Pharmacologic treatment of depression in Alzheimer’s disease

Abstract

Major depressive disorder and Alzheimer’s disease are common among older people, frequently co-occur and severely impact the quality of life. Unfortunately, data on the efficacy of pharmacologic treatment of depressive symptoms in patients with the neurodegenerative disease remain inconclusive. The heterogeneity of treatment study designs, from varying diagnostic specificity to diverse outcome measures, contributes to conflicting evidence across single trials and meta-analyses. In this literature review, we focus on commercially available products for antidepressant treatment in demented individuals and show how insights from randomized controlled trials could still guide and be aligned with common clinical practice.

What do we know about pseudodementia?

“…Reversible cognitive impairment in moderate-to-severe depression in older adults is considered a strong predictor of dementia according to most authors, although some consider that depression with reversible cognitive impairment may be a prodromal phase of dementia rather than a risk factor. 13 14 19 20 31 In these cases, the type of depression appears to be qualitatively different: more resistant to treatment and with a more chronic course. 15 …”

“… 27 A study published in 2023 shows that depression is a comorbidity often associated with dementia and also that depression increases the risk of dementia. 13 People with any type of dementia have a high incidence of major depression, particularly if they have vascular dementia or Parkinson’s disease dementia—these patients often have more insight and awareness of their condition than people with AD. 11 13 27–29 However, there is some disagreement on this point.…”

“…11 Furthermore, depression often co-occurs with a wide range of medical conditions, including Alzheimer's disease (AD), stroke and Parkinson's disease, making the diagnosis General Psychiatry of these diseases difficult and exacerbating the functional decline associated with each one. [12][13][14]…”

The challenge of managing difficult to treat psychiatric conditions

“…The use of traditional antidepressants in patients with Alzheimer's disease poses specific issues, linked to the concomitant cognitive decline, drug interactions, and risk of worsening of concomitant symptomatology. The review in this issue (Haussmann and Donix, 2023) focuses on the choice of the compound in this specific population of patients. As expected, it is not possible to state the 'best' treatment for all patients, and the specific symptomatology profile, concomitant medical illnesses, and other patient-specific features should guide the choice.…”