A double-blind, placebo-controlled study of fluoxetine in depressed patients with Alzheimer's disease. A double-blind placebo-controlled study of clomipramine in depressed patients with Alzheimer's disease. Video rating analysis of effect of maprotiline in patients with dementia and depression. Double-blind trial of imipramine in Alzheimer's disease patients with and without depression. Moclobemide in elderly patients with cognitive decline and depression: an international double-blind, placebo-controlled trial. A controlled multicenter clinical study of citalopram and placebo in elderly depressed patients with and without concomitant dementia. Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS.
To examine the efficacy of fluoxetine in the treatment of depression in patients with probable Alzheimer's disease (AD).
                This double-blind, parallel-design study included a consecutive series of 41 AD subjects meeting DSM-IV criteria for major or minor depression who were randomized to receive fluoxetine (up to 40 mg/day) or identical-appearing placebo. All patients received biweekly evaluations consisting of the Hamilton Depression Scale (HAM-D) and the Clinical Global Impression as primary efficacy measures, and the Mini-Mental State Exam, Hamilton Rating Scale for Anxiety, and the Functional Independence Measure as secondary efficacy measures.
                Complete remission of depression was found in 47% of subjects treated with fluoxetine and in 33% of subjects treated with placebo. Both the fluoxetine and the placebo groups showed a significant decline in HAM-D scores over time, but the magnitude of mood improvement was similar for both groups. Fluoxetine was well tolerated, and most side effects were mild.
                Fluoxetine treatment for depression in AD did not differ significantly from treatment with placebo. Our study also confirms the presence of a placebo effect in the treatment of depression in AD. Twenty-one depressed patients with probable Alzheimer's disease (AD) were randomized to receive a 6-week treatment with clomipramine or placebo in a study with a double-blind crossover design. Main outcome measures were Hamilton Depression, Mini-Mental State (MMSE), and Functional Independence Measure (FIM) scores. Mood improved significantly on both clomipramine and placebo, but clomipramine was significantly more effective than placebo during the first 6-week treatment period. Patients started on clomipramine maintained improvement during the washout and placebo periods, whereas patients started on placebo worsened during the washout period. However, patients on clomipramine showed significantly lower MMSE scores overall than patients on placebo. No significant drug effects were found on FIM scores. Clomipramine proved to be a useful treatment of depression in patients with probable AD. In patients with dementia and mild depression (DSM-III-R 290.21), the effect of low doses of the antidepressant maprotiline (up to 75 mg/d) was examined. The main parameter was a video rating of global impression. The Mini-Mental State Examination (MMS) and the Geriatric Depression Scale (GDS) were applied to evaluate the effect of maprotiline on cognitive and depressive symptoms. The double-blind, placebo-controlled trial was of eight weeks' duration and included 127 patients, randomized in two groups. The antidepressant effect of maprotiline was reflected in the GDS. There was, however, no indication of an effect of maprotiline on cognitive performance. The global impression, evaluated by video rating, gave no indication as to a beneficial effect of the treatment. - The video analysis showed a significant interrater reliability. The discrepancy between the results of the video rating and the GDS is discussed. - The results confirm similar findings of other authors; i.e., that a sedating antidepressant with some anticholinergic effects cannot be expected to improve cognitive functions despite its antidepressant effect. The main interest of this study, however, lies in its methodology (video analysis). The authors divided 61 subjects with primary degenerative dementia of the Alzheimer's type into a group who also met DSM-III criteria for depression (N = 28) and a group who did not (N = 33). Both groups were randomly assigned to an 8-week double-blind trial of imipramine or placebo. Scores on the Hamilton Rating Scale for Depression, administered at baseline and weeks 2, 4, 6, and 8, indicated significant improvement in both groups. Two measures of cognitive function yielded differing results. The results suggest that moderate depression is a treatable condition in patients with Alzheimer's disease. The new reversible MAOl moclobemide was compared with placebo in the treatment of elderly patients with DSM-III diagnosis of dementia and/or of major depression.
                Six hundred and ninety-four elderly patients with symptoms of depression and cognitive decline entered an international, multi-centre, double blind trial in which they were randomly allocated to treatment with either moclobemide 400 mg daily or placebo for 42 days. Five hundred and eleven patients met DSM-III criteria for dementia and were also depressed (DEM+D); 183 did not meet DSM-III criteria for dementia but met the criteria for DSM-III major depressive episode and also suffered from cognitive decline (MDE+CD).
                Analysis of the 17 and 24-item Hamilton Depression Scale scores showed that moclobemide, compared with placebo, produced significantly greater improvement in both the demented and depressed groups (P = 0.001 both diagnostic groups). There was an improvement in cognitive function as measured by the SCAG Factor 1 in moclobemide treated patients (P = 0.005 DEM+D; P = 0.02 MDE+CD). There was no evidence of decline in cognitive function as the result of treatment. Clinical global assessment of tolerance was 'excellent' and 'good' in 88% of the moclobemide and in 92% of the placebo treated patients. The proportion of patients discontinuing treatment prematurely was similar in both treatment groups. There were no significant differences in side-effects between treatment groups. There were no significant changes in vital signs, ECG or laboratory findings in either treatment group. There were no dietary restrictions and no report of any tyramine reaction.
                Moclobemide was shown to be a safe, well tolerated and effective antidepressant, which did not cause impairment of cognitive function in elderly patients with a DSM-III diagnosis of dementia and/or DSM-III major depression. A total of 149 patients in 7 centers in Denmark, Norway and Sweden entered a 6-week double-blind trial intended to assess the antidepressant effect and safety of citalopram vs placebo in depressed elderly patients (65 years of age or older) who might also suffer from somatic disorders and/or senile dementia. Results of ratings on the Hamilton Rating Scale for Depression, the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impression Scale provided consistent evidence that the citalopram-treated patients improved more than the placebo-treated patients. Results of ratings on the Gottfries-Bråne-Steen dementia rating scale indicated that both cognitive and emotional functioning improved significantly more in the citalopram-treated subgroup of patients with dementia than in the placebo-treated subgroup. Major depression affects about 25% of the patients who have Alzheimer disease and has serious adverse consequences for patients and caregivers. Results of prior antidepressant treatment studies have produced contradictory findings and have not fully assessed the benefits of depression reduction.
                To assess the efficacy and safety of sertraline hydrochloride for the treatment of major depression in Alzheimer disease, and to evaluate the effect of depression reduction on activities of daily living, cognition, and nonmood behavioral disturbance.
                Randomized, placebo-controlled, parallel, 12-week, flexible-dose clinical trial with a 1-week, single-blind placebo phase. The study was conducted between January 1, 1998, and July 19, 2001.
                University outpatient clinic.
                Forty-four outpatients who have probable Alzheimer disease and major depressive episodes.
                Sertraline hydrochloride, mean dosage of 95 mg/d, or identical placebo, randomly assigned.
                Response rate, Cornell Scale for Depression in Dementia, Hamilton Depression Rating Scale, Mini-Mental State Examination, Psychogeriatric Depression Rating Scale-activities of daily living subscale, and Neuropsychiatric Inventory to quantify patient behavior disturbance and caregiver distress.
                In the sertraline-treated group 9 patients (38%) were full responders and 11 (46%) were partial responders compared with 3 (20%) and 4 (15%), respectively, in the placebo-treated group (P =.007). The sertraline-treated group had greater improvements in the scores for the Cornell Scale for Depression in Dementia (P =.002) and Hamilton Depression Rating Scale (P =.01), and a statistical trend toward less decline in activities of daily living on the Psychogeriatric Depression Rating Scale-activities of daily living subscale (P =.07). There was no difference between the treatment groups in Mini-Mental State Examination (P =.22) or Neuropsychiatric Inventory (P =.32) ratings over time. When full responders, partial responders, and nonresponders were compared, full responders only, or full and partial responders had significantly better ratings on activities of daily living (P =.04), behavioral disturbance (P =.01), and caregiver distress (P =.006), but not on the Mini-Mental State Examination (P =.76). Safety monitoring indicated few differences in adverse effects between the 2 treatment groups.
                Sertraline is superior to placebo for the treatment of major depression in Alzheimer disease. Depression reduction is accompanied by lessened behavior disturbance and improved activities of daily living, but not improved cognition.
Available evidence offers weak support to the contention that antidepressants are effective for patients with depression and dementia. However, only four studies are included in the meta-analysis relating to efficacy, and sample sizes are small. Moreover, only two included studies investigated the properties of the more commonly used SSRIs and no studies investigated the properties of newer classes of antidepressants (e.g. selective noradrenergic reuptake inhibitors). This review draws attention to the paucity of research and evidence in this area.