IAGS 39:1006-1007, 1991
Left Bundle Branch Block Developing in a Patient with Sub-Therapeutic Nortriptylin.e Levels: A Case Report I
Joel S. Gross and Glenn Zwerin
I
n therapeutic doses, the heterocyclic antidepressants have a remarkably high benefit-risk ratio. However, with high serum concentrations, these antidepressants can have significant cardiac toxicity, including conduction disorders, heart block, and rhythm disturbances.’ Such electrocardiographic disturbances are recognized as prolonged P-R, QRS, and QT intervals as well as T-wave inversions.’ More serious conduction abnormalities occur at very high or toxic plasma levels and can include right or left bundle branch block or even partial or complete heart block.3 We report an exceptional case of nortriptyline-induced left bundle branch block in a patient who was clinically free of underlying cardiac conduction disorders and received subtherapeutic doses.
CASE REPORT A 63-year old male was admitted to a community nursing home with a diagnosis of probable Alzheimer’s disease. His past medical history was unremarkable for cardiac disease or any other significant disorder. On admission he was alert and exhibited partial expressive dysphasia felt to be secondary to Alzheimer’s disease. He appeared anxious and had a flattened affect and depressed mood along with emotional lability manifested by frequent crying episodes. A Mini-Mental Status Examination score was recorded as 5. Standardized depression scale testing was not possible due to difficulty in expressing himself. It was felt that a possible underlying depression was present and the patient was begun on nortriptyline, 25 mg each evening. An admission ECG revealed normal sinus rhythm and a normal QRS and QTc interval, 77 msec and 404, respectively. Blood chemistries were all within the nor-
From the Greenwall Geriatnc Program at Monmouth Medical Center, Long Branch, New Jersey and Crestwood Manor, Whiting, New Jersey.
01991 by the American Geriatrics Society
ma1 range. An ECG done on May 11, 1990 revealed a sinus tachycardia at 102 per minute with normal QRS and QTc intervals. On May 12, nortriptyline was begun. An ECG done 3 weeks later revealed a sinus tachycardia and a left bundle branch block. At that time serum nortriptyline level was less than 25 ng/mL. Nortriptyline was discontinued, and an ECG performed 6 days later revealed a return to normal sinus rhythm as well as normal QRS and QTc intervals. During the period of withholding the nortriptyline it was noted that the patient was becoming more depressed with frequent crying episodes and emotional lability. Because we thought it exceedingly unlikely for a left bundle branch block to be caused by such a low serum level of nortriptyline, a rechallenge of nortriptyline, 25 mg each evening, was administered. An ECG performed 3 days later again revealed complete left bundle branch block, again accompanied by serum level of nortriptyline of less than 25 ng/mL. Once again the nortriptyline was discontinued and another ECG revealed normal sinus rhythm and normal QRS and QTc intervals (Figure 1).
DISCUSSION The heterocyclic antidepressant medications are the drugs most commonly used for the treatment of depression. Over 30 million prescriptions are written each year for these drugs. Since their introduction in the 1950’s, it has become apparent that serious cardiac toxicity can occur with toxic levels. The relationship between plasma antidepressant levels and the ECG manifestations of toxicity have been explored by various investigators. Vohra4 showed that a significant drug-related increase in the P-R interval occurred with the use of nortriptyline as well as doxepin. There are no currently available heterocyclic antidepressants that are completely free of cardiac toxicity. In two studies of middle-aged depressed patients who achieved therapeutic plasma levels of nortriptyline, 0002-8614/91/$3.50
LEFT BUNDLE BRANCH BLOCK WITH NORTRIPTYLINE
IAGS-OCTOBER 1991-VOL. 39, NO. 10
NUMBER __
the QRS) in one of eight individuals with plasma nortriptyline levels less than 200 mg/mL.’ These data suggested that, at usual therapeutic concentrations, nortriptyline was unlikely to cause any change in intraventricular conduction in individuals free of pre-existing heart disease. Glassman suggested that, at therapeutic concentrations, the only depressed patients in danger of block are those with pre-existing conduction defects that involve the His Purkinje ~ y s t e m . ~ Our review of the literature failed to reveal the development of a left bundle branch block in a depressed individual who was free of underlying conduction disorders of the heart and had a subtherapeutic level of nortriptyline. Therefore, this case may increase concern about the possibility of bundle branch block and encourage physicians to perform an ECG soon after beginning an antidepressant.
DATE
I
5/5/90
I1
5/11/90
111
6/5/90
IV
6/11/90
1007
REFERENCES
V
6/25/90
VI
6/27/90
I
I
I
‘W~-~-~wwllv
I
I
r
! I
+,
FIGURE 1. Rhythm strips from patient under discussion.
Freyschuss et a15 and Ziegler et a16 demonstrated that increases in the P-R or QRS intervals were unlikely to be seen. Using His bundle studies, Vohra demonstrated increased H-V intervals (correlating with increases in
1. Jenike MA. Affective Disorders. In Jenike MA, ed. Geriatric Psychiatry and Psychopharmacology. Chicago: Year Book Medical Publishers, Inc., 1989. 2. Kantor SJ, Glassman AG, Bigger JTJ et al. The cardiac effects of therapeutic concentrations of imipramine. Am J Psychiatry 1978;135:534-538. 3. Glassman AH. Cardiovascular effects of tricyclic antidepressants. Ann Rev Med 1984;365:503-511. 4. Vohra J, Burrows GD, Sloman G. Assessment of cardiovascular side effects of therapeutic doses of tricyclic anti-depressant drugs. Aust N Z J Med 1975;5:7-11. 5. Freyschuss U, Sjoqvist F, Tuck D, Asberg M. Circulatory effects in man of nortriptyline, a tricyclic anti-depressant drug. Pharrnacol Clin 1970;2:68-71. 6. Ziegler VE, Co BT, Biggs JT. Plasma nortriptyline levels and ECG findings. Am J Psychiatry 1977;134:441-443. 7. Vohra J, Burrows G, Hunt D, Slornan G. The effect of toxic and therapeutic doses of tricyclic anti-depressant drugs on intracardiac conduction. Eur J Cardiol 1975;3(3):219-227.
Left Bundle Branch Block Developing in a Patient with Sub-Therapeutic Nortriptylin.e Levels: A Case Report I
Joel S. Gross and Glenn Zwerin
I
n therapeutic doses, the heterocyclic antidepressants have a remarkably high benefit-risk ratio. However, with high serum concentrations, these antidepressants can have significant cardiac toxicity, including conduction disorders, heart block, and rhythm disturbances.’ Such electrocardiographic disturbances are recognized as prolonged P-R, QRS, and QT intervals as well as T-wave inversions.’ More serious conduction abnormalities occur at very high or toxic plasma levels and can include right or left bundle branch block or even partial or complete heart block.3 We report an exceptional case of nortriptyline-induced left bundle branch block in a patient who was clinically free of underlying cardiac conduction disorders and received subtherapeutic doses.
CASE REPORT A 63-year old male was admitted to a community nursing home with a diagnosis of probable Alzheimer’s disease. His past medical history was unremarkable for cardiac disease or any other significant disorder. On admission he was alert and exhibited partial expressive dysphasia felt to be secondary to Alzheimer’s disease. He appeared anxious and had a flattened affect and depressed mood along with emotional lability manifested by frequent crying episodes. A Mini-Mental Status Examination score was recorded as 5. Standardized depression scale testing was not possible due to difficulty in expressing himself. It was felt that a possible underlying depression was present and the patient was begun on nortriptyline, 25 mg each evening. An admission ECG revealed normal sinus rhythm and a normal QRS and QTc interval, 77 msec and 404, respectively. Blood chemistries were all within the nor-
From the Greenwall Geriatnc Program at Monmouth Medical Center, Long Branch, New Jersey and Crestwood Manor, Whiting, New Jersey.
01991 by the American Geriatrics Society
ma1 range. An ECG done on May 11, 1990 revealed a sinus tachycardia at 102 per minute with normal QRS and QTc intervals. On May 12, nortriptyline was begun. An ECG done 3 weeks later revealed a sinus tachycardia and a left bundle branch block. At that time serum nortriptyline level was less than 25 ng/mL. Nortriptyline was discontinued, and an ECG performed 6 days later revealed a return to normal sinus rhythm as well as normal QRS and QTc intervals. During the period of withholding the nortriptyline it was noted that the patient was becoming more depressed with frequent crying episodes and emotional lability. Because we thought it exceedingly unlikely for a left bundle branch block to be caused by such a low serum level of nortriptyline, a rechallenge of nortriptyline, 25 mg each evening, was administered. An ECG performed 3 days later again revealed complete left bundle branch block, again accompanied by serum level of nortriptyline of less than 25 ng/mL. Once again the nortriptyline was discontinued and another ECG revealed normal sinus rhythm and normal QRS and QTc intervals (Figure 1).
DISCUSSION The heterocyclic antidepressant medications are the drugs most commonly used for the treatment of depression. Over 30 million prescriptions are written each year for these drugs. Since their introduction in the 1950’s, it has become apparent that serious cardiac toxicity can occur with toxic levels. The relationship between plasma antidepressant levels and the ECG manifestations of toxicity have been explored by various investigators. Vohra4 showed that a significant drug-related increase in the P-R interval occurred with the use of nortriptyline as well as doxepin. There are no currently available heterocyclic antidepressants that are completely free of cardiac toxicity. In two studies of middle-aged depressed patients who achieved therapeutic plasma levels of nortriptyline, 0002-8614/91/$3.50
LEFT BUNDLE BRANCH BLOCK WITH NORTRIPTYLINE
IAGS-OCTOBER 1991-VOL. 39, NO. 10
NUMBER __
the QRS) in one of eight individuals with plasma nortriptyline levels less than 200 mg/mL.’ These data suggested that, at usual therapeutic concentrations, nortriptyline was unlikely to cause any change in intraventricular conduction in individuals free of pre-existing heart disease. Glassman suggested that, at therapeutic concentrations, the only depressed patients in danger of block are those with pre-existing conduction defects that involve the His Purkinje ~ y s t e m . ~ Our review of the literature failed to reveal the development of a left bundle branch block in a depressed individual who was free of underlying conduction disorders of the heart and had a subtherapeutic level of nortriptyline. Therefore, this case may increase concern about the possibility of bundle branch block and encourage physicians to perform an ECG soon after beginning an antidepressant.
DATE
I
5/5/90
I1
5/11/90
111
6/5/90
IV
6/11/90
1007
REFERENCES
V
6/25/90
VI
6/27/90
I
I
I
‘W~-~-~wwllv
I
I
r
! I
+,
FIGURE 1. Rhythm strips from patient under discussion.
Freyschuss et a15 and Ziegler et a16 demonstrated that increases in the P-R or QRS intervals were unlikely to be seen. Using His bundle studies, Vohra demonstrated increased H-V intervals (correlating with increases in
1. Jenike MA. Affective Disorders. In Jenike MA, ed. Geriatric Psychiatry and Psychopharmacology. Chicago: Year Book Medical Publishers, Inc., 1989. 2. Kantor SJ, Glassman AG, Bigger JTJ et al. The cardiac effects of therapeutic concentrations of imipramine. Am J Psychiatry 1978;135:534-538. 3. Glassman AH. Cardiovascular effects of tricyclic antidepressants. Ann Rev Med 1984;365:503-511. 4. Vohra J, Burrows GD, Sloman G. Assessment of cardiovascular side effects of therapeutic doses of tricyclic anti-depressant drugs. Aust N Z J Med 1975;5:7-11. 5. Freyschuss U, Sjoqvist F, Tuck D, Asberg M. Circulatory effects in man of nortriptyline, a tricyclic anti-depressant drug. Pharrnacol Clin 1970;2:68-71. 6. Ziegler VE, Co BT, Biggs JT. Plasma nortriptyline levels and ECG findings. Am J Psychiatry 1977;134:441-443. 7. Vohra J, Burrows G, Hunt D, Slornan G. The effect of toxic and therapeutic doses of tricyclic anti-depressant drugs on intracardiac conduction. Eur J Cardiol 1975;3(3):219-227.
