Antidepressant Ineffective Against Apathy in Alzheimer’s Patients

A recent analysis of a randomized clinical trial found that the antidepressant bupropion was not superior to a placebo for the treatment of apathy in patients with dementia of Alzheimer type (DAT) without a depressed mood.

The double-blind, placebo-controlled, randomized clinical trial conducted between July 2010 and July 2014 in Germany enrolled patients with mild-to-moderate dementia of Alzheimer type. 

Patients were eligible for the study if they were aged 55 to 90 years old, had a Mini-Mental State Examination (MMSE) score between 10 and 25, and had a caregiver who was willing to participate as a study partner, researchers stated in the analysis published in JAMA Network Open.

As the most frequent neuropsychiatric symptom in patients with dementia of Alzheimer type, apathy greatly affects the disease course, activities of daily living, and quality of life, researchers noted. 

The analysis measured any change on the Apathy Evaluation Scale-Clinician Version (AES-C) between the baseline and week 12. The data analyses were performed between August 2018 and August 2019.

Out of 108 participants, half received 150 mg of bupropion and the other half received 150 mg of a placebo for four weeks plus 300 mg for eight weeks.  

Results for the primary outcome measure showed no statistically significant effect of bupropion compared with placebo on the mean change of the AES-C total score between baseline and 12 weeks.

Specifically, the mean apathy score was 7.2 versus 7.3 and the Neuropsychiatric Inventory (NPI) depression score was 0.6 versus 0.4. This indicated that change in the Apathy Evaluation Scale–Clinician Version score was not statistically significant between the treatment groups.

Apathy also increased caregiver burden and is associated with increased mortality, researchers found. 

Secondary outcomes showed that the mean change between the baseline and 12 weeks for NPI showed a greater reduction in neuropsychiatric symptoms in the placebo group than in the bupropion group and a higher reduction of caregiver’s distress in the placebo group than in the bupropion group.

Secondary outcomes also showed statistically significant differences between bupropion and placebo in terms of total neuropsychiatric symptoms and health-related quality of life. There was significantly greater improvement in the placebo group.

Seventy-two percent of bupropion-treated patients and 61.1 percent of placebo-treated patients experienced at least one adverse event. Of the 150 adverse events, 62.67 percent occurred in bupropion-treated patients and 37.33 percent occurred in the placebo-treated patients. 

The most frequent adverse events reported included gastrointestinal symptoms, which occurred more often in the placebo group than in the bupropion group. Other individuals experienced difficulty sleeping, falls, and unrest or confusion.

Although seven patients experienced serious adverse events that lead to hospitalization, researchers said that these serious events were most likely unrelated to the study medication.

The number of commercially insured Americans between the ages of 30 and 64 years diagnosed with early-onset dementia or Alzheimer’s disease increased by 200 percent from 2013 to 2017, according to an assessment of claims data from Blue Cross Blue Shield Association (BCBSA). 

The report was based on claims data for more than 48 million commercially insured members of BCBSA and uncovered that more than 37,000 commercially insured Americans between 30 and 64 were diagnosed in 2017, a 131 percent increase since 2013.

Researchers noted that an effective treatment of apathy may be achieved with a pharmacological compound that increases dopaminergic and noradrenergic neurotransmission. 

“In this study, bupropion was not superior to placebo for the treatment of apathy in patients with DAT and apathy in the absence of clinically relevant depression. Because of the substantial impact of apathy on patients’ quality of life, more randomized clinical trials are needed to find an efficient treatment,” researchers said in the study.

“Future studies are required to further analyze the pathophysiological mechanisms and neurotransmitter alterations underlying apathy in DAT.”