Long-Term ECG Changes in Depressed Elderly Patients Treated With Nortriptyline: A Double-Blind, Randomized, Placebo-Controlled Evaluation

doi:10.1097/00019442-199802000-00008

The American Journal of Geriatric Psychiatry

Volume 6, Issue 1, Winter 1998, Pages 59-66

https://doi.org/10.1097/00019442-199802000-00008 Get rights and content

ECGs of 50 patients who completed a long-term nortriptyline (NT) study are presented at baseline, after 7 weeks on NT, and after 1 year. The ECGs of patients with preexisting cardiac disease were compared with non-cardiac patients. Significant ECG changes and increases in heart rate were observed by Week 7 and persisted at a mean of 55 weeks (range: 24–111) in patients who were continued on NT. No significant difference was found in long-term ECG effects in patients with preexisting cardiac disease; ECG changes reverted to baseline when placebo was substituted. Patients with known cardiac disease did not show significantly worse ECG changes on NT than non-cardiac patients.

Section snippets

METHODS

The study group consisted of patients admitted to a study of maintenance therapies in late-life depression. Eligibility for this project required 1) current age, ≥60; 2) a diagnosis of recurrent major depression as determined by Research Diagnostic Criteria (RDC);¹² and 3) Hamilton Rating Scale for Depression (Ham-D; 17-item)¹³ score ≥17. Patients were excluded if they had a Mini-Mental State Examination (MMSE)¹⁴ score <27, a past history of mania or psychosis, or a medical problem that either

RESULTS

A total of 619 potential patients were screened for enrollment in the study, 43 of which were excluded because of serious medical problems. At the time of this analysis, 119 subjects had entered the study. Fifty patients had completed at least 1 year of the protocol at the time of this analysis. Complete ECG data were available in 48 subjects. Sixty-nine other patients were excluded from the study. Table 1 and Table 2 compare the ECGs in the included and excluded groups. There were no

DISCUSSION

The data obtained from our elderly depressed patients is consistent with previous studies that have shown increases in P–R interval, QRS duration, and Q–T interval in patients treated with TCAs.2, 5, 6, 10, 11 None of the patients who entered long-term maintenance treatment showed changes in cardiac conduction or rhythmicity likely to be of clinical significance, despite maintenance of NT levels within a range of 80–120 ng/ml. The intracardiac conduction delays were reversed in those patients

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Cited by (4)

Cardiovascular changes associated with venlafaxine in the treatment of late-life depression
2006, American Journal of Geriatric Psychiatry
Citation Excerpt :
A 12-lead electrocardiogram (EKG) was obtained while the patient was reclining at baseline and after 12 weeks of treatment (or at termination for participants who did not complete the protocol). QTc interval was calculated using the Bazett correction (QT interval divided by the square root of 60/heart rate).18 For patients who discontinued study medication before completing 12 weeks of acute treatment, the reasons for dropping out were determined and classified according to established rules.
Potential cardiovascular side effects from venlafaxine-XR must be considered when prescribing this medication, especially in geriatric patients, who often present with comorbid medical conditions.
Participants age 60 and older with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of a major depressive episode without psychotic features were treated openly with venlafaxine-XR for 12 weeks during which venlafaxine-XR was titrated based on tolerability and response according to predefined guidelines. Sitting and standing blood pressures and heart rates were measured. A 12-lead electrocardiogram was obtained at baseline and at week 12.
Sixty-two participants started treatment; 59 completed at least two weeks of the 12-week study. The mean final dose of venlafaxine-XR was 195.5 mg/day (standard deviation: 72.2). Twenty-four percent (95% confidence interval [CI]: 7.3%–40.7%) of initially normotensive participants and 54% (95% CI: 34.3%–74%) of those with preexisting hypertension experienced an increase in blood pressure. Twenty-nine percent (95% CI: 14.6%–43.4%) of participants developed orthostatic hypotension. Two participants experienced a clinically significant increase in QTc interval. One participant reported new-onset mild dizziness, whereas four participants reported new-onset tachycardia or palpitation. Overall, 17 unique participants (28.8%; 95% CI: 17.3%–40.4%) experienced a new-onset cardiovascular problem, potentially related to the study medication.
Overall, venlafaxine-XR was well tolerated. However, similar to previous reports, venlafaxine-XR was associated with some undesirable cardiovascular effects in some of the participants. Systematic monitoring of cardiovascular parameters during treatment with venlafaxine-XR should be strongly recommended, especially in the elderly.
Drug and ECT treatment of depression in the elderly, 1996-2001: A literature review
2002, Biological Psychiatry
A computer-based literature search of all antidepressant and electroconvulsive therapy (ECT) treatment studies published between 1995 and September 2001 was conducted. In addition, a review of published chapters, review articles, and metaanalyses was also conducted. Articles were categorized into those reporting comparative studies, those in which the therapeutic agent was not compared with another, articles about ECT, and review articles. These recent publications support the conclusions from prior reviews that antidepressants and ECT are effective and safe treatments for depressed elderly patients. Differences in efficacy and side effects appear to be slight among the various types of antidepressants. Research studies of depressed elderly increased markedly since 1995 compared with all previous years although more studies are still necessary.
Pharmacological Interventions in Older Adults
2019, Primary Care Mental Health in Older People: A Global Perspective
Safety of antidepressants in the elderly
2003, Expert Opinion on Drug Safety

The authors thank the staff of the Late-Life Depression Clinic for their clinical care of the patients included in this paper and Donna Ulrich for her administrative assistance.

This work was supported by NIMH grants MH52247, MH43832, MH37869, and MH00295.

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Regular ArticlesLong-Term ECG Changes in Depressed Elderly Patients Treated With Nortriptyline: A Double-Blind, Randomized, Placebo-Controlled Evaluation

Section snippets

METHODS

RESULTS

DISCUSSION

Am J Geriatr Psychiatry

J Psychiatr Res

Am J Geriatr Psychiatry

Am Heart J

Am Heart J

J Electrocardiol

Cardiac complications of tricyclic antidepressant therapy

Ann Intern Med

Major adverse reactions during desipramine treatment: relationships to plasma drug concentrations, concomitant antipsychotic treatment, and patient characteristics

Arch Gen Psychiatry

Antidepressant side effects: issues and options

J Clin Psych

Cardiovascular effects of therapeutic doses of tricyclic antidepressants: a review

Arch Gen Psychiatry

Regular Articles
Long-Term ECG Changes in Depressed Elderly Patients Treated With Nortriptyline: A Double-Blind, Randomized, Placebo-Controlled Evaluation