A 53-year-old woman is brought to the office by her husband for follow-up evaluation of behavioral-variant frontotemporal dementia, which was diagnosed 9 months ago. Her clinical symptoms of occasional aphasia, minor memory impairment, behavioral disinhibition, and obsessive-compulsive behaviors have worsened since diagnosis and have become disruptive. She is currently estranged from her son and his family after bringing a large bag filled with plastic bottles collected from his neighbors' trash cans to her granddaughter's birthday party 2 weeks ago. Her husband asks about possible medications to control her symptoms.
Which of the following is the most appropriate medication to recommend?
MKSAP Answer and Critique
The correct answer is A. Citalopram. This content is available to MKSAP 18 subscribers as Question 8 in the Neurology section. More information about MKSAP is available online.
This patient should be given the selective serotonin reuptake inhibitor citalopram to control her obsessive-compulsive behaviors. Early changes in social behavior and personality are the defining characteristics of behavioral-variant frontotemporal dementia (FTD). Apathy, diminished interest, loss of empathy, lack of initiative, increased emotionality, disinhibition, euphoria, impulsivity, changes in eating behaviors, hyperorality, and compulsiveness are the most common symptoms reported by families. Other changes include irritability, aggression, verbal abuse, hypomania, and restlessness. The treatment of behavioral-variant FTD is symptom based and should target the most troubling manifestations of the disorder. This patient's obsessive-compulsive tendencies not only have had embarrassing consequences but have resulted in a confrontation with family members. Selective serotonin reuptake inhibitors, such as citalopram, have the potential to alleviate these symptoms. Tricyclic antidepressants may also have this effect.
The acetylcholinesterase inhibitor donepezil is approved by the FDA to treat mild to moderate Alzheimer disease. This class of drug has shown modest benefit in improving cognitive performance in patients with this type of dementia without clear improvements in daily functioning. The body of evidence does not support acetylcholinesterase inhibitors as being beneficial in behavioral-variant FTD.
Similarly, the N-methyl-D-aspartate receptor antagonist memantine, which is approved for moderate to severe dementia in patients with Alzheimer disease associated with significant functional impairment, has shown no benefit in in patients with behavioral-variant FTD and may, in fact, worsen symptoms.
In patients with severe apathy, which can be a common and sometimes debilitating symptom of behavioral-variant FTD, stimulant medications, such as methylphenidate, are sometimes used. This patient has not exhibited apathy. More importantly, referral to a psychiatrist or neurologist is generally recommended before dispensing these medications.
Atypical antipsychotic agents (such as olanzapine) can be effective in treating agitation, aggression, delusions, and hallucinations. However, these drugs are not FDA approved for this clinical indication and have an associated black-box warning due to increased cerebrovascular events and mortality rates in patients with dementia. Olanzapine can be considered if there are psychotic symptoms, such as hallucinations or psychotic delusions. This patient has exhibited no psychotic symptoms. In general, antipsychotic agents should be avoided in patients with dementia.
- Because there are currently no disease-modifying treatments for behavioral-variant frontotemporal dementia, treatment is symptom based and should target the disease's most troublesome manifestations.