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Withdrawal versus continuation of chronic antipsychotic drugs for behavioural and psychological symptoms in older people with dementia

  1. Tom Declercq1,*,
  2. Mirko Petrovic2,
  3. Majda Azermai3,
  4. Robert Vander Stichele4,
  5. An IM De Sutter1,
  6. Mieke L van Driel5,
  7. Thierry Christiaens1

Editorial Group: Cochrane Dementia and Cognitive Improvement Group

Published Online: 28 MAR 2013

Assessed as up-to-date: 6 DEC 2012

DOI: 10.1002/14651858.CD007726.pub2


How to Cite

Declercq T, Petrovic M, Azermai M, Vander Stichele R, De Sutter AIM, van Driel ML, Christiaens T. Withdrawal versus continuation of chronic antipsychotic drugs for behavioural and psychological symptoms in older people with dementia. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD007726. DOI: 10.1002/14651858.CD007726.pub2.

Author Information

  1. 1

    Ghent University, Department of General Practice and Primary Health Care, Ghent, Belgium

  2. 2

    Ghent University Hospital, Department of Geriatrics, Ghent, Belgium

  3. 3

    Ghent University, Heymans Institute of Pharmacology, Ghent, Belgium

  4. 4

    Heymans Institute of Pharmacology, Ghent, Belgium

  5. 5

    The University of Queensland, Discipline of General Practice, School of Medicine, Brisbane, Queensland, Australia

*Tom Declercq, Department of General Practice and Primary Health Care, Ghent University, De Pintelaan 185, UZ-6K3, Ghent, B-9000, Belgium. tomrw.declercq@ugent.be.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 28 MAR 2013

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References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Ballard 2004 {published data only}
  • Ballard C. A randomised double blind placebo controlled trial to compare the progression of cognitive impairment in dementia patients continuing to take or discontinued from neuroleptic treatment. National Research Register 2003b.
  • Ballard C. A randomised, double blind, placebo-controlled clinical trial to compare the progression of cognitive impairment in dementia patients continuing to take, or discontinued from, treatment with neuroleptics. ISRCTN Register 2006.
  • Ballard CG, Thomas A, Fossey J, Lee L, Jacoby R, Lana MM, et al. A 3-month, randomized, placebo-controlled, neuroleptic discontinuation study in 100 people with dementia: the Neuropsychiatric Inventory median cutoff is a predictor of clinical outcome. Journal of Clinical Psychiatry 2004;65:114-9.
  • Ballard J. Stopping neuroleptics: does it improve the quality of life for people with dementia. National Research Register 2000.
  • Fossey J, Ballard C. Stopping neuroleptics: does it improve quality of life for people with dementia. National Research Register 2003.
Ballard The DART-AD Trial {published data only}
  • Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K, et al. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurology 2009;8(2):151-7. [Ballard 2009, The Lancet]
  • Ballard C, Lana MM, Theodoulou M, Douglas S, McShane R, Jacoby R, et al. A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial). PLoS Medicine 2008;5(4):e76. [Ballard 2008, PLoS Medicine]
Bridges-Parlet 1997 {published data only}
  • Bridges-Parlet S, Knopman D, Steffes S. Withdrawal of neuroleptic medications from institutionalized dementia patients: results of a double-blind, baseline-treatment-controlled pilot study. Journal of Geriatric Psychiatry and Neurology 1997;10:119-26.
  • Bridges-Parlet S, Lyn S. The Effect of Neuroleptic Withdrawal on Physically Aggressive Behaviour in Dementia [Dissertation]. University of Minnesota, 1996.
Cohen-Mansfield 1999 {published data only}
  • Cohen-Mansfield J, Lipson S, Werner P, Billig N, Taylor L, Woosley R. Withdrawal of haloperidol, thioridazine, and lorazepam in the nursing home. Archives of Internal Medicine 1999;159:1733-40.
  • Cohen-Mansfield J, Lipson S, Werner P, Billig N, Woosley R. Discontinuation of psychotropic drugs in the nursing home: a double blind controlled study. Proceedings of the 12th International Conference on Alzheimer's Disease and Related Disorders, 1996 Oct 8-11, Jerusalem. 1996.
Devanand 2011 {published data only}
  • Devanand D, Pelton G, Cunqueiro K, Sackeim HA, Marder K. A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimer's disease. International Journal of Geriatric Psychiatry 2011;26(9):937-43.
Devanand ADAD 2012 {published data only}
  • Devanand DP, Mintzer J, Schultz SK, Andrews HF, Sultzer DL, de la Pena D, et al. Relapse risk after discontinuation of risperidone in Alzheimer's disease. The New England Journal of Medicine 2012;367(16):1497-507.
Findlay 1989 {published data only}
Ruths The BEDNURS Study {published data only}
  • Ruths S, Straand J, Nygaard H, Aarsland D. Stopping antipsychotic drug therapy in demented nursing home patients: a randomized, placebo-controlled study - the Bergen District Nursing Home Study (BEDNURS). International Journal of Geriatric Psychiatry 2008;23:889-95. [Ruths 2008, Int J Geriatr Psychiatry]
  • Ruths S, Straand J, Nygaard H, Bjorvatn B, Pallesen S. Effect of antipsychotic withdrawal on behavior and sleep/wake activity in nursing home residents with dementia: a randomized, placebo-controlled, double-blinded study. The Bergen district nursing home study. Journal of American Geriatric Society 2004;52:1737-43. [Ruths 2004, JAGS]
van Reekum 2002 {published data only}
  • van Reekum R, Clarke D, Conn D, Herrmann N, Eryavec G, Cohen T, et al. A randomized, placebo-controlled trial of the discontinuation of long-term antipsychotics in dementia. International Psychogeriatrics 2002;14:197-210.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Horwitz 1995 {published data only}
  • Horwitz G, Tariot P, Mead K, Cox C. Discontinuation of antipsychotics in nursing home patients with dementia. American Journal of Geriatric Psychiatry 1995;3(4):290-9.
McLennan 1992 {published data only}
Rule 2003 {unpublished data only}
  • Rule S. A randomised double blind placebo controlled clinical trial to compare the progression of cognitive impairment in dementia patients continuing to take or discontinued from treatment with typical neuroleptics. National Research Register 2003.
Wessels 2010 {published data only}
  • Wessels A, Pollock B, Anyama N, Schneider LS, Lieberman JA, Marder SR, et al. Association of 9-hydroxy risperidone concentrations with risk of switching or discontinuation in the Clinical Antipsychotic Trial of Intervention Effectiveness-Alzheimer's Disease trial. Journal of Clinical Psychopharmacology 2010;30(6):683-7.
Westbury 2011 {published data only}
  • Westbury J, Tichelaar L, Peterson G, Gee P, Jackson S. A 12-month follow-up study of "REDuse": a trial aimed at reducing antipsychotic and benzodiazepine use in nursing homes. International Psychogeriatrics 2011;23(8):1260-9.

References to ongoing studies

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Engedal {unpublished data only}
  • Engedal K, Bergh S. Discontinuation of antipsychotics and antidepressants among patients with dementia and BPSD living in nursing homes - a 24 weeks double blind RCT. clinicaltrials.gov/ct2/show/NCT00594269 (accessed 4 February 2013).

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Azermai 2011
Ballard 2006
Ballard 2008
  • Ballard C, Margallo Lana M, Theodoulou M, Douglas S, McShane R, Jacoby R, et al. A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial). PLoS Medicine 2008;5:e76.
Ballard 2010
Banerjee 2009
  • Banerjee S. The use of antipsychotic medication for people with dementia: time for action. A Report for the Minister of State for Care Services by Professor Sube Banerjee. London: The Stationary Office 2009.
Briesacher 2005
  • Briesacher B, Limcangco M, Simoni-Wastila L, Doshi JA, Levens SR, Shea DG, et al. The quality of antipsychotic drug prescribing in nursing homes. Archives of Internal Medicine 2005;165:1280-5.
CADTH 2010
  • Canadian Agency for Drugs and Technologies in Health. Short-acting benzodiazepines versus other strategies for the management of agitation in older patients: clinical effectiveness and guidelines, 2010. www.cadth.ca/media/pdf/k0209_managing_agitation_older_patients_htis_1-5.pdf (accessed 4 February 2013).
Deudon 2009
Devanand 2012a
  • Devanand D, Mintzer J, Schultz S, Sultzer D, de la Pena D, Gupta S, et al. The antipsychotic discontinuation in Alzheimer disease trial: clinical rationale and study design. American Journal of Geriatric Psychiatry 2012;20(4):362-73.
FDA 2005
  • US Food and Drug Administration Public Health Advisory. Deaths with antipsychotics in elderly patients with behavioral disturbances. www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm053171.htm (accessed 4 February 2013).
FDA 2008
  • US Food and Drug Administration Public Health Advisory. Antipsychotics are not indicated for the treatment of dementia-related psychosis. www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124830.htm (accessed 4 February 2013).
Ferri 2005
  • Ferri C, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. for Alzheimer's Disease International. Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366:2112-17.
Finkel 1996
  • Finkel S, Costa e Silva J, Cohen G, Miller S, Sartorius N. Behavioral and psychological signs and symptoms of dementia: a consensus statement on current knowledge and implications for research and treatment. International Psychogeriatrics 1996;8 Suppl 3:497-500.
Gauthier 2005
Gauthier 2010
Gilley 2000
  • Gilley DW. Are behavioral and psychological symptoms of dementia associated with mortality in Alzheimer's disease?. International Psychogeriatrics 2000;12:63-6.
Herrmann 2006
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Howard 2007
Huybrechts 2012
  • Huybrechts K, Gerhard T, Crystal S, Olfson M, Avorn J, Levin R, et al. Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study. BMJ 2012;344:e977.
IPA 2003
  • Anonymous. Primary care physicians guide to behavioral and psychological symptoms of dementia. Primary care physicians guide to behavioral and psychological symptoms of dementia. International Psychogeriatric Association, 2003:18.
McCleery 2012
Meador 1997
  • Meador K, Taylor J, Thaba P, Fought R, Ray W. Predictors of antipsychotic withdrawal or dose reduction in a randomized controlled trial of provider education. Journal of the American Geriatric Society 1997;45(2):207-10.
Mortimer 2005
  • Mortimer A, Shepherd C, Rymer M, Burrows A. Primary care use of antipsychotic drugs: an audit and intervention study. Annals of General Psychiatry 2005;4:18.
NICE 2006
  • National Institute for Health and Clinical Excellence. Dementia. guidance.nice.org.uk/CG42 (accessed 4 February 2013).
O'Brien 2008
Onyike 2008
Petrovic 2007
  • Petrovic M, Hurt C, Collins D, Burns A, Camus V, Liperoti R, et al. Clustering of behavioural and psychological symptoms in dementia (BPSD): a European Alzheimer's Disease in Consortium (EADC) Study. Acta Clinica Belgica 2007;62(6):426-32.
RevMan 2011 [Computer program]
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Robert 2005
  • Robert P, Verhey F, Byrne E, Hurt C, De Deyn P, Nobili F, et al. Grouping for behavioral and psychological symptoms in dementia: clinical and biological aspects. Consensus paper of the European Alzheimer Disease Consortium. European Psychiatry 2005;20:490-6.
Schneider 2005
Schneider 2006
  • Schneider L, Dagerman K, Insel P. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomised, placebo-controlled trials. American Journal of Geriatric Psychiatry 2006;14:191-210.
Sink 2005
Smith 2011
  • Smith T. Antipsychotics in dementia - mortality risks and strategies to reduce prescribing. Evidence Based Mental Health 2011;14(2):35-6.
Vander Stichele 2006
  • Vander Stichele R, Van de Voorde C, Elseviers M, Verrue C, Soenen K, Smet M, et al. Medication use in Belgian nursing homes, 2006. kce.fgov.be/publication/report/medication-use-in-rest-and-nursing-homes-in-belgium (accessed 4 February 2013).
Zuidema 2007
  • Zuidema S, Koopmans R, Verhey F. Prevalence and predictors of neuropsychiatric symptoms in cognitively impaired nursing home patients. Journal of Geriatric Psychiatry and Neurology 2007;20:41-9.