Effect of trazodone versus cognitive-behavioural treatment on high- and slow-frequency activity during non-rapid eye movement sleep in chronic insomnia: A pilot, randomized clinical trial

Yun Li, Alexandros N Vgontzas, Julio Fernandez-Mendoza, Jidong Fang, Kristina Puzino, Edward O Bixler, Yun Li, Alexandros N Vgontzas, Julio Fernandez-Mendoza, Jidong Fang, Kristina Puzino, Edward O Bixler

Abstract

Trazodone and cognitive-behavioural treatment for insomnia (CBT-I) are widely used to treat patients with chronic insomnia. Although both treatments improve sleep continuity, no study has compared their comparative effectiveness in modifying spectral electroencephalographic (EEG) activity during sleep in humans. In this study, participants included 19 men and women with chronic insomnia who were randomized to either trazodone (n = 8) or CBT-I (n = 11) treatment for 3 months. We examined delta (0.39-3.91 Hz), theta (4.30-7.81 Hz), alpha (8.20-11.72 Hz), sigma (12.11-14.84 Hz), beta (15.23-35.16 Hz) and gamma (35.55-49.61 Hz) relative power during non-rapid eye movement (NREM) sleep at pre-treatment, 3- month post-treatment and 6-month follow-up. This study was registered in Clinical Trials (NCT01348542). We found trazodone but not CBT-I significantly decreased sigma (p = .041, d = 0.88; time × group p = .009) and beta (p = .005, d = 1.41; time × group p = .016) power during NREM sleep at post-treatment. Compared to CBT-I, trazodone increased delta (p = .018) and decreased sigma (p = .013) and beta (p = .023) power during NREM sleep at post-treatment. At follow-up, we did not observe significant changes in relative EEG power during NREM sleep in either the CBT-I or trazodone group compared to pre-treatment. Compared to CBT-I, trazodone decreased alpha (p = .039) and sigma (p = .009) power during NREM sleep at follow-up. In conclusion, trazodone, but not CBT-I, decreased fast-frequency EEG activity during NREM sleep. Compared to CBT-I, trazodone appears to have a stronger impact on cortical and physiological hyperarousal in patients with chronic insomnia.

Keywords: cognitive-behavioural therapy for insomnia; electroencephalographic; insomnia; trazodone.

© 2021 European Sleep Research Society.

References

REFERENCES

    1. Baglioni, C., Nanovska, S., Regen, W., Spiegelhalder, K., Feige, B., Nissen, C., Reynolds, C. F., & Riemann, D. (2016). Sleep and mental disorders: A meta-analysis of polysomnographic research. Psychological Bulletin, 142(9), 969-990.
    1. Bastien, C. H., Vallieres, A., & Morin, C. M. (2001). Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Medicine, 2(4), 297-307.
    1. Bixler, E. O., Vgontzas, A. N., Lin, H. M., Vela-Bueno, A., & Kales, A. (2002). Insomnia in central Pennsylvania. Journal of Psychosomatic Research, 53(1), 589-592.
    1. Bonnet, M. H., & Arand, D. L. (2010). Hyperarousal and insomnia: State of the science. Sleep Medicine Reviews, 14(1), 9-15.
    1. Buysse, D. J., Germain, A., Hall, M. L., Moul, D. E., Nofzinger, E. A., Begley, A., Ehlers, C. L., Thompson, W., & Kupfer, D. J. (2008). EEG spectral analysis in primary insomnia: NREM period effects and sex differences. Sleep, 31(12), 1673-1682.
    1. Cervena, K., Dauvilliers, Y., Espa, F., Touchon, J., Matousek, M., Billiard, M., & Besset, A. (2004). Effect of cognitive behavioural therapy for insomnia on sleep architecture and sleep EEG power spectra in psychophysiological insomnia. Journal of Sleep Research, 13(4), 385-393.
    1. Corsi-Cabrera, M., Figueredo-Rodriguez, P., del Rio-Portilla, Y., Sanchez-Romero, J., Galan, L., & Bosch-Bayard, J. (2012). Enhanced frontoparietal synchronized activation during the wake-sleep transition in patients with primary insomnia. Sleep, 35(4), 501-511.
    1. Destexhe, A., & Sejnowski, T. J. (2002). The initiation of bursts in thalamic neurons and the cortical control of thalamic sensitivity. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 357(1428), 1649-1657.
    1. Edinger, J., & Carney, C. (2008). Overcoming Insomnia: A Cognitive Behavioral Therapy Approach. Oxford University Press.
    1. Fernandez-Mendoza, J., Li, Y., Fang, J., Calhoun, S. L., Vgontzas, A. N., Liao, D., & Bixler, E. O. (2019). Childhood high-frequency EEG activity during sleep is associated with incident insomnia symptoms in adolescence. Journal of Child Psychology and Psychiatry, 60(7), 742-751.
    1. Fernandez-Mendoza, J., Li, Y., Vgontzas, A. N., Fang, J., Gaines, J., Calhoun, S. L., Liao, D., & Bixler, E. O. (2016). Insomnia is associated with cortical hyperarousal as early as adolescence. Sleep, 39(5), 1029-1036.
    1. Fernandez-Mendoza, J., & Vgontzas, A. N. (2013). Insomnia and its impact on physical and mental health. Current Psychiatry Reports, 15(12), 418.
    1. Freedman, R. R. (1986). EEG power spectra in sleep-onset insomnia. Electroencephalography and Clinical Neurophysiology, 63(5), 408-413.
    1. Goldstein, M. R., Turner, A. D., Dawson, S. C., Segal, Z. V., Shapiro, S. L., Wyatt, J. K., Manber, R., Sholtes, D., & Ong, J. C. (2019). Increased high-frequency NREM EEG power associated with mindfulness-based interventions for chronic insomnia: Preliminary findings from spectral analysis. Journal of Psychosomatic Research, 120, 12-19.
    1. Hall, M., Buysse, D. J., Nowell, P. D., Nofzinger, E. A., Houck, P., Reynolds, C. F. 3rd, & Kupfer, D. J. (2000). Symptoms of stress and depression as correlates of sleep in primary insomnia. Psychosomatic Medicine, 62(2), 227-230.
    1. Israel, B., Buysse, D. J., Krafty, R. T., Begley, A., Miewald, J., & Hall, M. (2012). Short-term stability of sleep and heart rate variability in good sleepers and patients with insomnia: For some measures, one night is enough. Sleep, 35(9), 1285-1291.
    1. Jacobs, G. D., Benson, H., & Friedman, R. (1993). Home-based central nervous system assessment of a multifactor behavioral intervention for chronic sleep-onset insomnia. Behavior Therapy, 24(1), 159-174.
    1. Krystal, A. D., & Edinger, J. D. (2010). Sleep EEG predictors and correlates of the response to cognitive behavioral therapy for insomnia. Sleep, 33(5), 669-677.
    1. Krystal, A. D., Edinger, J. D., Wohlgemuth, W. K., & Marsh, G. R. (2002). NREM sleep EEG frequency spectral correlates of sleep complaints in primary insomnia subtypes. Sleep, 25(6), 630-640.
    1. Lelkes, Z., Obal, F. Jr, Alfoldi, P., Erdos, A., Rubicsek, G., & Benedek, G. (1994). Effects of acute and chronic treatment with trazodone, an antidepressant, on the sleep-wake activity in rats. Pharmacological Research, 30(2), 105-115.
    1. Ma, J., Svetnik, V., Snyder, E., Lines, C., Roth, T., & Herring, W. J. (2014). Electroencephalographic power spectral density profile of the orexin receptor antagonist suvorexant in patients with primary insomnia and healthy subjects. Sleep, 37(10), 1609-1619.
    1. Merica, H., Blois, R., & Gaillard, J. M. (1998). Spectral characteristics of sleep EEG in chronic insomnia. European Journal of Neuroscience, 10(5), 1826-1834.
    1. Monteleone, P. (1991). Effects of trazodone on plasma cortisol in normal subjects. A study with drug plasma levels. Neuropsychopharmacology, 5(1), 61-64.
    1. Morin, C., & Espie, C. (2003). Insomnia: A clinical guide to assessment and treatment. Kluwer Academic/Plenum Publishers.
    1. Morlock, R. J., Tan, M., & Mitchell, D. Y. (2006). Patient characteristics and patterns of drug use for sleep complaints in the United States: Analysis of National Ambulatory Medical Survey data, 1997-2002. Clinical Therapeutics, 28(7), 1044-1053.
    1. Ohayon, M. M. (2002). Epidemiology of insomnia: What we know and what we still need to learn. Sleep Medicine Reviews, 6(2), 97-111.
    1. Paterson, L. M., Wilson, S. J., Nutt, D. J., Hutson, P. H., & Ivarsson, M. (2009). Characterisation of the effects of caffeine on sleep in the rat: A potential model of sleep disruption. J Psychopharmacol, 23(5), 475-486.
    1. Perlis, M. L., Jungquist, C., Smith, M. T., & Posner, D. (2005). Cognitive behavioral treatment of insomnia: A session-by-session guide (Vol. 1). New York, NY: Springer Science & BusinessMedia.
    1. Perlis, M. L., Kehr, E. L., Smith, M. T., Andrews, P. J., Orff, H., & Giles, D. E. (2001). Temporal and stagewise distribution of high frequency EEG activity in patients with primary and secondary insomnia and in good sleeper controls. Journal of Sleep Research, 10(2), 93-104.
    1. Perlis, M. L., Merica, H., Smith, M. T., & Giles, D. E. (2001). Beta EEG activity and insomnia. Sleep Medicine Reviews, 5(5), 363-374.
    1. Perlis, M. L., Smith, M. T., Andrews, P. J., Orff, H., & Giles, D. E. (2001). Beta/Gamma EEG activity in patients with primary and secondary insomnia and good sleeper controls. Sleep, 24(1), 110-117.
    1. Rechtschaffen, A., & Kales, A. (1968). A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. NIMH Publication 204. : US Government Printing Office.
    1. Riemann, D., Spiegelhalder, K., Feige, B., Voderholzer, U., Berger, M., Perlis, M., & Nissen, C. (2010). The hyperarousal model of insomnia: A review of the concept and its evidence. Sleep Medicine Reviews, 14(1), 19-31.
    1. Riemann, D., Spiegelhalder, K., Nissen, C., Hirscher, V., Baglioni, C., & Feige, B. (2012). REM sleep instability-A new pathway for insomnia? Pharmacopsychiatry, 45(5), 167-176.
    1. Schabus, M., Gruber, G., Parapatics, S., Sauter, C., Klösch, G., Anderer, P., Klimesch, W., Saletu, B., & Zeitlhofer, J. (2004). Sleep spindles and their significance for declarative memory consolidation. Sleep, 27(8), 1479-1485.
    1. Spiegelhalder, K., Regen, W., Feige, B., Holz, J., Piosczyk, H., Baglioni, C., Riemann, D., & Nissen, C. (2012). Increased EEG sigma and beta power during NREM sleep in primary insomnia. Biological Psychology, 91(3), 329-333.
    1. Stahl, S. M. (2009). Mechanism of action of trazodone: A multifunctional drug. CNS Spectrums, 14(10), 536-546.
    1. Van Bemmel, A. L., Beersma, D. G., & Van Den Hoofdakker, R. H. (1993). Changes in EEG power density of NREM sleep in depressed patients during treatment with citalopram. Journal of Sleep Research, 2(3), 156-162.
    1. Van Bemmel, A. L., Beersma, D. G., & Van den Hoofdakker, R. H. (1995). Changes in EEG power density of non-REM sleep in depressed patients during treatment with trazodone. Journal of Affective Disorders, 35(1-2), 11-19.
    1. Vgontzas, A. N., Fernandez-Mendoza, J., Liao, D., & Bixler, E. O. (2013). Insomnia with objective short sleep duration: The most biologically severe phenotype of the disorder. Sleep Medicine Reviews, 17(4), 241-254.
    1. Vgontzas, A. N., Pejovic, S., Zoumakis, E., Lin, H. M., Bixler, E. O., Basta, M., Fang, J., Sarrigiannidis, A., & Chrousos, G. P. (2007). Daytime napping after a night of sleep loss decreases sleepiness, improves performance, and causes beneficial changes in cortisol and interleukin-6 secretion. American Journal of Physiology. Endocrinology and Metabolism, 292(1), E253-261.
    1. Vgontzas, A. N., Puzino, K., Fernandez-Mendoza, J., Krishnamurthy, V. B., Basta, M., & Bixler, E. O. (2020). Effects of trazodone versus cognitive behavioral therapy in the insomnia with short sleep duration phenotype: A preliminary study. Journal of Clinical Sleep Medicine, 16(12), 2009-2019.https://
    1. Wu, Y. M., Pietrone, R., Cashmere, J. D., Begley, A., Miewald, J. M., Germain, A., & Buysse, D. J. (2013). EEG power during waking and NREM sleep in primary insomnia. Journal of Clinical Sleep Medicine, 9(10), 1031-1037.

Source: PubMed

3
S'abonner