The primary goal of this revised application (MH59666) """"""""Continuation Pharmacotherapy for Agitation of Dementia"""""""" is to conduct a 12-week, double-blind study of the comparative effectiveness of the highly selective, serotonin reuptake inhibitor, citalopram, and the atypical antipsychotic, dsperidone in 103 patients suffering from behavioral disturbances associated with Alzheimer's dementia (BDAD). This study focuses on patients with Alzheimer's disease and its Lewy body variant who are most severely affected: those who have required initial hospitalization for BDAD. Symptomatic management of BDAD in the hospital has greatly improved over the past five years. Unfortunately, shortened lengths of stay are now mandated and BDAD has a high likelihood to recur and repeated hospitalizations are associated with more rapid functional decline. Our pilot data suggest that the antidepressant citalopram is acutely beneficial for both psychotic and non-psychotic BDAD symptoms in hospitalized patients, at least in the short-term. Attenuation of agitation and psychotic symptoms achieved with citalopram appeared to be equivalent to, or better than that achieved with our prior treatment standard, the conventional neuroleptic, perphenazine. The increase in side effect burden for the perphenazine-treated patients was significant, however, in contrast to the citalopram and placebo groups. Nonetheless, this efficacy study was conducted in a highly controlled, specialized, inpatient environment, for a very brief period of time (17 days). Moreover, in community-practice, the atypical antipsychotic, rispeddone has become a first-line medication for BDAD. To address continuing treatment in the community or in the nursing home (i.e., outside of our academic setting) we have established a system of treatment and assessment for BDAD patients upon their discharge from the hospital. Medication assignment and dosage adjustments will remain blinded and patients will be carefully monitored. In addition to clinical and behavioral assessments of outcomes, the proposed study will also examine whether therapeutic response is associated with inter-individual allelic variations in the serotonin transporter promoter, serotonin 2N2C receptors, and CYP2D6 drug metabolizing isoenzyme. Drug plasma level monitoring will be utilized to assess the impact of variance in drug exposure due to deviations in compliance or drug clearance.
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