Pharmacological Treatment of Neuropsychiatric Symptoms of DementiaPharmacological Treatment of Neuropsychiatric Symptoms of Dementia

To the Editor: In their Clinical Review, Dr Sink and colleagues¹ accurately capture the dilemma faced by clinicians caring for individuals with dementia: although neuropsychiatric symptoms are almost universal and adversely affect both patients and caregivers, evidence-based guidance toward effective pharmacological treatment is sparse. Inadequacy of present systems of symptom classification may account in part for the finding of limited usefulness for pharmacotherapy.

Agitation, delusions, and many other neuropsychiatric symptoms in dementia often present in ways that defy categorization by standard methods (eg, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]). Most treatment studies to date have defined these symptoms as isolated disturbances, such as aggression or anxiety, or as a score above a cutoff on instruments assessing multiple domains. However, neuropsychiatric symptoms frequently occur as specific clusters or syndromes² ; 1 study using latent class analysis³ found that neuropsychiatric symptoms in Alzheimer disease clustered into 3 groups: an affective, a psychotic, and an “other” syndrome.

Such clusters could have implications both for treatment and clinical research. Mood disorder may be a common underlying syndrome that occurs under multiple guises.³ Anxiety or irritability may thus be present in the absence of “depressed mood” per se. Some patients with dementia also have psychotic symptoms that respond to antidepressant therapy.⁴ Therefore, many patients with agitated, anxious, or irritable dementia may benefit from depression treatment, even if they have psychosis, despite not having classic DSM-IV depression symptoms.

Several provisional definitions for neuropsychiatric syndromes have recently been formulated, including depression of Alzheimer disease⁵ and Alzheimer-associated psychotic disorder,³ but have not yet been validated. Until there are improved treatment trials for both pharmacological and nonpharmacological interventions, clinicians may be best advised to vigilantly assess for potentially treatable symptom clusters in their patients with dementia.