The third clinical practice guideline to be published in the series developed by the Deprescribing guidelines for the elderly project, based at the Bruyère Research Institute in Ottawa, Ontario, Canada, is focused on antipsychotic drugs.[1] The aim is to help clinicians determine whether an antipsychotic drug is being used appropriately or whether (and how) it can be stopped. Lead author Lise Bjerre, MD, PhD, spoke with Medscape about the widespread overuse of these drugs and the development of the guideline and algorithm. Bjerre is a pharmacoepidemiologist, practicing family physician, assistant professor, and clinician investigator at the Department of Family Medicine at the University of Ottawa and the Bruyère Research Institute.

 

The three other guidelines in the series[2,3,4] discussed proton pump inhibitors, antihyperglycemics, and cholinesterase inhibitors.

 

Deprescribing Antipsychotics

Antipsychotic drugs are approved for a range of psychiatric disorders including schizophrenia and bipolar disorder, but they are also widely prescribed for control of behavioral and psychological symptoms of dementia (BPSD), such as delusions, hallucinations, aggression, agitation, anxiety, irritability, depression, apathy, and psychosis, in elderly patients. Antipsychotics are also used to treat insomnia. In the United States and Canada, these uses are all off-label, with the exception that in Canada risperidone is approved for short-term use for treatment of some symptoms associated with severe dementia.[5]

 

Is Antipsychotic Use in Dementia Ever Warranted?

Clinical studies with antipsychotic drugs showed small but statistically significant improvements in BPSD compared with placebo,[6] but the treatment was associated with an increased risk for adverse events, particularly cerebrovascular events including stroke, and death, as well as somnolence, extrapyramidal symptoms, urinary tract infections, edema, gait abnormalities, and major cardiovascular events.[6,7,8] Both the US Food & Drug Administration[9] and Health Canada[10] issued warnings about the increased mortality risk associated with antipsychotic drug use in older adults with dementia. In the United States, these drugs now carry a “boxed warning” about this risk. Health Canada also issued three separate warnings to health professionals about serious adverse events.[11,12,13]

 

Clinical practice guidelines all urge extreme caution with antipsychotics reserved as a last resort for dementia patients. In its 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults,[14] the American Geriatrics Society advises that antipsychotics should be avoided for BPSD unless nonpharmacologic options such as behavioral intervention have failed or are not possible and the patient is threatening “substantial” self-harm or harm to others. Clinical practice guidelines[15,16,17,18,19,20,21] all urge extreme caution with antipsychotics reserved as a last resort for treatment of behavioral symptoms in dementia patients.

 

Despite the warnings, antipsychotics are often prescribed for BPSD. In 2014, 39% of seniors in long-term care (LTC) facilities in Canada had one or more claims for an antipsychotic, and almost one quarter (22%) were chronic users of antipsychotic medications.[23] Almost a third of these residents did not have a diagnosis of psychosis.[24] “We focused on that in our guideline because it appears to be a common practice that is potentially problematic,” Bjerre said. “Dementia is a difficult condition, with no proven treatment, and nonpharmacologic approaches to managing these behavioral symptoms are quite resource-intensive. So it is understandable, particularly in a cost-cutting context, that the easiest or often the only resource available is to sedate people or at least to control agitation behaviors with medication. In some cases it may be necessary, where patients are at risk of harming themselves or others. We are not saying that antipsychotics are inappropriate in all circumstances,” Bjerre stressed.

The Evidence for the Guideline

The guideline and algorithm are based on evidence from studies of withdrawal versus continuation of antipsychotics used for BPSD.[25] Overall, these studies suggest that many older people with BPSD can be withdrawn from chronic antipsychotic medication without detrimental effects on their behavior.

 

Because no deprescribing studies of antipsychotics used to treat insomnia had been published, Bjerre and her colleagues based their recommendations on their own systematic review of studies of the efficacy of antipsychotics in treating insomnia.[26] They concluded that atypical antipsychotics should be avoided as first-line treatment of primary insomnia until further evidence is available and that more studies are needed.

 

While developing this guideline, Bjerre and her team piloted it at three primary care clinics and three LTC facilities for 3-4 months and incorporated their feedback into the final version, an unusual step in the development of guidelines. “The algorithm was reported to be the most helpful part because it was so concise,” she recalled.

 

“The main message of the guideline is that we should ask why the patient is taking the drug, whether it was appropriate initially, and whether it is still needed,” Bjerre said. “It may be that the final decision is to continue the medication at the same or a reduced dose or to try to stop it completely.”

 

How to Deprescribe in Dementia

According to the guideline algorithm, if a patient with dementia has been treated with an antipsychotic for 3 months or longer, and their symptoms are controlled or they have had no response, consideration should be given to stopping the drug. “Involvement of the caregivers, whether they are professionals or natural caregivers, is important and can make the difference between a successful or unsuccessful attempt at deprescribing,” Bjerre stressed. “These patients are often cognitively impaired and have someone who has power of attorney to make decisions on their behalf for health,” she noted.

 

Whether information is provided by staff or family, there are challenges in ensuring that everyone understands why deprescribing is being tried, what to watch out for, and when to intervene. “There is sometimes pressure from the nursing staff to prescribe, if, for example, a patient has been very agitated,” Bjerre admitted.

 

There is no evidence that one tapering approach is better than another. The guideline suggests a 25%-50% dose reduction every 1-2 weeks. If symptoms return and are completely unmanageable, it might be worthwhile considering another antipsychotic (Table). If three or four approaches to managing the patient’s behavioral symptoms have failed, it could be particularly helpful to consult a geriatric psychiatrist. “Where I work as a family doctor with outpatients, we have a psychiatrist and a psychiatric nurse to whom we can refer patients when we need to, and then the patient returns to the family doctor for continued care, with the possibility of either short-term follow-up or further consultation with the psychiatrist,” Bjerre noted.

 

Table. Treatment of Patients With BPSD Relapses

Consider nonpharmacologic approaches

Music therapy

Behavioral management strategies

Restart antipsychotic

Restart at lowest possible dose

Retrial of deprescribing in 3 months

At least two attempts to deprescribe should be made

Consider alternative antipsychotic

Consider risperidone, olanzapine, or aripiprazole

Adapted from Antipsychotic (AP) Deprescribing Algorithm

 

How to Deprescribe in Insomnia

Clinical practice guidelines all recommend against routine use of antipsychotics to treat primary insomnia in any age group[20,27,28,29,30]Nonetheless, “over the past 10 years in Canada we have seen a huge increase in the use of low-dose antipsychotics, particularly quetiapine, basically as a sleeping pill,” Bjerre stated. Between 2005 and 2012, there was a 300% increase in dispensed prescriptions for quetiapine ordered by primary care physicians and a 10-fold increase in quetiapine recommendations for sleep disturbances in Canada, observed in all age groups and settings, with almost all of the recommendations coming from primary care physicians.[31]

 

In Canada, many hospital patients are given a low-dose antipsychotic, particularly quetiapine 25 mg, for insomnia. “It is one thing to use it for a couple of nights; then it does have a sedative effect and will make you sleep,” she said. “The problem is that often the medication is continued after patients leave the hospital, and it is not appropriate for it to be used as a sleeping pill in the long term.”

 

Clinical practice guidelines all recommend against routine use of antipsychotics to treat primary insomnia in any age group. The guideline to deprescribing antipsychotics used to treat insomnia is applicable to all adults and “much more straightforward,” Bjerre said. The evidence, although limited, indicates that because the drugs are usually prescribed in lower doses for insomnia, they can be stopped without tapering. The algorithm includes “sleep hygiene” recommendations in this situation.

 

Guideline Limitations

“This guideline is a tool that contains many important context-specific parameters that only the people in that particular situation, whether they are the prescribers, the patients, the families, or the caregivers, can address,” Bjerre said. “Of course we are aware that people may not be able to apply or adapt some of the recommendations in their practice, but we believe that it can be helpful in many cases and that it will remind people to consider deprescribing.” Her team is looking forward to receiving feedback on the guideline, she added.

 

The algorithm is available online. DOWNLOAD THE ALGORITHM 

 

References

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Farrell B, Pottie K, Thompson W, et al. Deprescribing proton pump inhibitors. Can Fam Physician. 2017;63:354-364. Article. Accessed January 20, 2018.

Reeve E, Farrell B, Thompson W, et al. Evidence-based clinical practice guideline for deprescribing cholinesterase inhibitors and memantine. Sydney, NSW, Australia: University of Sydney: 2018. Article. Accessed February 6, 2018.

Farrell B, Black C, Thompson W, et al. Deprescribing antihyperglycemic agents in older persons: evidence-based clinical practice guideline. Can Fam Physician. 2017;63:832-843. Article. Accessed November 20, 2017.

Janssen. Risperdal, Risperdal M-Tab. Product monograph. 2017. Article. Accessed January 20, 2018.

Ma H, Huang Y, Cong Z, et al. The efficacy and safety of atypical antipsychotics for the treatment of dementia: a meta-analysis of randomized placebo-controlled trials. J Alzheimers Dis. 2014;42:915-937. Abstract

Maust DT, Kim HM, Seyfried LS, et al. Antipsychotics, other psychotropics, and the risk of death in patients with dementia: number needed to harm. JAMA Psychiatry. 2015;72:438-445. Abstract

Sahlberg M, Holm E, Gislason GH, Køber L, Torp-Pedersen C, Andersson C. Association of selected antipsychotic agents with major adverse cardiovascular events and noncardiovascular mortality in elderly persons. J Am Heart Assoc. 2015;4:e001666. Article. Accessed January 20, 2018.

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Health Canada. Atypical antipsychotic drugs and dementia – advisories, warnings and recalls for health professionals. Recalls and Safety Alerts. June 22, 2005. Article. Accessed January 20, 2018.

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Health Canada. Important drug safety information: ZYPREXA (olanzapine) and cerebrovascular adverse events in placebo-controlled elderly dementia trials. Recalls and Safety Alerts. March 17, 2004. Article. Accessed January 20, 2018.

Health Canada. Risperidone – restriction of the dementia indication. Recalls and Safety Alerts. February 18, 2015. Article. Accessed January 13, 2018.

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Gauthier S, Patterson C, Chertkow H, et al. Recommendations of the 4th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4). Can Geriatr J. 2012;15:120-126. Article. Accessed January 13, 2018.

Canadian Academy of Child and Adolescent Psychiatry, Canadian Academy of Geriatric Psychiatry, Canadian Psychiatric Association. Psychiatry: Thirteen things physicians and patients should question. Choosing Wisely. Article. Updated June 2017. Accessed January 13, 2018.

Canadian Geriatrics Society. Geriatrics: Five things physicians and patients should question. Choosing Wisely. 2017. Article. Accessed January 13, 2018.

Alzheimer Society of Canada. Use of antipsychotic medications to treat people with dementia in long-term care homes. Position Statement. June 7, 2017. Article. Accessed January 13, 2018.

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Declercq T, Petrovic M, Azermai M, et al. Withdrawal versus continuation of chronic antipsychotic drugs for behavioural and psychological symptoms in older people with dementia. Cochrane Database Syst Rev. 2013;(3):CD007726.

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Matheson E, Hainer BL. Insomnia: pharmacologic therapy. Am Fam Physician. 2017;96:29-35. Abstract

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Pringsheim T, Gardner D. Dispensed prescriptions for quetiapine and other second-generation antipsychotics in Canada from 2005 to 2012: a descriptive study. CMAJ Open. 2014;2:E225-E232. Article. Accessed January 18, 2018.