Imipramine in Patients with Chest Pain Despite Normal Coronary Angiograms
Richard O. Cannon, Arshed A. Quyyumi, Rita Mincemoyer, Annette M. Stine, Richard H. Gracely, Wendy B. Smith, Marilla F. Geraci, Bruce C. Black, Thomas W. Uhde, Myron A. Waclawiw, Kathleen Maher, and Stanley B. Benjamin
Background Ten to 30 percent of patients undergoing cardiaccatheterization because of chest pain are found to have normalcoronary angiograms. Because these patients may have a visceralpain syndrome unrelated to myocardial ischemia, we investigatedwhether drugs that are useful in chronic pain syndromes mightalso be beneficial in such patients.
Methods Sixty consecutive patients underwent cardiac, esophageal,psychiatric, and pain-sensitivity testing and then participatedin a randomized, double-blind, placebo-controlled three-weektrial of clonidine at a dose of 0.1 mg twice daily (20 patients),imipramine at a dose of 50 mg nightly with a morning placebo(20 patients), or placebo twice daily (20 patients); this treatmentphase was compared with an identical period of twice-daily placebofor all patients (placebo phase).
Results Thirteen (22 percent) of the 60 patients had ischemic-appearingelectrocardiographic responses to exercise, 22 of the 54 tested(41 percent) had abnormal esophageal motility, 38 of 60 (63percent) had one or more psychiatric disorders, and 52 of 60(87 percent) had their characteristic chest pain provoked byright ventricular electrical stimulation or intracoronary infusionof adenosine. During the treatment phase, the imipramine grouphad a mean (±SD) reduction of 52 ±25 percent inepisodes of chest pain, the clonidine group had a reductionof 39 ±51 percent, and the placebo group a reductionof 1 ±86 percent, all as compared with the placebo phaseof the trial. Only the improvement with imipramine was statisticallysignificant (P = 0.03). Repeat assessment of sensitivity tocardiac pain while the patients were receiving treatment showedsignificant improvement only in the imipramine group (P = 0.01).The response to imipramine did not depend on the results ofcardiac, esophageal, or psychiatric testing at base line, oron the change in the psychiatric profile during the course ofthe study, which generally improved in all three study groups.
Conclusions Imipramine improved the symptoms of patients withchest pain and normal coronary angiograms, possibly througha visceral analgesic effect.
Source Information
From the Cardiology Branch (R.O.C., A.A.Q., R.M., A.M.S.) and the Biostatistics Research Branch (M.A.W.), National Heart, Lung, and Blood Institute; the Neurobiology and Anesthesiology Branch, National Institute of Dental Research (R.H.G, W.B.S.); and the Section on Anxiety and Affective Disorders, National Institute of Mental Health (M.F.G., B.C.B., T.W.U.) -- all at the National Institutes of Health, Bethesda, Md.; and the Division of Gastroenterology, Georgetown University Hospital, Washington, D.C. (K.M., S.B.B.). Presented in part at the 57th Scientific Meeting, American College of Gastroenterology, Miami Beach, Fla., October 26, 1992, and at the 42nd Scientific Session, American College of Cardiology, Anaheim, Calif., March 18, 1993.
Address reprint requests to Dr. Cannon at Bldg. 10, Rm. 7B-15, National Institutes of Health, Bethesda, MD 20892.
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