sign in sign up
<<
Home , Anticholinergic

clinical Anticholinergic and sedative J Simon Bell Carmel Mezrani Prescribing considerations for people with Natalie Blacker Tammy LeBlanc Oliver Frank Christopher P Alderman Simone Rossi Debra Rowett Russell Shute

Medicines with Background anticholinergic properties Older people with dementia may be particularly susceptible to cognitive impairment associated with anticholinergic and sedative medicines. This The likelihood that medicines may produce impairment may be misattributed to the disease process itself. unwanted central anticholinergic effects depends Objective in part on age related and patient specific This review examines clinical considerations associated with using anticholinergic variability in pharmacokinetic parameters, blood- and sedative medicines in people with dementia or incipient cognitive brain barrier permeability, degree of impairment. It highlights issues associated with concomitant use of cholinesterase neuronal degeneration and a patient’s baseline inhibitors and anticholinergic medicines, and pharmacotherapy of conditions that cognitive status.4,5 Medicines specifically commonly occur in people with dementia. prescribed for their anticholinergic properties (eg. Discussion , benzhexol and benztropine) are well Use of medicines with anticholinergic or sedative properties may result in adverse recognised by clinicians. However, clinicians may events by increasing the overall anticholinergic or sedative load. Patients may be less aware that some medicines prescribed benefit from clinicians reviewing the anticholinergic load of the current for other purposes also have anticholinergic regimen before the initiation of cholinesterase inhibitors or . Reducing properties (Table 1).2,6–8 These include the the number and dose of anticholinergic and sedative medicines may improve inhaled anticholinergics, ipratropium and cognitive function and reduce the likelihood of adverse events. when prescribed in their Keywords usual therapeutic doses. Even medicines with hypnotics and sedatives; anticholinergic effects; cholinergic antagonists; minor anticholinergic properties may contribute dementia; cognition disorders to unwanted central and peripheral adverse events if used in combination with other agents with anticholinergic effects. Clinically significant adverse events (Table 2) range from mild cognitive The number of people with dementia in impairment to . The cumulative effect of Australia is predicted to quadruple from an taking one or more medicines with anticholinergic estimated 245 000 in 2009 to approximately properties has been termed ‘anticholinergic load’.9 1.13 million by 2050.1 Causes of dementia Use of medicines with anticholinergic include Alzheimer disease, dementia with properties in older people is associated with Lewy bodies, frontotemporal dementia, impaired physical and cognitive function. In vascular dementia and Parkinson disease. a cross sectional study of 364 people aged Medicines with anticholinergic and more than 80 years living in Italy, the use of sedative properties are widely prescribed medicines with serum anticholinergic activity for older people in Australia.2,3 People with was associated with poorer physical performance dementia may be particularly susceptible battery scores, reduced hand grip strength and to cognitive impairment caused by compromised activities of daily living.10 In 932 anticholinergic and sedative medicines.4 community dwelling people aged more than 65

Reprinted from Australian Family Physician Vol. 41, No. 1/2 january/february 2012 45 clinical Anticholinergic and sedative medicines – prescribing considerations for people with dementia

Table 1. Medicines with clinically significant anticholinergic effects that are commonly used in older people with dementia6–8

Antipsychotics Antidepressants Medicines for urinary incontinence Strong anticholinergic Tricyclic ** *** effects – avoid using in antidepressants Oxybutynin Chlorpheniramine*** people with dementia Pericyazine (eg. , Propantheline , ) ** *** ** *** Moderate Desvenlafaxine anticholinergic effects Prochlorperazine Duloxetine* – use with caution in Fluoxetine people with dementia Risperidone * Venlafaxine * New medicine: reported adverse effects profile is consistent with moderate anticholinergic effects ** Not included on the schedule of PBS/RPBS benefits *** Found in cold and flu treatments, may be purchased over-the-counter Reproduced from Veterans’ MATES Therapeutic brief 25. Available at www.veteransmates.net.au

also have sedative properties. Medicines and following the first date of supply.3 Dispensing Table 2. Examples of anticholin- with sedative properties have been linked to of anticholinergic medicines also increased ergic side effects depressive symptoms, worsening cognition, following initiation of cholinesterase inhibitors. Confusion//delirium respiratory depression, impaired muscle strength Some of these anticholinergic medicines may Dry mouth and falls and fractures.15–19 The cumulative effect have been prescribed to treat the adverse effects Pupil dilatation/blurred vision of taking one or more medicines with sedative of the (eg. medicines for properties has been termed ‘sedative load’.20 All ). Patients may benefit from medicines with sedative properties – not only clinicians reviewing the anticholinergic load of /arrhythmias those prescribed for intentional sedation – may their current medicine regimen before initiating Reproduced from Veterans’ MATES contribute to an older person’s sedative load. cholinesterase inhibitors or memantine, with Therapeutic brief 25. Available at the aim of minimising or ceasing medicines with Concomitant use of www.veteransmates.net.au anticholinergic properties. cholinesterase inhibitors and anticholinergic medicines years in the Women’s Health and Aging Study Reducing anticholinergic conducted in the United States, use of medicines Cholinesterase inhibitors (, and sedative load in with anticholinergic properties was associated and ) may modestly improve cognition patients with dementia with difficulties in balance and mobility.11 There via inhibiting the acetyl cholinesterase. Pharmacotherapy of specific is mixed evidence in relation to an association Restricted supply of these medicines is conditions between anticholinergic medicines and increased subsidised through the Pharmaceutical Benefits mortality.12–14 Scheme (PBS) using the authority system for Urinary incontinence the management of mild to moderate Alzheimer Incontinence is often multifactorial in older Medicines with sedative disease. Concomitant use of anticholinergic patients with dementia. Medicines may contribute properties medicines may decrease the effectiveness of to urinary incontinence via agonism of alpha-1- Medicines with sedative properties include cholinesterase inhibitors.21 Despite this, an adrenoceptors or nicotinic acid receptors leading and other hypnosedatives, Australian study revealed that of 5797 people to stress incontinence, or antagonism of beta-3- , anticonvulsants, antidepressants, who commenced treatment with a PBS subsidised adrenoceptors or agonism of muscarinic receptors and , and histamine H1 cholinesterase inhibitor between April and June leading to urge incontinence.22 Antagonism antagonists commonly used for allergic 2006, 32% also received a prescription for an of muscarinic receptors may lead to overflow conditions. Many anticholinergic medicines anticholinergic medicine in the 14 weeks before incontinence, while use of medicines with

46 Reprinted from Australian Family Physician Vol. 41, No. 1/2 january/february 2012 Anticholinergic and sedative medicines – prescribing considerations for people with dementia clinical sedative properties (eg. benzodiazepines, inhibitors (SSRIs) compared to tricyclic express pain in the form of facial expressions, and tricyclic antidepressants) may contribute to antidepressants (TCAs).28 The Health Technology body movements and behavioural disturbances functional incontinence. Anticholinergic medicines Assessment Study of the Use of Antidepressants such as aggression or agitation. These symptoms can cause constipation, which can result in urinary for Depression in Dementia (HTA-SADD), which may be misinterpreted as behavioural symptoms retention and urge and . included 326 patients, reported that sertraline and of dementia. Pain may be under-recognised and Cholinesterase inhibitors prescribed for mirtazapine were not more effective than placebo undertreated, especially in advanced stages patients with Alzheimer disease have also been and were associated with an increased risk of of dementia.36 Research has reported lower associated with urinary incontinence.23 In a adverse events.29 This finding contradicted an overall use of analgesics among people with retrospective population based cohort study earlier meta-analysis that included 165 patients dementia.37,38 However, while people with of 44 884 older people with dementia, use which supported the efficacy of antidepressants dementia may receive less analgesics overall, of cholinesterase inhibitors was associated for treating depression in Alzheimer disease.30 A they may be more likely to be prescribed strong with an increased likelihood of receiving an Cochrane review has also reported that sertraline opioids (eg. transdermal fentanyl) instead of anticholinergic medicine to manage urinary and citalopram were associated with a reduction paracetamol and other analgesics with lower incontinence.24 induced urinary incontinence in agitation in people with dementia when likelihoods of adverse events.38 Transdermal in people with dementia may be misattributed to compared to placebo in two studies.31 Selective fentanyl patches should not be prescribed to progression of the underlying disease processes.25 serotonin reuptake inhibitors tend to be less people with chronic nonmalignant pain who This may result in a ‘prescribing cascade’ if an sedating than TCAs, or mirtazapine. are opioid naive.8 Antiepileptics used in the anticholinergic medicine is then prescribed to Some TCAs (eg. amitryptiline, doxepin) are both treatment of neuropathic pain (eg. , treat the incontinence.24 highly sedative and anticholinergic. Combination , carbamazepine, valproate) may Nonpharmacological approaches are antidepressant treatment is not appropriate due impair cognition and cause sedation. People with recommended as first line treatment. Prompted to the increased risk of adverse events, including dementia may also be particularly susceptible or timed voiding may reduce urinary incontinence those related to anticholinergic and sedative to memory impairment and cognitive decline among residents of aged care facilities with load.32 associated with some antiepileptics.39 dementia. For people with functional incontinence Behavioural and psychological related to impaired mobility, an occupational symptoms therapist or physiotherapist may advise measures Sleep complaints are common among people to improve toilet access (eg. removal of clutter, with Alzheimer disease and other .33 Behavioural and psychological symptoms good lighting, nonslip flooring, ensuring the toilet Underlying issues that may contribute to disturbed of dementia are common and include is clearly marked, hand rails, raised toilet seat sleep include medicines, medical conditions and agitation, aggression, hallucinations and height and appropriate clothing). With these environmental factors. Older people often require wandering. Nonpharmacological strategies interventions, treatment with anticholinergic less sleep than younger people and it is useful are considered first line treatment. Treatment medicines may not be necessary. However, if to explain this to patients. Nonpharmacological with antipsychotics should be reserved for anticholinergic medicines are to be trialled, treatments for insomnia are considered first line.34 people with aggression and psychosis who patients and carers may require education about Sedative-hypnotic medicines should be prescribed have not responded to nonpharmacological potential adverse events of anticholinergic for the shortest possible duration as an adjunct strategies. Use of both first (eg. haloperidol) and medicines. Consider ceasing anticholinergics to nonpharmacological treatments. It is useful to second generation (eg. olanzapine, quetiapine, administered for urinary symptoms if there is no agree a definite duration of treatment with the risperidone) antipsychotics is associated with benefit after 4 weeks of treatment.8 patient at the time of prescribing.8 People already an increased risk of death in people with taking long term benzodiazepines may benefit Alzheimer disease.40,41 In common with some Depression from dosage reduction and slow discontinuation other medicines commonly prescribed for older Depressive symptoms have been reported in to maximise cognitive function and reduce the people (eg. SSRIs, TCAs, opioids) antipsychotics up to 40% of people with Alzheimer disease, risk of falls. Despite their relatively widespread can also cause hyponatraemia that may result which is reflected in the high prevalence of use, TCAs and sedating antihistamines are best in confusion and lethargy. While second antidepressant use in this population.26 However, avoided in the management of insomnia due to generation antipsychotics have a lower risk there is a lack of evidence to guide antidepressant their anticholinergic properties. of tardive dyskinesia, they can cause sedation prescribing.27 Two recent studies have suggested and postural hypotension. Patients with Lewy a less favourable risk-to-benefit ratio than body dementia are especially susceptible to the previously thought. An observational study Opioid analgesics and tramadol may have extrapyramidal side effects of antipsychotics.42 reported an increased risk of falls and fractures, sedative effects. The ways in which people with The dementia withdrawal trial stroke/transient ischaemic attack and all cause dementia experience and express pain is a field (DART-AD) in the United Kingdom demonstrated mortality among users of selective serotonin of ongoing research.35 People with dementia may that for most patients with Alzheimer disease,

Reprinted from Australian Family Physician Vol. 41, No. 1/2 january/february 2012 47 clinical Anticholinergic and sedative medicines – prescribing considerations for people with dementia withdrawal of antipsychotics had no detrimental • For most patients with Alzheimer disease, Russell Shute BMBS, ClinDipPallMed, FRACGP, is a general practitioner, Australian Medicines effect on functional and cognitive status. People withdrawal of antipsychotics has no Handbook, Adelaide, South Australia and the who continued using antipsychotics had reduced detrimental effect on functional and cognitive Department of Veterans’ Affairs, Veterans’ survival compared to those who received placebo status. Medicines Advice and Therapeutics Education (ie. those who discontinued antipsychotics Services (Veterans’ MATES) Clinical Reference Authors treatment).43 In Australia, risperidone is the only Group. J Simon Bell BPharm(Hons), PhD, MPS, is antipsychotic PBS listed for the management Conflict of interest: All authors have completed Associate Professor, Quality Use of Medicines of behavioural disturbances characterised by and Pharmacy Research Centre, Sansom Institute, the ICMJE disclosure form of potential conflict psychotic symptoms and aggression in patients School of Pharmacy and Medical Sciences, of interest. Oliver Frank is employed by the with dementia where nonpharmacological University of South Australia. simon.bell@unisa. University of Adelaide which has a contract to methods have been unsuccessful. Problems edu.au provide GP advice to the DVA MATES program. Christopher Alderman has received payment such as screaming/vocalising, ‘sundowning’ Carmel Mezrani BMedSc, BMBS, FRACGP, is from various pharmaceutical companies for and wandering do not reliably respond to Senior Lecturer, School of Medicine, University of Notre Dame, Sydney, New South Wales and lectures, consultancy, expert testimony and for antipsychotics. the Department of Veterans’ Affairs, Veterans’ the development of educational presentations. Key points Medicines Advice and Therapeutics Education Simone Rossi is employed by the National Services (Veterans’ MATES) Clinical Reference Prescribing Service Ltd. Debra Rowett is employed • Older people with dementia may be Group by the Repatriation General Hospital which particularly susceptible to impaired physical Natalie Blacker BBehavSc(Psych), is Research receives funding from DVA. and cognitive function associated with Associate, Quality Use of Medicines and anticholinergic and sedative medicines. Pharmacy Research Centre, Sansom Institute, Disclaimer This work has been produced with the assistance • Drug induced physical and cognitive School of Pharmacy and Medical Sciences, University of South Australia of funding provided by the Australian Government impairment in older people with dementia may Department of Veterans’ Affairs. However, the Tammy LeBlanc BA(Psych), is module develop- be misattributed to progression of underlying views expressed do not necessarily represent ment coordinator, Quality Use of Medicines and disease processes. the views of the Minister for Veterans’ Affairs Pharmacy Research Centre, Sansom Institute, or the Department of Veterans’ Affairs. The • Medicines with weak anticholinergic or School of Pharmacy and Medical Sciences, Commonwealth does not give any warranty nor sedative properties (including nonprescription University of South Australia accept any liability in relation to the contents of medicines) may cause adverse events Oliver Frank MBBS, PhD, FRACGP, FACHI, is this work. by contributing to an older person’s University Senior Research Fellow, Discipline anticholinergic or sedative load. This load may of General Practice, School of Population Acknowledgements be decreased by reducing the number and Health and Clinical Practice, The University of The Department of Veterans’ Affairs’ MATES Adelaide, South Australia and the Department program is provided by the Quality Use of dose of medicines with anticholinergic and of Veterans’ Affairs, Veterans’ Medicines Advice Medicines and Pharmacy Research Centre, sedative properties. and Therapeutics Education Services (Veterans’ Sansom Institute, University of South Australia in • Patients may benefit from clinicians MATES) Clinical Reference Group association with Discipline of General Practice, reviewing the anticholinergic load of their Christopher P Alderman BPharm, PhD, FSHP, University of Adelaide; Discipline of Public Health, current medicine regimen before initiating CGP, BCPP, is Associate Professor, Pharmacy University of Adelaide; Repatriation General cholinesterase inhibitors or memantine, with Department, Repatriation General Hospital, Hospital, Daw Park; National Prescribing Service; Australian Medicines Handbook; and Drug and the aim of minimising or ceasing if possible Adelaide, South Australia and the Department Therapeutics Information Service. Veterans’ medicines with anticholinergic properties. of Veterans’ Affairs, Veterans’ Medicines Advice and Therapeutics Education Services (Veterans’ MATES Program materials are available at www. • Urinary incontinence may be drug induced. MATES) Clinical Reference Group veteransmates.net.au. Anticholinergic medicines are often not Simone Rossi BPharm, is Editor, Australian needed to treat urinary incontinence. Consider References Medicines Handbook, Adelaide, South Australia 1. Access Economics. Keeping dementia front of ceasing anticholinergic medicines if there is no and the Department of Veterans’ Affairs, mind: incidence and prevalence 2009–2050. 2009. benefit after 4 weeks. Veterans’ Medicines Advice and Therapeutics Available at www.alzheimers.org.au/common/files/ Education Services (Veterans’ MATES) Clinical NAT/20090800_Nat__AE_FullKeepDemFrontMind. • Depressive symptoms are common in pdf [Accessed 31 May 2011]. Alzheimer disease. There is mixed evidence Reference Group 2. nishtala PS, Fois RA, McLachlan AJ, et al. for the safety and efficacy of antidepressants Debra Rowett BPharm, is Service Director, Anticholinergic activity of commonly prescribed and neuropsychiatric adverse events in in patients with dementia. Selective serotonin Drug and Therapeutics Information Service, Repatriation General Hospital, Adelaide, South older people. J Clin Pharmacol 2009;49:1176–84. reuptake inhibitors are less sedating than 3. Robinson M, Rowett D, Leverton A, et al. Changes in Australia and the Department of Veterans’ Affairs, TCAs, mianserin or mirtazapine. Tricyclic utilisation of anticholinergic after initiation of Veterans’ Medicines Advice and Therapeutics cholinesterase inhibitors. Pharmacoepidemiol Drug antidepressants may be both sedative and Education Services (Veterans’ MATES) Clinical Saf 2009;18:659–64. anticholinergic. Reference Group 4. sunderland T, Tariot PN, Cohen RM, et al.

48 Reprinted from Australian Family Physician Vol. 41, No. 1/2 january/february 2012 Anticholinergic and sedative medicines – prescribing considerations for people with dementia clinical

Anticholinergic sensitivity in patients with dementia Drugs Aging 2008;25:871–7. 2005;353:2335–41. of the Alzheimer type and age-matched controls. 22. tsakiris P, Oelke M, Michel MC. Drug-induced urinary 42. Weintraub D, Hurtig HI. Presentation and man- A dose-response study. Arch Gen Psychiatry incontinence. Drugs Aging 2008;25:541–9. agement of psychosis in Parkinson’s disease and 1987;44:418–26. 23. starr JM. Cholinesterase inhibitor treatment and dementia with Lewy bodies. Am J Psychiatry 5. Roe CM, Anderson MJ, Spivack B. Use of anticholin- urinary incontinence in Alzheimer’s disease. J Am 2007;164:1491–8. ergic medications by older adults with dementia. J Geriatr Soc 2007;55:500–1. 43. ballard C, Hanney ML, Theodoulou M, et al. The Am Geriatr Soc 2002;50:836–42. 24. Gill SS, Mamdani M, Naglie G, et al. A prescribing dementia antipsychotic withdrawal trial (DART-AD): 6. Rudolph JL, Salow MJ, Angelini MC, et al. The cascade involving cholinesterase inhibitors and anti- long-term follow-up of a randomised placebo- anticholinergic risk scale and anticholinergic cholinergic drugs. Arch Intern Med 2005;165:808–13. controlled trial. Lancet Neurol 2009;8:151–7. adverse effects in older people. Arch Intern Med 25. Resnick NM. Urinary incontinence. Lancet 2008;168:508–13. 1995;346:94–9. 7. carnahan RM, Lund BC, Perry PJ, et al. The 26. Arbus C, Gardette V, Bui E, et al. Antidepressant use Anticholinergic Drug Scale as a measure of drug- in Alzheimer’s disease patients: results of the REAL. related anticholinergic burden: associations with FR cohort. Int Psychogeriatr 2010;22:120–8. serum anticholinergic activity. J Clin Pharmacol 27. nelson JC, Devanand DP. A systematic review and 2006;46:1481–6. meta-analysis of placebo-controlled antidepressant 8. Rossi S, editor. Australian Medicines Handbook. studies in people with depression and dementia. J Adelaide: Australian Medicines Handbook Pty Ltd; Am Geriatr Soc 2011;59:577–85. 2011. 28. coupland C, Dhiman P, Morriss R, et al. 9. minzenberg MJ, Poole JH, Benton C, et al. Antidepressant use and risk of adverse outcomes in Association of anticholinergic load with impairment older people: population based cohort study. BMJ of complex attention and memory in schizophrenia. 2011;343:d4551. Am J Psychiatry 2004;161:116–24. 29. banerjee S, Hellier J, Dewey M, et al. Sertraline or 10. landi F, Russo A, Liperoti R, et al. Anticholinergic mirtazapine for depression in dementia (HTA-SADD): drugs and physical function among frail elderly popu- a randomised, multicentre, double-blind, placebo- lation. Clin Pharmacol Ther 2007;81:235–41. controlled trial. Lancet 2011;378:403–11. 11. cao YJ, Mager DE, Simonsick EM, et al. Physical and 30. thompson S, Herrmann N, Rapoport MJ, et al. cognitive performance and burden of anticholiner- Efficacy and safety of antidepressants for treatment gics, sedatives, and ACE inhibitors in older women. of depression in Alzheimer’s disease: a metaanalysis. Clin Pharmacol Ther 2008;83:422–9. Can J Psychiatry 2007;52:248–55. 12. Kumpula EK, Bell JS, Soini H, et al. Anticholinergic 31. seitz DP, Adunuri N, Gill SS, et al. Antidepressants drug use and mortality among residents of long-term for agitation and psychosis in dementia. Cochrane care facilities: a prospective cohort study. J Clin Database Syst Rev 2011;2:CD008191. Pharmacol 2011;51:256–63. 32. Rush AJ, Trivedi MH, Stewart JW, et al. Combining 13. uusvaara J, Pitkala KH, Kautiainen H, et al. medications to enhance depression outcomes Association of anticholinergic drugs with (CO-MED): acute and long-term outcomes of a hospitalization and mortality among older cardio- single-blind randomized study. Am J Psychiatry vascular patients: A prospective study. Drugs Aging 2011;168:689–701. 2011;28:131–8. 33. bombois S, Derambure P, Pasquier F, et al. Sleep 14. panula J, Puustinen J, Jaatinen P, et al. Effects of disorders in aging and dementia. J Nutr Health Aging potent anticholinergics, sedatives and antipsychotics 2010;14:212–7. on postoperative mortality in elderly patients with 34. david R, Zeitzer J, Friedman L, et al. Non- hip fracture: a retrospective, population-based study. pharmacologic management of sleep disturbance Drugs Aging 2009;26:963–71. in Alzheimer’s disease. J Nutr Health Aging 15. van Vliet P, van der Mast RC, van den Broek M, et al. 2010;14:203–6. Use of benzodiazepines, depressive symptoms and 35. scherder E, Herr K, Pickering G, et al. Pain in demen- cognitive function in old age. Int J Geriatr Psychiatry tia. Pain 2009;145:276–8. 2009;24:500–8. 36. morrison RS, Siu AL. A comparison of pain and its 16. hartikainen S, Lönnroos E, Louhivuori K. treatment in advanced dementia and cognitively as a risk factor for falls: critical systematic review. J intact patients with hip fracture. J Pain Symptom Gerontol A Biol Sci Med Sci 2007;62:1172–81. Manage 2000;19:240–8. 17. pariente A, Dartigues JF, Benichou J, et al. 37. nygaard HA, Jarland M. Are nursing home patients Benzodiazepines and injurious falls in community with dementia diagnosis at increased risk for dwelling elders. Drugs Aging 2008;25:61–70. inadequate pain treatment? Int J Geriatr Psychiatry 18. Roth T. Hypnotic use for insomnia management in 2005;20:730–7. chronic obstructive pulmonary disease. Sleep Med 38. bell JS, Laitinen ML, Lavikainen P, et al. Use of 2009;10:19–25. strong opioids among community-dwelling persons 19. taipale HT, Bell JS, Gnjidic D, et al. Muscle strength with and without Alzheimer’s disease in Finland. Pain and sedative load in community-dwelling people 2011;152:543–7. aged 75 years and older: a population-based study. J 39. Kwan P, Brodie MJ. Neuropsychological effects Gerontol A Biol Sci Med Sci 2011; Epub Sept 20 DOI of epilepsy and antiepileptic drugs. Lancet 10.1093/gerona/glr170. 2001;357:216–22. 20. taipale HT, Bell JS, Soini H, et al. Sedative load 40. setoguchi S, Wang PS, Brookhart MA, et al. Potential and mortality among residents of long-term care causes of higher mortality in elderly users of conven- facilities: a prospective cohort study. Drugs Aging tional and medications. J Am 2009;26:871–81. Geriatr Soc 2008;56:1644–50. 21. johnell K, Fastbom J. Concurrent use of anti- 41. Wang PS, Schneeweiss S, Avorn J, et al. Risk cholinergic drugs and cholinesterase inhibitors: of death in elderly users of conventional . register-based study of over 700,000 elderly patients. atypical antipsychotic medications. N Engl J Med

Reprinted from Australian Family Physician Vol. 41, No. 1/2 january/february 2012 49