Comparison of paroxetine and nortriptyline in depressed patients with ischemic heart disease.
BACKGROUND
Depression and ischemic heart disease often are comorbid conditions and, in patients who have had a myocardial infarction, the presence of depression is associated with increased mortality. Patients with heart disease need a safe and effective treatment for depression.


OBJECTIVE
To compare the efficacy, cardiovascular effects, and safety of a specific serotonin reuptake inhibitor, paroxetine, with a tricyclic antidepressant, nortriptyline hydrochloride, in depressed patients with ischemic heart disease.


METHODS
Two-week placebo lead-in followed by a double-blind randomized 6-week medication trial.


METHODS
Research clinics in 4 university centers.


METHODS
Eighty-one outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder and with documented ischemic heart disease.


METHODS
Treatment with either paroxetine, 20 to 30 mg/d, or nortriptyline targeted to a therapeutic plasma level, 190 to 570 nmol/L (50-150 ng/mL), for 6 weeks.


METHODS
For effectiveness of treatment, a decline in the score of the Hamilton Rating Scale for Depression by 50% and final score of 8 or less; for cardiovascular safety, heart rate and rhythm, supine and standing systolic and diastolic blood pressures, electrocardiogram conduction intervals, indexes of heart rate variability, and rate of adverse events.


RESULTS
By intent-to-treat analysis, 25 (61%) of 41 patients improved during treatment with paroxetine and 22 (55%) of 40 improved with nortriptyline. Neither drug significantly affected blood pressure or conduction intervals. Paroxetine had no sustained effects on heart rate or rhythm or indexes of heart rate variability, whereas patients treated with nortriptyline had a sustained 11% increase in heart rate from a mean of 75 to 83 beats per minute (P<.001) and a reduction in heart rate variability, as measured by the SD of all normal R-R intervals over a 24-hour period, from 112 to 96 (P<.01). Adverse cardiac events occurred in 1 (2%) of 41 patients treated with paroxetine and 7 (18%) of 40 patients treated with nortriptyline (P<.03).


CONCLUSIONS
Paroxetine and nortriptyline are effective treatments for depressed patients with ischemic heart disease. Nortriptyline treatment was associated with a significantly higher rate of serious adverse cardiac events compared with paroxetine.
Roose
S P
SP
Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. spr2@columbia.edu
Laghrissi-Thode
F
F
Kennedy
J S
JS
Nelson
J C
JC
Bigger
J T
JT
Pollock
B G
BG
Gaffney
A
A
Narayan
M
M
Finkel
M S
MS
McCafferty
J
J
Gergel
I
I
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006334:Heart Function Tests; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications*; D009661:Nortriptyline / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017374:Paroxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D018759:Adrenergic Uptake Inhibitors; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D009661:Nortriptyline; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors