Robert E. McCue

Comparative Efficacy and Safety of MAOIs versus TCAs in Treating Depression in the Elderly

This comprehensive study investigated both the role of antidepressant drugs in the treatment of affective disorders of later life and their safety with careful clinical and pharmacological monitoring. A 7-week double-blind comparison was made of the efficacy and safety of nortriptyline (a tricyclic), phenelzine (a monoamine oxidase inhibitor), and placebo. The results indicated a response rate of approximately 60% for both nortriptyline and phenelzine versus a 13% response rate for placebo. Anticholinergic side effects were more frequently reported in the nortriptyline group. Orthostatic symptoms were reported with similar frequency in both drug groups. Overall, both drugs were well tolerated.

Factors affecting the delay of antidepressant effect in responders to nortriptyline and phenelzine

Seventy-six elderly depressed patients who had responded to either nortriptyline or phenelzine after a trial of up to 3 months were examined. The mean week of response was nearly 6 weeks. Patients who were more severely depressed took longer to respond. Patients with endogenous depression responded sooner on nortriptyline than did patients with nonendogenous depression. For patients on nortriptyline, lower plasma levels in the early weeks of treatment may delay response while differences in platelet monoamine oxidase inhibition in the early weeks of treatment do not appear to affect week of response for patients on phenelzine.

Clinical predictors of response to antidepressants in elderly patients.

A group of 42 patients, ages 55 and above, suffering from major depression were examined in an attempt to isolate clinical variables that would predict response to antidepressants. These patients were part of a placebo-controlled, double-blind study and were given either nortriptyline or phenelzine for 5-7 weeks. There was no significant difference in response rates between patients subclassified as endogenous or nonendogenous by either RDC or Newcastle criteria. No difference in response rates was found between the DSM-III melancholic and nonmelancholic subtypes. Neither drug preferentially treated a subtype. None of the 21 variables representing symptoms, demographic traits, or characteristics of the depressive illness were found to be significant predictors of antidepressant response.

The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients.

Seventy-eight nondemented elderly depressed patients underwent an extensive battery of cognitive tests both before and after seven weeks of treatment with nortriptyline, phenelzine, or placebo. Clinical and cognitive evaluations of the patients were under double-blind conditions. Response to treatment did not appear to significantly affect cognitive capacity; neither did treatment with an active substance as compared to placebo. In addition, the baseline level of cognitive functioning did not appear related to whether a patient responded to treatment. The authors conclude that under optimal conditions neither antidepressant produces measurable changes in the cognitive capacity of nondemented elderly patients.

Clinical and treatment effects on 3H-clonidine and 3H-imipramine binding in elderly depressed patients.

3H-clonidine and 3H-imipramine binding were measured in depressed patients, 55 years and older. There was no significant difference in either 3H-clonidine or 3H-imipramine binding between depressed patients and age- and sex-matched controls. There was no significant correlation between 3H-clonidine or 3H-imipramine binding and severity of depression before treatment. There was a significant negative correlation between the KD of 3H-imipramine binding sites and Hamilton score over seven weeks of antidepressant treatment. There was no significant difference between receptor data of responders and nonresponders to antidepressant treatment.

Relapse of depressed patients after effective continuation therapy.

Forty-one elderly depressed patients who had responded to either nortriptyline or phenelzine were given continuation treatment for approximately 4 months (mean = 16.5 weeks) after which 19 were switched under double-blind conditions to placebo. At the end of 8 weeks, three (15.8%) of the placebo patients had relapsed and three (13.6%) of the patients kept on antidepressants had relapsed. Patients who had more prior episodes of depression had a greater risk of relapsing. The implications of these findings for continuation pharmacologic treatment in the elderly depressed are discussed.

Relationship of platelet MAO activity to characteristics of major depressive illness

Sixty-seven patients (greater than or equal to 55 years of age) with major depressive disorder had pretreatment assays of platelet monoamine oxidase (MAO) activity. As in previous studies, women had higher MAO activity than men, and MAO activity was positively correlated with age. Patients with melancholia (DSM-III) had significantly higher MAO activity than those without melancholia. This finding may reflect the higher MAO activity associated with the symptoms of anhedonia and mood autonomy. Anxiety also was correlated with higher MAO activity, as was a positive family history of depression. In addition, postdexamethasone cortisol levels were correlated with platelet MAO activity.

A placebo-controlled comparison of the effect of nortriptyline and phenelzine on orthostatic hypotension in elderly depressed patients.

Seventy-five patients, 55 years or older, were treated for major depression with either nortriptyline, phenelzine, or placebo during a 7-week period. There was a significantly greater mean orthostatic fall in systolic pressure in patients treated with nortriptyline and phenelzine as compared to the placebo group, but no significant difference was evident between the nortriptyline and phenelzine groups. The orthostatic changes appeared during the first week of treatment and were not correlated with plasma level of nortriptyline, percent platelet monoamine oxidase inhibition, or pretreatment orthostatic changes.

The usefulness of DST in predicting response to antidepressants: A placebo-controlled study

Seventy-two out-patients, 55 years or older, suffering from major depression were treated with either nortriptyline or phenelzine for seven weeks under placebo-controlled double-blind conditions. The dexamethasone suppression test (DST) was administered at baseline and at weeks 3 and 7 of treatment, and its usefulness in predicting and/or paralleling clinical response was examined. No correlation was found between baseline DST results and treatment response with antidepressants. Of 13 patients whose abnormal baseline DSTs normalized during treatment, six were responders and seven were nonresponders (P = 0.24). However, all (seven) patients whose DSTs persisted to be abnormal throughout the seven weeks did not respond. The authors conclude that the DST has not been shown to have practical value as an indicator of impending recovery from major depression in the elderly, but its failure to normalize may have ominous prognostic significance.

Plasma levels of nortriptyline and 10-hydroxynortriptyline and treatment-related electrocardiographic changes in the elderly depressed

Thirty-one elderly depressed patients were treated for seven weeks with nortriptyline with plasma levels kept between 50-180 ng/ml. Electrocardiograms were taken at the third and seventh weeks of treatment. There were significant increases in the PR interval, QTc interval, and heart rate from before and after treatment. However, there were no consistent correlations between electrocardiographic changes during treatment and plasma levels of nortriptyline, 10-hydroxynortriptyline and either of its two isomers (E-10-hydroxynortriptyline, Z-10-hydroxynortriptyline). Increased QRS duration after seven weeks of treatment was correlated with daily dose of nortriptyline.