Effect of a Serotonin Reuptake Inhibitor on Irritability, Apathy, and Psychotic Symptoms in Patients With Alzheimer's Disease

Abstract

Objective To ascertain the impact of treatment with citalopram on irritability, apathy, delusions and hallucinations in non-depressed behaviorally disturbed Alzheimer’s disease (AD) patients. Method This was a retrospective review of data from the 36-week CATIE trial in which AD patients were treated in a naturalistic manner with placebo, citalopram, risperidone, olanzapine or quetiapine, comparing scores on the Irritability, Apathy, Delusions and hallucinations subscales of the Neuropsychiatric Inventory. Results Of the 421 patients enrolled, 34 had been started on placebo and had been later randomized to citalopram treatment. There were data available for 34 subjects who had been on placebo for at least 14 days. In this group there was a 60% reduction in irritability and apathy scores, no effect on score for delusions, and a clinically insignificant drop in score for hallucinations. Conclusion The use of citalopram was associated with greatly reduced irritability without sedation in a group of behaviorally disturbed AD patients.

Apathy in Neuropsychiatric Disease: Diagnosis, Pathophysiology, and Treatment

“…Although pharmacologic studies in animal models of apathy have also lent insight into mechanisms contributing to the regulation of motivated behaviors, the lack of full model validation constrains use of the results. Drugs claimed to benefit apathy in humans include serotonergic antidepressants (Siddique et al 2009), antipsychotics (Marangell et al 2002), catecholaminergic psychostimulants (Padala et al 2010), antidementia cholinomimetics, and antiglutamatergics (Swanberg 2007;Rodda et al 2009), and antiparkinsonian dopaminergics ). All presumably act through effects on neurotransmitters mediating frontal-subcortical circuit function.…”

“…The ventral pallidum receives substantial GABAergic input from the nucleus accumbens and serves as a component of pathways regulating response allocation and effort-related choice behavior by conveying information from the accumbens to other parts of these forebrain circuits. Evidence favoring the participation of cholinergic, serotonergic, and glutamatergic systems in the pathogenesis of apathy derives primarily from observations made during the clinical evaluation of pharmaceuticals that selectively act upon these transmitters (Swanberg 2007;Rodda et al 2009;Siddique et al 2009). Taken together, the foregoing observations suggest that the successful treatment of apathy will probably involve drugs affecting one or more of these frontal-subcortical systems.…”

“…Apathy is often left undiagnosed and thus untreated, not only because it is confused with depression and other similar behavioral disorders but also because it not uncommonly occurs in a mild and transient form in the general population. On the other hand, a mounting body of preclinical and clinical evidence now indicates that apathy reflects dysfunction of fronto-subcortical projection systems, including monoaminergic, cholinergic, glutamatergic, and GABAergic pathways, and thus should be potentially amenable to pharmacotherapeutic interventions targeting these systems (Bressan and Crippa 2005;Gauthier et al 2007;Swanberg 2007;Farrar et al 2008;Leentjens et al 2009;Siddique et al 2009;Padala et al 2010). Current data further raise the possibility that more than one type of apathy exists, reflecting involvement of more than one cortical-subcortical system, and that therapies directed toward more than one pharmacologic target might prove most efficacious.…”

Treatment of Alzheimer’s Disease: Current Management and Experimental Therapeutics

“…Tricyclic antidepressants are typically avoided because of their anticholinergic side-effects. Antidepressants often improve patients’ sense of well-being, sleep cycles, anxiety, and irritability, [17,18] and may sometimes improve concentration, but do not improve cognition. Psychotic symptoms generally respond best to antipsychotic medications, the neuroleptics.…”

“…Psychotic symptoms generally respond best to antipsychotic medications, the neuroleptics. Some reports suggest either limited, or no improvement of psychotic symptoms with acetylcholinesterase inhibitor therapy [19,20], memantine [21], or antidepressant therapy [18]. However, in general, dopaminergic antagonists are required to significantly treat these symptoms, and most frequently the atypical neuroleptics are used.…”