Exploring psychotherapeutic issues and agents in clinical practice
Polypharmacotherapy, the therapeutic use of multiple concurrently prescribed medications, occurs in patients who are being treated for multiple co-existing psychiatric disorders, medical conditions, or both. Polypharmacotherapy can also be an appropriate and justifiable therapeutic strategy to enhance response and remission rates, prevent chronicity and relapse, and improve patients' overall functional outcome and quality of life (Howland, 2006). However, polypharmacotherapy is not without risks, especially among older patients. In the literature, the term “polypharmacy” is used more commonly and has more of a negative connotation that encompasses the risks or potential inappropriateness of combining multiple medications. The concurrent use of multiple medications is associated with an increased risk of somatic and central nervous system adverse effects, drug–drug interactions, morbidity, and mortality (Scott et al., 2015).
Falls are the leading cause of fatal and nonfatal injuries among older adults in the United States, and medications are commonly implicated (Bergen, Stevens, & Burns, 2016). Medication use therefore is a potentially modifiable risk factor for falls, and deprescribing medication can be an important clinical strategy for patient management.
What Is Deprescribing?
The term “deprescribing” was first used in 2003 (Woodward, 2003), and various definitions have appeared in the literature since then (Reeve, Gnjidic, Long, & Hilmer, 2015). Based on their review of the literature, Reeve et al. (2015) suggested deprescribing be defined as the process of withdrawal of an inappropriate medication, supervised by a health care professional with the goal of managing polypharmacy and improving outcomes. Although this definition specifies the withdrawal of an inappropriate medication, deprescribing may also appropriately involve a reduction in dose of a suspect medication, switching to a potentially safer alternative medication, or eliminating an unnecessary medication (Woodward, 2003). Experienced clinicians also know that many patients will self-deprescribe medications through dose reductions, tapering, or abruptly stopping medications without supervision by a health care professional. Patients self-deprescribe for various reasons (Howland, 2007): adverse drug effects, perception that medication is not helping, desire to test the waters without medication, burden of taking too many pills, medication costs, medication fears from family or media reports, and a preference to pursue non-pharmacological therapies.
What makes a medication potentially inappropriate for a patient depends on the pharmacological properties of the drug when it is used in the context of the clinical characteristics of the patient. Hence, medication appropriateness/inappropriateness must be assessed on a case-by-case basis as well as from visit to subsequent visit over time. For older patients especially, whose age, health status, and medication regimen places them at higher risk, potentially inappropriate medications should be flagged for further assessment and a possible deprescribing intervention. The Beers Criteria is an updated list of potentially inappropriate medications that should be consulted (American Geriatrics Society 2015 Beers Criteria Update Expert Panel, 2015). Another clinically useful screening tool is the STOPP (Screening Tool of Older Person's Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment), which provides criteria not only to assess potentially inappropriate medications but also to prompt consideration of potentially appropriate and indicated medications in older patients (Gallagher, Ryan, Byrne, Kennedy, & O'Mahony, 2008).
Does Deprescribing Medication Result in Improved Outcomes?
The goals of deprescribing medication are to decrease the incidence and prevalence of adverse events, decrease the risks or consequences associated with drug–drug interactions, simplify medication regimens to enhance treatment adherence, and reduce the direct and indirect costs associated with medication use while maintaining or improving clinical outcomes. Indirect costs associated with medication use include the need for laboratory testing and other medical interventions (e.g., hospitalizations).
Although deprescribing can result in a decreased number of prescribed medications, simply decreasing the number of medications may not necessarily result in functional improvements and can conceivably be associated with adverse outcomes. In a recent study of 95 older adults who were randomized to a deprescribing intervention or treatment as usual, the mean reduction in number of medications (i.e., the primary study objective) was greater in the deprescribed group (Potter, Flicker, Page, & Etherton-Beer, 2016). However, there were no differences between the groups on secondary outcome measures, including subsequent survival; falls; fractures; hospitalizations; quality of life; sleep; or cognitive, physical, and bowel function.
In a systematic review of previous studies on the feasibility and effect of deprescribing medication in older adults, Page, Clifford, Potter, Schwartz, and Etherton-Beer (2016) identified 134 studies. These studies demonstrated that deprescribing reduced the number of medications and potentially inappropriate medications. Nonrandomized studies found that deprescribing was significantly associated with decreased mortality, but no significant effect on mortality was found in randomized studies. In studies where general educational deprescribing interventions were compared to patient-specific interventions (which identified target medications to deprescribe), mortality was significantly reduced when patient-specific interventions were applied. Deprescribing was not significantly associated with increased adverse drug withdrawal events and did not change the incidence of adverse events, quality of life, and cognitive function. Deprescribing also did not improve the risk of falls, although patients who fell had fewer falls.
Gnjidic, Le Couteur, Kouladjian, and Hilmer (2012) also reviewed deprescribing trials and their impact on prescribing and clinical outcomes. Clinical controlled studies to reduce medication exposure found that medication use can be reduced, but that the impact of medication reduction on outcomes (e.g., hospitalizations, falls, mortality) was not assessed in most studies. Randomized clinical trials of interventions to reduce medication exposure had mixed results on prescribing and outcomes, which were often not assessed. Gnjidic et al. (2012) concluded that various interventions may decrease medication exposure in older patients, but that the effectiveness of deprescribing medication on clinical outcomes was conflicted or lacking.
Potentially Serious Outcomes Associated with Deprescribing Medication
Studies of groups of patients have suggested that deprescribing medication is feasible and safe (Page et al., 2016). One of the problems with looking at group data, however, is that individual trees may be obscured by the forest. I provide two personal examples where deprescribing medication resulted in unfortunate outcomes.
More than one decade ago, I saw a female patient at a community mental health center who was taking fluoxetine (Prozac®) 60 mg per day, haloperidol (Haldol®) 2 mg per day, and benztropine (Cogentin®) 0.5 mg per day for major depression with psychotic features. I inherited this patient already taking this medication regimen, and she remained stable throughout routine follow-up visits. During one visit, she asked about the necessity of taking haloperidol, which she wanted to stop. After a discussion about the risks of doing so, we agreed to first lower the dosage to 1 mg per day and reassess at follow up. Within 1 to 2 weeks of lowering the dosage, she called the clinic and told a nurse that she was not feeling right. The nurse paged me to discuss this, and I recommended that the patient resume her previous dose of 2 mg per day. I then saw the patient in person 2 days later. She reported feeling nervous and anxious, and was having “bad” thoughts that preoccupied her. She denied hallucinations or suicidal thoughts and was taking all medications as prescribed, including the haloperidol 2 mg per day. We agreed to maintain each medication at the same doses. The next day, she killed herself. The family hired an attorney to review the case records, but no further action was ever pursued.
At the same community mental health center, I saw another female patient who was taking many different psychotropic medications for bipolar disorder. She had a history of multiple psychiatric hospitalizations, past serious suicide attempts, and alcohol abuse. I first met her after her most recent psychiatric admission. When I saw her during subsequent follow-up visits, she was relatively stable, but always concerned about the number of different medications she was taking and expressed a desire to eliminate certain medications. We discussed her medication concerns, preferences, and overall risk of relapse or suicide at each visit. Based on her known psychiatric history, I consistently recommended against medication changes. My justification was maintaining her stability and sobriety. Eventually, the patient requested to change psychiatrists within the same clinic because of my stance regarding her medications, and she was transferred to the care of another clinic psychiatrist. I subsequently learned that this psychiatrist ultimately stopped certain medications in accordance with her request and that she later killed herself.
Barriers to Deprescribing Medication
Barriers to deprescribing medication exist for providers and patients (Anderson, Stowasser, Freeman, & Scott, 2014; Reeve et al., 2013). Deprescribing in patients taking medication from multiple prescribers will be difficult if there is no communication or collaboration. Uncertainty about the past or future can make it difficult to make a decision about deprescribing one or more medications. Patients may have taken a medication(s) for so long that the rationale for its use is unclear, and there may be a reluctance to test reducing or stopping its use. Patients and prescribers often are especially fearful of or resistant to deprescribing medication based on the potential for adverse drug withdrawal effects or relapse of an underlying condition (Howland 2010a,b,c,d). Such fears may be managed conservatively by patients or prescribers who will ask, “Why mess with success by stopping one or more current medications?”
The Process of Deprescribing Medication
Scott et al. (2015) proposed a five-step deprescribing medication protocol: (a) ascertain all current medications and the reasons for each drug; (b) consider the overall risk of drug-induced harm in individual patients to determine the required intensity of a deprescribing intervention; (c) assess each medication regarding its current or future benefit versus harm potential; (d) prioritize medications for discontinuation based on their benefit–harm ratio, the likelihood of adverse withdrawal reactions, or disease rebound risk; and (e) discuss and implement a discontinuation plan while closely monitoring patients during follow up.
When should you consider deprescribing medication? The relative risks and benefits of existing medications, new medications, and changes in health status of patients should be assessed at every visit. Reports of new adverse effects should be assessed for their likely relationship to existing medications, with a consideration of stopping or changing medications that might be implicated. New information regarding adverse drug effects or drug–drug interactions often becomes available from recently published studies or the U.S. Food and Drug Administration. Over time, patients or their families may have changes in their perception or preferences about the use of medication and may wish to stop certain medications. Medication cost burden to patients can change, necessitating a discussion about stopping or changing medication. Patients' adherence to taking medication may be sporadic. Why this is happening and whether there is a need to continue the medication(s) in question should be discussed. Deprescribing should then be considered if sporadic adherence continues.
Deprescribing is the process of discontinuing inappropriate or unnecessary medications, with the intent of decreasing adverse events and adverse drug–drug interactions, simplifying medication regimens to enhance adherence, and reducing costs associated with medication use, while maintaining or improving clinical outcomes. Because polypharmacy can be associated with adverse effects, deprescribing medication is a good idea in theory. The literature on deprescribing using group data suggests it is feasible (i.e., the number of medications taken can be reduced) and safe (i.e., serious problems generally are not seen). However, a closer inspection of outcomes does not consistently demonstrate general benefits from deprescribing medication (e.g., fewer falls, better functioning, no death), either because the studies do not assess outcomes or the outcomes did not consistently differ from treatment as usual. Adverse outcomes from deprescribing can be buried in group data just as adverse outcomes in clinical trials of new or existing treatments can be buried in group data. Group data do not tell us anything about individuals. Adverse outcomes are certainly possible, as illustrated by my two case examples. Medication necessity or appropriateness should be assessed on a case-by-case basis and from visit to subsequent visit over time. Nurses and physicians should be highly vigilant during the process of deprescribing medication, monitoring closely for adverse drug withdrawal effects or relapse of an underlying condition.
- American Geriatrics Society 2015 Beers Criteria Update Expert Panel. (2015). American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society, 63, 2227–2246. doi:10.1111/jgs.13702 [CrossRef]
- Anderson, K., Stowasser, D., Freeman, C. & Scott, I. (2014). Prescriber barriers and enablers to minimising potentially inappropriate medications in adults: A systematic review and thematic synthesis. BMJ Open, 4, e006544. doi:10.1136/bmjopen-2014-006544 [CrossRef]
- Bergen, G., Stevens, M.R. & Burns, E.R. (2016). Falls and fall injuries among adults aged >65 years—United States, 2014. Morbidity and Mortality Weekly Report, 65, 993–998. doi:10.15585/mmwr.mm6537a2 [CrossRef]
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- Howland, R.H. (2007). Medication adherence. Journal of Psychosocial Nursing and Mental Health Services, 45(9), 15–19.
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- Page, A., Clifford, R.M., Potter, K., Schwartz, D. & Etherton-Beer, C.D. (2016). The feasibility and effect of deprescribing in older adults on mortality and health: A systematic review and meta-analysis. British Journal of Clinical Pharmacology, 82, 583–623. doi:10.1111/bcp.12975 [CrossRef]
- Potter, K., Flicker, L., Page, A. & Etherton-Beer, C. (2016). Deprescribing in frail older people: A randomised controlled trial. PloS One, 11, e0149984. doi:10.1371/journal.pone.0149984 [CrossRef]
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