While ongoing research is leading to a greater understanding of the molecular basis of FTD, no disease-modifying treatments have yet been approved by the U.S. Food and Drug Administration. There is no available medication or treatment that has been proven to prevent, cure or slow the decline of these disorders.
However, many FTD symptoms can be treated. Both pharmacologic and behavioral interventions are available for symptomatic benefit of specific cognitive and behavioral features. In FTD, non-pharmacological interventions should be considered first, with medications considered in conjunction with such treatments.
When prescribing drugs to FTD patients, clinicians should ask the patient and caregivers which symptom is most problematic and target that for treatment first. Such clarity helps to manage expectations and facilitates the family’s understanding of whether the clinician is attempting to treat a symptom that is directly related to FTD (e.g., obsessive-compulsive behaviors) or one that is a responsive behavior (e.g., patient is bored and seeking stimulation). Involving and educating caregivers in this way helps them to be better partners in monitoring the medications for their effects.
A limited number of open-label studies and placebo controlled studies have researched the use of psychiatric, Alzheimer’s and other medications in FTD (Tsai and Boxer 2016; Boxer and Boeve, 2007; Huey et al., 2006). While pharmacological intervention is expected to improve with advancing research, existing agents can be used to address symptoms and contribute to patient and caregiver quality of life (Jicha and Nelson, 2011).
Selective Serotonin Reuptake Inhibitors
Selective serotonin reuptake inhibitors (SSRIs) are often useful treating a wide range of behavioral symptoms in FTD, including apathy, depression, agitation, anxiety, and obsessive-compulsive behaviors. These agents are considered relatively safe in the dementia population.
Aggressive and agitated behavior can be difficult to treat, and are problematic for caregivers. Antipsychotic medications should be avoided when possible due to the increased mortality, stroke and cardiac complications of these medications in (elderly) dementia patients. The risk of these life-threatening complications in younger FTD patients is not known, but florid psychotic features and other safety-related behaviors that do not respond to SSRIs may require the use of this class of agents. However, other serious adverse responses may also occur. Similar to patients with other non-Alzheimer’s dementias, FTD patients may be overly sensitive to adverse responses with these agents, especially those involving motor functioning (e.g. Parkinsonism and tardive dystonia).
Clinicians must weigh the pros and cons of using neuroleptics in general, and specifically which class to use (typical or atypical), which specific agent to use, and at which dose. There are no evidence-based analyses to assist the clinician in making these decisions. Side effects (sedation, parkinsonism, tardive dyskinesia) are far more common in the typical neuroleptics, but this class — specifically haloperidol — may be a reasonable choice if cost is a major concern. Most clinicians nowadays use the atypical neuroleptics as they tend to be better tolerated, have reasonable efficacy (based purely on anecdotal experience) and are not cost-prohibitive for most patients/families. The usual dictum is critical: “Start low and go slow” when any medication in the antipsychotic class is commenced, and titrate upward as necessary and tolerated.
Several medications are approved for symptomatic treatment of the cognitive symptoms of AD. These are sometimes prescribed off-label for FTD patients. Cholinesterase inhibitors provide temporary stabilization or modest improvement in attention/memory, activities of daily living and global functioning in Alzheimer’s because those patients have reduced CNS acetylcholine levels. FTD patients do not have cholinergic loss; however, these agents have been studied in the treatement of FTD and have shown disappointing results. Routine use is not recommended (Tsai and Boxer, 2016).
Although cholinesterase inhibitors help with behavioral symptoms (including apathy) in Alzheimer’s, FTD patients may have adverse responses, including worsening impulsivity and disinhibition, so care should be taken in using these agents in FTD patients with prominent behavior problems. Many doctors prescribe these medications as a trial, especially when the etiology of disease is not definitive.
Northwestern Medicine’s Cognitive Neurolology and Alzheimer’s Disease Center’s resource on PPA diagnosis and treatment notes: “Because of the 30%-40% probability of Alzheimer’s disease (AD), some physicians will prescribe AD drugs such as Exelon (rivastigmine), Razadyne (galantamine), Aricept (donepezil) or Namenda (memantine). None have been shown to improve PPA.”
The N-methyl-D-aspartate receptor antagonist memantine (Namenda) is the other FDA approved cognitive enhancer for Alzheimer’s. However, research on the use of this drug in FTD using a placebo-controlled, double-blind approach has not shown it to be efficacious. Some studies suggest that this agent may actually have a detrimental effect on cognition in some individuals with FTD (Boxer, et al., 2013).
Benzodiazepine Antianxiety Drugs
The use of benzodiazepines such as lorazepam (Ativan®); alprazolam (Xanax®); clonazepam (Klonopin®); and diazepam (Valium®) in people with FTD may increase confusion and risk of falls and should therefore be used with caution.
Many people with FTD present with parkinsonism including tremors, rigidity, movement difficulties and bradykinesia. PSP and CBD are FTD disorders that are characterized by atypical Parkinson symptoms. Unfortunately, parkinsonism in FTD is not very treatable. Patients are minimally responsive to L-DOPA (van Swieten, et al., 2010).
Another class of medications that needs to be used with extreme caution for behaviors in FTD are the psychostimulant agents [e.g., methylphenidate (Ritalin), dextroamphetamine (Dexedrine), etc.]. Adverse outcomes are not rare and these drugs should be a last resort (Dolder, Davis and McKinsey, 2010).
The UCSF Memory and Aging Center also offers a helpful resource, Medications in Dementia, that you may wish to consider.
Since the medication management of this patient group is complicated, primary care physicians may want to refer FTD patients with behavior problems to academic centers specializing in FTD. Unfortunately, there are no medications that help with the poor judgment and inappropriate behaviors that are so common in FTD. Non-pharmacological interventions – including OT, PT, speech therapy, behavioral and environmental changes, and support – are the most effective interventions available today. These are essential as supplement and general alternative to medications. Caregiver education is key. Caregivers should also be referred to AFTD for advice on available resources in their area.
- Boxer AL, Tsai RM. Therapy and clinical trials in frontotemporal dementia: past, present, and future. Journal of Neurochemistry. 2016 Aug; 138(Suppl 1): 211–221.
- Boxer AL, Knopman DS, Kaufer DI, Grossman M, Onyike C, Graf-Radford N, Mendez M, Kerwin D, Lerner A, Wu CK, Koestler M, Shapira J, Sullivan K, Klepac K, Lipowski K, Ullah J, Fields S, Kramer JH, Merrilees J, Neuhaus J, Mesulam MM, Miller BL. Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2013 Feb; 12(2): 149-56.
- Jicha GA and Nelson PT. Management of frontotemporal dementia: targeting symptom management in such a heterogeneous disease requires a wide range of therapeutic options. Neurodegener Dis Manag. 2011 April; 1(2): 141–156.Alagiakrishnan K, Bhanji RA, Kurian M. Evaluation and management of oropharyngeal dysphagia in different types of dementia: a systematic review. Arch Gerontol Geriatr. 2013 Jan-Feb; 56(1):1-9.