Depression in Alzheimer's disease: an alternative role for selective serotonin reuptake inhibitors?

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 randomised controlled trials have shown selective serotonin reuptake inhibitors (SSRI’s), 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 SSRI’s 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 SSRI’s in early AD. Even in the absence of depression, SSRI’s have been shown to slow the conversion from mild cognitive impairment to AD. This may be attributed to the effect of SSRI’s on the processing of amyloid-β precursor protein (AβPP), which may cause a reduction in the accumulation of amyloid-β (Aβ). Thus, although SSRI’s 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 SSRI’s being a treatment option for delaying the progression of AD.