Pharmacotherapy for behavioural manifestations in frontotemporal dementia: An expert consensus from the European Reference Network for Rare Neurological Diseases (ERN-RND)

Abstract

Background and purpose: Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by pervasive personality and behavioural disturbances with severe impact on patients and caregivers. In current clinical practice, treatment is based on nonpharmacological and pharmacological approaches. Unfortunately, trial-based evidence supporting symptomatic pharmacological treatment for the behavioural disturbances in FTD is scarce despite the significant burden this poses on the patients and caregivers.

Method: The study examined drug management decisions for several behavioural disturbances in patients with FTD by 21 experts across European expert centres affiliated with the European Reference Network for Rare Neurological Diseases (ERN-RND).

Results: The study revealed the highest consensus on drug treatments for physical and verbal aggression, impulsivity and obsessive delusions. Antipsychotics (primarily quetiapine) were recommended for behaviours posing safety risks to both patients and caregivers (aggression, self-injury and self-harm) and nightly unrest. Selective serotonin reuptake inhibitors were recommended for perseverative somatic complaints, rigidity of thought, hyperphagia, loss of empathy and for impulsivity. Trazodone was specifically recommended for motor unrest, mirtazapine for nightly unrest, and bupropion and methylphenidate for apathy. Additionally, bupropion was strongly advised against in 10 out of the 14 behavioural symptoms, emphasizing a clear recommendation against its use in the majority of cases.

Conclusions: The survey data can provide expert guidance that is helpful for healthcare professionals involved in the treatment of behavioural symptoms. Additionally, they offer insights that may inform prioritization and design of therapeutic studies, particularly for existing drugs targeting behavioural disturbances in FTD.

Keywords: drug therapy; expert testimony; frontotemporal dementia; neurobehavioural manifestations; neurodegenerative diseases.

FIGURE 1

Distribution of physicians by the number of treatments selected for each behavioural symptom recommended by physicians (a) or marked as contraindicated (b). The symptoms are ordered along the x‐axis, with those having the highest number of physicians not selecting any recommended treatment on the right, whilst symptoms where all physicians chose at least one treatment are positioned on the left. The same ordering was applied in the contraindication figure. For example, in the case of loss of empathy: amongst the 21 physicians 14 (67%) did not recommended any treatment, one (5%) recommended a single treatment and six (29%) recommended three treatments.

FIGURE 2

The top five most selected treatments by physicians for each behavioural symptom recommended by physicians (a) or marked as contraindicated (b). This figure shows, for each behavioural symptom and drug, the percentages of physicians (out of 21) who selected the drug, regardless of the rank, with their 95% bootstrapped confidence intervals. The n value in parentheses for each symptom represents the number of physicians who selected at least one treatment, giving insight into the sample size contributing to the calculations.

FIGURE 3

The top five treatments with highest mean score for each behavioural symptom recommended by physicians (a) or marked as contraindicated (b). This figure portrays the mean score allocated to a treatment per behavioural symptom. The scoring system is structured as follows: the first choice is awarded 3 points, the second choice receives 2 points, the third choice is given 1 point, subsequent choices, if any, get 0.5 points each, and, if the physician did not choose any treatment, 0 points are assigned. The n value in parentheses for each symptom represents the number of physicians who selected at least one treatment, providing context about the sample size contributing to the mean scores.

FIGURE 4

Results of the PCA based on the percentage of physicians who selected a treatment, regardless of its rank, using the treatments as observations and the behavioural disturbances as variables. PCA, principal components analysis.