Treating Insomnia and Depression – The Evidence for Eszopiclone

Andrew Krystal
European Psychiatric Review, 2008;1(2):30-34
pdf icon download pdf ejournal view ejournal

Abstract

Insomnia, a widespread condition that affects individuals of all ages and genders, is frequently associated with psychiatric conditions such as major depression and generalised anxiety disorder (GAD). In recent years, a growing body of evidence has resulted in a shift in the view of insomnia as just a secondary manifestation of other psychiatric disorders to insomnia as a comorbid condition. This important change in the understanding of the relationship between insomnia and other psychiatric disorders will help lead to changes in clinical practice and support the need to institute insomnia-specific treatment when insomnia occurs in association with another psychiatric disorder.

Limited data from clinical studies suggest that directly addressing the insomnia in co-morbid patients will not only improve sleep impairments but may also improve the effect of concomitant antidepressant treatment. Currently, several approaches can be considered when devising a pharmacological treatment strategy for a patient suffering from insomnia with co-morbid psychiatric conditions, including single-agent therapy or concomitant insomnia therapy together with a non-sedating antidepressant therapy. Further research will help to identify the optimal therapeutic regimen.
Keywords
Insomnia, depression, generalised anxiety disorder (GAD), co-morbid, pharmacological treatment, major depressive disorder
Disclosure Andrew Krystal has received grants or research support from the National Institutes of Health (NIH), sanofiaventis, Cephalon, GlaxoSmithKline, Merck, Neurocrine, Pfizer, Sepracor, Somaxon, Takeda, Transcept, Respironics, Neurogen, Evotec, Astellas and Neuronetics. He has been a consultant for Actelion, Arena, Astellas, Axiom, AstraZeneca, Bristol-Myers- Squibb, Cephalon, Eli Lilly, GlaxoSmithKline, Jazz, Johnson & Johnson, King, Merck, Neurocrine, Neurogen, Novartis, Organon, Ortho-McNeil-Janssen, Pfizer, Respironics, Roche, sanofi-aventis, Sepracor, Somaxon, Takeda, Transcept, Astellas, Research Triangle Institute and Kingsdown Inc.
Received: November 19, 2008 Accepted December 20, 2008
Correspondence: Andrew Krystal, Department of Psychiatry, Duke University School of Medicine, 129 Davison Bldg, Durham, NC 27710, US. E: kryst001@mc.duke.edu

Insomnia is a widespread condition affecting individuals of all ages and genders. Many conditions are known to accompany insomnia, the most common being psychiatric disorders such as major depressive disorder (MDD) and generalised anxiety disorder (GAD). In the past insomnia was considered to be a result of these disorders that did not require direct intervention, but was expected to be resolved through treatment of the primary disorder. In recent years this view has changed, and insomnia is now considered to be more of a co-morbid disorder requiring separate attention and therapeutic treatment. Several drugs are available separately for the treatment of depression or insomnia, although some antidepressants have additional sedatory effects. The main target of insomnia treatment is the γ-aminobutyric acid (GABA) receptor type A. The most widely used drugs for insomnia treatment enhance the inhibitory effects of GABA by binding to the benzodiazepine site on the GABA receptor complex. These agents include a group of chemically related agents referred to as benzodiazepines and a set of chemically distinct medications often referred to as ‘non-benzodiazepines’. The non-benzodiazepines tend to bind in a relatively selective manner to some subtypes of the GABA receptor complexes. Some evidence suggests that treating insomnia in depression patients results in an improvement of sleep indices as well as producing better results from the antidepressant treatment. When considering treatment options for patients with insomnia co-occurring with depression, one can consider either the use of a single agent to alleviate both depression and insomnia or a combination of a non-sedating antidepressant drug together with a sedating antidepressant or a specific sedative. Further research is needed to identify which of these strategies will contribute to a more favourable prognosis and the best drug combination.

Insomnia

Insomnia is a common condition among both adults and adolescents. It is usually defined by a patient’s report of recurring difficulty in falling sleep, which may include long sleep-onset latency, frequent awakenings, long periods of wakefulness, frequent transient arousals and inadequate restoration from sleep. The diagnosis requires that the sleep difficulty be present despite adequate opportunities and circumstances for sleep. In addition to difficulties with sleep, the diagnosis criteria for insomnia include daytime distress or disability such as memory impairment, fatigue, social dysfunction, mood disturbances, daytime sleepiness, motivation or initiative reduction and proneness to errors or accidents at work or while driving.1

References:
  1. Edinger JD, Bonnet MH, Bootzin RR, et al., Derivation of research diagnostic criteria for insomnia, Sleep, 2004;8: 1567–96.
  2. National Institutes of Health State of the Science Conference statement on Manifestations and Management of Chronic Insomnia in Adults, Sleep, 2005;9:1049–57.
  3. Simon GE, VonKorff M, Prevalence, burden, and treatment of insomnia in primary care, Am J Psychiatry, 1997;10:1417–23.
  4. Ohayon MM, Prevalence of DSM-IV diagnostic criteria of insomnia, J Psychiatr Res, 1997;3:333–46.
  5. Hatoum HT, Kong SX, Kania CM, et al., Insomnia, health-related quality of life and healthcare resource consumption, Pharmacoeconomics, 1998;6:629–37.
  6. Reimer MA, Flemons WW, Quality of life in sleep disorders, Sleep Med Rev, 2003;4:335–49.
  7. Katz DA, McHorney CA, Clinical correlates of insomnia in patients with chronic illness, Arch Intern Med, 1998;10: 1099–1107.
  8. Leger D, Guilleminault C, Bader G, et al., Medical and socio-professional impact of insomnia, Sleep, 2002;6:625–9.
  9. Balter MB, Uhlenhuth EH, New epidemiologic findings about insomnia and its treatment, J Clin Psychiatry, 1992;34–39.
  10. Zammit GK, Weiner J, Damato N, et al., Quality of life in people with insomnia, Sleep, 1999;S379–85.
  11. Johnson EO, Roth T, Schultz L, et al., Epidemiology of DSMIV insomnia in adolescence, Pediatrics, 2006;2:e247–56.
  12. Roth T, Insomnia: definition, prevalence, etiology, and consequences, J Clin Sleep Med, 2007;(Suppl. 5):S7–10.
  13. Ford DE, Kamerow DB, Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention?, JAMA, 1989;11:1479–84.
  14. Krystal AD, Psychiatric Comorbidity: The Case for Treating Insomnia, Sleep Med Clin, 2006;359–65.
  15. Nierenberg AA, Keefe BR, Leslie VC, et al., Residual symptoms in depressed patients who respond acutely to fluoxetine, J Clin Psychiatry, 1999;4:221–5.
  16. Manber R, Rush AJ, Thase ME, et al., The effects of psychotherapy, nefazodone, and their combination on subjective assessment of disturbed sleep in chronic depression, Sleep, 2003;2:130–36.
  17. Reynolds CF III, Frank E, Houck PR, et al., Which elderly patients with remitted depression remain well with continued interpersonal psychotherapy after discontinuation of antidepressant medication?, Am J Psychiatry, 1997;7:958–62.
  18. Nierenberg AA, Adler LA, Peselow E, et al., Trazodone for antidepressant-associated insomnia, Am J Psychiatry, 1994;7: 1069–72.
  19. Asnis GM, Chakraburtty A, DuBoff EA, et al., Zolpidem for persistent insomnia in SSRI-treated depressed patients, J Clin Psychiatry, 1999;10:668–76.
  20. Fava M, McCall WV, Krystal A, et al., Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder, Biol Psychiatry, 2006;11:1052–60.
  21. Londborg PD, Smith WT, Glaudin V et al., Short-term cotherapy with clonazepam and fluoxetine: anxiety, sleep disturbance and core symptoms of depression, J Affect Disord, 2000;1-2:73-79.
  22. Fontaine R, Beaudry P, Le MP, et al., Zopiclone and triazolam in insomnia associated with generalized anxiety disorder, Int Clin Psychopharmacol, 1990;3:173–83.
  23. Agnoli A, Manna V, Martucci N, Double-blind study on the hypnotic and antianxiety effects of zopiclone compared with nitrazepam in the treatment of insomnia, Int J Clin Pharmacol Res, 1989;4:277–81.
  24. Breslau N, Roth T, Rosenthal L, et al., Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults, Biol Psychiatry, 1996;6:411–18.
  25. Weissman MM, Greenwald S, Nino-Murcia G, et al., The morbidity of insomnia uncomplicated by psychiatric disorders, Gen Hosp Psychiatry, 1997;4:245–50.
  26. Johnson EO, Roth T, Breslau N, The association of insomnia with anxiety disorders and depression, J Psychiatr Res, 2006;8:700–708.
  27. Ohayon MM, Roth T, Place of chronic insomnia in the course of depressive and anxiety disorders, J Psychiatr Res, 2003;1:9–15.
  28. Dew MA, Whyte EM, Lenze EJ, et al., Recovery from major depression in older adults receiving augmentation of antidepressant pharmacotherapy, Am J Psychiatry, 2007;6: 892–899.
  29. Thase ME, Simons AD, Reynolds CF III, Abnormal electroencephalographic sleep profiles in major depression, Arch Gen Psychiatry, 1996;2:99–108.
  30. Saper CB, Scammell TE, Lu J, Hypothalamic regulation of sleep and circadian rhythms, Nature, 2005;7063:1257–63.
  31. Roth T, Franklin M, Bramley TJ, The state of insomnia and emerging trends, Am J Manag Care, 2007;(Suppl. 5):S117–20.
  32. Vgontzas AN, Bixler EO, Lin HM, et al., Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications, J Clin Endocrinol Metab, 2001;8:3787–94.
  33. Szabadi E, Drugs for sleep disorders: mechanisms and therapeutic prospects, Br J Clin Pharmacol, 2006;6:761–6.
  34. Krystal AD, A Compendium of Placebo-Controlled Trials of the Risk/Benefits of Pharmacologic Treatments for Insomnia: The Empirical Basis for US Clinical Practice, Sleep Med Rev, 2008;5.
  35. Sieghart W, Structure and pharmacology of gamma-aminobutyric acidA receptor subtypes, Pharmacol Rev, 1995;2:181–234.
  36. Henschel O, Gipson KE, Bordey A, GABAA receptors, anesthetics and anticonvulsants in brain development, CNS Neurol Disord Drug Targets, 2008;2:211–24.
  37. Korpi ER, Grunder G, Luddens H, Drug interactions at GABA(A) receptors, Prog Neurobiol, 2002;2:113–59.
  38. Sieghart W, Structure, pharmacology, and function of GABAA receptor subtypes, Adv Pharmacol, 2006;231–63.
  39. Drover DR, Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives: zaleplon, zolpidem and zopiclone, Clin Pharmacokinet, 2004;4:227–38.
  40. Zimovane LS, Summary of Product Characteristics, sanofiaventis, 2009.
  41. Melton ST, Wood JM, Kirkwood CK, Eszopiclone for insomnia, Ann Pharmacother, 2005;10:1659–66.
  42. Zammit GK, McNabb LJ, Caron J, et al., Efficacy and safety of eszopiclone across six weeks of treatment for primary insomnia, Curr Med Res Opin, 2004;12:1979–91.
  43. Roth T, Walsh JK, Krystal A, et al., An evaluation of the efficacy and safety of eszopiclone over 12 months in patients with chronic primary insomnia, Sleep Med, 2005;6:487–95.
  44. Krystal AD, Walsh JK, Laska E, et al., Sustained efficacy of eszopiclone over 6 months of nightly treatment, Sleep, 2003;7:793–9.
  45. Nowell PD, Mazumdar S, Buysse DJ, et al., Benzodiazepines and zolpidem for chronic insomnia: a meta-analysis of treatment efficacy, JAMA, 1997;24:2170–77.
  46. Ware JC, Brown FW, Moorad PJ Jr, et al., Effects on sleep, Sleep, 1989;6:537–49.
  47. Scharf MB, Hirschowitz J, Zemlan FP, et al., Comparative effects of limbitrol and amitriptyline on sleep efficiency and architecture, J Clin Psychiatry, 1986;12:587–91.
  48. Guelfi JD, Ansseau M, Timmerman L, et al., Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features, J Clin Psychopharmacol, 2001;4:425–31.
  49. Rush AJ, Armitage R, Gillin JC, et al., Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder, Biol Psychiatry, 1998;1:3–14.
  50. Kerkhofs M, Rielaert C, de M V, et al., Fluoxetine in major depression: efficacy, safety and effects on sleep polygraphic variables, Int Clin Psychopharmacol, 1990;4:253–60.
  51. Hicks JA, Argyropoulos SV, Rich AS, et al., Randomised controlled study of sleep after nefazodone or paroxetine treatment in out-patients with depression, Br J Psychiatry, 2002;528–35.
  52. Jindal RD, Thase ME, Treatment of insomnia associated with clinical depression, Sleep Med Rev, 2004;1:19–30.
  53. Furukawa TA, Streiner DL, Young LT, Antidepressant and benzodiazepine for major depression, Cochrane Database Syst Rev, 2002;1:CD001026.
  54. Cohn JB, Triazolam treatment of insomnia in depressed patients taking tricyclics, J Clin Psychiatry, 1983;11:401–6.
  55. Smith WT, Londborg PD, Glaudin V, et al., Short-term augmentation of fluoxetine with clonazepam in the treatment of depression, Am J Psychiatry, 1998;10:1339–45.
  56. Smith WT, Londborg PD, Glaudin V, et al., Is extended clonazepam cotherapy of fluoxetine effective for outpatients with major depression?, J Affect Disord, 2002;3:251–9.
  57. Fava M, Asnis G, Shrivastava R, et al., Improved insomnia symptoms and daily functioning in patients with comorbid major depressive disorder and insomnia following zolpidem extended-release 12.5mg and escitalopram co-treatment. Poster presented at SLEEP 2008 22nd Annual Meeting of the Associated Professional Sleep Societies on June 10, 2008; Poster #0984.
  58. Krystal A, Fava M, Rubens R, et al., Evaluation of eszopiclone discontinuation after cotherapy with fluoxetine for insomnia with co-existing depression, J Clin Sleep Med, 2007;1:48–55.
  59. Fava M, Asnis G, Shrivastava R, et al., Improved insomnia symptoms and next-day functioning in patients with comorbid insomnia and generalized anxiety disorder following concomitant zolpidem extended-release 12.5 mg and escitalopram treatment, Poster presented at the 46th ACNP Annual Meeting; December 2007.
  60. Pollack M, Kinrys G, Krystal A, et al., Eszopiclone coadministered with escitalopram in patients with insomnia and comorbid generalized anxiety disorder, Arch Gen Psychiatry, 2008;5:551–62.
  61. Walsh JK, Krystal AD, Amato DA, et al., Nightly treatment of primary insomnia with eszopiclone for six months, Sleep, 2007;8:959–968.
  62. Scharf M, Erman M, Rosenberg R, et al., A two-week efficacy and safety study of eszopiclone in elderly patients with primary insomnia, Sleep, 2005;6:720–27.
close

This content is copyright protected

However, if you would like to share the information on this webpage, you may use the headline and link below:

Treating Insomnia and Depression – The Evidence for Eszopiclone

Read more: Treating Insomnia and Depression – The Evidence for Eszopiclone