TY - JOUR
T1 - Identifying the specific clinical actions of amitriptyline
T2 - Interrelationships of behaviour, affect and plasma levels in depression
AU - Katz, Martin M.
AU - Koslow, Stephen H.
AU - Maas, James W.
AU - Frazer, Alan
AU - Kocsis, James
AU - Secunda, Steven
AU - Bowden, Charles L
AU - Casper, Regina C.
N1 - Funding Information:
The above study was completed with the cooperation and participation of the Collaborative Program Investigators: S. H. Koslow (Project Director), S. Secunda (Deputy Project Director), I. Hanin (Consultant), B. Harris (Protocol Monitor) (National Institute of Mental Health); M. M. Katz (Senior Investigator) (Albert Einstein College of Medicine-Montefiore Medical Center); J. W. Maas (Chairman) (The University of Texas Health Sciences Center at San Antonio); D. E. Redmond, Jr., A. Swann (Yale University School of Medicine); J.M.Davis, R. Casper, S. Chang, D. Garver, J. Javaid (Illinois State Psychiatric Institute); J. Mendels, D. Brunswick, A. Frazer, A. Ramsey, S. Stern (Philadelphia VA Medical Center); P. E. Stokes, J. Kocsis (Cornell University Medical Center); E. Robins (Washington University School of Medicine, St Louis); J. Croughan (Washington University School of Medicine & Jewish Hospital, St Louis); C. Bowden, R. Shulman (The University of Texas Health Sciences Center at San Antonio). The research was supported by National Institute of Mental Health Grants U01 MH26976, U01 MH26975, U01 MH26977, U01 MH26979, U01 MH26978, U01 MH31921 and U01 MH44403.
PY - 1991
Y1 - 1991
N2 - 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.
AB - 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.
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U2 - 10.1017/S0033291700022236
DO - 10.1017/S0033291700022236
M3 - Article
C2 - 1946849
AN - SCOPUS:0025816231
SN - 0033-2917
VL - 21
SP - 599
EP - 611
JO - Psychological Medicine
JF - Psychological Medicine
IS - 3
ER -