Download PDF
Semin Neurol 2009; 29(4): 340-353
DOI: 10.1055/s-0029-1237125
© Thieme Medical Publishers

Chronic Insomnia

David N. Neubauer1 , Kelleen N. Flaherty2
  • 1Johns Hopkins Sleep Disorders Center, Johns Hopkins Bayview Medical Center and Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 2Biomedical Writing Programs, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania
Further Information

Publication History

Publication Date:
09 September 2009 (online)

    Permissions and Reprints

ABSTRACT

Chronic insomnia afflicts millions of people in the United States. It is associated with decreased quality of life, accidents, several comorbid conditions, increased morbidity, and substantial direct and indirect costs. Chronic insomnia is a multifactorial and individualized disorder. Its etiology may be cognitive or physiologic in nature (or both), and is more often than not associated with a comorbid condition, complicating its recognition, evaluation, and treatment. Effective nonpharmacotherapeutic (cognitive–behavioral therapy for insomnia) and pharmacotherapeutic (hypnotic medications) treatment modalities are available. Treatment of chronic insomnia can make a significant improvement in quality of life, and may also be associated with an improvement in comorbid conditions.

KEYWORDS

Chronic insomnia - sleep - comorbidity - cognitive–behavioral therapy - hypnotic

REFERENCES

  • 1 Bulfinch T. Bulfinch's Age of Fable or Beauties of Mythology. Boston, MA; SW Tilton 1894
    PubMedGoogle Scholar
  • 2 American Academy of Sleep Medicine .International Classification of Sleep Disorders, 2nd ed: Diagnostic and Coding Manual. Westchester, IL; American Academy of Sleep Medicine 2005
    PubMedGoogle Scholar
  • 3 Buysse D J, Reynolds III C F, Kupfer D J et al.. Effects of diagnosis on treatment recommendations in chronic insomnia—a report from the APA/NIMH DSM-IV field trial.  Sleep. 1997;  20(7) 542-552
    PubMedGoogle Scholar
  • 4 Buysse D J. Insomnia. In: Buysse DJ Sleep Disorders and Psychiatry. Washington, DC; American Psychiatric Publishing Inc 2005
    PubMedGoogle Scholar
  • 5 Perlis M L, Smith L J, Lyness J M et al.. Insomnia as a risk factor for onset of depression in the elderly.  Behav Sleep Med. 2006;  4(2) 104-113
    CrossrefPubMedGoogle Scholar
  • 6 Mallon L, Broman J E, Hetta J. Sleep complaints predict coronary artery disease mortality in males: a 12-year follow-up study of a middle-aged Swedish population.  J Intern Med. 2002;  251(3) 207-216
    CrossrefPubMedGoogle Scholar
  • 7 Daley M, Morin C M, LeBlanc M, Grégoire J P, Savard J. The economic burden of insomnia: direct and indirect costs for individuals with insomnia syndrome, insomnia symptoms, and good sleepers.  Sleep. 2009;  32(1) 55-64
    PubMedGoogle Scholar
  • 8 Ozminkowski R J, Wang S, Walsh J K. The direct and indirect costs of untreated insomnia in adults in the United States.  Sleep. 2007;  30(3) 263-273
    PubMedGoogle Scholar
  • 9 Walsh J K, Engelhardt C L. The direct economic costs of insomnia in the United States for 1995.  Sleep. 1999;  22(Suppl 2) S386-S393
    PubMedGoogle Scholar
  • 10 Edinger J D, Bonnet M H, Bootzin R R American Academy of Sleep Medicine Work Group et al. Derivation of research diagnostic criteria for insomnia: report of an American Academy of Sleep Medicine Work Group.  Sleep. 2004;  27(8) 1567-1596
    PubMedGoogle Scholar
  • 11 Zammit G K, Weiner J, Damato N, Sillup G P, McMillan C A. Quality of life in people with insomnia.  Sleep. 1999;  22(Suppl 2) S379-S385
    PubMedGoogle Scholar
  • 12 Léger D, Scheuermaier K, Philip P, Paillard M, Guilleminault C. SF-36: evaluation of quality of life in severe and mild insomniacs compared with good sleepers.  Psychosom Med. 2001;  63(1) 49-55
    PubMedGoogle Scholar
  • 13 Katz D A, McHorney C A. Clinical correlates of insomnia in patients with chronic illness.  Arch Intern Med. 1998;  158(10) 1099-1107
    CrossrefPubMedGoogle Scholar
  • 14 Katz D A, McHorney C A. The relationship between insomnia and health-related quality of life in patients with chronic illness.  J Fam Pract. 2002;  51(3) 229-235
    PubMedGoogle Scholar
  • 15 Harvey A G. A cognitive model of insomnia.  Behav Res Ther. 2002;  40(8) 869-893
    CrossrefPubMedGoogle Scholar
  • 16 Taylor D J, Lichstein K L, Durrence H H. Insomnia as a health risk factor.  Behav Sleep Med. 2003;  1(4) 227-247
    CrossrefPubMedGoogle Scholar
  • 17 Marchetti L M, Biello S M, Broomfield N M, Macmahon K M, Espie C A. Who is pre-occupied with sleep? A comparison of attention bias in people with psychophysiological insomnia, delayed sleep phase syndrome and good sleepers using the induced change blindness paradigm.  J Sleep Res. 2006;  15(2) 212-221
    CrossrefPubMedGoogle Scholar
  • 18 Krystal A D. Treating the health, quality of life, and functional impairments in insomnia.  J Clin Sleep Med. 2007;  3(1) 63-72
    PubMedGoogle Scholar
  • 19 Léger D, Guilleminault C, Bader G, Lévy E, Paillard M. Medical and socio-professional impact of insomnia.  Sleep. 2002;  25(6) 625-629
    PubMedGoogle Scholar
  • 20 Leigh J P. Employee and job attributes as predictors of absenteeism in a national sample of workers: the importance of health and dangerous working conditions.  Soc Sci Med. 1991;  33(2) 127-137
    CrossrefPubMedGoogle Scholar
  • 21 Pack A I, Pack A M, Rodgman E, Cucchiara A, Dinges D F, Schwab C W. Characteristics of crashes attributed to the driver having fallen asleep.  Accid Anal Prev. 1995;  27(6) 769-775
    CrossrefPubMedGoogle Scholar
  • 22 Zammit G K, Weiner J, Damato N, Sillup G P, McMillan C A. Quality of life in people with insomnia.  Sleep. 1999;  22(Suppl 2) S379-S385
    PubMedGoogle Scholar
  • 23 Powell N B, Schechtman K B, Riley R W, Li K, Guilleminault C. Sleepy driving: accidents and injury.  Otolaryngol Head Neck Surg. 2002;  126(3) 217-227
    CrossrefPubMedGoogle Scholar
  • 24 Sagberg F. Driver health and crash involvement: a case-control study.  Accid Anal Prev. 2006;  38(1) 28-34
    CrossrefPubMedGoogle Scholar
  • 25 008 State Bills on Drowsy Driving. Available at: http://www.drowsydriving.org/site/c.lqLPIROCKtF/b.3344259/ Accessed May 26, 2009
    Google Scholar
  • 26 Maggie's Law Introduced in Congress .Available at: http://www.drowsydriving.org/site/c.lqLPIROCKtF/b.3344249/k.449B/Maggies_Law_Introduced_in_Congress.htm Accessed May 26, 2009
    PubMed
  • 27 National Institutes of Health . National Institutes of Health State of the Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults, June 13–15, 2005.  Sleep. 2005;  28(9) 1049-1057
    PubMedGoogle Scholar
  • 28 Taylor D J, Mallory L J, Lichstein K L, Durrence H H, Riedel B W, Bush A J. Comorbidity of chronic insomnia with medical problems.  Sleep. 2007;  30(2) 213-218
    PubMedGoogle Scholar
  • 29 Ohayon M M. Nocturnal awakenings and comorbid disorders in the American general population.  J Psychiatr Res. 2008;  43(1) 48-54
    CrossrefPubMedGoogle Scholar
  • 30 Suka M, Yoshida K, Sugimori H. Persistent insomnia is a predictor of hypertension in Japanese male workers.  J Occup Health. 2003;  45(6) 344-350
    CrossrefPubMedGoogle Scholar
  • 31 Lanfranchi P A, Pennestri M H, Fradette L et al.. Nighttime blood pressure in normotensive subjects with chronic insomnia: implications for cardiovascular risk.  Sleep. 2009;  32(6) 760-766
    PubMedGoogle Scholar
  • 32 Mallon L, Broman J E, Hetta J. High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year follow-up study of a middle-aged population.  Diabetes Care. 2005;  28(11) 2762-2767
    CrossrefPubMedGoogle Scholar
  • 33 Meisinger C, Heier M, Loewel H. MONICA/KORA Augsburg Cohort Study . Sleep disturbance as a predictor of type 2 diabetes mellitus in men and women from the general population.  Diabetologia. 2005;  48(2) 235-241
    CrossrefPubMedGoogle Scholar
  • 34 Affleck G, Urrows S, Tennen H, Higgins P, Abeles M. Sequential daily relations of sleep, pain intensity, and attention to pain among women with fibromyalgia.  Pain. 1996;  68(2-3) 363-368
    CrossrefPubMedGoogle Scholar
  • 35 Drewes A M, Nielsen K D, Hansen B, Taagholt S J, Bjerregârd K, Svendsen L. A longitudinal study of clinical symptoms and sleep parameters in rheumatoid arthritis.  Rheumatology (Oxford). 2000;  39(11) 1287-1289
    CrossrefPubMedGoogle Scholar
  • 36 Roehrs T, Hyde M, Blaisdell B, Greenwald M, Roth T. Sleep loss and REM sleep loss are hyperalgesic.  Sleep. 2006;  29(2) 145-151
    PubMedGoogle Scholar
  • 37 Savard J, Laroche L, Simard S, Ivers H, Morin C M. Chronic insomnia and immune functioning.  Psychosom Med. 2003;  65(2) 211-221
    CrossrefPubMedGoogle Scholar
  • 38 Hall M, Baum A, Buysse D J, Prigerson H G, Kupfer D J, Reynolds III C F. Sleep as a mediator of the stress-immune relationship.  Psychosom Med. 1998;  60(1) 48-51
    PubMedGoogle Scholar
  • 39 Perlis M L, Giles D E, Buysse D J, Tu X, Kupfer D J. Self-reported sleep disturbance as a prodromal symptom in recurrent depression.  J Affect Disord. 1997;  42(2-3) 209-212
    CrossrefPubMedGoogle Scholar
  • 40 Benca R M. Consequences of insomnia and its therapies.  J Clin Psychiatry. 2001;  62(Suppl 10) 33-38
    PubMedGoogle Scholar
  • 41 Ford D E, Kamerow D B. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention?.  JAMA. 1989;  262(11) 1479-1484
    CrossrefPubMedGoogle Scholar
  • 42 Ohayon M M, Roth T. Place of chronic insomnia in the course of depressive and anxiety disorders.  J Psychiatr Res. 2003;  37(1) 9-15
    CrossrefPubMedGoogle Scholar
  • 43 Ramsawh H J, Stein M B, Belik S L, Jacobi F, Sareen J. Relationship of anxiety disorders, sleep quality, and functional impairment in a community sample.  J Psychiatr Res. 2009;  43(10) 926-933
    CrossrefPubMedGoogle Scholar
  • 44 Mellman T A. Sleep and anxiety disorders.  Psychiatr Clin North Am. 2006;  29(4) 1047-1058, abstract x
    CrossrefPubMedGoogle Scholar
  • 45 Mellman T A, Uhde T W. Patients with frequent sleep panic: clinical findings and response to medication treatment.  J Clin Psychiatry. 1990;  51(12) 513-516
    PubMedGoogle Scholar
  • 46 Green B. Post-traumatic stress disorder: symptom profiles in men and women.  Curr Med Res Opin. 2003;  19(3) 200-204
    CrossrefPubMedGoogle Scholar
  • 47 Bélanger L, Morin C M, Langlois F, Ladouceur R. Insomnia and generalized anxiety disorder: effects of cognitive behavior therapy for GAD on insomnia symptoms.  J Anxiety Disord. 2004;  18(4) 561-571
    CrossrefPubMedGoogle Scholar
  • 48 Stein M B, Kroft C D, Walker J R. Sleep impairment in patients with social phobia.  Psychiatry Res. 1993;  49(3) 251-256
    CrossrefPubMedGoogle Scholar
  • 49 Weissman M M, Greenwald S, Niño-Murcia G, Dement W C. The morbidity of insomnia uncomplicated by psychiatric disorders.  Gen Hosp Psychiatry. 1997;  19(4) 245-250
    CrossrefPubMedGoogle Scholar
  • 50 Breslau N, Roth T, Rosenthal L, Andreski P. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults.  Biol Psychiatry. 1996;  39(6) 411-418
    CrossrefPubMedGoogle Scholar
  • 51 Livingston G, Blizard B, Mann A. Does sleep disturbance predict depression in elderly people? A study in inner London.  Br J Gen Pract. 1993;  43(376) 445-448
    PubMedGoogle Scholar
  • 52 Roberts R E, Shema S J, Kaplan G A. Prospective data on sleep complaints and associated risk factors in an older cohort.  Psychosom Med. 1999;  61(2) 188-196
    PubMedGoogle Scholar
  • 53 Chang P P, Ford D E, Mead L A, Cooper-Patrick L, Klag M J. Insomnia in young men and subsequent depression. The Johns Hopkins Precursors Study.  Am J Epidemiol. 1997;  146(2) 105-114
    PubMedGoogle Scholar
  • 54 Ağargün M Y, Kara H, Solmaz M. Sleep disturbances and suicidal behavior in patients with major depression.  J Clin Psychiatry. 1997;  58(6) 249-251
    PubMedGoogle Scholar
  • 55 Smith M T, Perlis M L, Haythornthwaite J A. Suicidal ideation in outpatients with chronic musculoskeletal pain: an exploratory study of the role of sleep onset insomnia and pain intensity.  Clin J Pain. 2004;  20(2) 111-118
    CrossrefPubMedGoogle Scholar
  • 56 Neubauer D N, Flaherty K N. Pathophysiology, associations, and consequences of insomnia. In: Kushida C Handbook of Sleep Medicine. 2nd ed. New York, NY; Informa Healthcare 2008: 15-28
    PubMedGoogle Scholar
  • 57 Buysse D J. Chronic insomnia.  Am J Psychiatry. 2008;  165(6) 678-686
    CrossrefPubMedGoogle Scholar
  • 58 Spielman A J, Caruso L S, Glovinsky P B. A behavioral perspective on insomnia treatment.  Psychiatr Clin North Am. 1987;  10(4) 541-553
    CrossrefPubMedGoogle Scholar
  • 59 Drake C L, Roth T. Predisposition in the evolution of insomnia: evidence, potential mechanisms, and future directions.  Sleep Med Clin. 2006;  1 333-349
    CrossrefPubMedGoogle Scholar
  • 60 Kales A, Caldwell A B, Preston T A, Healey S, Kales J D. Personality patterns in insomnia. Theoretical implications.  Arch Gen Psychiatry. 1976;  33(9) 1128-24
    PubMedGoogle Scholar
  • 61 Bootzin R R, Nicassio P M. Behavioral treatments for insomnia.  Prog Behav Modif. 1978;  6 1-45
    PubMedGoogle Scholar
  • 62 Perlis M L, Smith M T, Pigeon W R. Etiology and pathophysiology of insomnia. In: Kryger MH, Roth T, Dement WC Principles and Practice of Sleep Medicine. 4th ed. Philadelphia, PA; Elsevier Inc 2005: 714-725
    PubMedGoogle Scholar
  • 63 Bonnet M H, Arand D L. Hyperarousal and insomnia.  Sleep Med Rev. 1997;  1(2) 97-108
    CrossrefPubMedGoogle Scholar
  • 64 Monroe L J. Psychological and physiological differences between good and poor sleepers.  J Abnorm Psychol. 1967;  72(3) 255-264
    CrossrefPubMedGoogle Scholar
  • 65 Stepanski E, Zorick F, Roehrs T, Young D, Roth T. Daytime alertness in patients with chronic insomnia compared with asymptomatic control subjects.  Sleep. 1988;  11(1) 54-60
    CrossrefPubMedGoogle Scholar
  • 66 Haynes S N, Follingstad D R, McGowan W T. Insomnia: sleep patterns and anxiety level.  J Psychosom Res. 1974;  18(2) 69-74
    CrossrefPubMedGoogle Scholar
  • 67 Vgontzas A N, Bixler E O, Lin H M et al.. Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications.  J Clin Endocrinol Metab. 2001;  86(8) 3787-3794
    CrossrefPubMedGoogle Scholar
  • 68 Kapsimalis F, Basta M, Varouchakis G, Gourgoulianis K, Vgontzas A, Kryger M. Cytokines and pathological sleep.  Sleep Med. 2008;  9(6) 603-614
    PubMedGoogle Scholar
  • 69 van den Heuvel C, Ferguson S, Dawson D. Attenuated thermoregulatory response to mild thermal challenge in subjects with sleep-onset insomnia.  Sleep. 2006;  29(9) 1174-1180
    PubMedGoogle Scholar
  • 70 Perlis M L, Smith M T, Andrews P J, Orff H, Giles D E. Beta/Gamma EEG activity in patients with primary and secondary insomnia and good sleeper controls.  Sleep. 2001;  24(1) 110-117
    PubMedGoogle Scholar
  • 71 Nofzinger E A, Buysse D J, Germain A, Price J C, Miewald J M, Kupfer D J. Functional neuroimaging evidence for hyperarousal in insomnia.  Am J Psychiatry. 2004;  161(11) 2126-2128
    Google Scholar
  • 72 Lieberman J A, Neubauer D N. Understanding insomnia: diagnosis and management of a common sleep disorder.  J Fam Pract. 2007;  56(10) 35A-50A
    PubMedGoogle Scholar
  • 73 Mastin D F, Bryson J, Corwyn R. Assessment of sleep hygiene using the Sleep Hygiene Index.  J Behav Med. 2006;  29(3) 223-227
    CrossrefPubMedGoogle Scholar
  • 74 Jefferson C D, Drake C L, Scofield H M et al.. Sleep hygiene practices in a population-based sample of insomniacs.  Sleep. 2005;  28(5) 611-615
    PubMedGoogle Scholar
  • 75 Morin C M. Cognitive-behavioral approaches to the treatment of insomnia.  J Clin Psychol. 2004;  65 Suppl 16 33-40
    PubMedGoogle Scholar
  • 76 Morin C M, Bootzin R R, Buysse D J, Edinger J D, Espie C A, Lichstein K L. Psychological and behavioral treatment of insomnia:update of the recent evidence (1998–2004).  Sleep. 2006;  29(11) 1398-1414
    PubMedGoogle Scholar
  • 77 Morin C M, Vallières A, Guay B et al.. Cognitive behavioral therapy, singly and combined with medication, for persistent insomnia: a randomized controlled trial.  JAMA. 2009;  301(19) 2005-2015
    CrossrefPubMedGoogle Scholar
  • 78 Bateson A N. Further potential of the GABA receptor in the treatment of insomnia.  Sleep Med. 2006;  7(Suppl 1) S3-S9
    PubMedGoogle Scholar
  • 79 Neubauer D N. Pharmacologic treatment of insomnia. In: Tasman A, Kay J, Lieberman J, First M, Maj M Psychiatry. 3rd ed. Hoboken, NJ; John Wiley & Sons 2008: 2254-2263
    PubMedGoogle Scholar
  • 80 Ancoli-Israel S, Richardson G S, Mangano R M, Jenkins L, Hall P, Jones W S. Long-term use of sedative hypnotics in older patients with insomnia.  Sleep Med. 2005;  6(2) 107-113
    CrossrefPubMedGoogle Scholar
  • 81 Erman M, Krystal A, Zammit G et al.. Zolpidem extended-release 12.5 mg, taken for 24 weeks “as needed” up to 7 nights/week, improves subjective measures of therapeutic global impression, sleep onset, and sleep maintenance in patients with chronic insomnia.  Int J Neuropsychopharmacol. 2006;  9(Suppl 1) S256
    PubMedGoogle Scholar
  • 82 Krystal A D, Walsh J K, Laska E et al.. Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia.  Sleep. 2003;  26(7) 793-799
    Google Scholar
  • 83 Perlis M L, McCall W V, Krystal A D, Walsh J K. Long-term, non-nightly administration of zolpidem in the treatment of patients with primary insomnia.  J Clin Psychiatry. 2004;  65(8) 1128-1137
    CrossrefPubMedGoogle Scholar
  • 84 Roth T, Walsh J K, Krystal A, Wessel T, Roehrs T A. An evaluation of the efficacy and safety of eszopiclone over 12 months in patients with chronic primary insomnia.  Sleep Med. 2005;  6(6) 487-495
    CrossrefPubMedGoogle Scholar
  • 85 Kato K, Hirai K, Nishiyama K et al.. Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist.  Neuropharmacology. 2005;  48(2) 301-310
    CrossrefPubMedGoogle Scholar
  • 86 Seiden D, Zee P, Weigand S et al.. Double-blind, placebo-controlled outpatient clinical trial of ramelteon for the treatment of chronic insomnia in an elderly population.  Sleep. 2005;  28(Suppl) A228
    PubMedGoogle Scholar
  • 87 Zammit G, Roth T, Erman M et al.. Double-blind, placebo-controlled polysomnography and outpatient trial to evaluate the efficacy and safety of ramelteon in adult patients with chronic insomnia.  Sleep. 2005;  28(Suppl) A228-A229
    PubMedGoogle Scholar
  • 88 Stahl S. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2nd ed. New York, NY; Cambridge University Press 2008
    PubMedGoogle Scholar
  • 89 Brisbare-Roch C, Dingemanse J, Koberstein R et al.. Promotion of sleep by targeting the orexin system in rats, dogs and humans.  Nat Med. 2007;  13(2) 150-155
    CrossrefPubMedGoogle Scholar
  • 90 Wiegand M H. Antidepressants for the treatment of insomnia : a suitable approach?.  Drugs. 2008;  68(17) 2411-2417
    CrossrefPubMedGoogle Scholar
  • 91 Wilson S, Nutt D. Management of insomnia: treatments and mechanismsi.  Br J Psychiatry. 2007;  191 195-197
    CrossrefPubMedGoogle Scholar
  • 92 Drici M D, Priori S. Cardiovascular risks of atypical antipsychotic drug treatment.  Pharmacoepidemiol Drug Saf. 2007;  16(8) 882-890
    CrossrefPubMedGoogle Scholar
  • 93 Doxylamine. Drug Bank Web Page. Available at: http://www.drugbank.ca/drugs/DB00366 Accessed May 30, 2009
    Google Scholar
  • 94 Rickels K, Morris R J, Newman H, Rosenfeld H, Schiller H, Weinstock R. Diphenhydramine in insomniac family practice patients: a double-blind study.  J Clin Pharmacol. 1983;  23(5-6) 234-242
    PubMedGoogle Scholar
  • 95 Richardson G S, Roehrs T A, Rosenthal L, Koshorek G, Roth T. Tolerance to daytime sedative effects of H1 antihistamines.  J Clin Psychopharmacol. 2002;  22(5) 511-515
    CrossrefPubMedGoogle Scholar
  • 96 Roehrs T, Roth T. Sleep, sleepiness, and alcohol use.  Alcohol Res Health. 2001;  25(2) 101-109
    PubMedGoogle Scholar
  • 97 Bliwise D L, Ansari F P. Insomnia associated with valerian and melatonin usage in the 2002 National Health Interview Survey.  Sleep. 2007;  30(7) 881-884
    PubMedGoogle Scholar
  • 98 Huntley A. Over-the-counter herbals and drug interactions: getting the (right) message across.  Expert Opin Drug Saf. 2006;  5(1) 5-6, author reply 5–6
    CrossrefPubMedGoogle Scholar
  • 99 Curry D T, Eisenstein R D, Walsh J K. Pharmacologic management of insomnia: past, present, and future.  Psychiatr Clin North Am. 2006;  29(4) 871-893, abstract vii–viii
    CrossrefPubMedGoogle Scholar
  • 100 Miller L G. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions.  Arch Intern Med. 1998;  158(20) 2200-2211
    CrossrefPubMedGoogle Scholar
  • 101 Fugh-Berman A, Cott J M. Dietary supplements and natural products as psychotherapeutic agents.  Psychosom Med. 1999;  61(5) 712-728
    PubMedGoogle Scholar
  • 102 Winslow L C, Kroll D J. Herbs as medicines.  Arch Intern Med. 1998;  158(20) 2192-2199
    CrossrefPubMedGoogle Scholar
  • 103 Clouatre D L. Kava kava: examining new reports of toxicity.  Toxicol Lett. 2004;  150(1) 85-96
    CrossrefPubMedGoogle Scholar
  • 104 Greeson J M, Sanford B, Monti D A. St. John's wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature.  Psychopharmacology (Berl). 2001;  153(4) 402-414
    CrossrefPubMedGoogle Scholar
  • 105 Hammerness P, Basch E, Ulbricht C Natural Standard Research Collaboration et al. St John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist.  Psychosomatics. 2003;  44(4) 271-282
    CrossrefPubMedGoogle Scholar

David N NeubauerM.D. 

Associate Director, Johns Hopkins Sleep Disorders Center, Johns Hopkins Bayview Medical Center

4940 Eastern Avenue, Box 151, Baltimore, MD 21224

Email: neubauer@jhmi.edu