Personality in recovered depressed elderly.

Personality traits in euthymic elderly subjects with and without past histories of major depressive episodes were assessed using the Structured Clinical Interview for DSM-III-R and the Social Adjustment Scale-SR. Recovered depressed subjects were characterized by significantly more personality traits from DSM-III-R Clusters B and C than controls, and they exhibited differences in social adjustment, as well. Subjects who have recovered from depressive episodes may show significant differences in personality and social adjustment that might represent residua of past depression, a trait characteristic, or a risk factor for recurrence.

A pilot study of low-dose L-deprenyl in Alzheimer's disease.

The use of low-dose L-deprenyl, a selective MAO-B inhibitor, in Alzheimer's disease patients has been associated previously with improvements in agitation and episodic learning and memory. Behavioral, cognitive, and regional electroencephalogram (EEG) measures were obtained in a 4-week open pilot study of 14 patients with probable Alzheimer's disease by NINCDS criteria who were administered 10 mg L-deprenyl per day. L-Deprenyl administration was associated with significant improvements on the agitation and depression factors of the Brief Psychiatric Rating Scale, the Cornell Scale for Depression in Dementia, and spouses' blind ratings. Recall improved on the Buschke Selective Reminding Task, but intrusions also tended to increase; verbal fluency decreased. Absolute EEG delta measures were selectively suppressed in the right frontal region. The pattern of changes suggests that L-deprenyl may be associated with improvement in behavioral and cognitive performance, in part through a mild behavioral disinhibiting effect.

Do blood pressure and age predict response to tacrine (THA) in Alzheimer's disease? A preliminary report.

Recent studies in major depression suggest that a pretreatment systolic orthostatic blood pressure (PSOP) fall of greater than or equal to 10 mm Hg in response to changing from a supine to a standing position may predict response to antidepressant treatment in older depressed patients. Because orthostatic blood pressure response is regulated, in part, by central cholinergic and noradrenergic systems, and both are implicated in Alzheimer's disease, PSOP was assessed as a predictor of initial response in Alzheimer's disease outpatients in a treatment protocol with tacrine, a cholinesterase inhibitor. We found that the magnitude of PSOP fall and increasing age each contributed to the prediction of response to tacrine. These results may suggest a relatively greater involvement of other neurotransmitter systems in younger, nonresponding Alzheimer's disease patients, and the results differ from those of a previous study.

Relationship of hydroxynortriptyline to nortriptyline concentration and creatinine clearance in depressed elderly outpatients.

Plasma concentration of E-10-hydroxynortriptyline is increased in the elderly and may be related to both renal clearance of hydroxynortriptyline and rate of liver hydroxylation of nortriptyline. In 25 ambulatory, depressed elderly outpatients treated with therapeutic doses of nortriptyline, relationships among plasma levels of nortriptyline and E-10-hydroxynortriptyline, and an estimate of creatinine clearance were examined. Plasma levels of E-10-hydroxynortriptyline (corrected for varying dosage) were significantly correlated with age and inversely correlated (r = -0.50) with creatinine clearance but not with notriptyline or Z-10-hydroxynortriptyline concentration. E-10-hydroxynortriptyline concentration was about 5 1/2 times that of Z-10-hydroxynortriptyline. By best subsets multiple regression analyses, the ratio of E-10-hydroxynortriptyline to nortriptyline level was best predicted by plasma nortriptyline concentration, creatinine clearance, and age, all of which accounted for 63% of the variance. These results corroborate and extend previous findings in elderly inpatients in whom creatinine clearance was measured directly. In addition, age had an effect on E-10-hydroxynortriptyline independently of creatinine clearance. Since E-10-hydroxynortriptyline concentration has been related to both therapeutic efficacy and toxicity during nortriptyline treatment, it may be important to assess nortriptyline hydroxymetabolites in elderly patients and in those with renal insufficiency.

Visual evoked potentials in dementia: a meta-analysis and empirical study of Alzheimer's disease patients.

A meta-analytic review of flash and pattern reversal visual evoked potential research indicates that elderly demented patients have longer P100 latencies than age-matched control subjects. In the present empirical research, patients with research diagnoses of probable Alzheimer's disease were compared with sex- and age-matched control subjects using P100 latencies of visual evoked potentials (VEP) elicited by flash and pattern reversal. As compared to control subjects, Alzheimer's disease patients showed significantly longer P100 latencies of the VEP elicited by pattern reversal; the flash P100 only marginally distinguished them. These findings are discussed within the context of VEP recording practices, patient selection, sex and age matching of control subjects, and the visual system.

Electrocardiographic changes with nortriptyline and 10-hydroxynortriptyline in elderly depressed outpatients.

Pharmacokinetic factors may contribute to altered nortriptyline effects in the elderly. Plasma concentrations of nortriptyline's principal metabolite, E-10-hydroxynortriptyline, tend to be greater than nortriptyline, increase with age, and may contribute to cardiotoxicity. Electrocardiogram changes were evaluated in 21 ambulatory, elderly, depressed outpatients who were treated with therapeutic doses of nortriptyline. Resting electrocardiograms were obtained before and after 6 weeks of treatment. Plasma samples were assayed simultaneously for nortriptyline, E-, and Z-10-hydroxynortriptyline. Three subjects developed a first degree atrioventricular block and one developed a right bundle branch block during treatment. Mean daily nortriptyline dose and steady state plasma level in these subjects did not differ from those who did not develop conduction defects, but E-10-hydroxynortriptyline levels were significantly higher. Overall, there were significant correlations between changes in the PR interval and QRS duration with plasma concentrations of nortriptyline, E-10-hydroxynortriptyline, Z-10-hydroxynortriptyline, and the sum of nortriptyline and its 10-hydroxynortriptyline metabolites. Multiple regression analyses suggested that increases in PR interval were associated with increasing nortriptyline concentration, while increases in QRS duration and Q-Tc intervals were associated with increasing Z-10-hydroxynortriptyline concentration. E- and Z-10-hydroxynortriptyline may contribute substantially to the cardiac conduction effects of nortriptyline treatment and may be of particular importance in the elderly.

Platelet tritiated imipramine binding and MAO activity in Alzheimer's disease patients with agitation and delusions.

Decreased platelet 3H-imipramine binding density and decreased monoamine oxidase (MAO) activity have been considered as biological characteristics of several neuropsychiatric disorders, and may be related to central serotonin defects. Since serotonin system defects occur in Alzheimer's disease (AD), and decreased brain 3H-imipramine binding density, and increased brain and platelet MAO activity are reported also, we studied platelet 3H-imipramine binding density (Bmax) and platelet MAO activity in AD outpatients without antecedent psychiatric disorder. AD subjects with significant symptomatic behavioral disorder, predominantly agitation and delusions, and AD subjects without symptomatic behaviors were compared with controls. Age, sex, mini-mental state examination score, and illness duration did not distinguish the two AD groups. The agitated/delusional group showed significantly lower Bmax values than uncomplicated AD subjects or controls. MAO activity was significantly increased among female AD subjects without symptomatic behaviors compared to those who were agitated or to controls. These results indicate that 3H-imipramine binding and MAO activity may distinguish AD subjects with agitation or delusions from those without symptomatic behaviors, and suggest the existence of a biologically based Alzheimer's behavioral subtype.

Decreased platelet 3H-imipramine binding in primary major depression compared with depression secondary to medical illness in elderly outpatients.

Platelet 3H-imipramine binding and monoamine oxidase (MAO) activity were investigated in elderly outpatients with primary major depression, and in a group with depression secondary to medical illness (organic mood disorder, depressed by DSM-III-R criteria) in a multidisciplinary geriatric clinic. The density of the binding of 3H-imipramine (Bmax) was decreased significantly in subjects with major depression compared to subjects with secondary depression, and to controls. There was no difference in Bmax values between subjects with secondary depression and controls. MAO activity was increased in the group with secondary depression, but not in the group with primary major depression. These results provide preliminary evidence for the relative specificity of platelet 3H-imipramine binding as a marker for primary major depressive disorder compared to secondary depression in medically ill elderly people, supports the concept of biological heterogeneity in secondary depression, and extends the findings of decreased Bmax values in two previous studies in non-medically ill depressed elderly patients.

Prediction of individual dosage of nortriptyline in depressed elderly outpatients.

Individual daily dosages of nortriptyline (NT) can be predicted from administration of a 50-mg or 100-mg single test dose, with a determination of the plasma level 24 hours later. Because the 50-mg or 100-mg test dose used in previous studies may cause unmanageable acute side effects in elderly patients, a 25-mg NT test dose was used to establish a 24-hour plasma level in 18 physically healthy, moderately depressed, geriatric outpatients. Correlations between the 24-hour test dose plasma level and steady state levels were done for maintenance dosages of 50, 75, and 100 mg/day. A nomogram was made from the regression equations to predict the dosage required to achieve a steady state concentration within a 50 to 150 ng/ml range. The importance of the ability to predict NT dosage requirements in geriatric patients is indicated by findings that at daily NT doses of 50 and 100 mg, nearly one-half of subjects had steady state levels below or above 50 or 150 ng/ml, respectively.

Platelet monoamine oxidase activity in elderly depressed outpatients.

Platelet monoamine oxidase (MAO) activity was assayed in 42 unmedicated, elderly, RDC depressed, unipolar outpatients over 60 years of age, 17 nondepressed controls, and 17 younger volunteers without psychiatric illness. Elderly depressed women (n = 22) had significantly higher MAO activity than sex- and age-comparable controls. No significant relationships between MAO activity and duration of current depressive episode, duration of illness, or family history of affective disorder were obtained. These results extend to elderly female outpatients the finding that depression is associated with increased platelet MAO activity, exceeding the normal age-related increase.

3H-imipramine binding in depressed elderly: relationship to family history and clinical response.

Platelet 3H-imipramine binding (Bmax) was determined in 34 elderly (mean age 64.8) unipolar depressed outpatients who were being treated with either nortriptyline or interpersonal psychotherapy for 10 to 16 weeks, and in nondepressed elderly controls. Bmax values were decreased in the depressed group. In addition, Bmax values were depressed further in subjects with a history of depression in first degree relatives. Good clinical response with either nortriptyline or psychotherapy was associated with lower Bmax compared to those subjects who had a poorer response to treatment. Treatment nonresponders and those with a negative family history of depression had Bmax values that were somewhat decreased but not significantly different from controls. This study extends to the elderly the potential applicability of platelet 3H-imipramine binding as a marker of depressive illness, and proposes a predictor for treatment response in elderly unipolar depressed patients.

Pretreatment orthostatic hypotension as a predictor of response to nortriptyline in geriatric depression.

The consequences of orthostatic hypotension, a serious and common problem among the elderly, are falls, transient ischemic attacks, strokes, and myocardial infarctions. Depressed elderly taking tricyclic antidepressants (TCAs) are at increased risk, and the pretreatment presence of orthostatic hypotension is considered a relative contraindication to TCA treatment. Recently, it was reported that the presence of pretreatment orthostatic hypotension in geriatric outpatients with unipolar depression predicted good clinical response to imipramine or doxepin. We investigated the predictive value of pretreatment systolic orthostatic pressure changes (PSOP) in unipolar depressed elderly outpatients (mean age, 64) who were to receive a 16-week course of nortriptyline or interpersonal psychotherapy. Overall, PSOP was significantly correlated with improvement on both the Beck Depression Inventory and the Hamilton Depression Rating Scale. Although both groups responded equally to treatment, PSOP was more strongly correlated with improvement on the Beck Depression Inventory (r = 0.74, p less than 0.01) in the nortriptyline-treated group than in the group treated with interpersonal therapy (r = 0.31, not significant). The nortriptyline-treated subjects with a PSOP of greater than or equal to 10 mm Hg had a greater improvement than those with a PSOP of less than 10 mm HG (t = -2.36, p less than 0.05). No episodes of symptomatic orthostatic hypotension occurred in the nortriptyline-treated subjects. The results suggest that orthostatic hypotension, a relative contraindication to TCA use, may potentially identify patients more likely to respond to TCAs.

Tranylcypromine vs nortriptyline vs placebo in depressed outpatients: a controlled trial.

This study was designed to compare the therapeutic and adverse effects of tranylcypromine (a monoamine oxidase inhibitor), nortriptyline (a tricyclic antidepressant), and placebo. A total of 122 depressed outpatients randomly assigned to double-blind treatment with one of these agents completed the 4-week protocol. Treatment groups were balanced for proportions of endogenous versus nonendogenous depressions, defined according to the Research Diagnostic Criteria; however, nonendogenous depressions outnumbered endogenous depressions by such a large proportion (4:1) that meaningful statistical comparisons were limited to the nonendogenous group. In this group, both active drugs proved more effective than placebo, with little differences between the two active drugs except in the areas of side effects and of differential sensitivity of the outcome scales to a given drug. It was concluded that tranylcypromine, a drug which has received relatively little use and study in recent years, represents an effective and reasonably safe treatment for nonendogenous depression, although significant advantages over tricyclics with this disorder remain to be demonstrated.

The safety and efficacy of combined amitriptyline and tranylcypromine antidepressant treatment. A controlled trial.

Sixty patients meeting DSM-III criteria for major depression were assigned randomly to double-blind treatment for four weeks according to fixed-dosage steps with (1) amitriptyline hydrochloride alone, up to a maximum dosage of 300 mg/day; (2) tranylcypromine alone, up to 40 mg/day; or (3) the combination of amitriptyline hydrochloride, up to 150 mg/day, and tranylcypromine, up to 20 mg/day. The conditions of patients in all three treatment groups improved equally. The combined treatment did not produce a higher frequency of side effects, and no side effects, such as hypertensive or hyperthermic crises, occurred in any patient. Both amitriptyline alone and combined treatment produced substantially more anticholinergic side effects than did tranylcypromine. These results support the safety and efficacy of the combined treatment, although claims for superior efficacy over single-antidepressant treatments in this heterogenous population were not supported.