Correspondence
Imipramine in Patients with Chest Pain Despite Normal Coronary Angiograms
N Engl J Med 1994; 331:882-883September 29, 1994
- Article
To the Editor:
Cannon et al. (May 19 issue)1 stated that the frequency of chest pain in response to the antidepressant imipramine did not depend on the presence of a previous psychiatric diagnosis or on the change in the psychiatric profile during the course of the study.
Seventeen patients (28 percent) had a history of major depression, only six of whom were randomly assigned to imipramine. Only three patients (one in the imipramine group) had major depression at base line. With such small numbers, it is clear that the study would not be able to compare patients with and those without major depression.
Many patients with symptoms of depression do not fulfill the criteria for major depression outlined in the Diagnostic and Statistical Manual of Mental Disorders (third edition, revised)2. In this study, there does not appear to be any overall measure of the wide range of depressive symptoms that could be present. The absence of a responsive, valid measure for depression means that smaller, but still clinically significant, effects of imipramine on depression will be missed.
It it clear that an increased pain threshold from a reduction in psychological depression cannot be excluded as the cause of improved chest pain in these patients with normal coronary angiograms.
2 ReferencesDavid L. Hare, M.B., B.S.
Austin Hospital, Melbourne 3084, Australia1
Cannon RO III ,Quyyumi AA ,Mincemoyer R , et al. Imipramine in patients with chest pain despite normal coronary angiograms. N Engl J Med 1994;330:1411-1417
Full Text | Web of Science | Medline2
Diagnostic and statistical manual of mental disorders, 3rd ed. rev.: DSM-III-R. Washington, D.C.: American Psychiatric Association, 1987.
To the Editor:
Cannon and colleagues report that imipramine reduces the frequency of chest pain in patients with normal coronary arteries. Before physicians use this drug in practice, several measures of clinical efficacy need further review. Did the authors investigate (during their two-year follow-up of patients) whether imipramine therapy decreased emergency room visits and hospital admissions for chest pain among the study population, affected the subsequent need for expensive testing, eliminated chest-pain symptoms completely in any patient, increased patients' satisfaction with their care and quality of life, or improved the productivity of the study patients? Questions such as these must be answered in assessing any treatment of patients with this syndrome; many are acknowledged in the introduction to the article. If they have not been addressed, what is the basis for the authors' conclusion that “this drug may have wide applicability in the management of chest pain in patients with normal coronary angiograms”?
Donald J. Venes, M.D.
P.O. Box 8277, Portland, OR 97207-8277Author/Editor Response
Dr. Cannon replies:
To the Editor: Dr. Hare points out that of the 20 patients randomly assigned to imipramine therapy in our study, only 6 fulfilled the criteria for past major depression outlined in the Diagnostic and Statistical Manual of Mental Disorders (third edition, revised),1 and only 1 had evidence of current major depression. He also suggests that not all patients with depression may be identified by such criteria. Thus, he questions whether our conclusion that imipramine was beneficial irrespective of the presence or absence of psychiatric morbidity (e.g., depression) is tenable. Although it is possible that not all patients with depression were identified in our study, the benefit of imipramine was achieved at a dose of 50 mg daily -- a dose substantially lower than that commonly used to treat depression. Furthermore, our results are consistent with those of other randomized, placebo-controlled studies using tricyclic antidepressant agents in chronic pain syndromes, in which benefit was demonstrable irrespective of evidence of depression at base line2-5. Of interest, Max et al. reported that the serotonin-specific antidepressant fluoxetine was ineffective in relieving pain in patients with diabetic neuropathy, in contrast to the benefit afforded by the use of the tricyclic agents desipramine and amitriptyline5. Taken together, the data suggest that the analgesic effects of tricyclic antidepressants may be independent of their antidepressant effects.
Dr. Venes asks about the clinical efficacy of imipramine over time. We reported that 73 percent of the patients who were taking imipramine at hospital discharge and who could be contacted subsequently were still taking the drug at an average follow-up of 21 months. At the present time, with up to 46 months of follow-up, 38 of 55 patients who could be contacted are still taking imipramine. None of these patients has used emergency room facilities or has been hospitalized because of chest pain. To date, we have brought 17 patients back for outpatient visits, discontinuing imipramine for one month in all cases. Sixteen have asked to resume imipramine therapy because of the recurrence of chest-pain symptoms. We do not have an instrument for objectively assessing the quality of life during the follow-up period. However, we believe that our conclusion was appropriately worded and is supported by the data and our follow-up experience. Wider experience with drugs useful in the management of chronic pain syndromes in patients with chest pain despite normal coronary angiograms will be the ultimate judge of our study.
5 ReferencesRichard O. Cannon, III, M.D.
National Institutes of Health, Bethesda, MD 208921
Diagnostic and statistical manual of mental disorders, 3rd ed. rev.: DSM-III-R. Washington, D.C.: American Psychiatric Association, 1987.
2
Watson CP ,Evans RJ ,Reek K ,Merskey H ,Goldsmith L ,Warsh J . Amitriptyline versus placebo in postherpetic neuralgia. Neurology 1982;32:671-673
Web of Science | Medline3
Max MB ,Culnane M ,Schafer SC , et al. Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology 1987;37:589-596
Web of Science | Medline4
Max MB ,Schafer SC ,Culnane M ,Smoller B ,Dubner R ,Gracely RH . Amitriptyline, but not lorazepam, relieves postherpetic neuralgia. Neurology 1988;38:1427-1432
Web of Science | Medline5
Max MB ,Lynch SA ,Muir J ,Shoaf SE ,Smoller B ,Dubner R . Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. N Engl J Med 1992;326:1250-1256
Full Text | Web of Science | Medline
