Psychopharmacology

, Volume 177, Issue 4, pp 357–365 | Cite as

Comparative effects of duloxetine and desipramine on sleep EEG in healthy subjects

  • Stephan Chalon
  • Alvaro Pereira
  • Eric Lainey
  • François Vandenhende
  • John G. Watkin
  • Luc Staner
  • Luc-André Granier
Original Investigation

Abstract

Rationale

Antidepressants are known to modify human sleep patterns.

Objectives

Duloxetine is a new antidepressant with a mechanism of action involving reuptake inhibition of both serotonin (5-HT) and norepinephrine (NE). In this study, the effects of two dosing regimens of duloxetine on sleep electroencephalography (EEG) were investigated at steady-state plasma concentrations in young, healthy, male subjects.

Methods

Placebo (n=12), desipramine (50 mg BID; n=12) and two regimens of duloxetine (80 mg QD, n=6; or 60 mg BID, n=6) were compared in a randomized, double-blind, three-period crossover study, each treatment being administered from day 1 to day 7. Sleep polygraphic recordings took place at baseline (day −1) and day 6 of each period. The Leeds sleep evaluation questionnaire (LSEQ) was also administered on the morning of day 7.

Results

Both regimens of duloxetine produced a significant increase in the onset latency of REM sleep as well as a significant mean decrease in total REM sleep duration. Desipramine exhibited comparable effects. When compared to placebo, sleep continuity was significantly reduced with desipramine and duloxetine 60 mg BID whereas a significant improvement was observed with duloxetine 80 mg QD. On the LSEQ, duloxetine 80 mg QD produced a significant improvement in the “getting to sleep” subscale compared to placebo, whereas desipramine demonstrated a significant reduction (worsening) in the “quality of sleep” score versus placebo.

Conclusions

The two dose regimens of duloxetine (80 mg QD and 60 mg BID) produced a REM sleep pattern comparable to that of most antidepressant medications. Duloxetine 80 mg QD appeared to exhibit less impact upon sleep quality than duloxetine 60 mg BID in healthy subjects.

Keywords

Duloxetine Desipramine Sleep Polysomnography REM sleep 

References

  1. Bixler EO, Kales A, Soldatos CR, Kales JD, Healey S (1979) Prevalence of sleep disorders in the Los Angeles metropolitan area. Am J Psychiatry 136:1257–1262PubMedGoogle Scholar
  2. Breslau N, Roth T, Rosenthal L, Andreski P (1996) Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry 39:411–418CrossRefPubMedGoogle Scholar
  3. Brezinova V, Adam K, Chapman K, Oswald I, Thomson J (1977) Viloxazine, sleep, and subjective feelings. Psychopharmacology 55:121–128PubMedGoogle Scholar
  4. Brunello N, Armitage R, Feinberg I, Holsboer-Trachsler E, Leger D, Linkowski P, Mendelson WB, Racagni G, Saletu B, Sharpley AL, Turek F, Van Cauter E, Mendlewicz J (2000) Depression and sleep disorders: clinical relevance, economic burden and pharmacological treatment. Neuropsychobiology 42:107–119CrossRefPubMedGoogle Scholar
  5. Buysse DJ, Frank E, Lowe KK, Cherry CR, Kupfer DJ (1997) Electroencephalographic sleep correlates of episode and vulnerability to recurrence in depression. Biol Psychiatry 41:406–418CrossRefPubMedGoogle Scholar
  6. Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT (2001) Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology 25:871–880CrossRefPubMedGoogle Scholar
  7. Chalon S, Granier LA, Vandenhende FR, Bieck PR, Bymaster FP, Joliat MJ, Hirth C, Potter WZ (2004) Duloxetine increases serotonin and norepinephrine availability in healthy subjects: a double-blind, controlled study. Neuropsychopharmacology 28:1685–1693CrossRefGoogle Scholar
  8. Crismon ML, Trivedi M, Pigott TA, Rush AJ, Hirschfeld RM, Kahn DA, DeBattista C, Nelson JC, Nierenberg AA, Sackeim HA, Thase ME (1999) The Texas medication algorithm project: report of the Texas consensus conference panel on medication treatment of major depressive disorder. J Clin Psychiatry 60:142–156PubMedGoogle Scholar
  9. Detke MJ, Lu Y, Goldstein DJ, Hayes JR, Demitrack MA (2002a) Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry 63:308–315PubMedGoogle Scholar
  10. Detke MJ, Lu Y, Goldstein DJ, McNamara RK, Demitrack MA (2002b) Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression. J Psychiatr Res 36:383CrossRefPubMedGoogle Scholar
  11. Engleman EA, Perry KW, Mayle DA, Wong DT (1995) Simultaneous increases of extracellular monoamines in microdialysates from hypothalamus of conscious rats by duloxetine, a dual serotonin and norepinephrine uptake inhibitor. Neuropsychopharmacology 12:287–295PubMedGoogle Scholar
  12. Farina B, Della M, Mennuni G, Mazza S, De Risio S, Di Giannantonio M (2002) The effects of reboxetine on human sleep architecture in depression: preliminary results. J Affect Disord 71:273–275CrossRefPubMedGoogle Scholar
  13. Feuillade P, Pringuey D, Belugou JL, Robert P, Darcourt G (1992) Trimipramine: acute and lasting effects on sleep in healthy and major depressive subjects. J Affect Disord 24:135–145CrossRefPubMedGoogle Scholar
  14. Giles DE, Jarrett RB, Roffwarg HP, Rush AJ (1987) Reduced rapid eye movement latency. A predictor of recurrence in depression. Neuropsychopharmacology 1:33–39PubMedGoogle Scholar
  15. Gillin JC, Rapaport M, Erman MK, Winokur A, Albala BJ (1997) A comparison of nefazodone and fluoxetine on mood and on objective, subjective, and clinician-rated measures of sleep in depressed patients: a double-blind, 8-week clinical trial. J Clin Psychiatry 58:185–192PubMedGoogle Scholar
  16. Goldstein DJ, Mallinckrodt C, Lu Y, Demitrack MA (2002) Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. J Clin Psychiatry 63:225–231PubMedGoogle Scholar
  17. Gumnick JF, Nemeroff CB (2000) Problems with currently available antidepressants. J Clin Psychiatry 61(Suppl 10):5–15Google Scholar
  18. Gursky JT, Krahn LE (2000) The effects of antidepressants on sleep: a review. Harv Rev Psychiatry 8:298–306CrossRefPubMedGoogle Scholar
  19. Hartmann E, Cravens J (1973) The effects of long-term administration of psychotropic drugs on human sleep. III. The effects of amitriptyline. Psychopharmacologia 33:185–202PubMedGoogle Scholar
  20. Kennedy GJ, Kelman HR, Thomas C (1991) Persistence and remission of depressive symptoms in late life. Am J Psychiatry 148:174–178PubMedGoogle Scholar
  21. Kihara T, Ikeda M (1995) Effects of duloxetine, a new serotonin and norepinephrine uptake inhibitor, on extracellular monoamine levels in rat frontal cortex. J Pharmacol Exp Ther 272:177–183PubMedGoogle Scholar
  22. Kupfer DJ, Foster FG (1972) Interval between onset of sleep and rapid-eye-movement sleep as an indicator of depression. Lancet 2:684–686CrossRefPubMedGoogle Scholar
  23. Kupfer DJ, Frank E (1984) The relationship of EEG sleep to vital depression. J Affect Disord 7:249–263CrossRefPubMedGoogle Scholar
  24. Kupfer DJ, Foster FG, Reich L, Thompson SK, Weiss B (1976) EEG sleep changes as predictors in depression. Am J Psychiatry 133:622–626PubMedGoogle Scholar
  25. Kupfer DJ, Foster FG, Coble P, McPartland RJ, Ulrich RF (1978) The application of EEG sleep for the differential diagnosis of affective disorders. Am J Psychiatry 135:69–74PubMedGoogle Scholar
  26. Kupfer DJ, Perel JM, Pollock BG, Nathan RS, Grochocinski VJ, Wilson MJ, McEachran AB (1991) Fluvoxamine versus desipramine: comparative polysomnographic effects. Biol Psychiatry 29:23–40CrossRefPubMedGoogle Scholar
  27. Kupfer DJ, Pollock BG, Perel JM, Miewald JM, Grochocinski VJ, Ehlers CL (1994) Effect of pulse loading with clomipramine on EEG sleep. Psychiatry Res 54:161–175CrossRefPubMedGoogle Scholar
  28. Le Bon O, Staner L, Murphy JR, Hoffmann G, Pull CH, Pelc I (1997) Critical analysis of the theories advanced to explain short REM sleep latencies and other sleep anomalies in several psychiatric conditions. J Psychiatr Res 31:433–450CrossRefPubMedGoogle Scholar
  29. Luthringer R, Toussaint M, Schaltenbrand N, Bailey P, Danjou PH, Hackett D, Guichoux JY, Macher JP (1996) A double-blind, placebo-controlled evaluation of the effects of orally administered venlafaxine on sleep in inpatients with major depression. Psychopharmacol Bull 32:637–646PubMedGoogle Scholar
  30. McCarley RW (1982) REM sleep and depression: common neurobiological control mechanisms. Am J Psychiatry 139:565–570PubMedGoogle Scholar
  31. Mellinger GD, Balter MB, Uhlenhuth EH (1985) Insomnia and its treatment. Prevalence and correlates. Arch Gen Psychiatry 42:225–232PubMedGoogle Scholar
  32. Mendlewicz J, Kerkhofs M (1991) Sleep electroencephalography in depressive illness. A collaborative study by the World Health Organization. Br J Psychiatry 159:505–509PubMedGoogle Scholar
  33. Mendlewicz J, Kempenaers C, de Maertelaer V (1991) Sleep EEG and amitryptiline treatment in depressed inpatients. Biol Psychiatry 30:691–702CrossRefPubMedGoogle Scholar
  34. Nelson JC (1998) Synergistic benefits of serotonin and noradrenaline reuptake inhibition. Depress Anxiety 7(Suppl 1):5–6Google Scholar
  35. Nelson JC, Mazure CM, Bowers MB Jr, Jatlow PI (1991) A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression. Arch Gen Psychiatry 48:303–307PubMedGoogle Scholar
  36. Nemeroff CB, Schatzberg AF, Goldstein DJ, Detke MJ, Mallinckrodt C, Lu Y, Tran PV (2002) Duloxetine for the treatment of major depressive disorder. Psychopharmacol Bull 36:106–132PubMedGoogle Scholar
  37. Nicholson AN, Pascoe PA (1986) 5-Hydroxytryptamine and noradrenaline uptake inhibition: studies on sleep in man. Neuropharmacology 25:1079–1083CrossRefPubMedGoogle Scholar
  38. Nicholson AN, Pascoe PA (1991) Monoaminergic transmission and sleep in man. In: Idzikowski C, Cowen PJ (eds) Serotonin, sleep and mental disorder. Wrightson Biomedical Publishers, Petersfield, pp 215–226Google Scholar
  39. Nowell PD, Buysse DJ (2001) Treatment of insomnia in patients with mood disorders. Depress Anxiety 14:7–18CrossRefPubMedGoogle Scholar
  40. Owens MJ, Morgan WN, Plott SJ, Nemeroff CB (1997) Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther 283:1305–1322PubMedGoogle Scholar
  41. Parrott AC, Hindmarch I (1980) The leeds sleep evaluation questionnaire in psychopharmacological investigations—a review. Psychopharmacology 71:173–179PubMedGoogle Scholar
  42. Perlis ML, Giles DE, Buysse DJ, Tu X, Kupfer DJ (1997) Self-reported sleep disturbance as a prodromal symptom in recurrent depression. J Affect Disord 42:209–212CrossRefPubMedGoogle Scholar
  43. Rechtschaffen A, Kales A (1968) A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Brain Information Service Brain Research Institute, University of California Los AngelesGoogle Scholar
  44. Reynolds CF III, Kupfer DJ (1987) Sleep research in affective illness: state of the art circa 1987. Sleep 10:199–215PubMedGoogle Scholar
  45. Saletu B, Frey R, Krupka M, Anderer P, Grunberger J, See WR (1991) Sleep laboratory studies on the single-dose effects of serotonin reuptake inhibitors paroxetine and fluoxetine on human sleep and awakening qualities. Sleep 14:439–447PubMedGoogle Scholar
  46. Salin-Pascual RJ, Galicia-Polo L, Drucker-Colin R (1997) Sleep changes after 4 consecutive days of venlafaxine administration in normal volunteers. J Clin Psychiatry 58:348–350PubMedGoogle Scholar
  47. Schatzberg AF (1999) Antidepressant effectiveness in severe depression and melancholia. J Clin Psychiatry 60(Suppl 4):14–21Google Scholar
  48. Schlosser R, Roschke J, Rossbach W, Benkert O (1998) Conventional and spectral power analysis of all-night sleep EEG after subchronic treatment with paroxetine in healthy male volunteers. Eur Neuropsychopharmacol 8:273–278CrossRefPubMedGoogle Scholar
  49. Seeman R (1993) Receptor tables, volume 2: dissociation constants for neuroreceptors and transporters. SZ Research, TorontoGoogle Scholar
  50. Seth R, Jennings AL, Bindman J, Phillips J, Bergmann K (1992) Combination treatment with noradrenalin and serotonin reuptake inhibitors in resistant depression. Br J Psychiatry 161:562–565PubMedGoogle Scholar
  51. Sharma A, Goldberg MJ, Cerimele BJ (2000) Pharmacokinetics and safety of duloxetine, a dual-serotonin and norepinephrine reuptake inhibitor. J Clin Pharmacol 40:161–167CrossRefPubMedGoogle Scholar
  52. Shipley JE, Kupfer DJ, Griffin SJ, Dealy RS, Coble PA, McEachran AB, Grochocinski VJ, Ulrich R, Perel JM (1985) Comparison of effects of desipramine and amitriptyline on EEG sleep of depressed patients. Psychopharmacology 85:14–22PubMedGoogle Scholar
  53. Smith D, Dempster C, Glanville J, Freemantle N, Anderson I (2002) Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis. Br J Psychiatry 180:396–404CrossRefPubMedGoogle Scholar
  54. Staner L, Luthringer R, Macher J-P (1999) Effects of antidepressant drugs on sleep EEG in patients with major depression: mechanisms and therapeutic implications. CNS Drugs 11:49–60Google Scholar
  55. Steiger A (1988) Effects of clomipramine on sleep EEG and nocturnal penile tumescence: a long-term study in a healthy man. J Clin Psychopharmacol 8:349–354PubMedGoogle Scholar
  56. Thase ME, Entsuah AR, Rudolph RL (2001) Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 178:234–241CrossRefPubMedGoogle Scholar
  57. Thase ME, Detke MJ, Joliat M, Lu Y (2003) Remission in placebo-controlled trials of duloxetine with an SSRI comparator. Presented at the 156th Annual Meeting of the American Psychiatric Association, 22 May 2003Google Scholar
  58. Turcotte JE, Debonnel G, de Montigny C, Hebert C, Blier P (2001) Assessment of the serotonin and norepinephrine reuptake blocking properties of duloxetine in healthy subjects. Neuropsychopharmacology 24:511–521CrossRefPubMedGoogle Scholar
  59. Van Bemmel AL, Vermeeren MT, Ruigt G, Sennef C (1999) The acute effects of the noradrenaline reuptake inhibitor Org 4428 on EEG sleep in healthy volunteers. Neuropsychobiology 40:107–114CrossRefPubMedGoogle Scholar
  60. Vasar V, Appelberg B, Rimon R, Selvaratnam J (1994) The effect of fluoxetine on sleep: a longitudinal, double-blind polysomnographic study of healthy volunteers. Int Clin Psychopharmacol 9:203–206PubMedGoogle Scholar
  61. Vogel GW, Buffenstein A, Minter K, Hennessey A (1990) Drug effects on REM sleep and on endogenous depression. Neurosci Biobehav Rev 14:49–63PubMedGoogle Scholar
  62. Winokur A, Reynolds CF III (1994) Overview of effects of antidepressant therapies on sleep. Primary Psychiatry 1:22–27Google Scholar
  63. Winokur A, Gary KA, Rodner S, Rae-Red C, Fernando AT, Szuba MP (2001) Depression, sleep physiology, and antidepressant drugs. Depress Anxiety 14:19–28CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Stephan Chalon
    • 2
  • Alvaro Pereira
    • 1
  • Eric Lainey
    • 3
  • François Vandenhende
    • 1
  • John G. Watkin
    • 4
  • Luc Staner
    • 5
  • Luc-André Granier
    • 1
  1. 1.Lilly Research LaboratoriesMont-Saint-GuibertBelgium
  2. 2.Lilly Research LaboratoriesIndianapolisUSA
  3. 3.Unité Inserm 288, Sleep UnitCHU Pitié-SalpêtrièreParisFrance
  4. 4.Lilly Research LaboratoriesIndianapolisUSA
  5. 5.Unité d’Exploration des Rythmes Veille-SommeilCentre Hospitalier de RouffachRouffachFrance

Personalised recommendations