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Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up

BMJ 1997; 314 doi: (Published 25 January 1997) Cite this as: BMJ 1997;314:266
  1. Rupert McShane, clinical lecturera,
  2. Janet Keene, research assistanta,
  3. Kathy Gedling, research assistanta,
  4. Christopher Fairburn, professorb,
  5. Robin Jacoby, clinical readera,
  6. Tony Hope, readera
  1. a Section of Old Age Psychiatry, University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX
  2. b University Department of Psychiatry, Warneford Hospital, Oxford, OX3 7JX
  1. Correspondence to: Dr McShane
  • Accepted 31 October 1996


Objective: To investigate the contribution of neuroleptic drugs to cognitive decline in dementia.

Design: Two year prospective, longitudinal study consisting of interviews every four months, with necropsy follow up.

Setting: Community settings in Oxfordshire.

Subjects: 71 subjects with dementia, initially living at home with informant.

Main outcome measures: Cognitive function (score from expanded minimental state examination); behavioural problems (physical aggression, hallucinations, persecutory ideas, and disturbance of diurnal rhythm); and postmortem neuropathological assessment (cortical Lewy body pathology).

Results: The mean (SE) decline in cognitive score in the 16 patients who took neuroleptics was twice that in the patients who did not (20.7 (2.9) v 9.3 (1.3), P=0.002). An increased rate of decline was also associated with aggression, disturbed diurnal rhythm, and persecutory ideas. However, only use of neuroleptics and severity of persecutory ideas were independently associated with more rapid cognitive decline when all other variables were adjusted for. The start of neuroleptic treatment coincided with more rapid cognitive decline: median rate of decline was 5 (interquartile range 8.5) points per year before treatment and 11 (12) points per year after treatment (P=0.02). Cortical Lewy body pathology did not account for association between neuroleptic use and more rapid decline.

Conclusions: Neuroleptic drugs that are sometimes used to treat behavioural complications of dementia may worsen already poor cognitive function. Randomised controlled trials are needed to confirm a causal relation.

Key messages

  • Neuroleptic drugs are used to treat behavioural problems in patients with dementia, but they may cause more rapid decline in cognitive function

  • In our longitudinal study of patients with dementia we found that the rate of cognitive decline in patients taking neuroleptics was twice that in those not taking neuroleptics

  • Furthermore, the start of neuroleptic treatment was associated with an increase in the rate of cognitive decline

  • Cortical Lewy body pathology at necropsy did not account for the association between neuroleptic use and more rapid decline

  • Although our study does not prove a causal relation, we suggest that there should be regular review of the need for patients to continue taking neuroleptic drugs


    • Accepted 31 October 1996
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