Pick Disease Medication
- Author: Anna M Barrett, MD; Chief Editor: Michael Hoffmann, MBBCh, MD, FCP(SA), FAAN, FAHA more...
Medication Summary
Unfortunately, no available drugs arrest or reverse Pick disease. Currently, practitioners use a combination of neuroprotective and symptomatic therapies—including the administration of vitamins, antidepressants, cholinergic agents, and/or dopaminergic agents—in patients with the disorder.
Research studies suggest that a number of agents may actively inhibit neurodegeneration in animals, cellular models, or other disorders (see Scott and Barrett for a review[24] ), but none of these drugs are currently standard for use in Pick disease.
Vitamins
Class Summary
These are cofactors that are needed in metabolic reactions and that are essential for normal deoxyribonucleic acid (DNA) synthesis, with some vitamins providing antioxidant effects.
Vitamin E (E-Gem, Gamma-E-Gems, Aqua Gem-E, Aquasol E)
Vitamin E may protect polyunsaturated acid in membranes from attack by free radicals.
Thiamine
Thiamine is an essential coenzyme that combines with adenosine triphosphate (ATP) to form thiamine pyrophosphate.
Antidepressants
Class Summary
Although selective serotonin reuptake inhibitors (SSRIs) have been suggested for behavioral symptoms (eg, a craving for sweets, hypersexual behavior) in these patients,[25, 26] exercise care in using these agents in patients with parkinsonism, who may develop adverse effects of akathisia or dyskinesias.
Agents with mixed noradrenergic and serotonergic action may be helpful in treating patients with depression and frontal cognitive disorder.
Mirtazapine (Remeron)
Mirtazapine may be sedating, especially at the lower 15mg dose, and may be useful for patients with agitation or disinhibition and depression.
Venlafaxine (Effexor, Effexor XR)
Venlafaxine may be helpful for abulic patients who also have symptoms of depression or decreased initiative.
Trazodone (Oleptro)
Trazodone is a 5-HT2–receptor antagonist that inhibits the reuptake of 5-HT. It has a negligible affinity for cholinergic, adrenergic, dopaminergic, or histaminic receptors. Trazodone has good hypnotic properties and is effective in reducing agitation in patients with head trauma or dementia. This agent is also useful for sleep disturbances. It is structurally unrelated to tricyclic antidepressants (TCAs), tetracyclics, or monoamine oxidase inhibitors (MAOIs). The cardiac conduction effects of trazodone are qualitatively dissimilar to and quantitatively less pronounced than those of TCAs and so are less toxic in cases of trazodone overdose.[27]
Acetylcholinesterase Inhibitors, Central
Class Summary
Cholinergic therapy may be helpful for patients with aphasia,[28] and preliminary studies indicate that cholinesterase inhibitors may be useful for aphasia in Pick disease,[29] as well as for other dementia-related symptoms in this disorder.[30]
Donepezil (Aricept)
Donepezil is an acetylcholinesterase inhibitor that is used in dementia of the Alzheimer type. Cholinergic stimulation may improve naming[28] and increase neuronal plasticity[31] ; thus, it is reasonable to attempt therapy in patients with primary progressive aphasia. Unfortunately, no clinical studies are available on the effect of donepezil in patients with Pick disease.
Ergot Derivatives
Class Summary
Although these agents may worsen sexual or behavioral disinhibition, they may improve executive function, perseveration, and abulia.[32, 33, 34]
Bromocriptine (Parlodel, Cycloset)
Bromocriptine is a semisynthetic ergot alkaloid derivative. It is a strong dopamine D2-receptor agonist and a partial dopamine D1-receptor agonist. Bromocriptine inhibits prolactin secretion, with no effect on other pituitary hormones. It may be given with food to minimize the possibility of gastrointestinal (GI) irritation.
Approximately 28% of this agent is absorbed from the GI tract and metabolized in liver. Bromocriptine's approximate elimination half-life is 50 hours, with 85% excreted in feces and 3-6% eliminated in urine.
Initiate this drug at a low dosage; slowly increase the dosage to individualize therapy. Assess the dosage titration every 2 weeks. Gradually reduce the dose in 2.5-mg decrements if severe adverse reactions occur.
Antiparkinson Agents, Dopamine Agonists
Class Summary
Although these agents may worsen sexual or behavioral disinhibition, they may improve executive function, perseveration, and abulia.
Amantadine
Amantadine inhibits N-methyl-D-aspartic acid (NMDA) receptor–mediated stimulation of acetylcholine release in rat striatum. It may enhance dopamine release, inhibit dopamine reuptake, stimulate postsynaptic dopamine receptors, or enhance dopamine receptor sensitivity.
Kertesz A, Hudson L, Mackenzie IR, Munoz DG. The pathology and nosology of primary progressive aphasia. Neurology. Nov 1994;44(11):2065-72. [Medline].
Kertesz A. Pick Complex: an integrative approach to frontotemporal dementia: primary progressive aphasia, corticobasal degeneration, and progressive supranuclear palsy. Neurologist. Nov 2003;9(6):311-7. [Medline].
Haugarvoll K, Wszolek ZK, Hutton M. The genetics of frontotemporal dementia. Neurol Clin. Aug 2007;25(3):697-715, vi. [Medline].
Weintraub S, Rubin NP, Mesulam MM. Primary progressive aphasia. Longitudinal course, neuropsychological profile, and language features. Arch Neurol. Dec 1990;47(12):1329-35. [Medline].
Forman MS, Farmer J, Johnson JK, Clark CM, Arnold SE, Coslett HB, et al. Frontotemporal dementia: clinicopathological correlations. Ann Neurol. Jun 2006;59(6):952-62. [Medline].
Jellinger KA. Neuropathological criteria for Pick disease and frontotemporal lobe dementia. In: Cruz-Sanchez et al, eds. Neuropathological Diagnostic Criteria. Amsterdam: IOS Press; 1995:35-54.
Piguet O, Halliday GM, Reid WG, Casey B, Carman R, Huang Y. Clinical phenotypes in autopsy-confirmed Pick disease. Neurology. Jan 18 2011;76(3):253-9. [Medline].
Graff-Radford NR, Woodruff BK. Frontotemporal dementia. Semin Neurol. Feb 2007;27(1):48-57. [Medline].
Graham A, Hodges J. Frontotemporal dementia. Psych. 2008;7(1):24-8.
Hodges JR, Davies R, Xuereb J, Kril J, Halliday G. Survival in frontotemporal dementia. Neurology. Aug 12 2003;61(3):349-54. [Medline].
Ratnavalli E, Brayne C, Dawson K, Hodges JR. The prevalence of frontotemporal dementia. Neurology. Jun 11 2002;58(11):1615-21. [Medline].
Rascovsky K, Salmon DP, Lipton AM, Leverenz JB, DeCarli C, Jagust WJ, et al. Rate of progression differs in frontotemporal dementia and Alzheimer disease. Neurology. Aug 9 2005;65(3):397-403. [Medline].
Nadeau SE. Multi-infarct dementia, subcortical dementia, and hydrocephalus. South Med J. May 1991;84(5 Suppl 1):S41-52. [Medline].
Banks S, Weintraub S. Self-awareness and self-monitoring of cognitive and behavioral deficits in behavioral variant frontotemporal dementia, primary progressive aphasia and probable Alzheimer's disease. Brain Cogn. Jun 2008;67(1):58-68. [Medline]. [Full Text].
Whitwell JL, Sampson EL, Loy CT, et al. VBM signatures of abnormal eating behaviours in frontotemporal lobar degeneration. Neuroimage. Mar 2007;35(1):207-13. [Medline].
Srikanth S, Nagaraja AV, Ratnavalli E. Neuropsychiatric symptoms in dementia-frequency, relationship to dementia severity and comparison in Alzheimer's disease, vascular dementia and frontotemporal dementia. J Neurol Sci. Sep 15 2005;236(1-2):43-8. [Medline].
Lhermitte F. 'Utilization behaviour' and its relation to lesions of the frontal lobes. Brain. Jun 1983;106 (Pt 2):237-55. [Medline].
Shimomura T, Mori E. Obstinate imitation behaviour in differentiation of frontotemporal dementia from Alzheimer's disease. Lancet. Aug 22 1998;352(9128):623-4. [Medline].
Beversdorf DQ, Heilman KM. Facilitory paratonia and frontal lobe functioning. Neurology. Oct 1998;51(4):968-71. [Medline].
Knopman DS, Mastri AR, Frey WH 2nd, Sung JH, Rustan T. Dementia lacking distinctive histologic features: a common non- Alzheimer degenerative dementia. Neurology. Feb 1990;40(2):251-6. [Medline].
Grossman M, Farmer J, Leight S, Work M, Moore P, Van Deerlin V. Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer's disease. Ann Neurol. May 2005;57(5):721-9. [Medline].
Verbeek MM, Pijnenburg YA, Schoonenboom NS, Kremer BP, Scheltens P. Cerebrospinal fluid tau levels in frontotemporal dementia. Ann Neurol. Oct 2005;58(4):656-7; author reply 657. [Medline].
Steinbart EJ, Smith CO, Poorkaj P, Bird TD. Impact of DNA testing for early-onset familial Alzheimer disease and frontotemporal dementia. Arch Neurol. Nov 2001;58(11):1828-31. [Medline].
Scott KR and Barrett AM. Dementia Syndromes: Evaluation and Treatment. Expert Review of Neurotherapeutics. 2007;7:407-422.
Litvan I. Therapy and management of frontal lobe dementia patients. Neurology. Jun 2001;56(11 Suppl 4):S41-5. [Medline].
Swartz JR, Miller BL, Lesser IM, Schuman S. Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors. J Clin Psychiatry. May 1997;58(5):212-6. [Medline].
Lebert F, Stekke W, Hasenbroekx C, Pasquier F. Frontotemporal dementia: A randomised, controlled trial with trazodone. In: Dementia & Geriatric Cognitive Disorders. Vol 17(4). Jun 2004: 355-59.
Tanaka Y, Miyazaki M, Albert ML. Effects of increased cholinergic activity on naming in aphasia. Lancet. Jul 12 1997;350(9071):116-7. [Medline].
Kertesz A, Blair M, Davidson W. A Pilot Study of the Safety and Efficacy of Galantamine for Pick Complex/Frontotemporal Dementia (FTD). Abstracts of the 130th Annual Meeting of the American Neurological Association. 2005;61.
Lampl Y, Sadeh M, Lorberboym M. Efficacy of acetylcholinesterase inhibitors in frontotemporal dementia. Ann Pharmacother. Nov 2004;38(11):1967-8. [Medline].
Kilgard MP, Merzenich MM. Cortical map reorganization enabled by nucleus basalis activity. Science. Mar 13 1998;279(5357):1714-8. [Medline].
Imamura T, Takanashi M, Hattori N, Fujimori M, Yamashita H, Ishii K, et al. Bromocriptine treatment for perseveration in demented patients. Alzheimer Dis Assoc Disord. Jun 1998;12(2):109-13. [Medline].
McDowell S, Whyte J, D'Esposito M. Differential effect of a dopaminergic agonist on prefrontal function in traumatic brain injury patients. Brain. Jun 1998;121 (Pt 6):1155-64. [Medline].
Drayton SJ, Davies K, Steinberg M, Leroi I, Rosenblatt A, Lyketsos CG. Amantadine for executive dysfunction syndrome in patients with dementia. Psychosomatics. May-Jun 2004;45(3):205-9. [Medline].
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