Behaviour, Stroke, Age related illnesses, Mental Health | April 6, 2015 | Author: The Super Pharmacist
Antipsychotic drugs are widely used to treat the behavioural and psychological symptoms of dementia such as agitation, loss of inhibitions, delusions, hallucinations, and aggression. These symptoms may place both the patient and those who care for them at risk, with an estimated 90% of dementia patients experiencing at least one of these symptoms in the later stages of the disease (1). There are a number of different treatment options for dementia patients, although antipsychotics and dementia prescription is the first line treatment in many circumstances to reduce (or eliminate) the intensity of psychotic episodes.
A number of randomised controlled trials, comparing the efficacy of antipsychotics and a placebo, found some antipsychotics to have a small but beneficial effect on the management of aggression in some patients, and some positive impact on the treatment of psychosis over a period of 12 weeks (2,3).
However, many antipsychotic medicines are prescribed for significant periods of time, with studies highlighting average prescribing times of between 1-2 years for some patients in hospital care, despite no knowledge of the long-term health impacts regarding their use (4). Much of the literature in this area suggests that a large majority of antipsychotic medications only have modest benefits, for specific symptoms, over a short period of time.
A number of studies concerned with the dosage and duration of antipsychotic medication have also highlighted serious safety concerns and recommend that more effort should be made to avoid unnecessary and prolonged prescription of such medicines (5). An additional study of 9000 patients with Alzheimer’s disease in Finland also concluded that clinicians and pharmacists should evaluate dosing levels and associated side effects on a regular basis, particularly in men and patients with a history of additional psychiatric disorders (6).
There is concern regarding the widespread prescribing of antipsychotics to treat dementia, as many of the drugs used were initially licensed for schizophrenia and their suitability and safety for the treatment of dementia are not known. The side effects of antipsychotics have been well documented through a number of studies, and include
The negative health impacts associated with antipsychotics have also been highlighted through a number of experiments, with a recent study in the Netherlands highlighting a 9 fold risk of stroke in patients taking particular antipsychotic medication in the first four weeks of doing so (7).
Some drugs, such as risperidone, have very strict prescribing regulations that state it should be used for no more than six weeks, although a number of studies have evidenced its misuse in a large number of cases (8). Further studies suggest that risperidone should only be used for patients with psychotic or behavioural symptoms that cause significant distress, functional impairment and danger to self or others, and this is largely reflected in the prescribing guidelines of most countries.
A recent view by the Department of Health in the United Kingdom estimated that two thirds of 180,000 antipsychotic prescriptions for dementia patients nationally were inappropriate, with particular concern regarding levels of overprescribing in care home facilities and its impact on quality of care, patient safety and clinical effectiveness (9). The same study also noted that the misuse of antipsychotics contributed to an estimated 1800 deaths over the course of one year due to drug-related complications, and that they are often seen as a ‘quick and easy’ way of managing challenging behaviour where other treatment options would be more appropriate.
How drugs are prescribed is also another area of concern, with relatively minor symptoms such as restlessness attracting very strong antipsychotic medication. Much national guidance now reflects a growing concern regarding the longer term use of medication, noting that antipsychotics must be used only when all alternatives to drugs have been tried previously and there is clear evidence of a risk of harm to the patient or carer (10). There is also unease regarding possible negative interactions with other commonly used drugs in patients with Alzheimer’s, with many such interactions poorly understood due to a lack of available evidence.
A systematic review of all available antipsychotics for the treatment of aggression, agitation and psychosis in people with Alzheimer’s was undertaken by the Cochrane Collaboration in 2012, with a review of 16 trials suggesting that although risperidone and olanzapine were useful in reducing aggression and psychosis, both were clearly associated with serious adverse cerebrovascular events (including stroke) and other adverse outcomes (11). The same review highlighted significantly high dropout rates in patients who had begun courses of risperidone and olanzapine, as well as high numbers of relapse following completion of the course.
Some researchers, having considered the best available evidence and evaluated the risks versus the benefits, have called for the use of antipsychotic medication only within a strictly palliative care model to alleviate suffering in those whose life expectancy is short (12).
A number of additional studies have shown that the mortality risk associated with antipsychotics varies between drugs, with haloperidol presenting the highest risk and quetiapine the lowest (13,14).
It is clear that some antipsychotic drugs do have a role to play in the successful treatment and management of specific symptoms associated with Alzheimer’s Disease in certain individuals. However, the widespread misuse of such drugs currently results in the benefits being substantially outweighed by risk as a result of poor prescribing, and other therapies and treatment methods being underused. There is a clear need for more literature and experiments that investigate the health impacts of the longer term use of antipsychotics in patient with Alzheimer’s Disease, as well as further large, randomised, placebo-controlled trials to investigate the possible use of other existing medications that have less harmful side effects than risperidone and olanzapine.
1. Gallagher D, Herrmann N. (2015). Agitation and aggression in Alzheimer’s disease: an update on pharmacological and psychosocial approaches to care. Neuro Dis Manag 5(1)77-83
2. Ballard C, Howard R. (2006). Neuroleptic drugs in dementia: benefits and harm. Nature Reviews Neuroscience (7) pp.492-500.
3. Schneider LS. Dagerman K. Insel PS. (2006a). Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. American Journal of Geriatric Psychiatry 14: pp.191-210
4. Margallo-Lana, M., Swann, A., O'Brien, J., Fairbairn, A., Reichelt, K., Potkins, D., Mynt, P., & Ballard, C. (2001). Prevalence and pharmacological management of behavioural and psychiatric symptoms amongst dementia sufferers living in care environment. International Journal of Geriatric Psychiatry 16: 39-44.
5. Lin YT, Hwang TJ, Shan JC, Chiang HL, Sheu YH, Hwu HG. (2015). Dosage and duration of antipsychotic treatment in demented outpatients with agitation or psychosis. J Formos Med Assoc 114(2):147-53
6. Taipale H, Koponen M, Tanskanen A, Tolppanen AM, Tiihonen J, Hartkainen S. (2014). Antipsychotic doses among community-dwelling persons with Alzheimer disease in Finland. J Clin Psychopharmacol 34(4):435-40
7. Kleijer BC, van Marum RJ, Egberts AC, Jansen PA, Knol W, Heerdink ER. (2009). Risk of cerebrovascular events in elderly users of antipsychotics. J Psychopharmacol 23(8):909-14
8. Rocca P, Marino F, Montemagni C, Perrone D, Bogetto F. (2007). Risperidone, olanzapine and quetiapine in the treatment of behavioral and psychological symptoms in patients with Alzheimer's disease: preliminary findings from a naturalistic, retrospective study. Psych Clin Neurosci 61(6):622-29
9. Department of Health. (2009).The use of antipsychotic medication for people with dementia: time for action. Department of Health. London.
10. NICE. (2006). Dementia: The NICE-SCIE guideline on supporting people with dementia and their carers in health and social care. The British Psychological Society and the Royal College of Psychiatrists
11. Ballard CG, Waite J, Birks J. (2012). Atypical antipsychotics for aggression and psychosis in Alzheimer’s disease (Review). Available online at http://www.bibliotecacochrane.com/pdf/CD003476.pdf (last accessed 6th March 2015)
12. Treloar A, Crugel M, Prasanna A, Solomons L, Fox C, Paton C, Katona C. (2010). Ethical dilemmas: should antipsychotics ever be prescribed for people with dementia? Br J Psychiatry 197(2):88-90
13. Rossom RC, Rector TS, Lederle FA, et al. (2010). Are all commonly prescribed antipsychotics associated with greater mortality in elderly male veterans with dementia? J Am Geriatr Soc 58:1027-1034
14. Moore R, DeJoseph D, Simmons BB. (2014). Managing patients on antipsychotics: your domain, too. J Fam Pract 63(3):142-9