Abstract
Anticonvulsants are a class of medications that have received considerable interest as possible treatments in patients with behavioural disturbances in dementia. The role of these medications for such a use remains controversial. The current paper reviews the published evidence surrounding the safety and efficacy (i.e. as a behavioural and cognitive treatment) of newer anticonvulsants in patients with dementia. A MEDLINE, International Pharmaceutical Abstracts, PsycINFO and clinicaltrials.gov search through to December 2011 was conducted for anticonvulsants that have received regulatory approval since 1996. Studies reporting behavioural or cognitive outcomes in patients with dementia were included. Nine trials involving only four medications met selection criteria and were included: levetiracetam (n = 4), oxcarbazepine (n = 1), topiramate (n = 2) and zonisamide (n = 2). Levetiracetam may have a role in the treatment of behavioural symptoms in dementia but study limitations substantially hinder the strength of such a recommendation. Oxcarbazepine and topiramate, based on limited data, do not appear to be effective treatments of behavioural symptoms in dementia. A lack of trials do not allow for conclusions to be made regarding zonisamide. From a cognitive standpoint, levetiracetam was the anticonvulsant most examined in patients with dementia, it appears to have less deleterious effects than some anticonvulsants. Limited data are available on the safety of these medications in elderly patients; however, studies completed thus far have demonstrated some adverse events that are more common or problematic with the use of these drugs in this patient population (i.e. somnolence, dizziness, hyponatraemia, weight loss).
Similar content being viewed by others
References
American Psychiatric Association: Treatment of patients with Alzheimer’s disease and other dementias. 2nd ed. 2007 Oct [online]. Available from URL: http://psychiatryonline.org/data/Books/prac/AlzPG101007.pdf [Accessed 2011 Oct 4].
American Academy of Neurology. Practice parameter: management of dementia. 2003 Oct [online]. Available from URL: http://www.neurology.org/content/56/9/1154.full.pdf [Accessed 2011 Oct 4].
Lyketsos CG, Colenda CC, Beck C, et al. Position statement of the American Association for Geriatric Psychiatry regarding principles of care for patients with dementia resulting from Alzheimer disease. Am J Geriatr Psychiatry 2006 Jul; 14 (7): 561–72.
Jalbert JJ, Eaton CB, Miller SC. Antipsychotic use and the risk of hip fracture among older adults afflicted with dementia. J Am Med Dir Assoc 2010; 11: 120–7.
Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: II. Cardiac and analgesic drugs. J Am Geriatr Soc 1999 Jan; 47 (1): 40–50.
Mehta S, Chen H, Johnson ML, et al. Risk of falls and fractures in older adults using antipsychotic agents: a propensity-matched retrospective cohort study. Drugs Aging 2010 Oct 1; 27 (10): 815–29.
Mehta S, Johnson ML, Chen H, et al. Risk of cerebrovascular adverse events in older adults using antipsychotic agents: a propensity-matched retrospective cohort study. J Clin Psychiatry 2010 Jun; 71 (6): 689–98.
Parker C, Coupland C, Hippisley-Cox J. Antipsychotic drugs and risk of venous thromboembolism: nested case-control study. BMJ 2010 Sep 21; 341: c4245.
Rossom RC, Rector TS, Lederle FA, et al. Are all commonly prescribed antipsychotics associated with greater mortality in elderly male veterans with dementia? J Am Geriatr Soc 2010 Jun; 58 (6): 1027–34.
Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry 2006 Mar; 14 (3): 191–210.
United States Food and Drug Administration. Information for healthcare professionals: conventional antipsychotics. 2008 Jun 16 [online]. Available from URL: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124830.htm [Accessed 2011 Feb 4].
Ray WA, Chung CP, Murray KT, et al. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med 2009 Jan 15; 360 (3): 225–35.
Bierman EJ, Comijs HC, Gundy CM, et al. The effect of chronic benzodiazepine use on cognitive functioning in older persons: good, bad or indifferent? Int J Geriatr Psychiatry 2007 Dec; 22 (12): 1194–200.
Gray SL, LaCroix AZ, Hanlon JT, et al. Benzodiazepine use and physical disability in community-dwelling older adults. J Am Geriatr Soc 2006 Feb; 54 (2): 224–30.
Gray SL, Lai KV, Larson EB. Drug-induced cognition disorders in the elderly: incidence, prevention and management. Drug Saf 1999 Aug; 21 (2): 101–22.
Lavsa SM, Fabian TJ, Saul MI, et al. Influence of medications and diagnoses on fall risk in psychiatric inpatients. Am J Health Syst Pharm 2010 Aug; 67 (15): 1274–80.
Wagner AK, Zhang F, Soumerai SB, et al. Benzodiazepine use and hip fractures in the elderly: who is at greatest risk? Arch Int Med 2004 Jul 26; 164 (14): 1567–72.
Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Int Med 2009 Nov 23; 169 (21): 1952–60.
Pollock BG, Mulsant BH, Rosen J, et al. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Am J Psychiatry 2002 Mar; 159 (3): 460–5.
Pollock BG, Mulsant BH, Sweet R, et al. An open pilot study of citalopram for behavioral disturbances of dementia: plasma levels and real-time observations. Am J Geriatr Psychiatry 1997 Winter; 5 (1): 70–8.
Dolder CR, Nealy KL, McKinsey J. Valproic acid in dementia: Does an optimal dose exist? J Pharm Pract. Epub 2011 Nov 17.
Grossman F. A review of anticonvulsants in treating agitated demented elderly patients. Pharmacotherapy 1998 May–Jun; 18 (3): 600–6.
Herrmann N, Lanctot KL. Pharmacologic management of neuropsychiatric symptoms of Alzheimer disease. Can J Psychiatry 2007 Oct; 52 (10): 630–46.
Porsteinsson AP. Divalproex sodium for the treatment of behavioural problems associated with dementia in the elderly. Drugs Aging 2006; 23 (11): 877–86.
Sink KM, Holden KF, Yaffe K. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA 2005 Feb 2; 293 (5): 596–608.
Tariot PN, Schneider LS, Cummings J, et al. Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Arch Gen Psychiatry Aug; 68 (8): 853–61.
Amann B, Pantel J, Grunze H, et al. Anticonvulsants in the treatment of aggression in the demented elderly: an update. Clin Pract Epidemiol Ment Health 2009; 5: 14.
Guay DR. Newer antiepileptic drugs in the management of agitation/aggression in patients with dementia or developmental disability. Consult Pharm 2007 Dec; 22 (12): 1004–34.
Sommer BR, Fenn HH, Ketter TA. Safety and efficacy of anticonvulsants in elderly patients with psychiatric disorders: oxcarbazepine, topiramate and gabapentin. Expert Opin Drug Saf 2007 Mar; 6 (2): 133–45.
Sajatovic M, Ramsay E, Nanry K, et al. Lamotrigine therapy in elderly patients with epilepsy, bipolar disorder or dementia. Int J Geriatr Psychiatry 2007 Oct; 22 (10): 945–50.
Hauser WA, Morris ML, Heston LL, et al. Seizures and myoclonus in patients with Alzheimer’s disease. Neurology 1986 Sep; 36 (9): 1226–30.
Hesdorffer DC, Hauser WA, Annegers JF, et al. Dementia and adult-onset unprovoked seizures. Neurology 1996 Mar; 46 (3): 727–30.
Larner AJ. Epileptic seizures in AD patients. Neuromolecular Med 2010 Mar; 12 (1): 71–7.
Romanelli MF, Morris JC, Ashkin K, et al. Advanced Alzheimer’s disease is a risk factor for late-onset seizures. Arch Neurol 1990 Aug; 47 (8): 847–50.
Forsgren L, Bucht G, Eriksson S, et al. Incidence and clinical characterization of unprovoked seizures in adults: a prospective population-based study. Epilepsia 1996 Mar; 37 (3): 224–9.
Hommet C, Hureaux R, Barre J, et al. Epileptic seizures in clinically diagnosed Alzheimer’s disease: report from a geriatric medicine population. Aging Clin Exp Res 2007 Oct; 19 (5): 430–1.
Mendez M, Lim G. Seizures in elderly patients with dementia: epidemiology and management. Drugs Aging 2003; 20 (11): 791–803.
Rao SC, Dove G, Cascino GD, et al. Recurrent seizures in patients with dementia: frequency, seizure types, and treatment outcome. Epilepsy Behav 2009 Jan; 14 (1): 118–20.
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011 May; 7 (3): 263–9.
Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004 Feb 1; 69 (3): 548–56.
Sommer OH, Aga O, Cvancarova M, et al. Effect of oxcarbazepine in the treatment of agitation and aggression in severe dementia. Dement Geriatr Cogn Disord 2009; 27 (2): 155–63.
Cumbo E, Ligori LD. Levetiracetam, lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer’s disease. Epilepsy Behav 2010 Apr; 17 (4): 461–6.
Lippa CF, Rosso A, Hepler M, et al. Levetiracetam: a practical option for seizure management in elderly patients with cognitive impairment. Am J Alzheimers Dis Other Demen 2010 Mar; 25 (2): 149–54.
Kyomen HH, Whitfield TH, Baldessarini RJ. Levetiracetam for manic behavior in hospitalized geriatric patients with dementia of the Alzheimer’s type. J Clin Psychopharmacol 2007 Aug; 27 (4): 408–10.
Weiner MF, Womack KB, Martin-Cook K, et al. Levetiracetam for agitated Alzheimer’s disease patients. Int Psychogeriatr 2005 Jun; 17 (2): 327–8.
Mowla A, Pani A. Comparison of topiramate and risperidone for the treatment of behavioral disturbances of patients with Alzheimer disease: a double-blind, randomized clinical trial. J Clin Psychopharmacol 2010 Feb; 30 (1): 40–3.
Fhager B, Meiri IM, Sjogren M, et al. Treatment of aggressive behavior in dementia with the anticonvulsant to-piramate: a retrospective pilot study. Int Psychogeriatr 2003 Sep; 15 (3): 307–9.
Odawara T, Shiozaki K, Togo T, et al. Administration of zonisamide in three cases of dementia with Lewy bodies. Psychiatry Clin Neurosci 2010 Jun; 64 (3): 327–9.
Sato S, Mizukami K, Asada T. Successful treatment of extrapyramidal and psychotic symptoms with zonisamide in a patient with dementia with Lewy bodies. Prog Neuropsychopharmacol Biol Psychiatry 2010 Aug 16; 34 (6): 1130–1.
Belcastro V, Costa C, Galletti F, et al. Levetiracetam monotherapy in Alzheimer patients with late-onset seizures: a prospective observational study. Eur J Neurol 2007 Oct; 14 (10): 1176–8.
Zesiewicz TA, Sullivan KL, Hauser RA, et al. Open-label pilot study of levetiracetam (Keppra) for the treatment of chorea in Huntington’s disease. Mov Disord 2006 Nov; 21 (11): 1998–2001.
US National Institutes of Health. ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2011 Oct 4].
Kutluay E, McCague K, D’Souza J, et al. Safety and tolerability of oxcarbazepine in elderly patients with epilepsy. Epilepsy Behav 2003 Apr; 4 (2): 175–80.
Chapman IM. Weight loss in older persons. Med Clin North Am 2011 May; 95 (3): 579–93, xi.
Murata M, Hasegawa K, Kanazawa I. Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study. Neurology 2007 Jan 2; 68 (1): 45–50.
Aldenkamp AP, De Krom M, Reijs R. Newer antiepileptic drugs and cognitive issues. Epilepsia 2003; 44 Suppl. 4: 21–9.
Sempere AP, Medrano V, Berenguer-Ruiz L. Reversible dementia secondary to topiramate. Clin Neuropharmacol 2008 Jan-Feb; 31 (1): 62.
Lexicomp Online [subscription, online database]. Hudson (OH): Lexi-Comp, Inc., 2012 [online]. Available from URL: http://www.lexi.com [Accessed 2011 Feb 4].
Cicolin A, Magliola U, Giordano A, et al. Effects of levetiracetam on nocturnal sleep and daytime vigilance in healthy volunteers. Epilepsia 2006 Jan; 47 (1): 82–5.
Meador KJ. Cognitive and memory effects of the new antiepileptic drugs. Epilepsy Res 2006 Jan; 68 (1): 63–7.
Perucca E. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age. Clin Pharmacokinet 2006; 45 (4): 351–63.
Neyens LG, Alpherts WC, Aldenkamp AP. Cognitive effects of a new pyrrolidine derivative (levetiracetam) in patients with epilepsy. Prog Neuropsychopharmacol Biol Psychiatry 1995 May; 19 (3): 411–9.
Alsaadi TM, Koopmans S, Apperson M, et al. Levetiracetam monotherapy for elderly patients with epilepsy. Seizure 2004 Jan; 13 (1): 58–60.
Cramer JA, Leppik IE, Rue KD, et al. Tolerability of levetiracetam in elderly patients with CNS disorders. Epilepsy Res 2003 Oct; 56 (2–3): 135–45.
Chengappa KN, Rathore D, Levine J, et al. Topiramate as add-on treatment for patients with bipolar mania. Bipolar Disord 1999 Sep; 1 (1): 42–53.
White HS, Brown SD, Woodhead JH, et al. Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia 2000; 41 Suppl. 1: S17–20.
Mitchell PB, Malhi GS. The expanding pharmacopoeia for bipolar disorder. Annu Rev Med 2002; 53: 173–88.
Acknowledgements
The authors have no actual or potential conflicts of interest to disclose. All work related to the manuscript was completed as part of the authors’ regular job duties; no additional funding was used in preparation of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dolder, C.R., Nealy, K.L. The Efficacy and Safety of Newer Anticonvulsants in Patients with Dementia. Drugs Aging 29, 627–637 (2012). https://doi.org/10.1007/BF03262279
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03262279