TRANSITIONING PATIENTS WITH MAJOR NEUROCOGNITIVE DISORDERS FROM ANTIPSYCHOTIC MEDICATIONS TO CITALOPRAM - A PHARMACOGENETICALLY-INFORMED CASE SERIES

Introduction The successful and safe psychopharmacologic management of older adults suffering with major neurocognitive disorders with behavioral disturbances and has remained a challenging therapeutic dilemma – despite recently published guidelines on the topic. Available guidelines would suggest that individuals with severe agitation, violence, or distress related to their agitation or psychosis should receive pharmacotherapy in addition to behavioral and social management. Citalopram and other SSRIs have shown promise in treating agitation and psychosis in the context of major neurocognitive disorders, however treatment with antipsychotics for this indication has not appreciably declined on the national stage despite the increased risk of morbidity and mortality associated with these medications. While the literature has given much thought to the initial choice of medication for these patients, an important question remains as to whether there are patients whom might benefit from a transition to citalopram after an antipsychotic has already been initiated. Given the high potential for symptom recurrence when transitioning from an antipsychotic, methodology that would allow some measure of individualized response prediction would be of clinical value. Interestingly, low expression alleles of the SLC6A4 (serotonin transporter) gene have been linked to decreased response to citalopram in major neurocognitive disorders. Methods Three cases from the ambulatory Center of Excellence for Alzheimer's Disease at SUNY Downstate are presented in which patients suffering with major neurocognitive disorders and associated neuropsychiatric symptoms were transitioned from antipsychotic medications to citalopram. Case histories and scores on the neuropsychiatric inventory and CGI scales are presented for review. Pharmacogenetic testing results are presented for the final case in which transition to citalopram was not successful. Results Two of three cases were successfully transitioned from antipsychotic medications to citalopram, resulting in near total remission of psychosis and agitation on the CGI Agitation and Psychosis scales. The third case offers a compelling explanation for the treatment failure – pharmacogenetic polymorphisms that impacted both the metabolism (CYP2D6 ultrarapid metabolizer, CYP2C19 intermediate metabolizer) of citalopram and its effectiveness (homozygous for the short promoter of the serotonin transporter gene - SLC6A4). Conclusions This case series presents an important treatment approach for older adults with major neurocognitive disorders that have already been started on antipsychotics for their neuropsychiatric symptoms. Transitioning from an antipsychotic to citalopram was effective in two out of three cases, limiting their exposure to a class of medications with a higher risk profile. The third case, while unsuccessful, highlights the complexities of treatment choice and the importance of a personalized approach to medicine. Given previous reports that low expression alleles of the SLC6A4 gene may be linked to decreased response to citalopram, further controlled study evaluating the transition from antipsychotic medications to citalopram utilizing pharmacogenetic testing to personalize treatment could potentially improve treatment choice in this vulnerable population. This research was funded by This study received no outside support.