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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.

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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