Lack of Early Improvement with Antipsychotics is a Marker for Subsequent Nonresponse in Behavioral and Psychological Symptoms of Dementia: Analysis of CATIE-AD Data

Abstract

Objective Prediction of response/non-response to antipsychotics is especially important in patients with behavioral and psychological symptoms of dementia (BPSD) in whom antipsychotic exposure increases risks of death. We aimed to examine whether presence/absence of early improvement of BPSD with antipsychotics is associated with subsequent response/non-response. Design Post-hoc analysis of the Clinical Antipsychotic Trials in Intervention Effectiveness with Alzheimer’s Disease (CATIE-AD) study (2001–2004) (trial registration: NCT00015548). Setting 45 sites in the United States. Participants 245 subjects (olanzapine, n=90; quetiapine, n=81; risperidone, n=74) with a DSM-IV diagnosis of dementia of the Alzheimer’s type who presented with a score of 1 or more in the Brief Psychiatric Rating Scale (BPRS) at baseline (Phase 1 of CATIE-AD). Intervention Subjects were randomly assigned to treatment with olanzapine, quetiapine, risperidone, or placebo in a double-blind manner. Measurements We examined associations between response at week 8, and demographic and clinical characteristics, including BPRS total score reduction at week 2, using logistic regression analyses. Prediction performance of binary classification (presence/absence) of improvement/no improvement at week 2 for response at week 8 was examined. Results BPRS total score reduction at week 2 (mean percentage score reduction, 12.6%) was significantly associated with response at week 8 (odds ratio, 1.18; 95% CI, 1.11–1.26). The 5% score reduction cut-off at week 2 showed the highest accuracy (0.71) with sensitivity, specificity, PPV, and NPV of 0.76, 0.65, 0.69, and 0.72, respectively. Conclusion Lack of even a very small early improvement with antipsychotic treatment may be a marker of subsequent non-response in BPSD.

Association between antipsychotics and adverse outcomes in dementia

“…However, research suggests that the risk of mortality is associated with longer use and higher doses. 18 Despite our study indicating that adverse effects occurred when individuals took risperidone at a mean dose of 0.5mg daily (Table 5), other studies suggest that adverse outcomes are more likely to occur at 2mg dosing rather than 1mg dosing. 11 Studies suggest using doses of 5-10mg/day for aripiprazole (which occurred at a mean dose of 5mg/day in our study) to avoid side-effects.…”

Placebo effects in adult and adolescent patients with schizophrenia: combined analysis of nine RCTs

“…This has been identified to be the case for antipsychotic treatment for schizophrenia and antidepressant therapy for depression . Moreover, also in patients with behavioral and psychological symptoms of dementia, in whom a reduction in the Brief Psychiatric Rating Scale (BPRS) total score after 2‐week antipsychotic treatment was significantly associated with subsequent treatment response at week 8 . Furthermore, such a phenomenon has also been noted for placebo treatment for behavioral and psychological symptoms of dementia (BPSD) .…”

Assessment of the Risk of Antipsychotics in Patients with Dementia in Actual Clinical Practice in Primary Health Care

“…The proportion of adverse effects appearance in these patients is around 25% [18,24,29]. The most common are drowsiness, migraines, appetite changes, and weight gain or anticholinergic symptoms such as slow march, tremors, hypersalivation, and loosening of facial expressions.…”

“…Hence, the effectiveness of treatments should be evaluated within the first 2-4 weeks, and every 3-4 months, using the same scale and criteria used in previous evaluations [4][5][6][7][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Lack of clinical response or adverse effects occurrence are criteria to stop treatments with antipsychotic drugs [4,23,24]. These treatments should not become chronic if there is not a medical indication based on evidence.…”