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Anticonvulsants for the treatment of behavioral and psychological symptoms of dementia: a literature review

Published online by Cambridge University Press:  30 November 2007

Sergiy Konovalov ,
Sunanda Muralee  and
Rajesh R. Tampi
Sergiy Konovalov
Affiliation:
Department of Psychiatry, Yale University School of Medicine, New Haven, U.S.A.
Sunanda Muralee
Affiliation:
Department of Psychiatry, Yale University School of Medicine, New Haven, U.S.A.
Rajesh R. Tampi*
Affiliation:
Department of Psychiatry, Yale University School of Medicine, New Haven, U.S.A.
*
Correspondence should be addressed to: Dr. Rajesh R. Tampi, Director, Geriatric Psychiatry Fellowship Program, Yale University School of Medicine, LV-121 Yale New Haven Psychiatric Hospital, 184 Liberty Street, New Haven, CT 06519, U.S.A. Phone: +1 203 688 9893; Fax: +1 203 688 9709. Email: [email protected].
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Abstract

Objective: To review and summarize the currently available data on the use of anticonvulsant mood stabilizers (carbamazepine, valproic acid, gabapentin, lamotrigine, topiramate) in the treatment of behavioral and psychological symptoms of dementia (BPSD); to determine whether these medications can be recommended for routine clinical use.

Methods: Literature search in five databases (PubMed, MEDLINE, EMBASE, PsychINFO and COCHRANE collaboration) and analysis of the randomized controlled double-blinded clinical trials found therein.

Results: A total of seven RCTs were identified (two for carbamazepine and five for valproate). One study showed statistically significant improvement of BPSD in the medication group in comparison to the placebo group; five studies showed no significant differences; one study showed statistically significant worsening of the symptoms in the medication group vs. placebo. The majority of the studies reported significantly more frequent adverse effects in the medication group.

Conclusion: Although clearly beneficial in some patients, anticonvulsant mood stabilizers cannot be recommended for routine use in the treatment of BPSD at the present time.

Keywords

neuropsychiatric symptoms of dementiamood stabilizersdivalproex sodiumcarbamazepinegabapentinlamotriginetopiramate
Type
REVIEW
Information
International Psychogeriatrics , Volume 20 , Issue 2 , April 2008 , pp. 293 - 308
Copyright
Copyright © International Psychogeriatric Association 2007

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References

Alkhalil, C., Tanvir, F., Alkhalil, B. and Lowenthal, D. T. 2004. Treatment of sexual disinhibition in dementia: case reports and review of the literature. American Journal of Therapeutics, 11, 231–235.Google Scholar
Aulakh, J. S., Hawkins, J. W., Athwal, H. S., Sheikh, J. I., Yesavage, J. and Tinklenberg, J. R. 2005. Tolerability and effectiveness of lamotrigine in complex elderly patients. Journal of Geriatric Psychiatry and Neurology, 18, 8–11.CrossRefGoogle ScholarPubMed
Buchalter, E. N. and Lantz, M. S. 2001. Treatment of impulsivity and aggression in a patient with vascular dementia. Geriatrics, 56, 53–54.Google Scholar
Chambers, C. Bain, J. and Rosbottom, R. 1982. Carbamazepine in senile dementia and overactivity: a placebo controlled double blind trial. IRCS Medical Science, 10, 505–506.Google Scholar
Chengappa, K. N. et al. 1999. Topiramate as add-on treatment for patients with bipolar mania. Bipolar Disorders, 1, 42–53.CrossRefGoogle ScholarPubMed
Coen, R. F., Swanwick, G. R., O'Boyle, C. A. and Coakley, D. 1997. Behaviour disturbance and other predictors of carer burden in Alzheimer's disease. International Journal of Geriatric Psychiatry, 12, 331–336.3.0.CO;2-J>CrossRefGoogle ScholarPubMed
Cohen, D. et al. 1993. Psychopathology associated with Alzheimer's disease and related disorders. Journal of Gerontology, 48, M255–260.CrossRefGoogle ScholarPubMed
Cooney, C. Mortimer, A., Smith, A., Newton, K. and Wrigley, M. 1996. Carbamazepine use in aggressive behavior associated with senile dementia. International Journal of Geriatric Psychiatry, 11, 901–905.3.0.CO;2-7>CrossRefGoogle Scholar
Cummings, J. L. and Back, C. 1998. The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer's disease. American Journal of Geriatric Psychiatry, 6, S64–78.Google Scholar
De Leon, O. A. 2004. Treatment of psychotic symptoms with lamotrigine in Alzheimer's disease. Journal of Clinical Psychopharmacology, 24, 232–233.CrossRefGoogle Scholar
Fhager, B., Meiri, I. M., Sjogren, M. and Edman, A. 2003. Treatment of aggressive behavior in dementia with the anticonvulsant topiramate: a retrospective pilot study. International Psychogeriatrics, 15, 307–309.Google Scholar
Fitton, A. and Goa, K. L. 1995. Lamotrigine. an update of its pharmacology and therapeutic use in epilepsy. Drugs, 50, 691–713.CrossRefGoogle ScholarPubMed
Freymann, N., Michael, R., Dodel, R. and Jessen, F. 2005. Successful treatment of sexual disinhibition in dementia with carbamazepine – a case report. Pharmacopsychiatry, 38, 144–145.CrossRefGoogle ScholarPubMed
Gleason, R. P. and Schneider, L. S. 1990. Carbamazepine treatment of agitation in Alzheimer's outpatients refractory to neuroleptics. Journal of Clinical Psychiatry, 51, 115–118.Google ScholarPubMed
Goldberg, R. J. 1999. The use of adjunctive divalproex for neuroleptic unresponsive behavioral disturbances in nursing home residents with dementia. Annals of Long Term Care, 7, 63–66.Google Scholar
Hawkins, J. W., Tinklenberg, J. R., Sheikh, J. I., Peyser, C. E. and Yesavage, J. A. 2000. A retrospective chart review of gabapentin for the treatment of aggressive and agitated behavior in patients with dementias. American Journal of Geriatric Psychiatry, 8, 221–225.Google Scholar
Herrmann, N. 1998. Valproic acid treatment of agitation in dementia. Canadian Journal of Psychiatry/Revue Canadienne de Psychiatrie, 43, 69–72.Google Scholar
Herrmann, N., Lanctot, K. and Myszak, M. 2000. Effectiveness of gabapentin for the treatment of behavioral disorders in dementia. Journal of Clinical Psychopharmacology, 20, 90–93.CrossRefGoogle ScholarPubMed
Herrmann, N., Lanctot, K. L., Rothenburg, L. S. and Eryavec, G. 2007. A placebo-controlled trial of valproate for agitation and aggression in Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 23, 116–119.Google Scholar
Holmes, C. et al. 2001. Psychosis and aggression in Alzheimer's disease: the effect of dopamine receptor gene variation. Journal of Neurology, Neurosurgery and Psychiatry, 71, 777–779.Google Scholar
Jost, B. C. and Grossberg, G. T. 1996. The evolution of psychiatric symptoms in Alzheimer's disease: a natural history study. Journal of the American Geriatrics Society, 44, 1078–1081.CrossRefGoogle ScholarPubMed
Kasckow, J. W., McElroy, S. L., Cameron, R. L., Mahler, L. L. and Fudala, S. J. 1997. A pilot study on the use of divalproex sodium in the treatment of behavioral agitation in elderly patients with dementia: assessment with the BEHAVE-AD and CGI rating scales. Current Therapeutic Research, Clinical and Experimental, 58, 981–989.CrossRefGoogle Scholar
Kozman, M. N., Wattis, J. and Curran, S. 2006. Pharmacological management of behavioural and psychological disturbance in dementia. Human Psychopharmacology, 21, 1–12.Google Scholar
Lanari, A., Amenta, F., Silvestrelli, G., Tomassoni, D. and Parnetti, L. 2006. Neurotransmitter deficits in behavioural and psychological symptoms of Alzheimer's disease. Mechanisms of Ageing and Development, 127, 158–165.Google Scholar
Lawlor, B. 2002. Managing behavioural and psychological symptoms in dementia. British Journal of Psychiatry, 181, 463–465.CrossRefGoogle ScholarPubMed
Lemke, M. R. 1995. Effect of carbamazepine on agitation in Alzheimer's inpatients refractory to neuroleptics. Journal of Clinical Psychiatry, 56, 354–357.Google ScholarPubMed
Lyketsos, C. G., Steele, C., Baker, L., Galik, E., Kopunek, S., Steinberg, M. and Warren, A. 1997. Major and minor depression in Alzheimer's disease: prevalence and impact. Journal of Neuropsychiatry and Clinical Neuroscience, 9, 556–561.Google Scholar
Lyketsos, C. G., Steinberg, M., Tschanz, J. T., Norton, M. C., Steffens, D. C. and Breitner, J. C. 2000. Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. American Journal of Psychiatry, 157, 708–714.CrossRefGoogle Scholar
Marin, D. B. and Greenwald, B. S. 1989. Carbamazepine for aggressive agitation in demented patients during nursing care. American Journal of Psychiatry, 146, 805.Google Scholar
Meinhold, J. M., Blake, L.M., Mini, L. J., Welge, J. A., Schwiers, M. and Hughes, A. 2005. Effect of divalproex sodium on behavioural and cognitive problems in elderly dementia. Drugs & Aging, 22, 615–626.CrossRefGoogle ScholarPubMed
Mendez, M. and Lim, G. 2003. Seizures in elderly patients with dementia: epidemiology and management. Drugs & Aging, 20, 791–803.CrossRefGoogle Scholar
Miller, L. J. 2001. Gabapentin for treatment of behavioral and psychological symptoms of dementia. Annals of Pharmacotherapy, 35, 427–431.CrossRefGoogle ScholarPubMed
Moretti, R., Torre, P., Antonello, R. M., Cazzato, G. and Bava, A. 2003. Gabapentin for the treatment of behavioural alterations in dementia: preliminary 15-month investigation. Drugs & Aging, 20, 1035–1040.CrossRefGoogle ScholarPubMed
Murman, D. L., Chen, Q., Powell, M. C., Kuo, S.B., Bradley, C. J. and Colenda, C. C. 2002. The incremental direct costs associated with behavioral symptoms in AD. Neurology, 59, 1721–1729.CrossRefGoogle ScholarPubMed
Nakajima, Y., Suzuki, K., Tochigi, A., Nitta, I., Tsuchiya, K. and Koyama, T. 2002. Effect of sodium valproate on behavioral disturbances in three patients with vascular dementia. Seishin Igaku (Clinical Psychiatry), 44, 761–763.Google Scholar
Narayan, M. and Nelson, J. C. 1997. Treatment of dementia with behavioral disturbance using divalproex or a combination of divalproex and a neuroleptic. Journal of Clinical Psychiatry, 58, 351–354.Google Scholar
Olin, J. T., Fox, L. S., Pawluczyk, S., Taggart, N. A. and Schneider, L. S. 2001. A pilot randomized trial of carbamazepine for behavioral symptoms in treatment-resistant outpatients with alzheimer disease. American Journal of Geriatric Psychiatry, 9, 400–405.Google Scholar
Patterson, J. F. 1988. A preliminary study of carbamazepine in the treatment of assaultive patients with dementia. Journal of Geriatric Psychiatry and Neurology, 1, 21–23.Google Scholar
Porsteinsson, A. P., Tariot, P. N., Erb, R. and Gaile, S. 1997. An open trial of valproate for agitation in geriatric neuropsychiatric disorders. American Journal of Geriatric Psychiatry, 5, 344–351.CrossRefGoogle ScholarPubMed
Porsteinsson, A. P. et al. 2001. Placebo-controlled study of divalproex sodium for agitation in dementia. American Journal of Geriatric Psychiatry, 9, 58–66.Google Scholar
Porsteinsson, A. P. et al. 2003. Valproate therapy for agitation in dementia: open-label extension of a double-blind trial. American Journal of Geriatric Psychiatry, 11, 434–440.CrossRefGoogle ScholarPubMed
Raudino, F., Mascalzi, M. G. and Zagami, A. 2004. Gabapentin and behavioral disorders in severe Alzheimer disease. Journal of Clinical Psychopharmacology, 24, 459–460.CrossRefGoogle ScholarPubMed
Regan, W. M. and Gordon, S. M. 1997. Gabapentin for behavioral agitation in Alzheimer's disease. Journal of Clinical Psychopharmacology, 17, 59–60.CrossRefGoogle ScholarPubMed
Roane, D. M., Feinberg, T. E., Meckler, L., Miner, C. R., Scicutella, A. and Rosenthal, R. N. 2000. Treatment of dementia-associated agitation with gabapentin. Journal of Neuropsychiatry and Clinical Neurosciences, 12, 40–43.Google Scholar
Robert, P. 2002. Understanding and managing behavioural symptoms in Alzheimer's disease and related dementias: focus on rivastigmine. Current Medical Research Opinion, 18, 156–171.CrossRefGoogle ScholarPubMed
Rossi, P., Serrao, M. and Pozzessere, G. 2002. Gabapentin-induced worsening of neuropsychiatric symptoms in dementia with Lewy bodies: case reports. European Neurology, 47, 56–57.Google Scholar
Sandborn, W. D., Bendfeldt, F. and Hamdy, R. 1995. Valproic acid for physically aggressive behavior in geriatric patients. American Journal of Geriatric Psychiatry, 3, 239–242.CrossRefGoogle ScholarPubMed
Sheldon, L. J., Ancill, R. J. and Holliday, S. G. 1998. Gabapentin in geriatric psychiatry patients. Canadian Journal of Psychiatry, 43, 422–423.Google ScholarPubMed
Sink, K. M., Holden, K. F. and Yaffe, K. 2005. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA, 293, 596–608.Google Scholar
Sival, R. C., Haffmans, P. M. J., van Gent, P. P. and van Nieuwkerk, J. F. 1994. The effects of sodium valproate on disturbed behavior in dementia. Journal of the American Geriatrics Society, 42, 906–907.CrossRefGoogle ScholarPubMed
Sival, R. C., Haffmans, P. M., Jansen, P. A., Duursma, S. A. and Eikelenboom, P. 2002. Sodium valproate in the treatment of aggressive behavior in patients with dementia–a randomized placebo controlled clinical trial. International Journal of Geriatric Psychiatry, 17, 579–585.Google Scholar
Sival, R. C., Duivenvoorden, H. J., Jansen, P. A. F., Haffmans, J., Duursma, S. A. and Eikelenboom, P. 2004. Sodium valproate in aggressive behaviour in dementia: a twelve-week open label follow-up study. International Journal of Geriatric Psychiatry, 19, 305–312.Google Scholar
Steele, C., Rovner, B., Chase, G. A. and Folstein, M. 1990. Psychiatric symptoms and nursing home placement of patients with Alzheimer's disease. American Journal of Psychiatry, 147, 1049–1051.Google ScholarPubMed
Stern, Y. et al. 1994. Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer's disease: prospective analyses from the predictors study. Neurology, 44, 2300–2307.Google Scholar
Stern, Y., Mayeux, R., Sano, M., Hauser, W. A. and Bush, T. 1987. Predictors of disease course in patients with probable Alzheimer's disease. Neurology, 37, 1649–1653.Google Scholar
Takahashi, M. and Akagi, M. 1996. Case report of sodium valproate treatment of aggression associated with Alzheimer's disease. Noto Shinkei (Brain & Nerve), 48, 757–760.Google Scholar
Tariot, P. N. 2003. Valproate use in neuropsychiatric disorders in the elderly. Psychopharmacology Bulletin, 37, 116–128.Google Scholar
Tariot, P. N. et al. 1998. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. American Journal of Psychiatry, 155, 54–61.Google Scholar
Tariot, P. N. et al. 2001. Safety and tolerability of divalproex sodium in the treatment of signs and symptoms of mania in elderly patients with dementia: results of a double-blind, placebo-controlled trial. Current Therapeutic Research – Clinical and Experimental, 62, 51–67.Google Scholar
Tariot, P., Porsteinsson, A. P., Jakimovich, L. J., Kowalski, N. and Holt, C. 2002. Open valproate treatment following a double-blind trial for agitation. Proceedings of the 8th International Conference on Alzheimer's Disease and Related Disorders, 20–25 July, Stockholm, Sweden. Abstract No. 440.Google Scholar
Tariot, P. N. et al. . and Alzheimer's Disease Cooperative Study 2005. Divalproex sodium in nursing home residents with possible or probable Alzheimer disease complicated by agitation: a randomized, controlled trial. American Journal of Geriatric Psychiatry, 13, 942–949.Google Scholar
White, H. S., Brown, S. D., Woodhead, J. H., Skeen, G. A. and Wolf, H. H. 2000. Topiramate modulates gaba-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia, 41 (Suppl. 1), S17–S20.Google Scholar