Antidepressant medications in dementia: evidence and potential mechanisms of treatment-resistance

Depression in dementia is common, disabling and causes significant distress to patients and carers. Despite widespread use of antidepressants for depression in dementia, there is no evidence of therapeutic efficacy, and their use is potentially harmful in this patient group. Depression in dementia has poor outcomes and effective treatments are urgently needed. Understanding why antidepressants are ineffective in depression in dementia could provide insight into their mechanism of action and aid identification of new therapeutic targets. In this review we discuss why depression in dementia may be a distinct entity, current theories of how antidepressants work and how these mechanisms of action may be affected by disease processes in dementia. We also consider why clinicians continue to prescribe antidepressants in dementia, and novel approaches to understand and identify effective treatments for patients living with depression and dementia.