Case Report

Identifying and managing drug-related causes of common geriatric symptoms

Barbara Farrell PharmD FCSHP Anne Monahan MA MD CCFP CoE Nafsa Ingar

systematic approach that uses screening criteria for A potentially inappropriate medications, assesses of drug-related causes, and includes moni- toring of medication tapering and initiation of new drug therapies can effectively identify drug-related problems EDITOR’S KEY POINTS and manage their resolution. Patients presenting to the • Use the Beers or STOPP (Screening Tool of Older Bruyère Continuing Care Geriatric Day Hospital (GDH) in Persons’ potentially inappropriate Prescriptions) Ottawa, Ont, often display a constellation of symptoms screening criteria to identify “inappropriate” that worsen their quality of life; medication review focuses medications for the elderly. on potential drug-related causes and steps to address them. • When considering a patient’s new symptoms, always This case illustrates how medications might contrib- ask yourself, “Can this symptom be caused by a drug?” ute to common, distressing geriatric symptoms. Despite After identifying the potential drug-related causes of patient sensitivity to medication changes, we were suc- presenting symptoms (eg, nausea, low blood pressure, cessfully able to stop several medications without wors- depression), then begin to gradually reduce medication ening of symptoms for which the medications were being doses and monitor for improvement of symptoms. used. The case also emphasizes the importance of care- fully monitoring the implementation of any new medica- • Involve patients in monitoring side effects when tion for possible adverse effects so that new medications new medications are started and engage them so that can be stopped before another medication is added to they feel empowered to question the appearance of treat their side effects. potential drug-related problems.

Case POINTS DE REPÈRE DU RÉDACTEUR An 84-year-old woman was referred to the GDH for assess- • Utilisez les critères de dépistage Beers ou STOPP ment of mobility and falls, mood, and cognitive changes. (Screening Tool of Older Persons’ potentially inappro- She was diagnosed with Parkinson disease earlier that priate) pour identifier les ordonnances de médicaments year, and in the past couple of years had had a number possiblement «inappropriés» pour les aînés. of falls and near falls, during which she “felt her legs give way.” Her walking tolerance was diminished even with a • Lorsque vous examinez les nouveaux symptmes d’un 4-wheeled walker, and cognition had declined with slower patient, demandez-vous toujours si ces symptmes processing speed. Her past medical history was relevant peuvent être causés par un médicament. Après avoir for a probable dementia secondary to Parkinson disease, cerné les causes du symptme potentiellement reliées à benign positional , hemorrhagic stroke, diverticulo- un médicament (p. ex. nausée, hypotension, dépression), sis, osteoporosis, osteoarthritis, degenerative disk disease, commencez alors à réduire graduellement les doses du type 2 diabetes (diet controlled), glaucoma, and allergic médicament et surveillez si les symptmes s’améliorent. rhinitis. The patient received help in all of her instrumental activities of daily living including medication management • Faites participer les patients à la surveillance des (by staff at the retirement home). Bloodwork revealed a effets secondaires lorsque de nouveaux médicaments vitamin B12 level of 195 pmol/L and calculated creatinine sont ajoutés et mettez-les à contribution de manière à clearance was 38 mL/min (using Cockcroft-Gault equa- ce qu’ils se sentent en mesure de poser des questions tion with ideal body weight). The patient could not recall lorsque surviennent des problèmes possiblement reliés the names, dosages, or indications of her medications and aux médicaments. stated she did not know “if they were doing any good.” During the initial assessment, issues regarding cogni- tion (Mini-Mental State Examination was 13 out of 30) This article is eligible for Mainpro-M1 credits. To earn credits, and mood were highlighted in this university-educated go to www.cfp.ca and click on the Mainpro link. patient; she described herself as feeling “demoralized”

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owing to her increasing physical defcits, her partner’s to be used on an as-needed basis and medical conditions, and a recent move to a retirement stopped metoclopramide, eventually adding domperi- home. She also complained of nausea (particularly at done 4 times daily to the regimen. With these changes, mealtime and occasionally with vomiting) diminishing nausea and vomiting resolved and her blood pressure her appetite. Dizziness, dry mouth, itchy, watery eyes rose to within the desired target range. We added vita- (which the patient found extremely bothersome), and min B12 and calcium secondary to deficiencies and hypotension (blood pressure as low as 77/50 mm Hg) frequent falls. We tried 2 at low doses were also a concern. She reported having 2 to 3 falls in but found these caused more dizziness and falls and the past month, with “a bad fall in the bathtub” where subsequently stopped them. Over time, the patient’s par- she hit her head and hurt her wrist. She had frequently ticipation in group activities increased, her energy level interrupted sleep during the night; she was very fatigued improved and her mood was judged to be improved and compensated with napping up to 4 hours a day. with counseling by our social worker; additional follow- The GDH pharmacist, nurse, social worker, occupational up with the geriatric psychiatrist was recommended. In therapist, physiotherapist, and speech language pathol- addition, a recommendation was made for the neurolo- ogist were consulted. The GDH pharmacist conducted gist to follow up with tapering levodopa after metoclo- a medication assessment, which included a 45-minute pramide was stopped. Given the risk of swallowing dif- comprehensive interview with the patient, chart review, fculties in the setting of Parkinson disease, the patient and communication with both the patient and the staff was provided with strategies for safe eating, drinking, at the retirement home. Each medication was assessed and pill swallowing by the team’s speech pathologist; for indication, effectiveness, safety, compliance, and however, with ongoing cognitive deficits, carry-over patient understanding.1 The results of the initial part of of this education was limited. While at the GDH, the this assessment are outlined in Table 1. patient received physiotherapy twice a week, includ- ing balance exercises, gait and transfer training, and Stop here. If you are using this case report for group cardiovascular conditioning on a stationary bicycle. In discussion, you can obtain instructions, discussion parallel with this, she received falls prevention education questions, and a blank worksheet on identifying drug- from various members of the interdisciplinary team. Her related problems and developing an interprofessional balance and mobility improved slightly, with a change care plan from CFPlus.* You might print out the above in Berg Balance Score from 35 out of 56 to 38 out of 56 case description and Table 1 for discussion before mov- and an increase in 6-minute walking distance from 180 ing on to reading about the results of the medication m to 200 m. Her confdence with transfers increased, assessment. but she continued with poor safety awareness. There was no worsening of vertigo, and eye tearing resolved. Signs and symptoms were assessed to determine Chronologic steps taken to implement the action plan potential drug causes and drug-related problems were are outlined in Box 1 and a fnal medication list is pre- identifed.2 The complete medication assessment is out- sented in Box 2. lined in Table 2. Discussion Stop here. If you are using this case report for group When trying to determine whether the patient’s medica- discussion, you can obtain instructions, discussion tions were contributing to her symptoms, we considered questions, and a blank worksheet on planning interven- the following. tions from CFPlus.* You might print out the above case description and Table 2 for discussion before reading Using screening criteria to identify “inappropriate” about how the care plan was implemented. medications. Worsening of symptoms associated with Parkinson disease is a well-known side effect of meto- On review of the medications and recognizing that clopramide. This is highlighted in both the Beers and they might be contributing to the patient’s dizziness, the STOPP (Screening Tool of Older Persons’ poten- low blood pressure, nausea, fatigue, and low mood, the tially inappropriate Prescriptions) criteria, explicit crite- following changes were made: bisoprolol, candesar- ria used to identify potentially inappropriate medication tan, betahistine dihydrochloride, , dimenhydri- use in the elderly.3,4 It was unclear whether our patient nate, and rosuvastatin were discontinued. We changed began metoclopramide before or after Parkinson disease was diagnosed; nevertheless, the potential worsening *Instructions, discussion questions, and worksheets on identifying of parkinsonian symptoms was an important consider- drug-related problems and developing an interprofessional 5,6 medication care plan and planning interventions are available ation. Metoclopramide was stopped and the patient at www.cfp.ca. Go to the full text of the article online and click on was monitored for worsening nausea, vomiting, and CFPlus in the menu at the top right-hand side of the page. bloating. Nausea improved (as other medication doses

148 Canadian Family Physician  Le Médecin de famille canadien | VOL 60: FEBRUARY • FÉVRIER 2014 Identifying and managing drug-related causes of common geriatric symptoms | Case Report were being reduced) but recurred several weeks later, computer program for drug interactions7; incorporat- so domperidone was started at a low dose with good ing these strategies into medication assessment either effect (in addition to other ongoing changes to reduce at the time of prescribing or dispensing would help in drug-induced nausea). The risk of metoclopramide identifying medications considered to be “inappropri- use concurrently with Parkinson disease can be easily ate” in the elderly. After stopping metoclopramide, we identifed by health care professionals using screening sent an interoffce speedy memo to the patient’s neu- criteria (such as Beers or STOPP) or with the use of a rologist regarding the possibility of tapering levodopa;

Table 1. History of medication experience: Patient is allergic to valdecoxib and morphine.

kNowlEDgE, EFFECTIvENESS, CoMPlIANCE, MEDICATIoN REASoN FoR uSE (IF kNowN) goAlS, SAFETy ASSESSMENT DuRATIoN (IF kNowN) 4 mg/d of candesartan every Hypertension • Staff at retirement home checks NA morning BP • BP at GDH ranging from 77/50 1.25 mg/d bisoprolol every No history of AF, MI, mm Hg to 130/74 mm Hg in NA morning angina frst few wk • Heart rate of 52 to 62 beats/ min in frst few wk

20 mg of rosuvastatin at Possible hemorrhagic stroke • 1 y ago LDL was 1.48 mmol/L 1.5 y bedtime and HDL-C ratio was 2.0 mmol/L

2 tablets of 100/25 mg of Parkinson disease • Since diagnosis of Parkinson 1 y levodopa-carbidopa 3 times disease, walking is worse; now daily using a 4-wheeled walker

8 mg of betahistine Vertigo • Dizziness began about 1 y ago; 1 y dihydrochloride 3 times daily currently somewhat improved

150 mg of risedronate monthly Osteoporosis • High risk of fall NA

1000 units of vitamin D daily Osteoporosis NA

50 mg of trazodone at bedtime Insomnia • Reports going to bed between NA 8-9 PM; “worries” before falling asleep; light sleeper; often up; sleep is interrupted by husband’s needs or to go to the bathroom; naps for up to 4 h daily

0.05 mg/d of levothyroxine Hypothyroidism • TSH level of 3.46 mIU/L NA

40 mg/d of pantoprazole Possible nausea • Stomach has been worse: NA feeling of not being able to eat and digest food properly 10 mg of metoclopramide 3 Possible diverticulitis NA times daily

1 drop of 0.5% timolol in both Glaucoma • Concerned about watery and 10 y eyes twice daily itchy eyes, which have become worse in past 4 mo and are preventing daily activities

20 mg/d of cetirizine Watery, itchy eyes • No improvement in watery and 6 mo itchy eyes

50 mg of Nausea • Uses when needed (unclear how NA often)

AF—atrial fbrillation, BP—blood pressure, GDH—Bruyère Continuing Care Geriatric Day Hospital, HDL-C—high-density lipoprotein cholesterol, LDL—low-density lipoprotein, MI—myocardial infarction, NA—not available, TSH—thyroid-stimulating hormone.

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Table 2. Medication care plan DRug-RElATED PRoBlEM ACTIoN PlAN MoNIToRINg Low BP secondary to • Stop bisoprolol BP (target of 120/60 mm Hg to • bisoprolol (indication unclear; to our • Stop candesartan if BP does not increase to 150/80 mm Hg) knowledge, patient does not have target range history of AF, MI, or angina) • candesartan Dizziness, light-headedness, fatigue, and • Stop metoclopramide (see below) Dizziness, light-headedness, dry mouth can be caused by • Reduce trazodone dose to 25 mg/d at bedtime; if fatigue, dry mouth • metoclopramide (contributes to tolerated, reduce to 12.5 mg/d at bedtime, then Nausea, vomiting, or bloating with dizziness, light-headedness) as occasion requires (will counsel about sleep stopping metoclopramide • trazodone (contributes to all) hygiene) Sleep pattern • cetirizine (contributes to all), which • Stop cetirizine Worsening of watery, itchy eyes patient states is not helping with • Taper betahistine dihydrochloride (to twice daily Worsening of vertigo or dizziness watery, itchy eyes for 2 wk, then once daily for 1 wk, then stop) • betahistine dihydrochloride • Stop dimenhydrinate (contributes to fatigue and dry mouth) • dimenhydrinate (contributes to all) Risk of exacerbation of parkinsonism • Stop metoclopramide Nausea, vomiting, or bloating increased with metoclopramide • Start domperidone if nausea, vomiting, or bloating worsens • After metoclopramide is stopped, revisit dosing and timing of levodopa to maximize effectiveness* Unclear value of rosuvastatin (no apparent • Confrm with family doctor that the patient does NA CVD or cerebrovascular disease; patient not have CAD or CVD; if so, then need to consider has history of hemorrhagic stroke for whether to add ASA for secondary prevention which statin secondary prevention • Stop rosuvastatin (if for primary prevention) effectiveness is controversial) Patient’s nausea • Taper betahistine dihydrochloride (as above) Worsening of vertigo or dizziness • possibly secondary to betahistine • Stop cetirizine (see below) Nausea dihydrochloride, cetirizine (including • Stop rosuvastatin (see above) Fatigue or dry mouth anorexia), or rosuvastatin • Switch to 10 mg/d of rabeprazole for 2 wk, then Eye itchiness and wateriness • not relieved by pantoprazole (which stop (provide written information about Rebound heartburn (2-4 wk) does not appear to be indicated for aluminum-magnesium antacid or calcium heartburn), which might be carbonate antacid for rebound heartburn) contributing to low vitamin B12 level • Add 1000 μg of vitamin B12 daily (needs treatment) Patient’s low mood • Confrm with family doctor that patient does not Heart rate, angina with taper • might be due to use of β-blockers: have CAD or CVD; if she does, then need to BP (target of 120/60 mm Hg to bisoprolol (indication unclear as, to our consider whether to add ASA for secondary 150/80 mm Hg) knowledge, patient does not have prevention Improvements in mood, anxiety, history of AF, MI, or angina); timolol • If no, stop bisoprolol (already at lowest dose) interest in social activities systemic absorption • Consider adding either 7.5 mg/d of Improvements in sleep and • might be treated with mirtazapine or at bedtime or 5 mg of citalopram and increase insomnia, dizziness, etc, with citalopram gradually as tolerated initiation Patient at risk of fracture with falls (taking Add up to 1000 mg of calcium carbonate antacid twice GI side effects, constipation 150 mg of risedronate monthly and daily (check dietary intake) vitamin D) and would beneft from addition of calcium Itchy and watery eyes • Stop cetirizine Eye itchiness and wateriness • not responding to cetirizine • Hold timolol for 48 h to see if itchy and watery • might be result of allergy to timolol eyes improve (reassess need for timolol with eye drops ophthalmologist) Routine blood glucose monitoring not Stop routine blood glucose tests NA needed (diet controlled) AF—atrial fbrillation, ASA—acetylsalicylic acid, BP—blood pressure, CAD—coronary artery disease, CVD—cardiovascular disease, GI—gastrointestinal, MI—myocardial infarction, NA—not applicable. *Metoclopramide increases levodopa ; stopping it might reduce levodopa effect. This might then be balanced by reduced metoclopramide exacerbation of Parkinson disease symptoms.

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Box 1. Intervention timeline: Initial pill burden = 20 Box 2. Medication schedule at discharge pills daily; initial number of medications = 14; fnal pill burden = 16 pills daily; fnal number of Morning (around 8 AM) medications = 10. • 5 mg of domperidone • 2 tablets of 100/25 mg of levodopa-carbidopa Week 1 • 1000 IU of vitamin D • No new medication changes • Calcium carbonate tablet Week 2 • 1200 μg of vitamin B12 • No new medication changes • 0.05 mg of levothyroxine Week 3 • 40 mg of pantoprazole • Reduce betahistine dihydrochloride to 8 mg twice daily • 1 drop of 0.5% timolol in both eyes Week 4 • 150 mg of risedronate once a month • No new medication changes Afternoon (around 12 PM) Week 5 • 5 mg of domperidone • Stop bisoprolol • 2 tablets of 100/25 mg of levodopa-carbidopa • Stop metoclopramide • Calcium carbonate tablet Week 6 Supper (around 5 PM) • Start 1200 μg of vitamin B12 daily • 5 mg of domperidone • Stop candesartan • 2 tablets of 100/25 mg of levodopa-carbidopa • Reduce betahistine dihydrochloride to 8 mg daily Bedtime (around 10 PM) Week 7 • 5 mg of domperidone • Stop betahistine dihydrochloride • 1 drop of 0.5% timolol in both eyes • Stop cetirizine • 25 mg of trazodone when needed • Start calcium carbonate antacid twice daily • Stop routine blood glucose checks Week 8 • Start 7.5 mg of mirtazapine at bedtime and considering their pharmacologic mechanisms; they • Reduce trazodone to 25 mg at bedtime were assessed for continued indication and, if possible, Week 9 tapered and stopped. Betahistine dihydrochloride was • No new medication changes tapered and stopped with no return of vertigo; subse- Week 10 quently it was believed that the original dizziness might • Hold rosuvastatin for 1 week, then reassess have been due to balance impairment and not true ver- • Start 5 mg of domperidone 4 times daily tigo. Cetirizine was stopped with no worsening of the • Stop dimenhydrinate eye symptoms for which it had been started (watery • Stop mirtazapine eyes inexplicably resolved by end of GDH admission). Week 11 Dimenhydrinate was stopped and an attempt was made • Stop trazodone to stop trazodone, but the patient eventually required • Start 5 mg of citalopram daily Week 12 a small as-needed dose for occasional insomnia. The • Stop citalopram patient’s dry mouth improved. Finally, rosuvastatin was • Restart trazodone 25 mg at bedtime briefy stopped to determine its effect on nausea and • Stop rosuvastatin eventually it was completely stopped because of lack of Week 13 clear indication and because nausea improved without it • Change trazodone to 25 mg at bedtime only if needed (albeit during the time period domperidone was started). With resolution of nausea, a recommendation was made to the family physician to attempt a domperidone the patient was asked to follow up with the specialist taper in the future. Notwithstanding the improvement regarding this matter, and a description of the events in the patient’s nausea, she continued to have anorexia, was included in her medication chart, which was copied perhaps related to residual mood diffculties. to the family doctor on discharge. Low systolic and diastolic blood pressure measure- ments might have been contributing to the patient’s Assessing signs and symptoms of drug-related fatigue and dizziness (and hence risk of fall) and might causes. Bothersome symptoms such as nausea, have also been associated with an increased risk of anorexia, dry mouth, fatigue, and dizziness can severely cardiovascular events and mortality.8 Antihypertensive affect an elderly person’s quality of life. Drugs that might medication frequently contributes to hypotension, as the potentially be contributing to any of these symptoms absorption, distribution, metabolism, and of were identified by reviewing the side effects of each these drugs change considerably as people age.9,10 We

VOL 60: FEBRUARY • FÉVRIER 2014 | Canadian Family Physician  Le Médecin de famille canadien 151 Case Report | Identifying and managing drug-related causes of common geriatric symptoms identifed an appropriate target blood pressure range for dementia, we elected to focus on the deprescribing of her age (120/60 mm Hg to 150/90 mm Hg) and found other medications to try to improve her nausea and the patient consistently had blood pressure readings dizziness, along with trying antidepressant therapy for in the low end or below this range.8 We also consid- her mood. We recommended the family doctor pursue ered the possibility that the combination of oral biso- dementia treatment in collaboration with the patient’s prolol and topical timolol might have had an additive neurologist if the patient’s nausea remained stable and effect in contributing to depressive symptoms such as anorexia improved. The patient was also asked to follow fatigue.11 We gradually stopped her antihypertensives up with her neurologist regarding options to lower the (for which there were no other compelling indications) levodopa dose now that metoclopramide was stopped. and her blood pressure eventually rose and stabilized in Reducing the number of unneeded medications, and the appropriate target range.8 those potentially causing adverse effects, allowed us to feel comfortable adding to her pill burden with vitamin Monitoring the initiation of new drugs. Depression B12 and calcium. Finally, the patient was encouraged to can have a serious effect on morbidity and quality of stop her routine blood glucose monitoring, as her dia- life in older people. Given age-related changes in phar- betes was well controlled with diet.14 All medication macokinetic and pharmacodynamic parameters, as changes, rationale for changes, outcomes, and recom- well as adverse events associated with antidepressants, mendations were documented in plain language in a careful attention must be paid to choosing and using “medication chart” for the patient, a copy of which was an antidepressant.12,13 Minimizing β-blocker therapy forwarded to the family doctor on discharge from the (or other medications that can contribute to depres- 12-week program. sion) might help, but we also considered treatment in this patient. In collaboration with the geriatric psychia- Conclusion trist, we tried a low dose of mirtazapine; however, the This case highlights the importance of considering patient reported more dizziness and worsening bal- whether a patient’s medications are contributing to ance within 2 days of starting the medication and, as a his or her symptoms before initiating a new diagno- result, it was stopped. Next, we tried 5 mg of citalopram; sis or adding another drug. By using screening crite- however, within 2 days of initiating therapy, the patient ria, medications that are potentially inappropriate can again had increased dizziness and reported 2 falls over quickly be identifed. After identifying the potential drug- a weekend. The patient had been warned (verbally and related causes of presenting symptoms (such as nau- in writing) about this potential when we started the sea, dizziness, low blood pressure, depression), the citalopram. She brought her concerns to the attention next question—is this drug still needed?—can be asked, of the staff at the retirement home; however, the per- and then steps can be taken to gradually reduce doses son she spoke with denied that a new medication had and monitor for improvement of symptoms. Monitoring been started. The patient persisted in questioning the the initiation of new drugs and engaging the patient addition of citalopram when she returned to the GDH in monitoring for relevant, potentially serious adverse and we confrmed with the staff at the retirement home effects—or indeed, any change in function following that the medication had been started. This highlights drug initiation—is vital to reducing drug-related mor- the importance of involving patients in monitoring the bidity. Finally, this case also underlines the benefts of effects of medication and of engaging them so that they an interdisciplinary team-based approach in managing feel empowered to question the appearance of potential patient symptoms with nonpharmacologic interventions, drug-induced problems. The citalopram was stopped; such as counseling or psychotherapy for a mood disor- dizziness improved over the next few days. The patient der when a trial of antidepressants has failed. was reluctant to try another antidepressant and instead Dr Farrell is Pharmacist at the Bruyère Continuing Care Geriatric Day Hospital continued to receive counseling from the social worker in Ottawa, Ont, Scientist in the Bruyère Research Institute, Assistant Professor in the Department of Family Medicine at the University of Ottawa, and Adjunct at the GDH; follow up was planned with the geriatric Assistant Professor in the School of Pharmacy at the University of Waterloo in psychiatrist. Ontario. Dr Monahan is an attending physician at the Bruyère Continuing Care Geriatric Day Hospital and Lecturer in the Department of Family Medicine at the University of Ottawa. Ms Ingar is a student in the School of Pharmacy at Other drug-related problems. The need for ongoing the University of Waterloo. proton pump inhibitor therapy was reviewed (especially Acknowledgment Financial support for this project is provided by the Bruyère Academic Medical in light of low vitamin B12 levels), but plans to taper the Organization. patient’s pantoprazole were not carried out at the GDH Competing interests owing to the many other ongoing medication changes. None declared A recommendation was made to the family doctor to Correspondence pursue proton pump inhibitor tapering. With regard Dr Barbara Farrell, Bruyère Research Institute, 43 Bruyère St, Ottawa, ON K1N 5C8; telephone 613 562-6262, extension 1315; e-mail to adding a cholinesterase inhibitor for her Parkinson [email protected]

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