....
Original Research Reports Use of Tricyclic Antidepressants in Recipients of Heart Transplants JERALD KAy, M.D., DAVID BIENENFELD, M.D. MARcIA SLOMOWlTZ, M.D., JUDY BURK, M.D. LAWRENCE ZIMMER, M.D., GRACE NADOLNY, M.D. N. TRAVIS MARVEL, M.D., PETER GEIER, M.D.
Cardiac transplantation has become an accepted treatment for certain endstage cardiac disease patients. Depression and significant psychosocial stress among heart transplant recipients are not uncommon. but published reports about the use ofantidepressants in these persons are very rare. The authors ofthis study report on a group ofnine heart transplant recipients treated with antidepressant medicines. Seven patients achieved clinical remissions oftheir depression. and only two were unable to tolerate the noncardiac side effects ofthe medication. Indicators ofautonomic. electrocardiographic. and hemodynamic functions showed no adverse effects. Although the study is based on a small sample. it appears that tricyclic antidepressants are safe and effective in heart transplant recipients.
A
dvances in surgical technique and immunosuppressant therapy have allowed cardiac transplantation to become a widely accepted treatment for certain forms of serious heart disease. I In 1987, more than 2,000 cardiac transplantations were performed worldwide, more than 1,400 of these within the United States.2 The increasing frequency of all transplants performed, i.e., renal, liver, pancreas, heart, and heart-lung, have led to consideration of psychiatric sequelae. 3 The unique symbolic features and physical stresses of this surgery and its recovery pose an intriguing challenge for psychiatrists working with heart transplant patients. Worldwide, the I-year survival rate for cardiac transplantation exceeds 80%. In the experience of most investigators, the majority of patients also maintain considerable psychological stability.~ Nonetheless, cardiac surgery and immunosuppressant therapy are both associated with depression, and cardiac transplant patients VOLUME 32. NUMBER 2· SPRING 1991
are not exempt from this risk. Though depression is a common sequela, most cases are mild and managed with psychotherapy alone. Major depressions are not commonly reported, and use of antidepressant drugs in transplant recipients is rarely described in detail. Freeman et al. found dysthymia or adjustment disorders with depressed features in 16% of a group of 70 recipients, but no major depressions.' Mai et aI., in a group of 22 survivors, found one patient who was "diagnosed with clinical depression" after 6 months and who "responded well to antidepressant treatment.,,8 Shapiro and Kornfeld followed 64 patients and Received August 18. 1989; revised December 5.1989; accepted December 29. 1989. From the Department of Psychiatry. Wright State University School of Medicine. Dayton. Address reprint requests to Dr. Kay. P. O. Box 927. Dayton.
OH45401. Copyright © 1991 The Academy of Psychosomatic Medicine.
165
Tricyclics and Heart Transplant Recipients
TABLE ••
Patient and treatment data
•
or nine heart transplant recipients
2
3
4
5
6
7
8
9
Age
33
56
42
46
46
41
54
57
43
Sex
F
M
M
M
M
M
M
M
M
MOE
MOE
MOE
Dys
MOE
Oys
OMO
MOE
MOE
3
4
9
9
13
17
24
5.1"
18
150
25
100
75
25
75
25
300
100
50
50
75
15
5
Patient
Psychialric diagnosis Onset. months (post-transplant) Desipramine b dose. mg Nonriptyline b dose. mg Amilriptyline b dose. mg Ourationof antidepressant treatment. months
25
3
9
12
Side effects Desipramine Nonriptyline Prior psychialric history Prednisone dose. mg
37
3
Hyp Tin.Nau
Lib
Ret
MOE
MOE
MOE
MOE
GAD
Dys
7.5
12.5
10
15
5
5
Hyp
EtOH 7.5
7.5
10
Note: MOE--major depressive episode; Dys=dyslhymia; OMD--organic mood disorder; EtOH=a1cohol dependency; GAD=generalized anxiety disorder; Hyp=hypotension; Lib=diminished libido; Ret=urinary retention; Tin=tinnitus; Nau=nausea. "Patient 8 was transplanted twice. boose at best clinical response, or dose at time of discontinuation.
diagnosed four major depressive episodes requiring pharmacologic treabnent.9 Shapiro subsequently described the use of nortriptyline in eight cardiac transplant recipients and found it to be well tolerated clinically, without significant effects on cardiac output, vital signs, or electrocardiographic parameters. 10 METHODS Psychiatric collaboration with the cardiac transplantation team at the University of Cincinnati Medical Center, where this research was conducted, allowed us to observe closely the emotional sequelae of the procedure. One of the psychiatrist authors was assigned to each transplant patient and performed a semistructured interview as soon as possible after each candidate was accepted for the transplant waiting list, as well as at 6, 12, and 24 months postoperatively. 166
The interview (a modification of the routine consultation assessment, tailored for transplant recipients) examined for diagnosable clinical syndromes, also evaluating coping responses, dreams, and fantasies. Additionally, the Beck Depression Inventory (BOI), Brief Symptom Inventory, Ways of Coping questionnaire, and a quality-of-Iife survey were completed at these intervals. (Results of the latter three investigations are to be reported elsewhere.) All patients received cyclosporine, azathioprine, and prednisone for immunosuppression. Myocardial biopsies were performed weekly for the first 6 weeks, then tapered to one every 6 months, within 2 years postoperatively. Cardiac output and stroke volume were measured by thermodilution technique, utilizing a Swan-Ganz catheter placed at the time of biopsy. Cardiac index and stroke volume index were calculated by correcting cardiac output and PSYCHOSOMATICS
Kay et al.
stroke volume for body surface area. The investigators were also called upon by the patients and surgical team for perceived clinical needs. When use of an antidepressant medicine was deemed clinically advisable, it was started by the psychiatrist in accordance with routine practice. Oosage was determined by clinical response and tolerance of side effects. The patients studied were not compared to a nonmedication group. Individual supportive psychodynamic and cognitive psychotherapies, as well as marital and family therapy, were provided in addition to medication, according to patients' needs, and were continued as long as clinically necessary. Psychiatric, electrocardiographic, and myocardial function data were obtained retrospectively. RESULTS In a group of 45 transplant survivors, nine met OSM-III or OSM-III-R criteria for major depression, organic mood disorder, or dysthymia and required treatment with antidepressants. A tenth patient received 25 mg desipramine/day for 2 weeks during a period of transplant rejection, systemic fungal infection, and progressive physical deterioration, complicated by tearfulness and suicidal ideation. As his neurologic condition deteriorated inexorably, the family elected to withdraw all treatment. Table 1 lists patient characteristics, treatment, and side effects. Mean age (±SO) oftreated patients was 46.8±7.6, compared with a mean age of 49.9 for the entire survivor group. All but one TABLE 2. Beck Depression Inventory (BOI) Scores of four heart transplant recipients Patient
BDibefore TCAD
BOlon TCAD
1 2 3 4 MeanSD
27 14 26 14 20.25±7.23
15 9 17 9 12.50±4.12
NOle:TCAD=tricyclic antidepressants; 1=4.55. df=3. p
Original Research Reports Use of Tricyclic Antidepressants in Recipients of Heart Transplants JERALD KAy, M.D., DAVID BIENENFELD, M.D. MARcIA SLOMOWlTZ, M.D., JUDY BURK, M.D. LAWRENCE ZIMMER, M.D., GRACE NADOLNY, M.D. N. TRAVIS MARVEL, M.D., PETER GEIER, M.D.
Cardiac transplantation has become an accepted treatment for certain endstage cardiac disease patients. Depression and significant psychosocial stress among heart transplant recipients are not uncommon. but published reports about the use ofantidepressants in these persons are very rare. The authors ofthis study report on a group ofnine heart transplant recipients treated with antidepressant medicines. Seven patients achieved clinical remissions oftheir depression. and only two were unable to tolerate the noncardiac side effects ofthe medication. Indicators ofautonomic. electrocardiographic. and hemodynamic functions showed no adverse effects. Although the study is based on a small sample. it appears that tricyclic antidepressants are safe and effective in heart transplant recipients.
A
dvances in surgical technique and immunosuppressant therapy have allowed cardiac transplantation to become a widely accepted treatment for certain forms of serious heart disease. I In 1987, more than 2,000 cardiac transplantations were performed worldwide, more than 1,400 of these within the United States.2 The increasing frequency of all transplants performed, i.e., renal, liver, pancreas, heart, and heart-lung, have led to consideration of psychiatric sequelae. 3 The unique symbolic features and physical stresses of this surgery and its recovery pose an intriguing challenge for psychiatrists working with heart transplant patients. Worldwide, the I-year survival rate for cardiac transplantation exceeds 80%. In the experience of most investigators, the majority of patients also maintain considerable psychological stability.~ Nonetheless, cardiac surgery and immunosuppressant therapy are both associated with depression, and cardiac transplant patients VOLUME 32. NUMBER 2· SPRING 1991
are not exempt from this risk. Though depression is a common sequela, most cases are mild and managed with psychotherapy alone. Major depressions are not commonly reported, and use of antidepressant drugs in transplant recipients is rarely described in detail. Freeman et al. found dysthymia or adjustment disorders with depressed features in 16% of a group of 70 recipients, but no major depressions.' Mai et aI., in a group of 22 survivors, found one patient who was "diagnosed with clinical depression" after 6 months and who "responded well to antidepressant treatment.,,8 Shapiro and Kornfeld followed 64 patients and Received August 18. 1989; revised December 5.1989; accepted December 29. 1989. From the Department of Psychiatry. Wright State University School of Medicine. Dayton. Address reprint requests to Dr. Kay. P. O. Box 927. Dayton.
OH45401. Copyright © 1991 The Academy of Psychosomatic Medicine.
165
Tricyclics and Heart Transplant Recipients
TABLE ••
Patient and treatment data
•
or nine heart transplant recipients
2
3
4
5
6
7
8
9
Age
33
56
42
46
46
41
54
57
43
Sex
F
M
M
M
M
M
M
M
M
MOE
MOE
MOE
Dys
MOE
Oys
OMO
MOE
MOE
3
4
9
9
13
17
24
5.1"
18
150
25
100
75
25
75
25
300
100
50
50
75
15
5
Patient
Psychialric diagnosis Onset. months (post-transplant) Desipramine b dose. mg Nonriptyline b dose. mg Amilriptyline b dose. mg Ourationof antidepressant treatment. months
25
3
9
12
Side effects Desipramine Nonriptyline Prior psychialric history Prednisone dose. mg
37
3
Hyp Tin.Nau
Lib
Ret
MOE
MOE
MOE
MOE
GAD
Dys
7.5
12.5
10
15
5
5
Hyp
EtOH 7.5
7.5
10
Note: MOE--major depressive episode; Dys=dyslhymia; OMD--organic mood disorder; EtOH=a1cohol dependency; GAD=generalized anxiety disorder; Hyp=hypotension; Lib=diminished libido; Ret=urinary retention; Tin=tinnitus; Nau=nausea. "Patient 8 was transplanted twice. boose at best clinical response, or dose at time of discontinuation.
diagnosed four major depressive episodes requiring pharmacologic treabnent.9 Shapiro subsequently described the use of nortriptyline in eight cardiac transplant recipients and found it to be well tolerated clinically, without significant effects on cardiac output, vital signs, or electrocardiographic parameters. 10 METHODS Psychiatric collaboration with the cardiac transplantation team at the University of Cincinnati Medical Center, where this research was conducted, allowed us to observe closely the emotional sequelae of the procedure. One of the psychiatrist authors was assigned to each transplant patient and performed a semistructured interview as soon as possible after each candidate was accepted for the transplant waiting list, as well as at 6, 12, and 24 months postoperatively. 166
The interview (a modification of the routine consultation assessment, tailored for transplant recipients) examined for diagnosable clinical syndromes, also evaluating coping responses, dreams, and fantasies. Additionally, the Beck Depression Inventory (BOI), Brief Symptom Inventory, Ways of Coping questionnaire, and a quality-of-Iife survey were completed at these intervals. (Results of the latter three investigations are to be reported elsewhere.) All patients received cyclosporine, azathioprine, and prednisone for immunosuppression. Myocardial biopsies were performed weekly for the first 6 weeks, then tapered to one every 6 months, within 2 years postoperatively. Cardiac output and stroke volume were measured by thermodilution technique, utilizing a Swan-Ganz catheter placed at the time of biopsy. Cardiac index and stroke volume index were calculated by correcting cardiac output and PSYCHOSOMATICS
Kay et al.
stroke volume for body surface area. The investigators were also called upon by the patients and surgical team for perceived clinical needs. When use of an antidepressant medicine was deemed clinically advisable, it was started by the psychiatrist in accordance with routine practice. Oosage was determined by clinical response and tolerance of side effects. The patients studied were not compared to a nonmedication group. Individual supportive psychodynamic and cognitive psychotherapies, as well as marital and family therapy, were provided in addition to medication, according to patients' needs, and were continued as long as clinically necessary. Psychiatric, electrocardiographic, and myocardial function data were obtained retrospectively. RESULTS In a group of 45 transplant survivors, nine met OSM-III or OSM-III-R criteria for major depression, organic mood disorder, or dysthymia and required treatment with antidepressants. A tenth patient received 25 mg desipramine/day for 2 weeks during a period of transplant rejection, systemic fungal infection, and progressive physical deterioration, complicated by tearfulness and suicidal ideation. As his neurologic condition deteriorated inexorably, the family elected to withdraw all treatment. Table 1 lists patient characteristics, treatment, and side effects. Mean age (±SO) oftreated patients was 46.8±7.6, compared with a mean age of 49.9 for the entire survivor group. All but one TABLE 2. Beck Depression Inventory (BOI) Scores of four heart transplant recipients Patient
BDibefore TCAD
BOlon TCAD
1 2 3 4 MeanSD
27 14 26 14 20.25±7.23
15 9 17 9 12.50±4.12
NOle:TCAD=tricyclic antidepressants; 1=4.55. df=3. p
