Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

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all patients

1st line – supportive care

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1st line – 

supportive care

Provide education and support for the patient and their families and caregivers, focusing on the key behavioral and psychologic symptoms of frontotemporal dementia (FTD) and how these translate to care needs. Planning should focus on meeting current needs and anticipating future issues. It is important to address long-term care needs early, because early planning and action maximize options and the patient's ability to participate. Family and caregivers should be empowered to assist the patient in making decisions regarding health and property, managing finances, taking drug treatments, cooking meals, etc.

Case managers in collaboration with family physicians may have a role in addressing the needs of the patient. They should coordinate and integrate referral, transitions, and communication across all agencies involved in the assessment, treatment, support, and care of people with dementia, their caregiver(s), and families.[154]

It is essential to establish and record, early in the course of the illness, the preferences of the patient and family regarding end-of-life interventions, including treatment, resuscitation, and prolonging life when treatable conditions arise.[201][202]

A home safety evaluation should be undertaken, as well as an assessment of transport, driving, and self-care needs by an occupational therapist. Modification of the physical environment, such as room temperature and light and noise levels, may be appropriate.[155] Roaming behavior can serve a purpose for patients with behavioral variant FTD and so should not be completely discouraged, but may require supervision. The patient will typically follow the same pattern or routine. Providing a safe protected area for roaming that is free of clutter and obstacles, and wearing nonslip footwear, will help reduce fall risk.

Strategies that may improve communication between caregivers and patients with FTD include using short sentences, explaining things, making eye contact, and active listening.[156] Patients with dementia may be more willing to cooperate with care tasks when caregivers use high entitlement requests (e.g., "I’m going to do X" or "I need to do X") rather than low entitlement requests (e.g., "Is it ok if I do X?" or "Do you mind if I do X?").[157]​ Correcting or confronting the patient should be avoided; it is important to remain calm, and move away from the patient if challenging behavior occurs.[158]

Family and caregivers should be educated in communication and other techniques. Caregivers are often exposed to aggressive behavior from patients with behavioral variant FTD, which can cause significant stress; a behavior log may help to identify precipitators and patterns of aggression and warning signs.[156][159]​​ Caregivers should be advised about coping techniques, and about local and national support organizations. An intervention that provides caregivers with personalized, structured post-diagnostic support can help them provide high-quality care to patients with dementia at home.[160]

Many patients require professional help in the home to provide respite to the family, and supervision and assistance to the patient. Daycare services can offer respite to caregivers and patients, and may be used in combination with in-home care. In many cases, continued home care is no longer possible due to the nature of the care situation (e.g., a spouse who cannot retire) or to problem behaviors (e.g., night-time roaming, belligerent behavior). Patients who require residential care should generally be cared for in a specialist dementia unit.

End-of-life care generally is focused on providing comfort and basic needs (e.g., help with feeding and cleanliness, adequate pain control, good skin care, and prevention of injury through falls or misadventure). Behavioral complications other than loss of willpower and lethargy are uncommon at this stage and do not warrant pharmacologic intervention. Swallowing difficulties are not uncommon and can be managed by diligent hand feeding and varying the consistency of the diet. For patients who choke frequently on food or lose the ability to swallow, feeding by gastrostomy tube may help in the short term, but does not improve survival, morbidity, or quality of life in the long term.[204][205]​​​​

Consider – nonpharmacologic and behavioral interventions

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all patients
Consider – 

nonpharmacologic and behavioral interventions

Treatment recommended for SOME patients in selected patient group

The aim of nonpharmacologic strategies is to prevent problematic behaviors, relieve behavioral symptoms, and reduce caregiver distress.

Nonpharmacologic and behavioral approaches comprise various types of intervention: cognitive and emotion-oriented approaches (e.g., cognitive stimulation, reminiscence therapy, validation therapy), sensory stimulation (e.g., music and dance therapy, touch therapy), behavior management techniques, multicomponent interventions, and other therapies (e.g., exercise).[161]​ In addition, nonpharmacologic approaches to management in frontotemporal dementia (FTD) include lifestyle modifications, speech, occupational, and physical therapy, peer and caregiver support, and safety considerations.[162]​ Lifestyle modifications including aerobic exercise increase strength and balance, and may prevent falls.

Nonpharmacologic strategies may be as or more effective than pharmacologic treatments, and have fewer adverse effects.[163][164][165]​ One Cochrane review evaluating the effectiveness of psychologic interventions to reduce the use of antipsychotics in care home residents was unable to make a conclusion because of low certainty evidence. However, the study found that psychosocial interventions are not associated with an increase in harmful events such as accidental falling or hospital admissions.[166]

Cognitive stimulation therapy or cognitive training may improve cognitive function among patients with mild to moderate dementia, but evidence is of low quality.[167][168]

One meta-analysis concluded that music‐based therapeutic interventions may reduce depressive symptoms, and improve overall behavioral problems and social behavior, in people with dementia, but likely have no effect on agitation, aggression, anxiety, emotional well-being, or cognition.[169]​ Music therapy combined with physical activity may be useful in controlling anxiety, irritability, and restlessness in patients with FTD.[170]​ One systematic review found that massage and touch therapy, and cognitive stimulation combined with exercise and social interaction were more efficacious than usual care at reducing the symptoms of depression in people with dementia.[165]

Cognitive behavioral therapy and other types of psychologic therapy may help reduce symptoms of depression and/or anxiety in patients with dementia.[171][172]

Studies comparing pharmacologic and nonpharmacologic interventions for treating aggression and agitation in adults with dementia have found that multidisciplinary care, massage and touch therapy, music combined with massage and touch therapy, animal-assisted intervention, and personally tailored interventions were clinically more efficacious than usual care.[165][174]

Sleep disturbances (e.g., insomnia, night-time restlessness, night-time roaming) are not uncommon in patients with FTD.[175]​ There is no evidence about specific interventions for patients with FTD, but keeping active during the day, avoiding naps, and good sleep hygiene may improve sleep quality. One Cochrane review found that physical and social activities, as well as caregiver interventions, may have some benefits on sleep for people with dementia.[176]​

Treatment of some behavioral and psychologic symptoms, including disinhibition, apathy, compulsions, and hypersexuality, in people with FTD remains a challenge in clinical practice. Although some pharmacologic treatments show promise, none demonstrate clear symptom benefit and nonpharmacologic treatment continues to be a fundamental tool for the management of these symptoms. Some strategies that might be helpful include: encouraging engagement in recreational activities or games to reduce disinhibition; using receptive music therapy to help prevent apathy; providing alternative strategies to limit compulsive behaviors, such as using a stress ball to prevent touching strangers, or sucking a lollipop to diminish repetitive vocalization; delivering psychoeducation, support groups, and tailored interventions for patients and caregivers to alleviate emotional and psychologic distress caused by hypersexuality.[81][177][178][179]​​

Consider – benzodiazepine or antipsychotic

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all patients
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with acute irritability, restlessness, agitation, or aggression
Consider – 

benzodiazepine or antipsychotic

Treatment recommended for SOME patients in selected patient group

A benzodiazepine or an antipsychotic may be trialled if nonpharmacologic treatments have proved unsuccessful, although evidence for efficacy is limited.[180][182][183]

When rapid sedation is required and nondrug interventions (e.g., distraction techniques, de-escalation techniques, massage, touch therapy) have not been effective, or when personal injury seems likely, a benzodiazepine (e.g., lorazepam) can provide useful short-term benefits. These drugs can also be used in planned combination with nondrug treatments, although their benefit in the long-term management of aggressive behavior is not established.

Introduction of sedative drugs and principles governing their use, including risks, should be discussed with the patient's main caregivers or relatives. Treatment should be time-limited and regularly reviewed. Regular review of sedatives should include examination for possible parkinsonian adverse effects and akathisia, because these may prolong behavioral problems (or be misidentified as behavioral problems), as well as monitoring for metabolic and cardiovascular adverse effects.[182]

Alternatively, an antipsychotic drug can be used. Antipsychotic drugs are associated with serious adverse effects and increased mortality in patients with dementia.[184][185] ​Patients with frontotemporal dementia (FTD) are susceptible to adverse reactions to antipsychotics, especially their extrapyramidal adverse effects. Therefore, these drugs should only be considered if symptoms are severe, are dangerous, and/or cause significant distress to the patient; physicians and families must consider the potential risks and benefits of antipsychotics for the individual patient. The American Psychiatric Association has published practice guidelines on the use of antipsychotics to treat agitation in dementia.[182]​ Treatment should be time-limited and regularly reviewed. Use of these drugs is off-label for this indication. In patients with FTD and severe behavioral disturbances who invariably require an antipsychotic, atypical antipsychotics (e.g., risperidone, quetiapine, olanzapine) are preferred as they have fewer extrapyramidal effects. Atypical antipsychotics improve psychiatric and behavioral symptoms in some patients with FTD.[189]

Antipsychotics may increase the risk of falls, so strategies to prevent falls should be implemented.[186]

No advantages in terms of efficacy or safety have been identified for any specific antipsychotic drugs for the treatment of behavioral and psychologic symptoms of dementia, although one meta-analysis found that risperidone was probably the best option for short-term use.[187][188]​ In order to avoid polypharmacy, antipsychotics that can be used safely by both the oral route and injection are sometimes preferred. Initial doses of an antipsychotic should aim to achieve optimum benefit at the minimum possible dose.

Generally, antipsychotics should be avoided in patients who already manifest parkinsonism as a feature of the dementia. However, if the need for an antipsychotic arises, quetiapine would be the preferred option for cases complicated by parkinsonism.

There is an increased risk of stroke with antipsychotics for patients with dementia.

Antipsychotics may be used for other symptoms associated with dementia (e.g., psychosis), so it is important to make sure the patient is not already on an antipsychotic before starting treatment for this indication.

Primary options

lorazepam: 2 mg orally/intramuscularly every 30-60 minutes when required, maximum 10 mg/day

Secondary options

risperidone: 0.25 mg orally twice daily initially, increase gradually according to response, maximum 1 mg/day

OR

quetiapine: 25 mg orally once daily at bedtime initially, increase gradually according to response, maximum 150 mg/day given in 2 divided doses

OR

olanzapine: 2.5 mg orally once daily initially, increase gradually according to response, maximum 10 mg/day; 2.5 to 5 mg intramuscularly initially, may repeat at least 2 hours after first dose based on response, and may repeat again at least 1 hour after the second dose, maximum 12.5 mg/episode

Consider – antipsychotic

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all patients
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with psychosis
Consider – 

antipsychotic

Treatment recommended for SOME patients in selected patient group

​Managing psychosis in people with frontotemporal dementia (FTD) can be challenging. Antipsychotics are associated with serious adverse effects and increased mortality in patients with dementia.[184][185]​ Patients with FTD are susceptible to adverse reactions to antipsychotics, especially their extrapyramidal adverse effects. Therefore, these drugs should only be considered if symptoms are severe, are dangerous, and/or cause significant distress to the patient; physicians and families must consider the potential risks and benefits of antipsychotics for the individual patient. The American Psychiatric Association has published practice guidelines on the use of antipsychotics to treat psychosis in dementia.[182]​ Treatment should be time-limited and regularly reviewed. Use of these drugs is off-label for this indication. In patients with FTD and severe behavioral disturbances who invariably require an antipsychotic, atypical antipsychotics (e.g., risperidone, quetiapine, olanzapine) are preferred as they have fewer extrapyramidal effects. 

Atypical antipsychotics improve psychiatric and behavioral symptoms in some patients with FTD.[189]

Antipsychotics may increase the risk of falls, so strategies to prevent falls should be implemented.[186]​​

In order to avoid polypharmacy, antipsychotics that can be used safely by both the oral route and injection are sometimes preferred. Initial doses of an antipsychotic should aim to achieve optimum benefit at the minimum possible dose.

Generally, antipsychotics should be avoided in patients who already manifest parkinsonism as a feature of the dementia. However, if the need for an antipsychotic arises, quetiapine would be the preferred option for cases complicated by parkinsonism.

There is an increased risk of stroke with antipsychotics for patients with dementia.

Antipsychotics may be used for other symptoms associated with dementia (e.g., irritability, restlessness, agitation, aggression), so it is important to make sure the patient is not already on an antipsychotic before starting treatment for this indication.

Primary options

risperidone: 0.25 mg orally twice daily initially, increase gradually according to response, maximum 1 mg/day

OR

quetiapine: 25 mg orally once daily at bedtime initially, increase gradually according to response, maximum 150 mg/day given in 2 divided doses

OR

olanzapine: 2.5 mg orally once daily initially, increase gradually according to response, maximum 10 mg/day; 2.5 to 5 mg intramuscularly initially, may repeat at least 2 hours after first dose based on response, and may repeat again at least 1 hour after the second dose, maximum 12.5 mg/episode

Plus – treatment of concurrent illness

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all patients
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with concurrent urinary or pulmonary infection
Plus – 

treatment of concurrent illness

Treatment recommended for ALL patients in selected patient group

Behavioral complications of frontotemporal dementia may derive in part or full from concurrent illness, which may manifest as heightened confusion and disorientation, irritability, agitation, hallucinations, and paranoia. Treatment of the underlying illness will usually lead to a prompt resolution of the acute cognitive and behavioral state.

Choice of antibiotic regimen depends on disease severity, treatment setting, and causal agent; regimens should follow accepted guidelines for drug treatment of older adults.[200]

See Community-acquired pneumonia in adults, Urinary tract infections in women, and Urinary tract infections in men.

Decisions to withhold treatment must not be made when the patient is unwell and the infection is first detected. Rather, they must be made, if at all, when the patient is well and in consultation with relatives and senior nursing staff. This type of decision must be recorded and must be open to scrutiny.

Consider – pharmacotherapy

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all patients
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with sleep disturbances
Consider – 

pharmacotherapy

Treatment recommended for SOME patients in selected patient group

Sleep disturbances, such as insomnia, night-time restlessness, and night-time roaming, are not uncommon in patients with frontotemporal dementia (FTD).[175]

Pharmacologic intervention may be required when sleep hygiene regimens are not effective or impractical.

These interventions have not been formally evaluated in patients with FTD, their use deriving from experience in a wide range of neuropsychiatric conditions, including Alzheimer disease and other non-FTD dementias.

Successful treatment of sleep disturbances may have secondary benefits in improving mood and drive, and ameliorating distractibility and irritability.

A preferred pharmacologic approach is difficult to define due to the lack of evidence in patients with FTD, variation in the clinical picture and neuropathology, and uncertainty around the balance of benefits and risks. Drugs that may be considered include mirtazapine (at low doses), zolpidem, eszopiclone, zaleplon, trazodone, melatonin, ramelteon, and a benzodiazepine (e.g., clonazepam).[190]

Several of these drugs may be associated with an increased risk of falls and fractures in older people and those with dementia.[191][192]

Higher doses of zolpidem and eszopiclone may cause next-day drowsiness and psychomotor or memory impairment. Higher doses of zolpidem should not be used in women.

Primary options

mirtazapine: 7.5 to 15 mg orally once daily at bedtime

OR

zolpidem: 5 mg orally (immediate-release)/sublingually once daily at bedtime; 6.25 mg orally (extended-release) once daily at bedtime

OR

eszopiclone: 1-2 mg orally once daily at bedtime

OR

zaleplon: 5-10 mg orally once daily at bedtime

OR

trazodone: 25-150 mg orally once daily at bedtime

OR

melatonin: 0.3 to 2 mg orally once daily at bedtime

More

OR

ramelteon: 8 mg orally once daily at bedtime

OR

clonazepam: 0.25 to 0.5 mg orally once daily at bedtime

Consider – amantadine

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all patients
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with distractibility or perseveration
Consider – 

amantadine

Treatment recommended for SOME patients in selected patient group

Amantadine is an option for the treatment of dysexecutive states associated with dementia.[193]

Use of memantine (a drug related to amantadine that is used to treat moderate to severe Alzheimer disease) for treatment of frontotemporal dementia (FTD) is not uncommon, but there is insufficient evidence to support any conclusions about efficacy, and memantine has no place in the treatment of FTD.[194][195]

Careful observation in the first week after initial prescription and each increase in the dose of amantadine is required.

Primary options

amantadine: 50-100 mg orally twice daily initially, increase according to response, maximum 400 mg/day

Consider – valproate semisodium or topiramate

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all patients
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with euphoria, excitability, mania, impulsivity, irritability, persistent restlessness, persistent agitation, or persistent aggression
Consider – 

valproate semisodium or topiramate

Treatment recommended for SOME patients in selected patient group

Anticonvulsants are used widely in neuropsychiatry for the treatment of manias, hypomanias, labile emotions, impulsions, irritability, agitation, and aggression.

Typically valproate semisodium (valproic acid and sodium valproate in a 1:1 ratio) is prescribed (unless the main indication is a co-occurring epileptic state); there are reports suggesting value in the treatment of FTD complicated by agitation, but no controlled-trial data.[196][197]

There is some evidence for topiramate as an anti-impulsive agent.[180]

Valproic acid and its derivatives may cause major congenital malformations, including neurodevelopmental disorders and neural tube defects, after in utero exposure. These agents must not be used in female patients of childbearing potential unless other options are unsuitable, there is a pregnancy prevention program in place, and certain conditions are met. Precautionary measures may also be required in male patients owing to a potential risk that use in the 3 months leading up to conception may increase the likelihood of neurodevelopmental disorders in their children. Regulations and precautionary measures for female and male patients may vary between countries, with some countries taking a more heightened precautionary stance, and you should consult your local guidance for more information.

In some countries, topiramate is also contraindicated in pregnancy and in women of childbearing age unless the conditions of a pregnancy prevention program are fulfilled to ensure that women of childbearing potential: are using highly effective contraception; have a pregnancy test to exclude pregnancy before starting topiramate; and are aware of the risks associated with use of the drug.

Primary options

valproate sodium: consult specialist for guidance on dose

Secondary options

topiramate: consult specialist for guidance on dose

Consider – topiramate

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all patients
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with abnormal eating behavior
Consider – 

topiramate

Treatment recommended for SOME patients in selected patient group

Topiramate is known to suppress appetite for food. There have been some case reports suggesting effectiveness in patients with abnormal eating behavior associated with frontotemporal dementia.[180][198]

Primary options

topiramate: consult specialist for guidance on dose

Consider – dextromethorphan/quinidine

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all patients
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with pseudobulbar affect
Consider – 

dextromethorphan/quinidine

Treatment recommended for SOME patients in selected patient group

Patients with frontotemporal dementia with motor neuron disease and progressive supranuclear palsy may show symptoms of pseudobulbar affect, characterized by sudden bouts of uncontrollable crying or laughter.

Symptoms may respond to dextromethorphan/quinidine, which specifically targets pseudobulbar affect.[199]

Primary options

dextromethorphan/quinidine: 20 mg (dextromethorphan)/10 mg (quinidine) orally once daily for 7 days, followed by 20 mg (dextromethorphan)/10 mg (quinidine) twice daily

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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