Journal Article Annotations
2024, 3rd Quarter
Annotations by Nathan Praschan, MD, MPH and Laura Duque, MD
October, 2024
The finding:
Compared to placebo, SSRIs demonstrate potential benefits in managing depressive and behavioral symptoms in patients with Alzheimer’s Dementia (AD). There was no significant difference in cognitive outcomes between the SSRI and placebo groups. Although patients on SSRIs experienced more adverse effects, these reactions were not statistically significant when compared to the placebo group.
Strength and weaknesses:
The study had a robust sample size, examining 1586 patients diagnosed with ADfrom 14 articles. There was moderate heterogeneity in study designs and variability in sample sizes and dosing regimens. Notably, the authors included olanzapine and quetiapine within the SSRI category. This inclusion may obscure the overall findings, as these medications have different side effect profiles and target distinct symptoms. The absence of subgroup analyses, distinguishing between specific medications and symptom categories, further limits the analysis of the findings.
Relevance:
Patients with AD frequently exhibit a complex array of neuropsychiatric manifestations and are often evaluated by C-L psychiatrists. This meta-analysis highlights the potential efficacy of SSRIs, along with quetiapine and olanzapine, in managing depressive and behavioral symptoms in AD.
The finding:
The authors conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) for the management of behavioral and psychological symptoms of dementia (BPSD)—inclusive of Alzheimer’s disease, vascular dementia, mixed dementias, and exclusive of Parkinsonian dementias. They included 20 RCTs of over 6000 patients in the network meta-analysis, and found that brexpiprazole was the most efficacious medication against placebo, followed by risperidone, quetiapine, olanzapine, and aripiprazole. Meanwhile, aripiprazole was found to be best tolerated—defined by odds of discontinuation due to side effects compared to placebo—followed by quetiapine, risperidone, brexpiprazole, and olanzapine. Adverse events included mortality (no difference from placebo), sedation (quetiapine most likely), extra pyramidal symptoms (olanzapine), cardiovascular events (risperidone), and urinary symptoms (quetiapine).
Strength and weaknesses:
This is among the first meta-analyses to include brexpiprazole, a relatively new second-generation antipsychotic that has shown promise for managing BPSD. The study allows direct comparison between medications that have not been studied head-to-head in the same trial, which can meaningfully inform practice patterns. Furthermore, this study analyzed the relative likelihoods of common adverse events of neuroleptics compared to placebo and the other studied drug. There was low risk of publication bias based on a funnel plot. Unfortunately, this study did not include other medications commonly used to manage behavioral disturbances in dementia, including SSRIs and cholinesterase inhibitors.
Relevance:
While outpatient providers are faced with longitudinal management of milder behavioral symptoms, CL psychiatrists are often faced with the problem of acute and severe symptoms risking the safety of patients, family members, and staff. Thus, quickly and effectively managing agitation due to dementia is paramount and often necessitates the use of neuroleptics before the benefits of safer medications (SSRIs, cholinesterase inhibitors) can take effect. Based on this study, the CL psychiatrist would do well to consider brexpiprazole (given its efficacy) and aripiprazole (given its tolerability) for such presentations.