Treating depression in Alzheimer’s disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: The DIADS.
Lyketsos CG, DelCampo L, Steinberg M, Miles Q, Steele CD, Munro C, et al.;
Commented by , 25 Aug 2003
Aim of the Study
To assess the efficacy of sertraline in treating major depression in Alzheimer’s disease; and to assess if successful treatment of depression affects activities of daily living, cognition and behavioural disturbance.
Method
44 outpatients in Maryland, USA, were recruited over the time period 1998 – 2001. Patients included were medically stable and had established Alzheimer’s disease with Mini-Mental State Score > 10 – diagnosed by NINCDS-ADRDA criteria – complicated by a major depressive episode (DSM-IV criteria).
Patients were randomised to receive either placebo, or sertraline; the sertraline was titrated up weekly by the study psychiatrists to 150 mg per day, or the highest tolerated dose.
Outcome measures included the Hamilton Depression Rating Scale (HDRS), the Cornell Scale for Depression in Dementia (CSDD), the Psychogeriatric Dependency Rating Scale as a proxy for Activities of Daily Living (ADL), and the Neuropsychiatric Inventory. Double blind methodology was used, and outcomes analysed over a 12-week period.
Results
Analysis of the baseline measures confirmed successful randomization, i.e., placebo and treatment groups were similar. Drop-outs in the both the placebo and sertraline-treated groups were low, with no significant differences between the groups.
The mean dosage of sertraline used was 95 mg per day. The main finding was that depression was successfully treated in the treatment group – compared to placebo – though with variable response. The overall difference in response rate was 49 %, effect size 1.4.
Treatment with sertraline did not improve other outcome measures, i.e., did not improve cognition or behavioural disturbance. There was a non-significant trend towards less decline in ADL in the sertraline-treated group compared to placebo.
The data was further analysed to show that the few patients who showed no response to sertraline after 6 weeks, were also non-responders at 12 weeks.
Discussion
Research in this area is difficult to conduct; there are issues of consent, diagnostic criteria, sampling, high drop-out rates, and reliability of outcome measures.
This is one of the first rigorously conducted studies to demonstrate convincingly the efficacy of an SSRI in this commonly encountered condition. Although the sample size is small, the authors have analysed their data carefully to clarify the nature of the response.
As the authors acknowledge, other limitations are the recruitment of participants from specialty referral clinics; the requirement of meeting strict inclusion criteria for both Alzheimer’s disease and major depression; and the short study duration. These limitations do not greatly detract from the generalisability of the results, however.
The broader literature suggests that up to 20 % of people with Alzheimer’s disease have concomitant major depression, which is under-diagnosed and under-treated.
This study lends weight to the assertion that the treatment of first choice is an SSRI at good dosage, and switching to a noradrenergic antidepressant if there is no response at 6 weeks.