Pharmacologic treatment of major depression for elderly patients in residential care settings. A two-center double-blind study of nomifensine, imipramine, and placebo in depressed geriatric outpatients. The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients. A double-blind comparative evaluation of the efficacy and safety of nomifensine, imipramine, and placebo in depressed geriatric outpatients. Group cognitive therapy and alprazolam in the treatment of depression in older adults. Treatment of geriatric depression with trazodone, imipramine, and placebo: a double-blind study. Moclobemide and nortriptyline in elderly depressed patients. A randomized, multicentre trial against placebo. [Clinical double blind comparison of diclofensine and placebo in geriatric patients with depressive syndromes]. [Viloxazine in the treatment of depression in the aged. Double-blind placebo study]. Safety and efficacy of bupropion in elderly patients: preliminary observations. Placebo-controlled treatment trial of depression in elderly physically ill patients. Effective low dose tricyclic antidepressant treatment for depressed geriatric rehabilitation patients. A double-blind study. The effect of low dose lofepramine in depressed elderly patients in general medical wards. Analysis of the Hamilton Depression Rating Scale factors from a double-blind, placebo-controlled trial of fluoxetine in geriatric major depression.
A significant drug-placebo difference was found in a double-blind, placebo-controlled study of nortriptyline for treatment of major depression among frail elderly patients living in an institutional setting. This finding confirms the validity of the DSM-III-R diagnosis of major depression and establishes the need for specific psychiatric services for the chronically ill elderly living in nursing homes and congregate housing facilities. The incidence of adverse events requiring early termination of treatment was 34%, demonstrating the vulnerability of these patients and their need for careful monitoring during treatment. High levels of self-care disability and low levels of serum albumin were both associated with decreased therapeutic responses, demonstrating the need for further research on psychopathology in these settings. Both nomifensine and imipramine were superior to placebo in a 4-week double-blind study involving 63 geriatric patients (greater than 60 years) with primary affective disorder-depression. Significant improvement in the active drug groups was demonstrated on the Hamilton Depression Rating Scale, Clinical Global Impressions, Brief Psychiatric Rating Scale, and Hopkins Symptom Check List. Analysis of laboratory and physical examination data, including ECGs, revealed no clinically significant changes associated with either drug. Compared to the imipramine group, nomifensine-treated patients showed a more rapid rate of improvement and a lower incidence of discomforting side effects. 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. Nomifensine, imipramine, and placebo were compared in 61 depressed geriatric outpatients over a 35-day period. At average daily doses of 150 mg, nomifensine and imipramine were significantly more effective than placebo in reducing symptoms of depression in this sample of elderly depressed patients. Nomifensine and imipramine were generally comparable in clinical effect; 78% of the nomifensine-treated patients were rated as improved at the end of treatment as compared with 64% of imipramine and 20% of placebo patients. The findings suggest a more favorable side effect profile for nomifensine, which was associated with a lower frequency of sedating and anticholinergic effects than was seen in the imipramine group. nan Sixty unipolar depressed geriatric outpatients were subjects in a double-blind study of a new antidepressant, trazodone, versus imipramine and placebo. Over the four week study, patients in the two active medication groups improved significantly compared to placebo on both observer and self-ratings. Although imipramine and trazodone had similar therapeutic efficacy, trazodone was judged to have fewer side effects than imipramine, suggesting that trazodone may have particular clinical utility in the geriatric population which is especially vulnerable to cardiovascular and anticholinergic side effects. Moclobemide and nortriptyline were compared with placebo in a double-blind randomized multinational (Canada, Denmark and UK) trial comprising 109 patients of > 60 years of age with major depression (DSM-III-R). Patients were randomized to 7 weeks of treatment with doses of 400 mg/day moclobemide, 75 mg/day nortriptyline or placebo. It was necessary to adjust nortriptyline dosage in < 20% of patients to maintain serum levels within the postulated therapeutic window of 50-170 ng/ml. At end of treatment, the remission rates were 23% for moclobemide, 33% for nortriptyline and 11% for placebo. Anticholinergic and orthostatic events occurred more often with patients on nortriptyline than either moclobemide or placebo. The objective of this double-blind trial was to assess the effect of diclofensine on geriatric patients with depressive syndromes in comparison to placebo. 40 patients (age 60-75 years) were treated for 3 weeks with a mean daily dose of 57.5 mg diclofensine or placebo. Diclofensine was found effective in 18 (= 90%) cases (placebo 60%) after 2.9 days on an average (placebo, 4.2 days), mostly having a mood elevating effect and in only 2 cases (placebo 1) having a stimulatory effect. The results of the global assessments, the Hamilton depression scale, the d2-test, the block design test and the mood scale (Befindlichkeitsskala) demonstrated a statistically significant superiority of diclofensine over placebo. The critical flicker frequency, on the other hand, was not able to differentiate significantly between the two drugs. The tolerance was considered as very good in all cases. Unwanted effects were observed in 13 patients (= 65%) of the diclofensine group and in 9 patients (= 45%) of the placebo group. They disappeared in most cases within one week after their appearance. According to this trial diclofensine can be described as a well tolerated drug without pronounced anticholinergic side effects, capable of improving depressive states faster and more effectively than placebo. nan The efficacy and safety of bupropion, an atypical antidepressant, were assessed in depressed patients aged 55 and above. Data were analyzed for 38 patients who completed 4 weeks of double-blind treatment with bupropion in maximum doses of 150 or 450 mg/day; imipramine, up to 200 mg/day; or placebo. Preliminary results suggest that bupropion does have antidepressant activity and is well tolerated in this population. A particular advantage is suggested in terms of cardiovascular side effects. To determine the response of physically ill elderly depressed patients to treatment.
                Acute geriatric medical inpatients with depression, randomly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine.
                Response rate as defined by the 17-item Hamilton Depression Rating Scale.
                Eighty-two patients entered the trial; 62 patients (all those who had completed at least 3 weeks of treatment) were included in the efficacy analysis. Forty-two completed the full 8 weeks (21 in each group) with response rates of 67% in the fluoxetine group and 38% in the placebo group. No significant difference was found between the responses of the two groups (p = 0.12). There was a trend for results in the fluoxetine group to continue to improve with time. On secondary analysis those patients with serious physical illness who completed 5 or more weeks (N = 37) showed a significant improvement in mood if treated with fluoxetine (p = 0.02).
                The main benefit of antidepressants is to approximately double the chances of recovery. This trial showed the response rate of the fluoxetine treated group was increased by a factor of 1.8 over the placebo group in an 8-week period. The presence of physical illness, often severe and/or multiple, did not reduce the effectiveness of the medication, which was well tolerated overall. Those with serious physical disease responded significantly better to drug treatment; this will require further work. Psychological support was also considered to be important. The efficacy of low doses (10 to 20 mg daily) of doxepin in the treatment of depressive disorders in elderly inpatients was assessed by a double-blind study in 24 patients. The patients were treated for a three-week period to test for an early response. The Hamilton Depression Scale and the Geriatric Depression Scale were used to quantify symptoms of depression. The patients treated with doxepin had a significantly greater reduction in depressive symptoms than did those who received a placebo. No side effects were found and there were no major differences in the degree of physical dependency between the doxepin and placebo groups. A depressive disorder is a common occurrence among elderly inpatients and the effectiveness of low dose doxepin therapy without demonstrable side effects argues for the active treatment for this condition. A double-blind randomised controlled trial of the effect of low dose lofepramine (70 mg once daily) against placebo was carried out on depressed elderly inpatients on general medical wards for the elderly, comparing measures of depression and side-effects between the randomised groups. Patients were identified for the study using the Geriatric Depression Scale (GDS) and the Brief Assessment Schedule Depression Cards (BASDEC). Sixty-three subjects were randomised: 46 patients completed the entire trial of 28 days treatment. BASDEC and GDS were administered on day 8 post-admission, and depressed patients were randomised double-blind to either low dose lofepramine (70 mg daily) (n = 23) or placebo (n = 23). Assessment of changes in depressive states were made using the Montgomery Asberg Depression Rating Scale (MADRS) on days 8, 18 and 36 post-admission. Both groups improved by a similar amount during the trial. Lofepramine tended to be more effective than placebo in those patients who were more depressed (GDS > or = 18). On the other hand, subjects who were less depressed (i.e. GDS < 18) improved more on placebo than lofepramine. Low dose lofepramine may prove useful in moderately or severely depressed patients treated for only 4 weeks. However, low dose lofepramine is not indicated for mild (GDS 15-18) depression. Major depression during later life represents a clinical challenge. Conventional antidepressant pharmacotherapy is relatively less well tolerated in geriatric patients compared with younger patients. Despite the striking impairments associated with this disorder, clinical investigations into the relative risk-benefit ratio of various depression treatment strategies have been limited. In this multicentre, placebo-controlled, double-blind trial with fluoxetine, 671 major depressed (DSM-III-R-compatible) outpatients aged 60 years or older were evaluated. The 21-item Hamilton Depression Rating Scale (HAMD21) response (p = 0.014) and remission (p = 0.008) criteria favoured fluoxetine over placebo. Analysis of the treatment effect on change in the HAMD21 factors (anxiety/somatization, cognitive disturbance, psychomotor retardation, and sleep disturbance) revealed advantages for fluoxetine within the cognitive disturbance and psychomotor retardation factors. Overall, the rate of discontinuation for an adverse event between fluoxetine (11.6%) and placebo (8.6%) was not statistically significant. Baseline HAMD21 factor scores were not predictive of adverse events leading to premature treatment discontinuation. Fluoxetine, 20 mg/day, is a well-tolerated and effective treatment option in the management of geriatric major depression.
TCAs, SSRIs and MAOIs are effective in the treatment of older community patients and inpatients likely to have severe physical illness. At least six weeks of antidepressant treatment is recommended to achieve optimal therapeutic effect. There is little evidence concerning the efficacy of low dose TCA treatment. Further trials are required before low dose TCA treatment is routinely recommended.