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Identifying the specific clinical actions of amitriptyline: interrelationships of behaviour, affect and plasma levels in depression

Published online by Cambridge University Press:  09 July 2009

Martin M. Katz ,
Stephen H. Koslow ,
James W. Maas ,
Alan Frazer ,
James Kocsis ,
Steven Secunda ,
Charles L. Bowden  and
Regina C. Casper
Martin M. Katz*
Affiliation:
Division of Psychology, Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, New York; Neurosciences Research Branch, National Institute of Mental Health, Rockville, MD; Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX; Department of Psychiatry, University of Pennsylvania, Veterans Administration Hospital, Philadelphia, PA: Department of Psychiatry, Cornell University Medical College, New York; Springfield Professional Park, Springfield, PA; Department of Psychiatry, Michael Reese Hospital and Medical Center, Chicago IL, USA
Stephen H. Koslow
Affiliation:
Division of Psychology, Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, New York; Neurosciences Research Branch, National Institute of Mental Health, Rockville, MD; Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX; Department of Psychiatry, University of Pennsylvania, Veterans Administration Hospital, Philadelphia, PA: Department of Psychiatry, Cornell University Medical College, New York; Springfield Professional Park, Springfield, PA; Department of Psychiatry, Michael Reese Hospital and Medical Center, Chicago IL, USA
James W. Maas
Affiliation:
Division of Psychology, Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, New York; Neurosciences Research Branch, National Institute of Mental Health, Rockville, MD; Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX; Department of Psychiatry, University of Pennsylvania, Veterans Administration Hospital, Philadelphia, PA: Department of Psychiatry, Cornell University Medical College, New York; Springfield Professional Park, Springfield, PA; Department of Psychiatry, Michael Reese Hospital and Medical Center, Chicago IL, USA
Alan Frazer
Affiliation:
Division of Psychology, Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, New York; Neurosciences Research Branch, National Institute of Mental Health, Rockville, MD; Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX; Department of Psychiatry, University of Pennsylvania, Veterans Administration Hospital, Philadelphia, PA: Department of Psychiatry, Cornell University Medical College, New York; Springfield Professional Park, Springfield, PA; Department of Psychiatry, Michael Reese Hospital and Medical Center, Chicago IL, USA
James Kocsis
Affiliation:
Division of Psychology, Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, New York; Neurosciences Research Branch, National Institute of Mental Health, Rockville, MD; Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX; Department of Psychiatry, University of Pennsylvania, Veterans Administration Hospital, Philadelphia, PA: Department of Psychiatry, Cornell University Medical College, New York; Springfield Professional Park, Springfield, PA; Department of Psychiatry, Michael Reese Hospital and Medical Center, Chicago IL, USA
Steven Secunda
Affiliation:
Division of Psychology, Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, New York; Neurosciences Research Branch, National Institute of Mental Health, Rockville, MD; Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX; Department of Psychiatry, University of Pennsylvania, Veterans Administration Hospital, Philadelphia, PA: Department of Psychiatry, Cornell University Medical College, New York; Springfield Professional Park, Springfield, PA; Department of Psychiatry, Michael Reese Hospital and Medical Center, Chicago IL, USA
Charles L. Bowden
Affiliation:
Division of Psychology, Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, New York; Neurosciences Research Branch, National Institute of Mental Health, Rockville, MD; Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX; Department of Psychiatry, University of Pennsylvania, Veterans Administration Hospital, Philadelphia, PA: Department of Psychiatry, Cornell University Medical College, New York; Springfield Professional Park, Springfield, PA; Department of Psychiatry, Michael Reese Hospital and Medical Center, Chicago IL, USA
Regina C. Casper
Affiliation:
Division of Psychology, Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, New York; Neurosciences Research Branch, National Institute of Mental Health, Rockville, MD; Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX; Department of Psychiatry, University of Pennsylvania, Veterans Administration Hospital, Philadelphia, PA: Department of Psychiatry, Cornell University Medical College, New York; Springfield Professional Park, Springfield, PA; Department of Psychiatry, Michael Reese Hospital and Medical Center, Chicago IL, USA
*
1 Address for correspondence: Dr Martin M. Katz, Department of Psychiatry, Albert Einstein College of Medicine, Montefiore Medical Center, 111 East 210 street, Bronx, NY 10467, USA.
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Synopsis

Despite increasing knowledge of the neurochemical bases of the action of the tricyclic drugs, little is known about the sequence of psychological effects which precede recovery in drug-responsive patients. This research was aimed at identifying the specific behavioural effects associated with the therapeutic action of amitriptyline in depression. The design involved measurement (post-hoc) of weekly changes in a severely depressed placebo-resistant group who recovered with drug treatment, compared with a group of similar patients treated for the equivalent four weeks, who showed minimal to no clinical response. The research strategy, in accordance with a dose–response paradigm, was to determine which of the early changes in emotion and behaviour found in treatment responders were systematically associated with plasma concentrations of amitriptyline or its major metabolite. Amitriptyline was found to act within seven days on the components of anxiety and on hostility in the responders, and on sleep disorder in all patients. After 12 to 14 days of treatment these effects increased, with improvements in other significant components distinguishing the responders from the non-responders. At the 12th to 14th treatment days when a steady state concentration of drug in plasma was approached, reductions in anxiety and hostility and in certain somatic components correlated significantly with plasma concentrations of amitriptyline. Implications of the findings for clarifying the specificity of clinical actions of the tricyclic drugs, and for understanding the psychobiological dynamics underlying rapid drug-induced recovery in depression, were explored.

Information

Type
Original Articles
Information
Psychological Medicine , Volume 21 , Issue 3 , August 1991 , pp. 599 - 611
Copyright
Copyright © Cambridge University Press 1991

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References

Åsberg, M., Bertilsson, L., Tuck, D., Cronholm, B. & Sjoqvist, F. (1972). Indoleamine metabolites in the cerebrospinal fluid of depressed patients before and during treatment with nortriptyline. Clinical Pharmacology and Therapeutics 14, 277–286.CrossRefGoogle Scholar
Biggs, J. T., Holland, S. W., Chang, S., Hipps, P. P. & Sherman, W. F. (1976). The electron beam ionization mass fragmentographic analysis of tricyclic antidepressants in human plasma. Journal of Pharmaceutical Science 65, 261–268.CrossRefGoogle ScholarPubMed
Bowden, C. L., Koslow, S. H., Hanin, I., Maas, J. W., Davis, J. M. & Robins, E. (1985). Effects of amitriptyline and imipramine on brain and amine neurotransmitter metabolites in cerebrospinal fluid. Clinical Pharmacology and Therapeutics 37, 316–324.CrossRefGoogle ScholarPubMed
Cole, J. O. & Davis, J. M. (1975). Antidepressant drugs. In Comprehensive Textbook of Psychiatry II (ed. Freedman, A. M., Kaplan, H. I. and Sadock, B. J.), pp.2290–2315. Williams & Wilkins: Baltimore.Google Scholar
DiMascio, A., Weissman, M. M., Prusoff, B. A., Neu, C., Zwilling, M. & Klerman, G. L. (1979). Differential symptom reduction by drugs and psychotherapy in acute depression. Archives of General Psychiatry 36, 1450–1456.CrossRefGoogle ScholarPubMed
Edwards, A. L. (1962). Experimental Design in Psychological Research (Revised edition). Holt, Rinehart and Winston: New York.Google Scholar
Endicott, J. & Spitzer, R. (1978). A diagnostic interview: the schedule for affective disorders and schizophrenia. Archives of General Psychiatry 35, 837–844.CrossRefGoogle ScholarPubMed
Fava, G. A., Kellner, R., Lisansky, J., Park, S., Perini, G. I. & Zielezny, M. (1986). Hostility and recovery from melancholia. Journal of Nervous and Mental Disease 174, 414–417.CrossRefGoogle ScholarPubMed
Fingel, E. & Woodbury, D. M. (1975). General principles. In Pharmacological Basis of Therapeutics 5th Edition (ed. Goodman, L. S. and Gilman, A.), pp. 1–46. Macmillan: New York.Google Scholar
Frazer, A. & Conway, P. (1984). Pharmacological mechanisms of action of antidepressants. Psychiatric Clinics of North America 7, 575–586.CrossRefGoogle ScholarPubMed
Freud, S. (1959). Mourning and melancholia. In Collected Papers, V. 4.. Basic Books: New York.Google Scholar
Glassman, T., Kantor, S. J. & Shostak, M. (1975). Depression, delusions and drug response. American Journal of Psychiatry 132, 716–719.Google ScholarPubMed
Hamilton, M. (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 23, 56–62.CrossRefGoogle ScholarPubMed
Hollister, L. E., Overall, J. E., Johnson, M., Pennington, V., Katz, G. & Sheldon, J. (1964). Controlled comparison of amitriptyline, imipramine and placebo in hospitalized depressed patients. Journal of Nervous and Mental Disease 139, 370–375.CrossRefGoogle ScholarPubMed
Joyce, R. P. & Paykel, E. S. (1989). Predictors of drug response in depression. Archives of General Psychiatry 46, 89–99.CrossRefGoogle ScholarPubMed
Kahn, R. J., McNair, D. M., Lipman, R. S., Covi, L., Rickels, K., Downing, R., Fisher, S. & Frankenthaler, L. M. (1979). Imipramine and chlordiazepoxide in depression and anxiety disorders. II. Efficacy in anxious outpatients. Archives of General Psychiatry 43, 79–85.CrossRefGoogle Scholar
Katz, M. M., Secunda, S., Hirschfeld, R. M. S. & Koslow, S. H. (1979). NIMH Clinical Research Collaborative Program on the Psycho-biology of Depression. Archives of General Psychiatry 36, 765–771.CrossRefGoogle Scholar
Katz, M. M., Robins, E., Croughan, J., Secunda, A. & Swann, A. (1982). Behavioural measurement and drug response characteristics of unipolar and bipolar depression. Psychological Medicine 12, 25–36.CrossRefGoogle ScholarPubMed
Katz, M. M., Koslow, S. H., Berman, N., Secunda, S., Maas, J. W., Casper, R., Kocsis, J. & Stokes, P. (1984). Multivantaged approach to the measurement of behavioural and affect states for clinical and psychobiological research. Psychological Reports 55, 619–671.CrossRefGoogle Scholar
Katz, M. M., Koslow, S. H., Maas, J., Frazer, A., Bowden, C. L., Casper, R., Croughan, J., Kocsis, J. & Redmond, E. Jr., (1987). The timing, specificity and clinical prediction of tricyclic drug effects in depression. Psychological Medicine 17, 297–309.CrossRefGoogle ScholarPubMed
Klein, D. F., Zitrin, C. M. & Woerner, M. (1978). Antidepressants, anxiety panic and phobia. In Psychopharmacology: A Generation of Progress (ed. Lipton, M. A., DiMascio, A. and Killam, K. F.), pp. 1401–1410. Raven Press: New York.Google Scholar
Klerman, G. L. & Cole, J. O. (1965). Clinical pharmacology of imipramine and related antidepressant compounds. Pharmacology Review 17, 101–141.Google ScholarPubMed
Kocsis, J. H., Davis, J. M., Katz, M. M., Koslow, S. H., Stokes, P. E., Casper, R. & Redmond, D. E. (1985). Depressive behavior and hyperactive adrenocortical function. American Journal of Psychiatry 142, 1291–1298.Google ScholarPubMed
Kocsis, J., Hanin, I., Bowden, C. L. & Brunswick, D. (1986). Imipramine and amitriptyline plasma concentration and clinical response in major depression. British Journal of Psychiatry 148, 52–57.CrossRefGoogle ScholarPubMed
Koslow, S., Maas, J. W., Bowden, C., Davis, J., Hanin, I. & Javard, J. (1986). Letter to the editor: tricyclic anti-depressant washout effects on cerebrospinal fluix and urinary monoamine and metabolites. Archives of General Psychiatry 43, 1012–1013.Google Scholar
Lader, M., Lang, R. A. & Wilson, G. D. (1987). Patterns of Improvement in Depressed In-patients. Maudsley Monograph No. 30, Oxford University Press: Oxford.Google Scholar
LeDoux, J. E. (1987). Emotion. In Handbook of Physiology: The Nervous System, Vol. v, (ed. Geiger, S. R., Plum, F. and Mountcastle, V. B.), pp. 419–461. American Physiological Society: Bethesda, Maryland.Google Scholar
Maas, J. W., Koslow, S., Davis, J., Katz, M. M., Mendels, J., Robins, E., Stokes, P. & Bowden, C. (1980). Biological component of the NIMH Clinical Research Branch Collaborative Program in the Psychobiology of Depression. I. Background theoretical considerations. Psychological Medicine 10, 759–776.CrossRefGoogle ScholarPubMed
Maas, J. W., Koslow, S. H., Katz, M. M., Bowden, C. L., Gibbons, R. L., Stokes, P. E., Robins, E. & Davis, J. M. (1984). Pretreatment neurotransmitter metabolite levels and response to tricyclic antidepressant drugs. American Journal of Psychiatry 141, 1159–1171.Google ScholarPubMed
Mason, J. W. (1968). A review of psychoendocrine research on the pituitary–adrenal cortical system. Psychosomatic Medicine 30 (09.–10. suppl.), 576–607.CrossRefGoogle ScholarPubMed
Medical Research Council (1965). Clinical trial of the treatment of depressive illness. British Medical Journal 6, 881–886.Google Scholar
Nelson, J. C., Mazure, C., Quinlan, D. M. & Jatlow, P. I. (1984). Drug-responsive symptoms in melancholia. Archives of General Psychiatry 41, 663–668.CrossRefGoogle ScholarPubMed
Preskorn, S. H. & Mac, D. S. (1984). The implication of concentration/response studies of tricyclic antidepressants for psychiatric research and practice. Psychiatric Developments 3, 201–222.Google Scholar
Quitkin, F. M., Rabkin, J. G., Ross, D. & Stewart, J. W. (1984). Identification of true drug response to anti-depressants: use of pattern analysis. Archives of General Psychiatry 41, 782–786.CrossRefGoogle Scholar
Redmond, D. Jr., Katz, M. M., Maas, J., Swann, A. & Casper, R. (1986). Cerebrospinal fluid biogenic amine metabolite relationships with behavioral measurements in unipolar and bipolar depressed, manic and healthy control subjects. Archives of General Psychiatry 43, 938–947.CrossRefGoogle Scholar
Schatzberg, A. F. & Cole, J. O. (1978). Benzodiasepines in depressive disorders. Archives of General Psychiatry 35, 1359–1365.CrossRefGoogle Scholar
Secunda, S., Koslow, S., Redmond, D., Garner, D., Ramsey, T., Croughan, J., Kocsis, J., Hanin, I. & Lieberman, K. (1980). Biological component of the NIMH Clinical Research Branch Collaborative Program on the Psychobiology of Depression. I. Methodology and data analysis. Psychological Medicine 10, 777–793.CrossRefGoogle ScholarPubMed
Spitzer, R. L., Endicott, J. & Robins, E. (1978). Research diagnostic criteria: rationale and reliability. Archives of General Psychiatry 35, 773–782.CrossRefGoogle ScholarPubMed
Sulser, F., Vetulani, J. & Mobley, P. L. (1978). Commentary on mode of action of antidepressant drugs. Biochemical Pharmacology 27, 257–261.CrossRefGoogle Scholar
Task Force on the Use of Laboratory Tests in Psychiatry. (1985). Tricyclic Antidepressants – Blood Level Measurements and Clinical Outcome: An APA Task Force Report. American Journal of Psychiatry 142, 155–162.CrossRefGoogle Scholar
van Praag, H. M., Plutchik, R. & Conte, H. (1986). The serotonin-hypothesis of (auto) aggression. Critical appraisal of the evidence. In Psychobiological Suicide Behavior (ed. Mann, J. J. and Stanley, M.). Annals of the New York Academy of Science 487, 150–167.Google Scholar
Weissman, M., Klerman, G. L. & Paykel, E. S. (1971). Clinical evaluations of hostility in depression. American Journal of Psychiatry 128, 41–46.CrossRefGoogle ScholarPubMed
Winer, B. J. (1971). Statistical Principles in Experimental Design (2nd edition). McGraw Hill: New York.Google Scholar
Wittenborn, J. R. (1966 a). The Clinical Psychopharmacology of Anxiety. Charles C. Thomas: Springfield, Illinois.Google Scholar
Wittenborn, J. R. (1966 b). The assessment of clinical change. In Pharmacotherapy of Depression (ed. Cole, J. O. & Wittenborn, J. R.), pp. 67–90. Charles C. Thomas: Springfield, Illinois.Google Scholar