Depression in Alzheimer's Disease: An Alternative Role for Selective Serotonin Reuptake Inhibitors?

Abstract

Depression is a common co-morbidity seen in people with Alzheimer's disease (AD). However, the successful treatment of depressive symptoms in people with AD is rarely seen. In fact, multiple randomized controlled trials have shown selective serotonin reuptake inhibitors (SSRIs), the current best recommended treatment for depression, to be ineffective in treating depressive symptoms in people with AD. One explanation for this lack of treatment effect may be that depressive symptoms can reflect the progression of AD, rather than clinical depression and are a consequence of more severe neurodegeneration. This raises several questions regarding not only the efficacy of SSRIs in the treatment of depression in people with AD but also regarding the accuracy of diagnosis of depression in AD. However, there may be a rationale for the prescription of SSRIs in early AD. Even in the absence of depression, SSRIs have been shown to slow the conversion from mild cognitive impairment to AD. This may be attributed to the effect of SSRIs on the processing of amyloid-β precursor protein, which may cause a reduction in the accumulation of amyloid-β. Thus, although SSRIs may lack efficacy in treating depression in people with AD, they may hold therapeutic potential for treating and delaying the progression of AD especially if treatment begins in the early stages of AD. This article reviews the current consensus for SSRI treatment of depression in people with AD and highlights the possibility of SSRIs being a treatment option for delaying the progression of AD.