Management of Neuropsychiatric Symptoms in FTD Pharmacological Treatments
There are a limited number of randomized placebo-controlled trials in FTD compared with AD. Therefore, the selection of a drug to control neuropsychiatric symptoms in FTD is a quite challenging task. Despite the scarcity of evidence, recommendations from the British Association for Psychopharmacology can be used as guidelines [83].
Serotonergic Agents
There is evidence from cerebrospinal fluid, molecular imaging, and autopsy studies that FTD patients show deficiencies in the serotonergic system. A deficit in serotonin is implicated in many behavioral signs [84] . Selective serotonin reuptake inhibitors (SSRIs) are recommended as a treatment for the behavioral symptoms of FTD by the British Association for Psychopharmacology (grade B) [83].
Of the randomized trials for serotonergic agents, only those for trazodone have shown a clear benefit over placebo [84, 85], though many have reported small positive effects on disinhibition, repetitive behaviors, and hyperorality.
Citalopram
A daily dose of 30 mg of citalopram over 6 weeks decreased three sub-scores of the NPI: depression, irritability, and disinhibition in an open-label study [86]. Recently, using a Go/NoGo paradigm, magnetoencephalography and electroencephalography, a single 30-mg dose of citalopram enhanced the NoGo-P3 signal in bvFTD [87]. The inhibition tasks, involving the right inferior frontal gyrus and anterior temporal lobe activity, are impaired in FTD. With citalopram, the evoked response in the right inferior frontal gyrus increased compared to placebo in FTD patients. These data confirmed that the response inhibition deficit can be partially restored by increasing serotonergic transmission in FTD.
Fluvoxamine
A 12-week open-label study showed an improvement of stereotyped behaviors with a mean dose of 110 mg of fluvoxamine [88]. Association with topiramate seemed to increase the positive effect of fluvoxamine [89].
Sertraline
Mendez et al. [49] reported a benefit of sertraline (with doses from 50 to 100 mg for 6 months) on verbal and motor stereotypies in a small open-label study of patients with FTD.
Paroxetine
Treatment with paroxetine shows contrasting results. In a small randomized study of paroxetine versus piracetam over 14 months, a group of eight FTD patients treated with a 20-mg daily dose of paroxetine showed significantly greater improvement of behavioral symptoms than those treated with piracetam [73]. On the other hand, in a short time, 6-week, double-blind, placebo-controlled trial, there was no decrease of behavioral disturbances with 40 mg of paroxetine daily [90].
Trazodone
In a randomized placebo-controlled crossover study, trazodone (at a daily dose of 300 mg) was proposed to 26 FTD patients. Behavior was assessed with the NPI
[18]. There was a significant decrease on the NPI total score after 6 weeks of trazodone, whereas NPI score remained stable in the placebo group. Positive effects were especially noticed on irritability, agitation, depressive symptoms, and eating disorders [72]. Trazodone remained effective for at least 3 years [91].
Clomipramine
Because of the absence of cholinergic deficit, tricyclic agents can be used in FTD patients with a safer side effect profile than in AD patients. A positive effect of clomipramine on compulsive behaviors, at daily dosages varying from 20 to 175 mg in three FTD patients, has been reported [92].
