Abstract
The acute effects of dexfenfluramine on nocturnal sleep were studied in ten healthy male subjects by means of sleep EEG recordings and ratings of subjective sleep quality. Four different dosages (3 mg, 7 mg, 15 mg, and 30 mg) were tested, administered over a period of 3 days each. Under 15 mg and 30 mg dexfenfluramine, only slight effects on sleep were observed: 15 mg led to decreased sleep efficiency in the first night of medication, and to reduced percentage of slow wave sleep in the first and third night. A significant lengthening of REM latency was present in the third night under 30 mg dexfenfluramine, without changes in other REM sleep parameters. Daily doses of 3 mg and 7 mg dexfenfluramine did not influence sleep, except for a significant REM latency reduction observed in the first night under 3 mg. Apart from a transient slight impairment under 30 mg, ratings of subjective sleep quality did not mirror any impact of dexfenfluramine. The data suggest that therapeutic dosages of dexfenfluramine only slightly influence nocturnal sleep, which contrasts with the known impact of other anti-obesity agents like the amphetamines. Unlike classical antidepressants, dexfenfluramine does not reduce REM sleep; in light of a hypothetical link between REM sleep reduction and antidepressant action of a drug, dexfenfluramine is not expected to have a pronounced antidepressant effect.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alvi MY (1969) Unusual effect of fenfluramine. Br Med J IV:237
Berger M, Riemann D, Wiegand M, Joy D, Höchli D, Zulley J (1988) Are REM-sleep abnormalities in depression more than an epiphenomenon? In: Koella WP, Obál F, Schulz H, Visser P (eds) Sleep '86. Gustav Fischer, Stuttgart, pp 218–222
Caccia S, Conforti I, Duchier J, Garattini S (1985) Pharmacokinetics of fenfluramine and norfenfluramine in volunteers givend- anddl-fenfluramine for 15 days. Eur J Clin Pharmacol 29:221–224
Chen CN (1979) Sleep, depression and antidepressants. Br J Psychiatry 135:385–402
Dugovic C, Wauquier A (1987) 5-HT-2 receptors could be primarily involved in the regulation of slow-wave sleep in the rat. Eur J Pharmacol 137:145–146
Fink M, Shapiro DM, Itil TM (1971) EEG profiles of fenfluramine, amobarbital and dextroamphetamine in normal volunteers. Psychopharmacologia 22:369–383
Firth H, Lewis SA, Ogunremi OO, Oswald I (1970) The effect of acute administration of (meta-trifluoro-methyl-phenyl)-1-(benzoyol-oxy) ethyl-amino-2-propane (780 SE) and fenfluramine on human sleep. Br J Pharmacol Chemother 39:462–463
Fornal C, Radulovacki (1983a) Sleep suppressant action of fenfluramine in rats. I. Relation to postsynaptic serotonergic stimulation. J Pharmacol Exp Ther 225:667–674
Fornal C, Radulovacki M (1983b) Sleep suppressant action of fenfluramine in rats. II. Evidence against the involvement of presynaptic serotonergic mechanism. J Pharmacol Exp Ther 225:675–681
Foxwell MH, Funderburk WH, Ward JW (1969) Studies on the site of action of a new anorectic agent, fenfluramine. J Pharmacol Exp Ther 165:60–70
Gagnon MA, Bordeleau JW, Tetreault TL (1969) Fenfluramine: study of its central action through its effects on sleep. Int J Clin Pharmacol 1:74
Garattini S, Mennini T, Samanin R (1987) From fenfluramine racemate tod-fenfluramine. Specificity and potency of the effects on the serotoninergic system and food intake. Ann NY Acad Sci 499:156–166
Garattini S, Bizzi A, Caccia S, Mennini T, Samanin R (1988) Progress in assessing the role of serotonin in the control of food intake. Clin Neuropharmacol 11 [suppl 1]:8–32
Hill AJ (1988) Dexfenfluramine, weight control and premenstrual syndrome. Vth International Symposium on Dexfenfluramine (Satellite symposium to the XIXth International Congress of Internal Medicine), Brussels, Belgium, September 2, 1988
Idzikowsky C, Mills IJ, Glennard R (1986) 5-Hydroxytryptamine-2-antagonist increases human slow wave sleep. Brain Res 378:164–168
Johnson DN, Funderburk WH, Ward JW (1971) Effects of fenfluramine on sleep-wakefulness in cats. Psychopharmacologia 20:1–9
Lewis SA (1970) Comparative effects of some amphetamine derivates on human sleep. In: Costa E, Garattini S (eds) Amphetamines and related compounds. Raven Press, New York, pp 873–888
Lewis SA, Oswald I, Dunleavy DLF (1971) Chronic fenfluramine administration: some cerebral effects. Br Med J III:67–70
Maggini C, Guazzelli M, Ciapparelli A, Starnini S, Bonollo L, Martini A (1988) The effects of oxiracetam andd-amphetamine on all-night electroencephalographic sleep in young healthy subjects. Curr Ther Res 43:979–990
McCarley RW (1982) REM sleep and depression: common neurobiological control mechanisms. Am J Psychiatry 139:565–570
Metropolitan Life Insurance Company (1959) New weight standards for men and women. Statistical Bulletin. Metropolitan Life Insurance Company 40:1–4
Mullen A, Wilson CWM (1974) Fenfluramine and dreaming. Lancet ii:594
Nathan C (1987) Dexfenfluramine hydrochloride. Drugs of the future 12:845–848
O'Rourke D, Wurtman J, Brzezinski A, Abou-Nader T, Marchant P, Wurtman RJ (1987) Treatment of seasonal affective disorder withd-fenfluramin. Ann NY Acad Sci 499:329–330
Oswald I (1970) Effects on sleep of amphetamine and its derivates. In: Costa E, Garattini S (eds) Amphetamines and related compounds. Raven Press, New York, pp 865–872
Oswald I, Jones HS, Mannerheim JE (1968) Effects of two slimming drugs on sleep. Br Med J I:796–799
Parrott AC, Rogers PJ, Brownlie V (1980) Effects of amphetamine and fenfluramine upon subjective self-reports on sleep and morning awakening. IRCS Med Sci 8:312
Pinder RM, Brogden RN, Sawyer PR, Speight TM, Avery GS (1975) Fenfluramine: a review of its pharmacological properties and therapeutic efficacy in obesity. Drugs 10:241–323
Rechtschaffen A, Kales A (eds) (1968) A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. US Department of Health, Education, and Welfare, Bethesda, Maryland
Riley LD, Corson JC, Haider I, Oswald I (1966) Fenfluramine overdosage: clinical and EEG features. Lancet i:1162–1163
Russell GFM, Checkley SA, Feldman J, Eisler I (1988) A controlled trial ofd-fenfluramine in bulimia nervosa. Clin Neuropharmacol 11 [suppl 1]:S149–S159
Saletu B (1976) Psychopharmaka, Gehirntätigkeit und Schlaf. Karger, Basel
Saletu B, Grünberger J, Linzmayer L, Karobath M (1977) Zur ZNS-und Psychoaktivität der Appetitzügler Phentermin und Fenfluramin: Serumkonzentration, quantitatives EEG und psychometrische Analysen. Z EEG-EMG 8:137–144
Silverstone T, Smith G, Richards R (1987) A comparative evaluation of dextrofenfluramine anddl-fenfluramine on hunger, food intake, psychomotor function and side-effects in normal human subjects. In: Bender AE, Brookes LJ (eds) Body weight control. The physiology, clinical treatment and prevention of obesity. Churchill Livingstone, Edinburgh London Melbourne New York, pp 240–246
Stunkard A, Rickels K, Hesbacher P (1973) Fenfluramine in the treatment of obesity. Lancet i:503–505
Wiegand M, Berger M (1989) Action of trimipramine on sleep and pituitary hormone secretion. Drugs 38 [suppl. 1]:35–42
World Medical Association (1964) Declaration of Helsinki. Recommendations guiding medical doctors in biomedical research involving human subjects, adapted by the 18th World Medical Assembly, Helsinki
World Medical Association (1975) Declaration of Tokyo. Recommendations guiding medical doctors in biomedical research involving human subjects, revised by the 29th World Medical Assembly, Tokyo
Wurtman JJ (1988) Carbohydrate cravings: a disorder of food intake and mood. Clin Neuropharmacol 11 [suppl 1]:139–145
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wiegand, M., Bossert, S., Kinney, R. et al. Effect of dexfenfluramine on sleep in healthy subjects. Psychopharmacology 105, 213–218 (1991). https://doi.org/10.1007/BF02244312
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244312