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Prescription of antipsychotics in people with dementia

  • Clive Ballard (a1), Anne Corbett (a1) and Robert Howard (a2)


Gerhard et al clarify our understanding of mortality associated with antipsychotic use in people with dementia, by demonstrating a clear dose relationship and highlighting key questions regarding the relative mortality risk of different atypical antipsychotics. The study also suggests that antipsychotics may confer risks of increased mortality in older people without dementia.

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Corresponding author

Clive Ballard, Professor of Age-Related Diseases, Wolfson Centre for Age-Related Diseases, Guy's Campus, King's College London, London SE1 1UL, UK. Email:


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See pp. 44–51, this issue.

Declaration of interest

C.B. has received speaker fees and consultancy honoraria from Acadia, Lundbeck, Bristol-Myers Squibb, Napp, Takeda, Onsaka, Synexus and Novartis. A.C. has received honoraria from Bial, Lundbeck, Novartis and Acadia.



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1 Ballard, CG, Gauthier, S, Cummings, JL, Brodaty, H, Grossberg, GT, Robert, P et al. Management of agitation and aggression associated with Alzheimer disease. Nat Rev Neurosci 2009; 5: 245–55.
2 Alzheimer's Society. Optimising Treatment and Care for Behavioural and Psychological Symptoms of Dementia. Alzheimer's Society, 2013.
3 Ballard, C, Howard, R. Neuroleptic drugs in dementia: benefits and harm. Nat Rev Neurosci 2006; 7: 492500.
4 Ballard, C, 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 Med 2008; 5: 76.
5 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. N Engl J Med 2012; 367: 1497–507.
6 Schneider, LS, Dagerman, KS, Insel, P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005; 294: 1934–43.
7 Banerjee, S. The Use of Antipsychotic Medication for People with Dementia: Time for Action. Department of Health, 2009.
8 Health and Social Care Information Centre. National Dementia & Antipsychotic Prescribing Audit 2012. HSCIC, 2012.
9 Gerhard, T, Huybrechts, K, Olfson, M, Schneeweiss, S, Bobo, WV, Doraiswamy, PM, et al. Comparative mortality risks of antipsychotic medications in community-dwelling older adults. Br J Psychiatry 2014; 205: 4451.
10 Kales, HC, Kim, HM, Zivin, K, Valenstein, M, Seyfried, LS, Chiang, C, et al. Risk of mortality among individual antipsychotics in patients with dementia. Am J Psychiatry 2012; 169: 71–9.
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The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
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Prescription of antipsychotics in people with dementia

  • Clive Ballard (a1), Anne Corbett (a1) and Robert Howard (a2)
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Is dose response relationship to mortality the only explanation!

12 August 2014

I read the Ballard et al review (1) of Gerhard et al (2) with some interest. However I would like to highlight additional aspects which Ballard et al should have mentioned.Prescribing antipsychotics has been demonstrated to increase risk of mortality in community samples including patients with or without dementia(3). Another study, led by Jussi Honkola (4), found that victims of suddencardiac death more frequently used antidepressants and antipsychotic medication compared to survivors of acute coronary events.However it has been demonstrated with Tiihonen et al (5) that there is a lower mortality in patients, suffering from Schizophrenia, taking antipsychotic medication, than not and this observation should not be ignored.Ballard et al suggest "It would be important for Gerhard and colleagues tore-examine their data-set, looking specifically at patients who did have adiagnosis of schizophrenia or bipolar disorder to confirm this." But Gerhard et al have clearly stated "People with clinical diagnoses of schizophrenia, bipolar disorder or cancer during the 180-day period preceding the index date were excluded." Importantly though patients with depression were not excluded and the ramifications is known to us all, including consequent suicide rates.Hence if Gerhard et al feel dementia is underestimated in their sample, and Ballard et al feel patients with the above diagnosis might have been included, can I rely on the relationship postulated?It is disappointing that Gerhard et al did not concentrate on outcomes related to the one third of patients diagnosed with dementia. Its is suggested that more than 90% of patients will experience at least one behavioural and psychological symptom of Dementia(BPSD), during the course of their condition, with the most common ones being delusions, hallucinations, agitation and aggression. Ballard et al could have also suggested that there should have been a scale to measure the behavioural disturbances before and after treatment in this subgroup. If patients had been more disturbed before treatment, that would have led to increase dosing and increased the risk of death, potentially with or without initiation of antipsychotic treatment. Ballard et al noted that the best practice guides emphasize on the assessment and treatment of contributing medical conditions, appropriate analgesia for pain relief and the efficacy of simple, non- pharmacologicalinterventions. However this is not sufficient and there is an important role for pharmacological management. Additionally these disadvantages in treatment of aggression have to be balanced against the risk posed to staff and residents/patients.Patients with behavioural problems are usually prescribed benzodiazepines and hypnotics, which could also increase mortality. We should actually consider, if the mortality rate could have been potentially even higher, if patients in Gerhard et al sample were left untreated. Moreover depression is uncontrolled for in the sample.

I would also like to link this subject to (6) Kripke at al ,which found that patients prescribed hypnotics had substantially elevated hazard of dying, compared to those who had no hypnotics. Patients receiving prescriptions for zolpidem, temazepam and other hypnotics suffered over four times the mortality as the matched hypnotic-free control patients. Even patients prescribed fewer than 18 hypnotic doses per year experienced increased mortality, with greater mortality associated with greater dosage prescribed.

I also want to mention the research of Weich and colleagues, which found that people taking anxiolytic and hypnotic drugs are at increased risk of premature mortality (7). It would have been meaningful, if Gerhardet al had controlled for this type of co-prescribing.Even though Gerhard et al seem to make a good case, I will be looking forward to see more research in this area.References:1.Ballard C, Corbett A, Howard R . Prescription of antipsychotics in people with dementiaBr J Psychiatry. (2014 )205, 4-5.

2. Gerhard T, Huybrechts K, Olfson M, Schneeweiss S, Bobo WV, Doraiswamy PM, Devanand DP, Lucas JA, Huang C, Malka ES, Levin R, Crystal S. Comparative mortality risks of antipsychotic medications in community- dwelling older adults. Br J Psychiatry. (2014) Jul;205(1):44-51

3. Ray W, Chung C, Murray K, Hall K, Stein M. Atypical AntipsychoticDrugs and the Risk of Sudden Cardiac Death, N Engl J Med 2009; 360:225-2354. Honkola, J,Hookana, E, Malinen, S, Kaikkonen, K, Junttila, M, Isohanni,M, Kortelainen, M, Huikuri, H. Psychotropic Medications and the Risk of Sudden Cardiac Death During an Acute Coronary Events; European Heart Journal; 2012; 33(6):745-751

5. Tiihonen J1, Lannqvist J, Wahlbeck K, Klaukka T, Niskanen L, Tanskanen A, Haukka J. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet. 2009Aug 22;374 (9690):620-7.

6. Kripke D , Langer R , Kline L ,Hypnotics' association with mortality or cancer: a matched cohort study, BMJ Open 2012;2:e000850 doi:10.1136/bmjopen-2012-0008507. Weich S ,Pearce H, Croft P , Singh S, Crome I, Bashford J , Frisher M . Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: retrospective cohort study.BMJ 2014;348:g1996

Dr Galina Nikolova CT2 trainee, PsychiatryDr Mukesh Kripalani, Consultant Psychiatrist

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Conflict of interest: None declared

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