Early individual symptom response to antipsychotics impacts later response in patients with Alzheimer's

Early improvements of individual symptoms might contribute to later treatment response among patients with Alzheimer’s disease receiving antipsychotics for neuropsychiatric symptoms, according to findings of a re-analysis study published in Journal of Clinical Psychiatry.

“Given that it may be difficult to examine all of the clinical symptoms to assess overall symptom severity in daily clinical practice, focusing on specific early improvements of individual symptoms (ie, irritability and suspiciousness) during the course of treatment with antipsychotics may help predict patients’ subsequent treatment outcomes,” Tomoyuki Nagata, MD, PhD, of the department of psychiatry at The Jikei University School of Medicine in Tokyo, and colleagues wrote.

According to the researchers, much of the prior research in this area focused on early improvement of the overall severity of neuropsychiatric symptoms, whereas the present study examined specific symptoms. To determine the relationship between these symptoms and subsequent antipsychotic treatment response, they analyzed data from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer’s Disease. They included data from 421 patients with DSM-IV Alzheimer’s Disease receiving antipsychotics for neuropsychiatric symptoms. They defined treatment response as a reduction of nine or more points in the Neuropsychiatric Inventory (NPI) score or a reduction of 25% or higher from baseline in Brief Psychiatric Rating Scale (BPRS) total scare at 8 weeks. They then examined associations between clinical and response and demographic characteristics, including each total or individual symptom score reduction at 2 weeks, using logistic regression analyses.

Nagata and colleagues found that reductions in NPI or BPRS total score at 2 weeks were significantly associated with subsequent treatment response at 8 weeks. This association was also significant for several individual symptom score reductions, including euphoria/elation, irritability, hallucinations, anxiety and depressive mood. They noted that early nonimprovements of suspiciousness and irritability were particularly influential clinical markers in predicting subsequent treatment nonresponse. Moreover, healthier baseline condition was significantly associated with treatment response at 8 weeks.

“Ultimately, this prediction will lead to the prevention of excessive exposure to antipsychotics that are unlikely to have a beneficial impact on patients,” the researchers wrote. “Although our preliminary findings warrant further research to validate them, the current results suggest that focusing on trajectories of the emotional, motivational and cognitive domains as well as the positive symptomatic domain would be helpful for clinicians to judge risk and benefit as early as possible to determine whether continuing the current antipsychotics is the best course; doing so would eventually lead to the patient’s benefit.” – by Joe Gramigna

Disclosures: Nagata reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.