Ethanol interactions with serotonin uptake selective and non-selective antidepressants: Fluoxetine and amitriptyline
Carolyn A. Shaw B.Sc.N.
Coordinator
Clinical Research Unit, Addiction Research Foundation, Toronto, Ontario
Search for more papers by this authorJohn T. Sullivan M.B., Ch.B., F.R.A.C.P.
Assistant Professor of Medicine, Johns Hopkins University and Attending Physician, Francis Scott Key Hospital, Baltimore, Maryland
Search for more papers by this authorKaren E. Kadlec B.Sc.
Senior Research Assistant
Addiction Research Foundation, Toronto, Ontario
Search for more papers by this authorHoward L. Kaplan Ph.D.
Head
Research Methods Units, Addiction Research Foundation, Toronto, Ontario
Search for more papers by this authorClaudio A. Naranjo M.D.
Head
Clinical Pharmacology Program, Addiction Research Foundation and Associate Professor of Pharmacology and Medicine, University of Toronto, Toronto, Ontario
Search for more papers by this authorCorresponding Author
Edward M. Sellers M.D., Ph.D., F.R.C.P.(C)
Head
Psychopharmacological Research, Addiction Research Foundation and Professor of Pharmacology and Medicine, University of Toronto, Toronto, Ontario
The views expressed in this publication are those of the authors and do not necessarily reflect those of the Addiction Research Foundation.
Psychopharmacological Research, Addiction Research Foundation and Professor of Pharmacology and Medicine, University of Toronto, Toronto, OntarioSearch for more papers by this authorCarolyn A. Shaw B.Sc.N.
Coordinator
Clinical Research Unit, Addiction Research Foundation, Toronto, Ontario
Search for more papers by this authorJohn T. Sullivan M.B., Ch.B., F.R.A.C.P.
Assistant Professor of Medicine, Johns Hopkins University and Attending Physician, Francis Scott Key Hospital, Baltimore, Maryland
Search for more papers by this authorKaren E. Kadlec B.Sc.
Senior Research Assistant
Addiction Research Foundation, Toronto, Ontario
Search for more papers by this authorHoward L. Kaplan Ph.D.
Head
Research Methods Units, Addiction Research Foundation, Toronto, Ontario
Search for more papers by this authorClaudio A. Naranjo M.D.
Head
Clinical Pharmacology Program, Addiction Research Foundation and Associate Professor of Pharmacology and Medicine, University of Toronto, Toronto, Ontario
Search for more papers by this authorCorresponding Author
Edward M. Sellers M.D., Ph.D., F.R.C.P.(C)
Head
Psychopharmacological Research, Addiction Research Foundation and Professor of Pharmacology and Medicine, University of Toronto, Toronto, Ontario
The views expressed in this publication are those of the authors and do not necessarily reflect those of the Addiction Research Foundation.
Psychopharmacological Research, Addiction Research Foundation and Professor of Pharmacology and Medicine, University of Toronto, Toronto, OntarioSearch for more papers by this authorAbstract
Fluoxetine, unlike amitriptyline, selectively blocks serotonin uptake. The interactions of steady state levels of fluoxetine with ethanol and of amitriptyline with ethanol were measured in a double-blind, chronic dose, randomized study. Sixteen healthy men, ages 21 to 28 years, were tested with placebo and ethanol (dosed to maintain blood ethanol concentration of 17–22 mM) and placebo and juice on two separate days. For 14 nights, 8 subjects took fluoxetine 40 mg, 8 took amitriptyline 50 mg, and all were re-tested with ethanol and juice as before. Ethanol had no effect on inhibition of serotonin uptake or on pharmacokinetics of fluoxetine or amitriptyline. The deleterious effects of ethanol on memory, manual tracking, body sway, intoxication and sedation (p<0·05) were not modified by either fluoxetine or amitriptyline. This study design, which is sensitive enough to detect ethanol effects, suggests that ethanol dose not interact importantly with clinically relevant doses of fluoxetine or low doses of amitriptyline administered chronically.
References
- Amit, Z., Sutherland, E. A., Gill, K. and Ogren, S. O. (1984). Zimelidine: A review of its effect on ethanol consumption. Neuroscience and Biobehavioral Reviews, 8, 35–54.
- Antal, A., Mercik, S. and Kramer, P. A. (1980). Technical considerations in gas chromatographic analysis of disipramine. Journal of Chromatography, 183, 149–157.
- Anthony, R. M., Sutheimer, C. A. and Sunshine, I. (1980). Acetaldehyde, methanol, and ethanol analysis by head space gas chromatography. Journal of Analytical Toxicology, 4, 43–45.
- Brotman, A. W., Falk, W. E. and Gelenberg, A. J. (1987). Pharmacologic treatment of acute depressive subtypes. In: Psychopharmacology: The Third Generation of Progress, H. Y. Meltzer (Ed.), Raven Press, New York, pp. 1031–1040.
- Coppen, A., Snade, C. and Wood, K. (1978). Platelet 5-hydroxytryptamine accumulation in depressive illness. Clinica Chimica Acta, 87, 165–168.
- Dorian, P., Sellers, E. M., Reed, K. L., Warsh, J. J., Hamilton, C., Kaplan, H. and Fan, T. (1983). Amitriptyline and ethanol: Pharmacokinetic and pharmacodynamic interaction. European Journal of Clinical Pharmacology, 25, 325–331.
- Hindmarch, I., Subhan, Z. and Stoker, M. J. (1983). The effects of zimelidine and amitriptyline on car driving and psychomotor performance. Acta Psychïatrica Scandinavica, 68 (Suppl. 308), 141–146.
- Johanson, C. E. and Uhlenhuth, E. H. (1980). Drug preference and mood in humans. Diazepam. Psychopharmacology, 71, 269–273.
- Kaplan, H. L. (1985). When do professional psychologists need professional programmers' tools? Behavioral Research Methods, Instuments and Computers, 17(5), 546–550.
- Kaplan, H. L. (1987). Incorporating good programs into the larger laboratory context. Behavioral Research Methods, Instruments and Computers, 19(2), 210–214.
- Kaplan, H. L., Sellers, E. M., Hamilton, C., Naranjo, C. A. and Dorian, P. (1985). It is there acute tolerance to alcohol at steady state? Journal of Studies on Alcohol, 46(3), 253–256.
- Lemberger, L., Rowe, H., Carmichael, R., Crabtree, R., Horng, J. S., Bymaster, F. and Wong, D. (1978). Fluoxetine, a selective serotonin uptake inhibitor. Clinical Pharmacology and Therapeutics, 24, 421–429.
- Lemberger, L., Bergstrom, R. F., Wolen, R. L., Faird, N. A., Enas, G. G. and Aronoff, G. R. (1985). Fluoxetine: Clinical pharmacology and physiologic disposition. Journal of Clinical Psychiatry, 46, (3, Sec. 2), 14–19.
- Naranjo, C. A., Sellers, E. M., Roach, C. A., Woodley, D. V., Sanchez-Craig, M. and Sykora, K. (1984a). Zimelidine-induced variations in ethanol intake in non-depressed heavy drinkers. Clinical Pharmacology and Therapeutics, 35, 374–381.
- Naranjo, C. A., Sellers, E. M., Kaplan, H. L., Hamilton, C. and Khouw, V. (1984b). Acute kinetic and dynamic interactions of zimelidine with ethanol. Clinical Pharmacology and Therapeutics, 36, 654–659.
- Naranjo, C. A., Sellers, E. M., Sullivan, J. T., Woodley, D. V., Kadlec, K. and Sykora, K. (1987). The serotonin uptake inhibitor citalopram attenuates ethanol intake. Clinical Pharmacology and Therapeutics, 41, 266–274.
- Nash, J., Bopp, R. J., Carmichael, R. H., Farid, K. Z. and Lemberger, L. (1981). Determination of fluoxentine and norfluoxetine in plasma by gas chromatography with electron capture detection. Clinical Chemistry, 28, 2100–2102.
- Ross, S. B., Aperiam, B., Beck-Friis, J., Jamsa, S., Wetterberg, L. Aberg, A. (1980). Inhibition of 5-hydroxytryptamine uptake in human platelets by antidepressive agent in vivo. Psychopharmacology, 67, 1–7.
- Scott, D. B., Fagan, D. and Tiplady, B. (1982). Effects of amitriptyline and zimelidine in combination with ethanol. Psychopharmacology, 76, 209–211.
- Seppala, T. (1977). Psychomotor skills during acute and two-week treatment with mianserin and amitriptyline and their combined effects with alcohol. Annals of Clinical Research, 9, 66–72.
- Seppala, T., Liljequist, R., Linnoila, M., Overo, K. F. and Dorrity, F. (1977). Correlationships between serum ami- and nortriptyline concetrations and psychomotor performance. Acta Pharmacologica et Toxicologica, 41, 472–480.
- SPSS-X User's Guide, 2nd Edition (1986). New York. McGraw-Hill Book Co.
- Stromberg, C. and Mattila, M. J. (1985). Acute and subacute effects on psychomotor performance of fluoxetine alone with alcohol. European Journal of Clinical Pharmacology, 28, 641–647.
- Weingartner, H., Buchsbaum, M. S. and Linnoila, M. (1983a). Zimelidine effects on memory impirments produced by ethanol. Life Sciences, 33, 2159–2163.
- Weingartner, H., Rudolph, M. V., Buchsbaum, M. S. and Linnoila, M. (1983b). Effects of serotonin on memory impairments produced by ethanol. Science, 221, 472–474.
- Wernicke, J. F. (1985). The side effect profile and safety of fluoxetine. Journal of Clinical Psychiatry, 46, (3, Sec. 2), 59–67.
- Zabik, J. E., Roache, J. D., Sidor, R. and Nash, J. F., Jr. (1982). The effects of fluoxetine on ethanol preference in the rat. Pharmacologist, 24, 204.
