionable4 |
| Behavioral therapy (cognitive-behavioral therapy,30 stimulus control therapy, sleep restriction therapy, sleep hygiene, hypnotherapy, biofeedback) | Limited data in menopausal women |
| Sedatives/hypnotics/antidepressants (eg, zolpidem, 10 mg; eszopiclone, 3 mg; trazodone, 75 mg; ramelteon, 8 mg; SSRIs and SNRIs) | Benzodiazepines may be useful, although not specifically evaluated in menopausal women. Risk of tolerance, dependence, and psychomotor slowing |
| Herbal and dietary supplements (Cimicifuga racemosa [Black cohosh],31 valerian | Popular alternatives to HRT; however, evidence of efficacy as treatment for insomnia is inconclusive |
| SNRIs: serotonin-norepinephrine reuptake inhibitors; SSRIs: selective serotonin reuptake inhibitors | |
Comorbid psychiatric disorders
Women have a higher prevalence of psychiatric disorders such as major depressive disorder and anxiety disorders than men.1 Women have a 10% to 25% lifetime risk of developing major depression. Three quarters of depressed patients experience insomnia.1 Recent literature suggests insomnia is a risk factor for depression,33 which emphasizes the need to screen women who present with sleep problems for depression and anxiety.
Five percent to 20% of women experience postpartum depression. Depression and insomnia are correlated to the rapid decline in estrogen and progesterone after delivery.34
Treatment strategy. Insomnia is a common presenting symptom in patients with psychiatric conditions such as mood and anxiety disorders. Treating the underlying psychiatric disorder often alleviates sleeping difficulties. However, if the insomnia is disabling, treat the psychiatric disorder and insomnia concurrently.
CASE CONTINUED: Perimenopausal insomnia
Based on her history, you diagnose Ms. A with insomnia related to general medical condition (perimenopause). There are no indications to refer her for polysomnography. You educate Ms. A about sleep hygiene and recommend that she discuss her menstrual and physical complaints with her primary care physician or gynecologist. Ms. A is not interested in HRT because she has a strong family history of endometrial cancer. You reassure Ms. A and schedule a follow-up visit in 2 months to re-evaluate her insomnia.
Related resource
- Krahn LE. Perimenopausal depression? Ask how she’s sleeping. Current Psychiatry. 2005;4(6):39-53.
Drug brand names
- Carbamazepine • Carbatrol, Tegretol, others
- Escitalopram • Lexapro
- Eszopiclone • Lunesta
- Fluoxetine • Prozac
- Gabapentin • Neurontin, Gabarone
- Paroxetine • Paxil
- Pramipexole • Mirapex
- Ramelteon • Rozerem
- Ropinirole • Requip
- Sertraline • Zoloft
- Trazodone • Desyrel
- Zolpidem • Ambien
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Acknowledgements
The authors thank Dr. Namita Dhiman and Darrel E. Willoughby for their assistance with this article.
1. Krystal AD. Depression and insomnia in women. Clin Cornerstone. 2004;6(suppl 1B):S19-S28.
2. Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev. 2002;6(2):97-111.
3. Krishnan V, Collop NA. Gender differences in sleep disorders. Curr Opin Pulm Med. 2006;12(6):383-389.
4. Soares CN, Murray BJ. Sleep disorders in women: clinical evidence and treatment strategies. Psychiatr Clin North Am. 2006;29(4):1095-1113.
5. Ohayon M. Epidemiological study on insomnia in the general population. Sleep. 1996;19(3 suppl):S7-S15.
6. Daley M, Morin CM, LeBlanc M, et al. Insomnia and its relationship to health-care utilization, work absenteeism, productivity and accidents. Sleep Med. 2009;10(4):427-438.
7. Diagnostic and statistical manual of mental disorders, 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000.
8. Ancoli-Israel S, Roth T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Sleep. 1999;2(suppl 2):S347-S353.
9. Zhang B, Wing YK. Sex differences in insomnia: a meta-analysis. Sleep. 2006;29(1):85-93.
10. Buysse DJ, Reynolds CF, Monk TH, et al. The Pittsburgh Sleep Quality Index (PSQI): a new instrument for psychiatric research and practice. Psychiatry Res. 1989;28(2):193-213.
11. Manber R, Bootzin RR. Sleep and the menstrual cycle. Health Psychol. 1997;16:209-214.
12. Ito M, Kohsaka M, Fukuda N, et al. Effects of menstrual cycle on plasma melatonin level and sleep characteristics. Jpn J Psychiatry Neurol. 1993;47:478-479.
13. Driver HS, Dijk DJ, Werth E, et al. Sleep and the sleep electroencephalogram across the menstrual cycle in young healthy women. J Clin Endocrinol Metab. 1996;81:728-735.
14. Moline ML, Broch L, Zak R. Sleep in women across the life cycle from adulthood through menopause. Med Clin North Am. 2004;88(3):705-736.
15. Steiner M, Pearlstein T, Cohen LS, et al. Expert guidelines for the treatment of severe PMS, PMDD, and comorbidities: the role of SSRIs. J Womens Health (Larchmt). 2006;15(1):57-69.
16. Krystal AD. Insomnia in women. Clin Cornerstone. 2003;5(3):41-50.
17. Mindell JA, Jacobson BJ. Sleep disturbances during pregnancy. J Obstet Gynecol Neonatal Nurs. 2000;29(6):590-597.
18. Lee KA, Zaffke ME, McEnany G. Parity and sleep patterns during and after pregnancy. Obstet Gynecol. 2000;95(1):14-18.
19. Brunner DP, Münch M, Biedermann K, et al. Changes in sleep and sleep electroencephalogram during pregnancy. Sleep. 1994;17(7):576-582.
20. Ross LE, Murray BJ, Steiner M. Sleep and perinatal mood disorders: a critical review. J Psychiatry Neurosci. 2005;30(4):247-256.
21. Edwards N, Middleton PG, Blyton DM, et al. Sleep disordered breathing and pregnancy. Thorax. 2002;57(6):555-558.
22. Manconi M, Govoni V, De Vito A, et al. Restless legs syndrome and pregnancy. Neurology. 2004;63(6):1065-1069.
23. Lee KA, Zaffke ME, Baratte-Beebe K. Restless legs syndrome and sleep disturbance during pregnancy: the role of folate and iron. J Womens Health Gend Based Med. 2001;10(4):335-341.
24. Djokanovic N, Garcia-Bournissen F, Koren G. Medications for restless legs syndrome in pregnancy. J Obstet Gynaecol Can. 2008;30(6):505-507.
25. Freedman RR, Roehrs TA. Effects of REM sleep and ambient temperature on hot flash-induced sleep disturbance. Menopause. 2006;13(4):576-583.
26. Krystal AD, Edinger J, Wohlgemuth W, et al. Sleep in perimenopausal and postmenopausal women. Sleep Med Rev. 1998;2(4):243-253.
27. Polo-Kantola P, Erkkola R, Irjala K, et al. Effect of short-term transdermal estrogen replacement therapy on sleep: a randomized, double-blind crossover trial in postmenopausal women. Fertil Steril. 1999;71(5):873-880.
28. Watts NB, Notelovitz M, Timmons MC, et al. Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid-lipoprotein profiles in surgical menopause. Obstet Gynecol. 1995;85(4):529-537.Erratum in: Obstet Gynecol 1995;85(5 Pt 1):668.
29. Boyle GJ, Murrihy R. A preliminary study of hormone replacement therapy and psychological mood states in perimenopausal women. Psychol Rep. 2001;88(1):160-170.
30. Cistulli PA, Barnes DJ, Grunstein RR, et al. Effect of short-term hormone replacement in the treatment of obstructive sleep apnoea in postmenopausal women. Thorax. 1994;49:699-702.
31. Yang CM, Spielman AJ, Glovinsky P. Nonpharmacologic strategies in the management of insomnia. Psychiatr Clin North Am. 2006;29(4):895-919.
32. Mahady GB. Black cohosh (Actaea/Cimicifuga racemosa): review of the clinical data for safety and efficacy in menopausal symptoms. Treat Endocrinol. 2005;4(3):177-184.
33. Breslau N, Roth T, Rosenthal L, et al. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry. 1996;39:411-418.
34. Burt VK, Stein K. Epidemiology of depression throughout the female life cycle. J Clin Psychiatry. 2002;63(suppl 7):9-15.
Discuss this article at http://currentpsychiatry.blogspot.com/2010/07/treating-insomnia-in-women.html#comments
Ms. A, age 44, reports a 3-month history of forgetfulness, difficulty concentrating, and insomnia. She says she can fall asleep but wakes up multiple times during the night and feels tired during the day. She has no history of a mood or anxiety disorder or medications that might be responsible for her symptoms.
Before her current insomnia began, Ms. A could sleep for 7 to 8 hours at night. Her husband suffers from obstructive sleep apnea (OSA), and his snoring occasionally would awaken her, but she slept well overall. Ms. A cannot identify anything that could be causing her sleep complaints. She states “The weird thing is that sometimes I am not sure if I’m cold or hot” and “I sometimes wake up drenched in sweat.” She also reports recent changes in the timing of her otherwise regular menstrual flow.
Ms. A attributes her memory problems to her poor sleep. A recent audit at her company held her responsible for several accounting errors, and Ms. A is worried that she might lose her job. She denies symptoms that would suggest major depression. You are unable to elicit a history of limb movements or excessive snoring.
Compared with men, women have a 1.3- to 1.8-fold greater risk for developing insomnia.Improve sleep with group CBT for insomnia,” Current Psychiatry, April 2009.) Pharmacotherapy during pregnancy and for breast-feeding mothers is guided by evaluating the risk/benefit ratio and safety considerations.
Maintain a high index of suspicion for breathing-related sleep disorders, such as OSA,21 and RLS.22 Atypical presentations of OSA are common in pregnant or postpartum women; compared with men, women with OSA are more likely to report fatigue and less likely than to report sleepiness. Refer patients whom you think may have OSA for polysomnography.
If you suspect RLS, check for low ferritin and folate levels. Nutritional supplements may be necessary for women in high-risk groups, including those who are pregnant or have varicose veins, venous reflux, folate deficiency, uremia, diabetes, thyroid problems, peripheral neuropathy, Parkinson’s disease, or certain autoimmune disorders, such as Sjögren’s syndrome, celiac disease, and rheumatoid arthritis.23 Advise these patients to avoid caffeine.
Although indicated for treating RLS, ropinirole and pramipexole are FDA Pregnancy Category C, which means animal studies have shown adverse effects on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite risks. Opioids, carbamazepine, or gabapentin may be safer for pregnant patients.24
Insomnia during menopause
The prevalence of insomnia increases from 33% to 36% in premenopausal women to 44% to 61% in postmenopausal women.14 Hot flashes, comorbid mood disturbances, sleep-disordered breathing, and RLS contribute to increased insomnia risk in postmenopausal women (Table 3).4,14,25,26
Treatment strategy. Always inquire about sleep in perimenopausal/postmenopausal women, even when her presenting complaint is related to menstrual cycle changes or vasomotor symptoms such as hot flashes.16 Assess patients for OSA, RLS, and mood, anxiety, and cognitive symptoms.26 In addition to pharmacotherapy and behavioral therapy, treatment options include hormone replacement therapy (HRT) and herbal and dietary supplements (Table 4).27-32
Table 3
Sleep difficulties during menopause: Differential diagnoses
| Condition | Features | Findings | Other considerations |
|---|---|---|---|
| Hot flashes (prevalence: 75% to 85%)14 | Vasomotor phenomenon characterized by feelings such as ‘spreading warmth,’ diaphoresis, palpitations, nausea, and insomnia Mediated through the preoptic area of the anterior hypothalamus, which regulates temperature and sleep Increased brain norepinephrine metabolism | Discrepancies between objective (PSG) and subjective measures (surveys)4 Discrepancies between self-reported and laboratory reported sleep data might be explained by thermoregulatory differences between NREM and REM sleep24 | Nocturnal hot flashes trigger awakenings and insomnia14 Hot flashes can follow arousals and awakenings HRT is highly effective in treating hot flashes; however, data on its direct effects on sleep complaints are inconsistent |
| Primary menopausal insomnia25 | Menopausal symptoms (eg, hot flashes) trigger insomnia that persists secondary to behavioral conditioning | Increase in nocturnal skin temperature coincides with decrease in skin resistance and waking episodes in PSG | Behavioral insomnia therapies are useful adjuncts to treatment of menopause symptoms |
| Sleep-disordered breathing (OSA) | Menopause increases risk for OSA independent of body weight Redistribution of body fat with an increase in the waist-to-hip circumference ratio occurs in menopause Loss of ventilatory drive because of diminished progesterone levels | Sleep fragmentation and daytime sleepiness are common, as opposed to apneic episodes or oxygen desaturation in men | Maintain a high index of suspicion and promptly refer patients to a sleep center |
| Restless legs syndrome | Related to iron deficiency | Low ferritin and folate levels | Advise patients to avoid caffeine |
| HRT: hormone replacement therapy; NREM: non-rapid eye movement; OSA: obstructive sleep apnea; PSG: polysomnography; REM: rapid eye movement | |||
Table 4
Treating insomnia in menopausal women
| Therapy | Comments |
|---|---|
| Hormone replacement therapy (HRT) | Effective for hot flashes, insomnia,26-28 and sleep apnea29 Long-term safety is questionable4 |
| Behavioral therapy (cognitive-behavioral therapy,30 stimulus control therapy, sleep restriction therapy, sleep hygiene, hypnotherapy, biofeedback) | Limited data in menopausal women |
| Sedatives/hypnotics/antidepressants (eg, zolpidem, 10 mg; eszopiclone, 3 mg; trazodone, 75 mg; ramelteon, 8 mg; SSRIs and SNRIs) | Benzodiazepines may be useful, although not specifically evaluated in menopausal women. Risk of tolerance, dependence, and psychomotor slowing |
| Herbal and dietary supplements (Cimicifuga racemosa [Black cohosh],31 valerian | Popular alternatives to HRT; however, evidence of efficacy as treatment for insomnia is inconclusive |
| SNRIs: serotonin-norepinephrine reuptake inhibitors; SSRIs: selective serotonin reuptake inhibitors | |
Comorbid psychiatric disorders
Women have a higher prevalence of psychiatric disorders such as major depressive disorder and anxiety disorders than men.1 Women have a 10% to 25% lifetime risk of developing major depression. Three quarters of depressed patients experience insomnia.1 Recent literature suggests insomnia is a risk factor for depression,33 which emphasizes the need to screen women who present with sleep problems for depression and anxiety.
Five percent to 20% of women experience postpartum depression. Depression and insomnia are correlated to the rapid decline in estrogen and progesterone after delivery.34
Treatment strategy. Insomnia is a common presenting symptom in patients with psychiatric conditions such as mood and anxiety disorders. Treating the underlying psychiatric disorder often alleviates sleeping difficulties. However, if the insomnia is disabling, treat the psychiatric disorder and insomnia concurrently.
CASE CONTINUED: Perimenopausal insomnia
Based on her history, you diagnose Ms. A with insomnia related to general medical condition (perimenopause). There are no indications to refer her for polysomnography. You educate Ms. A about sleep hygiene and recommend that she discuss her menstrual and physical complaints with her primary care physician or gynecologist. Ms. A is not interested in HRT because she has a strong family history of endometrial cancer. You reassure Ms. A and schedule a follow-up visit in 2 months to re-evaluate her insomnia.
Related resource
- Krahn LE. Perimenopausal depression? Ask how she’s sleeping. Current Psychiatry. 2005;4(6):39-53.
Drug brand names
- Carbamazepine • Carbatrol, Tegretol, others
- Escitalopram • Lexapro
- Eszopiclone • Lunesta
- Fluoxetine • Prozac
- Gabapentin • Neurontin, Gabarone
- Paroxetine • Paxil
- Pramipexole • Mirapex
- Ramelteon • Rozerem
- Ropinirole • Requip
- Sertraline • Zoloft
- Trazodone • Desyrel
- Zolpidem • Ambien
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Acknowledgements
The authors thank Dr. Namita Dhiman and Darrel E. Willoughby for their assistance with this article.
Discuss this article at http://currentpsychiatry.blogspot.com/2010/07/treating-insomnia-in-women.html#comments
Ms. A, age 44, reports a 3-month history of forgetfulness, difficulty concentrating, and insomnia. She says she can fall asleep but wakes up multiple times during the night and feels tired during the day. She has no history of a mood or anxiety disorder or medications that might be responsible for her symptoms.
Before her current insomnia began, Ms. A could sleep for 7 to 8 hours at night. Her husband suffers from obstructive sleep apnea (OSA), and his snoring occasionally would awaken her, but she slept well overall. Ms. A cannot identify anything that could be causing her sleep complaints. She states “The weird thing is that sometimes I am not sure if I’m cold or hot” and “I sometimes wake up drenched in sweat.” She also reports recent changes in the timing of her otherwise regular menstrual flow.
Ms. A attributes her memory problems to her poor sleep. A recent audit at her company held her responsible for several accounting errors, and Ms. A is worried that she might lose her job. She denies symptoms that would suggest major depression. You are unable to elicit a history of limb movements or excessive snoring.
Compared with men, women have a 1.3- to 1.8-fold greater risk for developing insomnia.Improve sleep with group CBT for insomnia,” Current Psychiatry, April 2009.) Pharmacotherapy during pregnancy and for breast-feeding mothers is guided by evaluating the risk/benefit ratio and safety considerations.
Maintain a high index of suspicion for breathing-related sleep disorders, such as OSA,21 and RLS.22 Atypical presentations of OSA are common in pregnant or postpartum women; compared with men, women with OSA are more likely to report fatigue and less likely than to report sleepiness. Refer patients whom you think may have OSA for polysomnography.
If you suspect RLS, check for low ferritin and folate levels. Nutritional supplements may be necessary for women in high-risk groups, including those who are pregnant or have varicose veins, venous reflux, folate deficiency, uremia, diabetes, thyroid problems, peripheral neuropathy, Parkinson’s disease, or certain autoimmune disorders, such as Sjögren’s syndrome, celiac disease, and rheumatoid arthritis.23 Advise these patients to avoid caffeine.
Although indicated for treating RLS, ropinirole and pramipexole are FDA Pregnancy Category C, which means animal studies have shown adverse effects on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite risks. Opioids, carbamazepine, or gabapentin may be safer for pregnant patients.24
Insomnia during menopause
The prevalence of insomnia increases from 33% to 36% in premenopausal women to 44% to 61% in postmenopausal women.14 Hot flashes, comorbid mood disturbances, sleep-disordered breathing, and RLS contribute to increased insomnia risk in postmenopausal women (Table 3).4,14,25,26
Treatment strategy. Always inquire about sleep in perimenopausal/postmenopausal women, even when her presenting complaint is related to menstrual cycle changes or vasomotor symptoms such as hot flashes.16 Assess patients for OSA, RLS, and mood, anxiety, and cognitive symptoms.26 In addition to pharmacotherapy and behavioral therapy, treatment options include hormone replacement therapy (HRT) and herbal and dietary supplements (Table 4).27-32
Table 3
Sleep difficulties during menopause: Differential diagnoses
| Condition | Features | Findings | Other considerations |
|---|---|---|---|
| Hot flashes (prevalence: 75% to 85%)14 | Vasomotor phenomenon characterized by feelings such as ‘spreading warmth,’ diaphoresis, palpitations, nausea, and insomnia Mediated through the preoptic area of the anterior hypothalamus, which regulates temperature and sleep Increased brain norepinephrine metabolism | Discrepancies between objective (PSG) and subjective measures (surveys)4 Discrepancies between self-reported and laboratory reported sleep data might be explained by thermoregulatory differences between NREM and REM sleep24 | Nocturnal hot flashes trigger awakenings and insomnia14 Hot flashes can follow arousals and awakenings HRT is highly effective in treating hot flashes; however, data on its direct effects on sleep complaints are inconsistent |
| Primary menopausal insomnia25 | Menopausal symptoms (eg, hot flashes) trigger insomnia that persists secondary to behavioral conditioning | Increase in nocturnal skin temperature coincides with decrease in skin resistance and waking episodes in PSG | Behavioral insomnia therapies are useful adjuncts to treatment of menopause symptoms |
| Sleep-disordered breathing (OSA) | Menopause increases risk for OSA independent of body weight Redistribution of body fat with an increase in the waist-to-hip circumference ratio occurs in menopause Loss of ventilatory drive because of diminished progesterone levels | Sleep fragmentation and daytime sleepiness are common, as opposed to apneic episodes or oxygen desaturation in men | Maintain a high index of suspicion and promptly refer patients to a sleep center |
| Restless legs syndrome | Related to iron deficiency | Low ferritin and folate levels | Advise patients to avoid caffeine |
| HRT: hormone replacement therapy; NREM: non-rapid eye movement; OSA: obstructive sleep apnea; PSG: polysomnography; REM: rapid eye movement | |||
Table 4
Treating insomnia in menopausal women
| Therapy | Comments |
|---|---|
| Hormone replacement therapy (HRT) | Effective for hot flashes, insomnia,26-28 and sleep apnea29 Long-term safety is questionable4 |
| Behavioral therapy (cognitive-behavioral therapy,30 stimulus control therapy, sleep restriction therapy, sleep hygiene, hypnotherapy, biofeedback) | Limited data in menopausal women |
| Sedatives/hypnotics/antidepressants (eg, zolpidem, 10 mg; eszopiclone, 3 mg; trazodone, 75 mg; ramelteon, 8 mg; SSRIs and SNRIs) | Benzodiazepines may be useful, although not specifically evaluated in menopausal women. Risk of tolerance, dependence, and psychomotor slowing |
| Herbal and dietary supplements (Cimicifuga racemosa [Black cohosh],31 valerian | Popular alternatives to HRT; however, evidence of efficacy as treatment for insomnia is inconclusive |
| SNRIs: serotonin-norepinephrine reuptake inhibitors; SSRIs: selective serotonin reuptake inhibitors | |
Comorbid psychiatric disorders
Women have a higher prevalence of psychiatric disorders such as major depressive disorder and anxiety disorders than men.1 Women have a 10% to 25% lifetime risk of developing major depression. Three quarters of depressed patients experience insomnia.1 Recent literature suggests insomnia is a risk factor for depression,33 which emphasizes the need to screen women who present with sleep problems for depression and anxiety.
Five percent to 20% of women experience postpartum depression. Depression and insomnia are correlated to the rapid decline in estrogen and progesterone after delivery.34
Treatment strategy. Insomnia is a common presenting symptom in patients with psychiatric conditions such as mood and anxiety disorders. Treating the underlying psychiatric disorder often alleviates sleeping difficulties. However, if the insomnia is disabling, treat the psychiatric disorder and insomnia concurrently.
CASE CONTINUED: Perimenopausal insomnia
Based on her history, you diagnose Ms. A with insomnia related to general medical condition (perimenopause). There are no indications to refer her for polysomnography. You educate Ms. A about sleep hygiene and recommend that she discuss her menstrual and physical complaints with her primary care physician or gynecologist. Ms. A is not interested in HRT because she has a strong family history of endometrial cancer. You reassure Ms. A and schedule a follow-up visit in 2 months to re-evaluate her insomnia.
Related resource
- Krahn LE. Perimenopausal depression? Ask how she’s sleeping. Current Psychiatry. 2005;4(6):39-53.
Drug brand names
- Carbamazepine • Carbatrol, Tegretol, others
- Escitalopram • Lexapro
- Eszopiclone • Lunesta
- Fluoxetine • Prozac
- Gabapentin • Neurontin, Gabarone
- Paroxetine • Paxil
- Pramipexole • Mirapex
- Ramelteon • Rozerem
- Ropinirole • Requip
- Sertraline • Zoloft
- Trazodone • Desyrel
- Zolpidem • Ambien
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Acknowledgements
The authors thank Dr. Namita Dhiman and Darrel E. Willoughby for their assistance with this article.
1. Krystal AD. Depression and insomnia in women. Clin Cornerstone. 2004;6(suppl 1B):S19-S28.
2. Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev. 2002;6(2):97-111.
3. Krishnan V, Collop NA. Gender differences in sleep disorders. Curr Opin Pulm Med. 2006;12(6):383-389.
4. Soares CN, Murray BJ. Sleep disorders in women: clinical evidence and treatment strategies. Psychiatr Clin North Am. 2006;29(4):1095-1113.
5. Ohayon M. Epidemiological study on insomnia in the general population. Sleep. 1996;19(3 suppl):S7-S15.
6. Daley M, Morin CM, LeBlanc M, et al. Insomnia and its relationship to health-care utilization, work absenteeism, productivity and accidents. Sleep Med. 2009;10(4):427-438.
7. Diagnostic and statistical manual of mental disorders, 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000.
8. Ancoli-Israel S, Roth T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Sleep. 1999;2(suppl 2):S347-S353.
9. Zhang B, Wing YK. Sex differences in insomnia: a meta-analysis. Sleep. 2006;29(1):85-93.
10. Buysse DJ, Reynolds CF, Monk TH, et al. The Pittsburgh Sleep Quality Index (PSQI): a new instrument for psychiatric research and practice. Psychiatry Res. 1989;28(2):193-213.
11. Manber R, Bootzin RR. Sleep and the menstrual cycle. Health Psychol. 1997;16:209-214.
12. Ito M, Kohsaka M, Fukuda N, et al. Effects of menstrual cycle on plasma melatonin level and sleep characteristics. Jpn J Psychiatry Neurol. 1993;47:478-479.
13. Driver HS, Dijk DJ, Werth E, et al. Sleep and the sleep electroencephalogram across the menstrual cycle in young healthy women. J Clin Endocrinol Metab. 1996;81:728-735.
14. Moline ML, Broch L, Zak R. Sleep in women across the life cycle from adulthood through menopause. Med Clin North Am. 2004;88(3):705-736.
15. Steiner M, Pearlstein T, Cohen LS, et al. Expert guidelines for the treatment of severe PMS, PMDD, and comorbidities: the role of SSRIs. J Womens Health (Larchmt). 2006;15(1):57-69.
16. Krystal AD. Insomnia in women. Clin Cornerstone. 2003;5(3):41-50.
17. Mindell JA, Jacobson BJ. Sleep disturbances during pregnancy. J Obstet Gynecol Neonatal Nurs. 2000;29(6):590-597.
18. Lee KA, Zaffke ME, McEnany G. Parity and sleep patterns during and after pregnancy. Obstet Gynecol. 2000;95(1):14-18.
19. Brunner DP, Münch M, Biedermann K, et al. Changes in sleep and sleep electroencephalogram during pregnancy. Sleep. 1994;17(7):576-582.
20. Ross LE, Murray BJ, Steiner M. Sleep and perinatal mood disorders: a critical review. J Psychiatry Neurosci. 2005;30(4):247-256.
21. Edwards N, Middleton PG, Blyton DM, et al. Sleep disordered breathing and pregnancy. Thorax. 2002;57(6):555-558.
22. Manconi M, Govoni V, De Vito A, et al. Restless legs syndrome and pregnancy. Neurology. 2004;63(6):1065-1069.
23. Lee KA, Zaffke ME, Baratte-Beebe K. Restless legs syndrome and sleep disturbance during pregnancy: the role of folate and iron. J Womens Health Gend Based Med. 2001;10(4):335-341.
24. Djokanovic N, Garcia-Bournissen F, Koren G. Medications for restless legs syndrome in pregnancy. J Obstet Gynaecol Can. 2008;30(6):505-507.
25. Freedman RR, Roehrs TA. Effects of REM sleep and ambient temperature on hot flash-induced sleep disturbance. Menopause. 2006;13(4):576-583.
26. Krystal AD, Edinger J, Wohlgemuth W, et al. Sleep in perimenopausal and postmenopausal women. Sleep Med Rev. 1998;2(4):243-253.
27. Polo-Kantola P, Erkkola R, Irjala K, et al. Effect of short-term transdermal estrogen replacement therapy on sleep: a randomized, double-blind crossover trial in postmenopausal women. Fertil Steril. 1999;71(5):873-880.
28. Watts NB, Notelovitz M, Timmons MC, et al. Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid-lipoprotein profiles in surgical menopause. Obstet Gynecol. 1995;85(4):529-537.Erratum in: Obstet Gynecol 1995;85(5 Pt 1):668.
29. Boyle GJ, Murrihy R. A preliminary study of hormone replacement therapy and psychological mood states in perimenopausal women. Psychol Rep. 2001;88(1):160-170.
30. Cistulli PA, Barnes DJ, Grunstein RR, et al. Effect of short-term hormone replacement in the treatment of obstructive sleep apnoea in postmenopausal women. Thorax. 1994;49:699-702.
31. Yang CM, Spielman AJ, Glovinsky P. Nonpharmacologic strategies in the management of insomnia. Psychiatr Clin North Am. 2006;29(4):895-919.
32. Mahady GB. Black cohosh (Actaea/Cimicifuga racemosa): review of the clinical data for safety and efficacy in menopausal symptoms. Treat Endocrinol. 2005;4(3):177-184.
33. Breslau N, Roth T, Rosenthal L, et al. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry. 1996;39:411-418.
34. Burt VK, Stein K. Epidemiology of depression throughout the female life cycle. J Clin Psychiatry. 2002;63(suppl 7):9-15.
1. Krystal AD. Depression and insomnia in women. Clin Cornerstone. 2004;6(suppl 1B):S19-S28.
2. Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev. 2002;6(2):97-111.
3. Krishnan V, Collop NA. Gender differences in sleep disorders. Curr Opin Pulm Med. 2006;12(6):383-389.
4. Soares CN, Murray BJ. Sleep disorders in women: clinical evidence and treatment strategies. Psychiatr Clin North Am. 2006;29(4):1095-1113.
5. Ohayon M. Epidemiological study on insomnia in the general population. Sleep. 1996;19(3 suppl):S7-S15.
6. Daley M, Morin CM, LeBlanc M, et al. Insomnia and its relationship to health-care utilization, work absenteeism, productivity and accidents. Sleep Med. 2009;10(4):427-438.
7. Diagnostic and statistical manual of mental disorders, 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000.
8. Ancoli-Israel S, Roth T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Sleep. 1999;2(suppl 2):S347-S353.
9. Zhang B, Wing YK. Sex differences in insomnia: a meta-analysis. Sleep. 2006;29(1):85-93.
10. Buysse DJ, Reynolds CF, Monk TH, et al. The Pittsburgh Sleep Quality Index (PSQI): a new instrument for psychiatric research and practice. Psychiatry Res. 1989;28(2):193-213.
11. Manber R, Bootzin RR. Sleep and the menstrual cycle. Health Psychol. 1997;16:209-214.
12. Ito M, Kohsaka M, Fukuda N, et al. Effects of menstrual cycle on plasma melatonin level and sleep characteristics. Jpn J Psychiatry Neurol. 1993;47:478-479.
13. Driver HS, Dijk DJ, Werth E, et al. Sleep and the sleep electroencephalogram across the menstrual cycle in young healthy women. J Clin Endocrinol Metab. 1996;81:728-735.
14. Moline ML, Broch L, Zak R. Sleep in women across the life cycle from adulthood through menopause. Med Clin North Am. 2004;88(3):705-736.
15. Steiner M, Pearlstein T, Cohen LS, et al. Expert guidelines for the treatment of severe PMS, PMDD, and comorbidities: the role of SSRIs. J Womens Health (Larchmt). 2006;15(1):57-69.
16. Krystal AD. Insomnia in women. Clin Cornerstone. 2003;5(3):41-50.
17. Mindell JA, Jacobson BJ. Sleep disturbances during pregnancy. J Obstet Gynecol Neonatal Nurs. 2000;29(6):590-597.
18. Lee KA, Zaffke ME, McEnany G. Parity and sleep patterns during and after pregnancy. Obstet Gynecol. 2000;95(1):14-18.
19. Brunner DP, Münch M, Biedermann K, et al. Changes in sleep and sleep electroencephalogram during pregnancy. Sleep. 1994;17(7):576-582.
20. Ross LE, Murray BJ, Steiner M. Sleep and perinatal mood disorders: a critical review. J Psychiatry Neurosci. 2005;30(4):247-256.
21. Edwards N, Middleton PG, Blyton DM, et al. Sleep disordered breathing and pregnancy. Thorax. 2002;57(6):555-558.
22. Manconi M, Govoni V, De Vito A, et al. Restless legs syndrome and pregnancy. Neurology. 2004;63(6):1065-1069.
23. Lee KA, Zaffke ME, Baratte-Beebe K. Restless legs syndrome and sleep disturbance during pregnancy: the role of folate and iron. J Womens Health Gend Based Med. 2001;10(4):335-341.
24. Djokanovic N, Garcia-Bournissen F, Koren G. Medications for restless legs syndrome in pregnancy. J Obstet Gynaecol Can. 2008;30(6):505-507.
25. Freedman RR, Roehrs TA. Effects of REM sleep and ambient temperature on hot flash-induced sleep disturbance. Menopause. 2006;13(4):576-583.
26. Krystal AD, Edinger J, Wohlgemuth W, et al. Sleep in perimenopausal and postmenopausal women. Sleep Med Rev. 1998;2(4):243-253.
27. Polo-Kantola P, Erkkola R, Irjala K, et al. Effect of short-term transdermal estrogen replacement therapy on sleep: a randomized, double-blind crossover trial in postmenopausal women. Fertil Steril. 1999;71(5):873-880.
28. Watts NB, Notelovitz M, Timmons MC, et al. Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid-lipoprotein profiles in surgical menopause. Obstet Gynecol. 1995;85(4):529-537.Erratum in: Obstet Gynecol 1995;85(5 Pt 1):668.
29. Boyle GJ, Murrihy R. A preliminary study of hormone replacement therapy and psychological mood states in perimenopausal women. Psychol Rep. 2001;88(1):160-170.
30. Cistulli PA, Barnes DJ, Grunstein RR, et al. Effect of short-term hormone replacement in the treatment of obstructive sleep apnoea in postmenopausal women. Thorax. 1994;49:699-702.
31. Yang CM, Spielman AJ, Glovinsky P. Nonpharmacologic strategies in the management of insomnia. Psychiatr Clin North Am. 2006;29(4):895-919.
32. Mahady GB. Black cohosh (Actaea/Cimicifuga racemosa): review of the clinical data for safety and efficacy in menopausal symptoms. Treat Endocrinol. 2005;4(3):177-184.
33. Breslau N, Roth T, Rosenthal L, et al. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry. 1996;39:411-418.
34. Burt VK, Stein K. Epidemiology of depression throughout the female life cycle. J Clin Psychiatry. 2002;63(suppl 7):9-15.