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Flurazepam Effects on Sleep EEG: Visual, Computer, and Cycle Analysis

Flurazepam Effects on Sleep EEG: Visual, Computer, and Cycle Analysis Abstract • Analysis of sleep effects of flurazepam hydrochloride on four normal subjects confirmed that this drug substantially suppresses both REM and stage 4 sleep. Computer analysis disclosed that delta wave amplitude was greatly reduced by flurazepam. However, low density delta wave activity (ie, stage 2 sleep, which was increased in duration beyond the reduction in stage 4), permitted the number of delta waves and the time they occupied per night to remain at baseline levels. This finding suggests that sedative-hypnotics increase total sleep time by slowing the metabolic processes of sleep so that a longer sleep duration is required for the same biological effects. New observations on the induction times of REM and stage 4 effects are also presented. In general, the distortions in sleep EEG produced by flurazepam qualitatively resemble, but are quantitatively greater than, those produced by barbiturates in equivalent hypnotic doses. References 1. Feinberg I, Wender PH, Koresko RL, et al: Differential effects of chlorpromazine and phenobarbital on EEG sleep patterns . J Psychiatr Res 7:101-109, 1969.Crossref 2. Kay DC, Blackburn AB, Buckingham JA, et al: Human pharmacology of sleep , in Williams RL, Karacan I (eds): Pharmacology of Sleep . New York, John Wiley & Sons Inc, 1976, pp 83-209. 3. Dement WC, Zarcone VP, Hoddes E, et al: Sleep laboratory and clinical studies with flurazepam , in Garattini S, Mussini E, Randall LO (eds): The Benzodiazepines . New York, Raven Press, 1973, pp 599-611. 4. Kales J, Tan T-L, Swearingen C, et al: Are over-the-counter sleep medications effective? All-night EEG studies . Curr Ther Res 13:143-151, 1971. 5. Carskadon MA, Dement WC, Mitler MM, et al: Self-reports vs sleep laboratory findings in 122 drug-free subjects with complaints of chronic insomnia . Am J Psychiatry 133:1382-1388, 1976. 6. Rechtschaffen A: Polygraphic aspects of insomnia, in Gastaut H, et al (eds): The Abnormalities of Sleep in Man: Proceedings of the 15th European meeting on electroencephalography. Bologna, North Italy, Aulo Gaggi Editore, 1967, pp 109-125. 7. Velok G, Passouant P, Cadilhac J, et al: Données polygraphiques sur les insomnies . Rev Neurol (Paris) 119:269-278, 1968. 8. Karacan I, Williams RL, Salis PJ, et al: New approaches to the evaluation and treatment of insomnia . Psychosomatics 12:81-88, 1971.Crossref 9. Karacan I, Williams RL, Littell RC, et al: Insomniacs: Unpredictable and idiosyncratic sleepers , in Koella WP, Levin p (eds): Sleep: Physiology, Biochemistry, Psychology, Pharmacology, Clinical Implications . proceedings of the First European Congress on Sleep Research, Basel, Switzerland, S Karger, 1973, pp 120-132. 10. Frankel BL, Coursey RD, Buchbinder R, et al: Recorded and reported sleep in chronic primary insomnia . Arch Gen Psychiatry 33:615-623, 1976.Crossref 11. Wyatt RJ, Fram DH, Kupfer DJ, et al: Total prolonged drug-induced REM sleep suppression in anxious-depressed patients . Arch Gen Psychiatry 24:145-155, 1971.Crossref 12. Feinberg I: Changes in sleep cycle patterns with age . J Psychiatr Res 10:283-306, 1974.Crossref 13. Webb WB, Agnew HW Jr: Stage 4 sleep: Influence of time course variables . Science 174:1354-1356, 1971.Crossref 14. Feinberg I, Carlson VR: Sleep variables as a function of age in man . Arch Gen Psychiatry 18:239-250, 1968.Crossref 15. Williams RL, Karacan I, Hursch CJ: Electroencephalography (EEG) of Human Sleep: Clinical Applications . New York, John Wiley & Sons Inc, 1974. 16. Webb WB, Agnew HW Jr: Sleep: Effects of a restricted regimen . Science 150:1745-1746, 1965.Crossref 17. Dement WC, Greenburg S: Changes in total amount of stage 4 sleep as a function of partial sleep deprivation . Electroencephalogr Clin Neurophysiol 20:523-526, 1966.Crossref 18. Cohen J, Cohen P: Applied Multiple Regression/Correlation Analysis for the Behavioral Sciences . New York, John Wiley & Sons Inc, 1975. 19. Tukey JW: Some thoughts on clinical trials, especially problems of multiplicity . Science 198:679-684, 1977.Crossref 20. Feinberg I, Fein G, Walker JM, et al: Flurazepam effects on slow-wave sleep: Stage 4 suppressed but number of delta waves constant . Science 198:847-848, 1977.Crossref 21. Feinberg I, Koresko RL, Heller N: EEG sleep patterns as a function of normal and pathological aging in man . J Psychiatr Res 5:107-144, 1967.Crossref 22. Feinberg I, March JD, Fein G, et al: Period and amplitude analysis of 0.5-3 c/second activity in NREM sleep of young adults . Electroencephalogr Clin Neurophysiol 44:202-213, 1978.Crossref 23. Lester BK, Coulter JD, Cowden LC, et al: Secobarbital and nocturnal physiological patterns . Psychopharmacologia 13:275-286, 1968.Crossref 24. Johnson LC, Hanson K, Bickford RG: Effect of flurazepam on sleep spindles and K complexes . Electroencephalogr Clin Neurophysiol 40:67-77, 1976.Crossref 25. Johnson L, Lubin A, Naitoh P, et al: Spectral analysis of the EEG of dominant and nondominant alpha subjects during waking and sleeping . Electroencephalogr Clin Neurophysiol 26:361-370, 1969.Crossref 26. Dumermuth G, Walz W, Scollo-Lavizzari G, et al: Spectral analysis of EEG activity in different sleep stages in normal adults . Eur Neurol 7:265-296, 1972.Crossref 27. Itil TM, Saletu B, Akpinar S: Classification of psychotropic drugs based on digital computer sleep prints , in Itil TM (ed): Modern Problems in Pharmacopsychiatry , Basel, Switzerland, S Karger, 1974, vol 8, pp 193-215. 28. Frost JD Jr, Carrie JRG, Borda RP, et al: The effects of Dalmane (flurazepam hydrochloride) on human EEG characteristics . Electroencephalogr Clin Neurophysiol 34:171-175, 1973.Crossref 29. Kales A, Kales JD, Scharf MB, et al: Hypnotics and altered sleepdream patterns: II. All-night EEG studies of chloral hydrate, flurazepam, and methaqualone . Arch Gen Psychiatry 23:219-225, 1970.Crossref 30. Gaillard JM, Aubert C: Specificity of benzodiazepine action on human sleep confirmed: Another contribution of automatic analysis of polygraph records . Biol Psychiatry 10:185-197, 1975. 31. Gaillard JM, Tissot R: EEG sleep studies of insomniacs under flunitrazepam treatment . Int Pharmacopsychiatry 10:199-207, 1975. 32. Smith JR, Karacan I, Keane BP, et al: Automated sleep EEG analysis applied to the evaluation of drugs: Illustration by study of chlorazepate dipotassium . Electroencephalogr Clin Neurophysiol 41:587-594, 1976.Crossref 33. Dumermuth G, Gasser T, Hecker A, et al: Exploration of EEG components in the beta frequency range , in Kellaway P, Petersen I (ed): Quantitative Analytic Studies in Epilepsy . New York, Raven Press, 1976, pp 533-558. 34. Feinberg I, Braun M, Koresko RL, et al: Stage 4 sleep in schizophrenia . Arch Gen Psychiatry 21:262-266, 1969.Crossref 35. Feinberg I, Hibi S, Cavness C, et al: Absence of REM rebound after barbiturate withdrawal . Science 185:534-535, 1974.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Flurazepam Effects on Sleep EEG: Visual, Computer, and Cycle Analysis

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Publisher
American Medical Association
Copyright
Copyright © 1979 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1979.01780010101012
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Abstract

Abstract • Analysis of sleep effects of flurazepam hydrochloride on four normal subjects confirmed that this drug substantially suppresses both REM and stage 4 sleep. Computer analysis disclosed that delta wave amplitude was greatly reduced by flurazepam. However, low density delta wave activity (ie, stage 2 sleep, which was increased in duration beyond the reduction in stage 4), permitted the number of delta waves and the time they occupied per night to remain at baseline levels. This finding suggests that sedative-hypnotics increase total sleep time by slowing the metabolic processes of sleep so that a longer sleep duration is required for the same biological effects. New observations on the induction times of REM and stage 4 effects are also presented. In general, the distortions in sleep EEG produced by flurazepam qualitatively resemble, but are quantitatively greater than, those produced by barbiturates in equivalent hypnotic doses. References 1. Feinberg I, Wender PH, Koresko RL, et al: Differential effects of chlorpromazine and phenobarbital on EEG sleep patterns . J Psychiatr Res 7:101-109, 1969.Crossref 2. Kay DC, Blackburn AB, Buckingham JA, et al: Human pharmacology of sleep , in Williams RL, Karacan I (eds): Pharmacology of Sleep . New York, John Wiley & Sons Inc, 1976, pp 83-209. 3. Dement WC, Zarcone VP, Hoddes E, et al: Sleep laboratory and clinical studies with flurazepam , in Garattini S, Mussini E, Randall LO (eds): The Benzodiazepines . New York, Raven Press, 1973, pp 599-611. 4. Kales J, Tan T-L, Swearingen C, et al: Are over-the-counter sleep medications effective? All-night EEG studies . Curr Ther Res 13:143-151, 1971. 5. Carskadon MA, Dement WC, Mitler MM, et al: Self-reports vs sleep laboratory findings in 122 drug-free subjects with complaints of chronic insomnia . Am J Psychiatry 133:1382-1388, 1976. 6. Rechtschaffen A: Polygraphic aspects of insomnia, in Gastaut H, et al (eds): The Abnormalities of Sleep in Man: Proceedings of the 15th European meeting on electroencephalography. Bologna, North Italy, Aulo Gaggi Editore, 1967, pp 109-125. 7. Velok G, Passouant P, Cadilhac J, et al: Données polygraphiques sur les insomnies . Rev Neurol (Paris) 119:269-278, 1968. 8. Karacan I, Williams RL, Salis PJ, et al: New approaches to the evaluation and treatment of insomnia . Psychosomatics 12:81-88, 1971.Crossref 9. Karacan I, Williams RL, Littell RC, et al: Insomniacs: Unpredictable and idiosyncratic sleepers , in Koella WP, Levin p (eds): Sleep: Physiology, Biochemistry, Psychology, Pharmacology, Clinical Implications . proceedings of the First European Congress on Sleep Research, Basel, Switzerland, S Karger, 1973, pp 120-132. 10. Frankel BL, Coursey RD, Buchbinder R, et al: Recorded and reported sleep in chronic primary insomnia . Arch Gen Psychiatry 33:615-623, 1976.Crossref 11. Wyatt RJ, Fram DH, Kupfer DJ, et al: Total prolonged drug-induced REM sleep suppression in anxious-depressed patients . Arch Gen Psychiatry 24:145-155, 1971.Crossref 12. Feinberg I: Changes in sleep cycle patterns with age . J Psychiatr Res 10:283-306, 1974.Crossref 13. Webb WB, Agnew HW Jr: Stage 4 sleep: Influence of time course variables . Science 174:1354-1356, 1971.Crossref 14. Feinberg I, Carlson VR: Sleep variables as a function of age in man . Arch Gen Psychiatry 18:239-250, 1968.Crossref 15. Williams RL, Karacan I, Hursch CJ: Electroencephalography (EEG) of Human Sleep: Clinical Applications . New York, John Wiley & Sons Inc, 1974. 16. Webb WB, Agnew HW Jr: Sleep: Effects of a restricted regimen . Science 150:1745-1746, 1965.Crossref 17. Dement WC, Greenburg S: Changes in total amount of stage 4 sleep as a function of partial sleep deprivation . Electroencephalogr Clin Neurophysiol 20:523-526, 1966.Crossref 18. Cohen J, Cohen P: Applied Multiple Regression/Correlation Analysis for the Behavioral Sciences . New York, John Wiley & Sons Inc, 1975. 19. Tukey JW: Some thoughts on clinical trials, especially problems of multiplicity . Science 198:679-684, 1977.Crossref 20. Feinberg I, Fein G, Walker JM, et al: Flurazepam effects on slow-wave sleep: Stage 4 suppressed but number of delta waves constant . Science 198:847-848, 1977.Crossref 21. Feinberg I, Koresko RL, Heller N: EEG sleep patterns as a function of normal and pathological aging in man . J Psychiatr Res 5:107-144, 1967.Crossref 22. Feinberg I, March JD, Fein G, et al: Period and amplitude analysis of 0.5-3 c/second activity in NREM sleep of young adults . Electroencephalogr Clin Neurophysiol 44:202-213, 1978.Crossref 23. Lester BK, Coulter JD, Cowden LC, et al: Secobarbital and nocturnal physiological patterns . Psychopharmacologia 13:275-286, 1968.Crossref 24. Johnson LC, Hanson K, Bickford RG: Effect of flurazepam on sleep spindles and K complexes . Electroencephalogr Clin Neurophysiol 40:67-77, 1976.Crossref 25. Johnson L, Lubin A, Naitoh P, et al: Spectral analysis of the EEG of dominant and nondominant alpha subjects during waking and sleeping . Electroencephalogr Clin Neurophysiol 26:361-370, 1969.Crossref 26. Dumermuth G, Walz W, Scollo-Lavizzari G, et al: Spectral analysis of EEG activity in different sleep stages in normal adults . Eur Neurol 7:265-296, 1972.Crossref 27. Itil TM, Saletu B, Akpinar S: Classification of psychotropic drugs based on digital computer sleep prints , in Itil TM (ed): Modern Problems in Pharmacopsychiatry , Basel, Switzerland, S Karger, 1974, vol 8, pp 193-215. 28. Frost JD Jr, Carrie JRG, Borda RP, et al: The effects of Dalmane (flurazepam hydrochloride) on human EEG characteristics . Electroencephalogr Clin Neurophysiol 34:171-175, 1973.Crossref 29. Kales A, Kales JD, Scharf MB, et al: Hypnotics and altered sleepdream patterns: II. All-night EEG studies of chloral hydrate, flurazepam, and methaqualone . Arch Gen Psychiatry 23:219-225, 1970.Crossref 30. Gaillard JM, Aubert C: Specificity of benzodiazepine action on human sleep confirmed: Another contribution of automatic analysis of polygraph records . Biol Psychiatry 10:185-197, 1975. 31. Gaillard JM, Tissot R: EEG sleep studies of insomniacs under flunitrazepam treatment . Int Pharmacopsychiatry 10:199-207, 1975. 32. Smith JR, Karacan I, Keane BP, et al: Automated sleep EEG analysis applied to the evaluation of drugs: Illustration by study of chlorazepate dipotassium . Electroencephalogr Clin Neurophysiol 41:587-594, 1976.Crossref 33. Dumermuth G, Gasser T, Hecker A, et al: Exploration of EEG components in the beta frequency range , in Kellaway P, Petersen I (ed): Quantitative Analytic Studies in Epilepsy . New York, Raven Press, 1976, pp 533-558. 34. Feinberg I, Braun M, Koresko RL, et al: Stage 4 sleep in schizophrenia . Arch Gen Psychiatry 21:262-266, 1969.Crossref 35. Feinberg I, Hibi S, Cavness C, et al: Absence of REM rebound after barbiturate withdrawal . Science 185:534-535, 1974.Crossref

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Jan 1, 1979

References