Psychiatric symptoms in patients with frontotemporal dementia (FTD) are highly prevalent and may complicate clinical management of these patients. Purpose of the present article is to present and discuss available data about the pharmacological treatment of psychiatric symptoms in patients with FTD. A research in the main database sources has been conducted to obtain an overview of the pharmacological management of psychiatric symptoms in patients with FTD. The search strategy included the following terms—“FTD and psychiatry,” “FTD and behavioural disturbances,” and “FTD and treatment”. Pathophysiology of psychiatric symptoms in FTD is different from other types of dementia. Although drugs for Alzheimer disease appear to be ineffective for the treatment of psychiatric symptoms of FTD, preliminary evidence supports a possible usefulness of serotonergic antidepressants for these patients. Data are too scanty to draw definitive conclusions, but antidepressant treatment, particularly with serotonergic compounds, may improve psychiatric symptoms in patients with FTD. Large observational studies are needed to confirm this preliminary evidence, and a lot of effort and collaboration between neurologists and psychiatrists will be definitely crucial for future research of effective treatments for FTD.
BrodatyHConnorsMHXuJWoodwardMAmesD; PRIME Study Group. The course of neuropsychiatric symptoms in dementia: a 3-year longitudinal study. J Am Med Dir Assoc. 2015;16(5):380–387.
2.
SteffensDCMaytanMHelmsMJPlassmanBL. Prevalence and clinical correlates of neuropsychiatric symptoms in dementia. Am J Alzheimers Dis Other Demen. 2005;20(6):367–373.
3.
TsaiRMBoxerAL. Therapy and clinical trials in frontotemporal dementia: past, present, and future. J Neurochem. 2016;138(suppl 1):211–221.
LiuWMillerBLKramerJH. Behavioral disorders in the frontal and temporal variants of frontotemporal dementia. Neurology. 2004;62(5):742–748.
6.
BonakisAEconomouNTPaparrigopoulosT. Sleep in frontotemporal dementia is equally or possibly more disrupted, and at an earlier stage, when compared to sleep in Alzheimer’s disease. J Alzheimers Dis. 2014;38(1):85–91.
7.
AhmedRMIrishMHenningE. Assessment of eating behavior disturbance and associated neural networks in frontotemporal dementia. JAMA Neurol. 2016;73(3):282–290.
8.
AhmedRMLatheefSBartleyL. Eating behavior in frontotemporal dementia: peripheral hormones vs hypothalamic pathology. Neurology. 2015;85(15):1310–1317.
9.
Garcia-AllozaMGil-BeaFJDiez-ArizaM. Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer’s disease. Neuropsychologia. 2005;43(3):442–449.
10.
HueyEDPutnamKTGrafmanJ. A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology. 2006;66(1):17–22.
11.
LanctôtKLHerrmannNGanjaviH. Serotonin-1A receptors in frontotemporal dementia compared with controls. Psychiatry Res. 2007;156(3):247–250.
12.
BowenDMProcterAWMannDM. Imbalance of a serotonergic system in frontotemporal dementia: implication for pharmacotherapy. Psychopharmacology (Berl). 2008;196(4):603–610.
13.
EngelborghsSVloeberghsELe BastardN. The dopaminergic neurotransmitter system is associated with aggression and agitation in frontotemporal dementia. Neurochem Int. 2008;52(6):1052–1060.
14.
DucharmeSDickersonBC. The neuropsychiatric examination of the young-onset dementias. Psychiatr Clin North Am. 2015;38(2):249–264.
15.
Lima-SilvaTBBahiaVSCarvalhoVA. Neuropsychiatric symptoms, caregiver burden and distress in behavioral-variant frontotemporal dementia and Alzheimer’s disease. Dement Geriatr Cogn Disord. 2015;40(5-6):268–275.
16.
KimuraTTakamatsuJ. Pilot study of pharmacological treatment for frontotemporal dementia: risk of donepezil treatment for behavioral and psychological symptoms. Geriatr Gerontol Int. 2013;13(2):506–507.
17.
KerteszAMorlogDLightM. Galantamine in frontotemporal dementia and primary progressive aphasia. Dement Geriatr Cogn Disord. 2008;25(2):178–185.
18.
Diehl-SchmidJFörstlHPerneczkyRPohlCKurzA. A 6-month, open-label study of memantine in patients with frontotemporal dementia. Int J Geriatr Psychiatry. 2008;23(7):754–759.
19.
VercellettoMBoutoleau-BretonnièreCVolteauC.; French research network on Frontotemporal dementia. Memantine in behavioral variant frontotemporal dementia: negative results. J Alzheimers Dis. 2011;23(4):749–759.
20.
BoxerALKnopmanDSKauferDI. Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2013;12(2):149–156.
21.
LebertFPasquierF. Trazodone in the treatment of behaviour in frontotemporal dementia. Hum Psychopharmacol Clin Exp. 1999;14(4):279–281.
22.
MorettiRTorrePAntonelloRMCazzatoGBavaA. Frontotemporal dementia: paroxetine as a possible treatment of behavior symptoms. A randomized, controlled, open 14-month study. Eur Neurol. 2003;49(1):13–19.
23.
DeakinJBRahmanSNestorPJHodgesJRSahakianBJ. Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial. Psychopharmacology (Berl). 2004;172(4):400–408.
24.
HerrmannNBlackSEChowTCappellJTang-WaiDFLanctôtKL. Serotonergic function and treatment of behavioral and psychological symptoms of frontotemporal dementia. Am J Geriatr Psychiatry. 2012;20(9):789–797.
25.
IkedaMShigenobuKFukuharaR. Efficacy of fluvoxamine as a treatment for behavioral symptoms in frontotemporal lobar degeneration patients. Dement Geriatr Cogn Disord. 2004;17(3):117–121.
26.
PardiniMSerratiCGuidaS. Souvenaid reduces behavioral deficits and improves social cognition skills in frontotemporal dementia: a proof-of-concept study. Neurodegener Dis. 2015;15(1):58–62.
27.
JessoSMorlogDRossS. The effects of oxytocin on social cognition and behaviour in frontotemporal dementia. Brain. 2011;134(pt 9):2493–2501.
28.
MorettiRTorrePAntonelloRMCattaruzzaTCazzatoGBavaA. Rivastigmine in frontotemporal dementia: an open-label study. Drugs Aging. 2004;21(14):931–937.
29.
LebertFStekkeWHasenbroekxCPasquierF. Frontotemporal dementia: a randomised, controlled trial with trazodone. Dement Geriatr Cogn Disord. 2004;17(4):355–359.
HueyEDGarciaCWassermannEMTierneyMCGrafmanJ. Stimulant treatment of frontotemporal dementia in 8 patients. J Clin Psychiatry. 2008;69(12):1981–1982.
32.
AlbericiAArchettiSPilottoA. Results from a pilot study on amiodarone administration in monogenic frontotemporal dementia with granulin mutation. Neurol Sci. 2014;35(8):1215–1219.
33.
FingerECMacKinleyJBlairM. Oxytocin for frontotemporal dementia: a randomized dose-finding study of safety and tolerability. Neurology. 2015;84(2):174–181.
34.
Armijo-OlivoSStilesCRHagenNABiondoPDCummingsGG. Assessment of study quality for systematic reviews: a comparison of the Cochrane collaboration risk of bias tool and the effective public health practice project quality assessment tool: methodological research. J Eval Clin Pract. 2012;18(1):12–18.
35.
BeiHuRossLNeuhausJ. Off-label medication use in frontotemporal dementia. Am J Alzheimers Dis Other Demen. 2010;25(2):128–133.
36.
TartagliaMCHuBMehtaK. Demographic and neuropsychiatric factors associated with off-label medication use in frontotemporal dementia and Alzheimer’s disease. Alzheimer Dis Assoc Disord. 2014;28(2):182–189.
37.
ArciniegasDBAndersonCA. Donepezil-induced confusional state in a patient with autopsy-proven behavioral-variant frontotemporal dementia. J Neuropsychiatry Clin Neurosci. 2013;25(3):E25–E26.
38.
KishiTMatsunagaSIwataN. Memantine for the treatment of frontotemporal dementia: a meta-analysis. Neuropsychiatr Dis Treat. 2015;11:2883–2885.
39.
SwanbergMM. Memantine for behavioral disturbances in frontotemporal dementia: a case series. Alzheimer Dis Assoc Disord. 2007;21(2):164–166.
40.
HughesLERittmanTRegenthalRRobbinsTWRoweJB. Improving response inhibition systems in frontotemporal dementia with citalopram. Brain. 2015;138(pt 7):1961–1975.
41.
MorettiRTorrePAntonelloRMCazzatoGBavaA. Effects of selegiline on fronto-temporal dementia: a neuropsychological evaluation. Int J Geriatr Psychiatry. 2002;17(4):391–392.
42.
KerchnerGATartagliaMCBoxerA. Abhorring the vacuum: use of Alzheimer’s disease medications in frontotemporal dementia. Expert Rev Neurother. 2011;11(5):709–717.
43.
RubioGMartínez-GrasIManzanaresJ. Modulation of impulsivity by topiramate: implications for the treatment of alcohol dependence. J Clin Psychopharmacol. 2009;29(6):584–589.
44.
SingamCWalterfangMMocellinREvansAVelakoulisD. Topiramate for abnormal eating behaviour in frontotemporal dementia. Behav Neurol. 2013;27(3):285–286
45.
CruzMMarinhoVFontenelleLFEngelhardtELaksJ. Topiramate may modulate alcohol abuse but not other compulsive behaviors in frontotemporal dementia: case report. Cogn Behav Neurol. 2008;21(2):104–106.
46.
VictoroffJCoburnKReeveASampsonSShillcuttS. Pharmacological management of persistent hostility and aggression in persons with schizophrenia spectrum disorders: a systematic review. J Neuropsychiatry Clin Neurosci. 2014;26(4):283–312.
47.
JhaMKLambertFSBeadlesBA. A case of frontotemporal dementia presenting with treatment-refractory psychosis and extreme violence: response to combination of clozapine, medroxyprogesterone and sertraline. J Clin Psychopharmacol. 2015;35(6):732–733.
48.
PowellAFlynnPRischbiethSMcKellarD. Managing severe aggression in frontotemporal dementia. Australas Psychiatry. 2014;22(1):86–89.
49.
Dell’OssoBAllenAAltamuraACBuoliMHollanderE. Impulsive-compulsive buying disorder: clinical overview. Aust N Z J Psychiatry. 2008;42(4):259–266.
50.
FurlanJCHenri-BhargavaAFreedmanM. Clomipramine in the treatment of compulsive behavior in frontotemporal dementia: a case series. Alzheimer Dis Assoc Disord. 2014;28(1):95–98.
51.
FonsecaLSimõesSFerreiraPMesquitaJMachadoA. Ciproterone effect on compulsive masturbation in a frontotemporal dementia patient. Ciproterone effect on compulsive masturbation in a frontotemporal dementia patient. J Neuropsychiatry Clin Neurosci. 2010;22(3):352b.e3–352.e3.
52.
PoetterCEStewartJT. Treatment of indiscriminate, inappropriate sexual behavior in frontotemporal dementia with carbamazepine. J Clin Psychopharmacol. 2012;32(1):137–138.
53.
ReevesRRPerryCL. Aripiprazole for sexually inappropriate vocalizations in frontotemporal dementia. J Clin Psychopharmacol. 2013;33(1):145–146.
54.
AlquezarCEsterasNde la EncarnaciónAMorenoFLópez de MunainAMartín-RequeroÁ. Increasing progranulin levels and blockade of the ERK1/2 pathway: upstream and downstream strategies for the treatment of progranulin deficient frontotemporal dementia. Eur Neuropsychopharmacol. 2015;25(3):386–403.
55.
FingerEC. New potential therapeutic approaches in frontotemporal dementia: oxytocin, vasopressin, and social cognition. J Mol Neurosci. 2011;45(3):696–701.
56.
SchlachetzkiJCSchmidtkeKBeckervordersandforthJBorozdinWWilhelmCHüllMKohlhaseJ. Frequency of progranulin mutations in a German cohort of 79 frontotemporal dementia patients. J Neurol. 2009;256(12):2043–2051.
57.
FinchNBakerMCrookR. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain. 2009;132(3):583–591.
AltamuraACBuoliMPozzoliS. Role of immunological factors in the pathophysiology and diagnosis of bipolar disorder: comparison with schizophrenia. Psychiatry Clin Neurosci. 2014;68(1):21–36.
61.
LiuWZhaoLBlackmanB. Vectored intracerebral immunization with the anti-tau monoclonal antibody PHF1 markedly reduces tau pathology in mutant tau transgenic mice. J Neurosci. 2016;36(49):12425–12435.
62.
SeripaDSolfrizziVImbimboBP. Tau-directed approaches for the treatment of Alzheimer’s disease: focus on leuco-methylthioninium. Expert Rev Neurother. 2016;16(3):259–277.
63.
MinSWChenXTracyTE. Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits. Nat Med. 2015;21(10):1154–1162.
64.
GozesIIvashko-PachimaY. ADNP: in search for molecular mechanisms and innovative therapeutic strategies for frontotemporal degeneration. Front Aging Neurosci. 2015;7:205.
65.
Lagier-TourenneCBaughnMRigoF. Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proc Natl Acad Sci U S A. 2013;110(47):E4530–E4539.
66.
GalimbertiDDell’OssoBAltamuraACScarpiniE. Psychiatric symptoms in frontotemporal dementia: epidemiology, phenotypes, and differential diagnosis. Biol Psychiatry. 2015;78(10):684–692.
67.
KurisuKTeradaSOshimaE. Comparison of QOL between patients with different degenerative dementias, focusing especially on positive and negative affect. Int Psychogeriatr. 2016;28(8):1355–1361.
68.
BuoliMDell’ossoBBosiMFAltamuraC. Slow vs standard up-titration of paroxetine in the treatment of panic disorder: a prospective randomized trial. Psychiatry Clin Neurosci. 2010;64(6):612–619.
69.
LagardeJSarazinM. Reconciliating neurology and psychiatry: The prototypical case of frontotemporal dementia [in French]. Encephale. 2016. doi: 10.1016/j.encep.2016.09.001.
