How to Manage Your Patient's Dementia by Discontinuing

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Savvy Psychopharmacology

How to manage your patient’s dementia by discontinuing medications

Ryan M. Carnahan, PharmD, MS, BCPP

rs. J, age 75, has moderate Alzheimer’s dementia, environmental factors, medical Mdementia and lives at home with her hus- conditions, and medications may worsen band. Since her Alzheimer’s disease (AD) diag- functioning and should be considered in nosis 2 years ago, Mrs. J generally has been co- the assessment.1 operative and not physically aggressive, but has Mrs. J has no medical problems that were experienced occasional depressive symptoms. identified as possible triggers for her be- However, Mr. J reports that recently his wife is havior. Mr. J’s interference with his wife’s Vicki L. Ellingrod, becoming increasingly confused and agitated wandering could have increased her agita- PharmD, BCPP, FCCP and wanders the house at night. His efforts to tion, but he is gentle toward her and she has Series Editor calm and coax her back to bed often lead to become agitated with no apparent trigger. increased agitation and yelling. On 1 occasion “Sundowning” and poor sleep also may be Mrs. J pushed her husband. Mr. J is concerned involved, as sleep deprivation can lead to de- that if these behaviors continue he may not be lirium and worsen cognitive deficits and be- able to care for her at home. Mr. J read online havioral problems.1 Depression also should that antipsychotics might reduce aggressive be- be considered.1 Finally, Mrs. J is taking sev- havior, but is concerned about the increased risk eral medications with anticholinergic prop- of mortality and stroke with these medications. Mrs. J receives donepezil, 10 mg/d, sertraline, 50 mg/d, and extended-release oxybu- Practice Points tynin, 10 mg/d. Her over-the-counter (OTC) • During the initial evaluation of cognitive medications include acetaminophen, 650 mg complaints, look to discontinue as needed for pain, ranitidine, 150 mg/d, and medications that may cause cognitive docusate sodium, 100 mg/d. Several nights impairment, including anticholinergics. last week, Mr. J gave his wife an unknown • In addition to worsening cognitive OTC sleep medication, hoping it would stop impairment, anticholinergic medications her nighttime wandering, but it did not help. may contribute to behavioral Physical examination, laboratory testing, and disturbances, psychosis, and delirium in patients with dementia. urine culture are all normal. • Side effects of acetylcholinesterase Most dementia patients experience neuro- inhibitors can prompt anticholinergic use, which is likely to negate the beneficial psychiatric disturbances, especially at later effects of the acetylcholinesterase inhibitor. stages, that often lead to caregiver distress and nursing home placement. Although • Nonpsychiatric medications, including over- these symptoms may signal progressing the-counter drugs, can have anticholinergic properties. Consult with nonpsychiatric clinicians to discontinue inessential Dr. Carnahan is assistant professor (clinical), College of Public Health, department of epidemiology, Iowa Older Adults medications that may be harmful for Current Psychiatry Center for Education and Research on Therapeutics, The dementia patients. 34 July 2010 University of Iowa, Iowa City, IA. Savvy Psychopharmacology

Table Drugs with clinically significant anticholinergic effects*

Drug class Medication(s) Anticonvulsants Carbamazepine Antidepressants Amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline, paroxetine, protriptyline, trimipramine Antihistamines Azelastine nasal spray, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, dexbrompheniramine, dexchlorpheniramine, diphenhydramine, hydroxyzine, mepyramine olopatadine nasal spray, phenyltoloxamine, promethazine, triprolidine Antiparkinsonian agents Benztropine, procyclidine, trihexyphenidyl Antipsychotics Chlorpromazine, clozapine, loxapine, molindone, olanzapine, pimozide, promethazine, quetiapine, thioridazine Asthma and chronic Glycopyrrolate, ipratropium,† tiotropium† obstructive pulmonary disease medication Bladder antispasmodics Darifenacin, flavoxate, oxybutynin, solifenacin, tolterodine, trospium Clinical Point Gastrointestinal Atropine, belladonna alkaloids, clidinium, dicyclomine, hyoscyamine, Drugs with antispasmodics methscopolamine, propantheline anticholinergic Insomnia medications Diphenhydramine, doxylamine Motion sickness/dizziness/ Dimenhydrinate, meclizine, prochlorperazine, promethazine, effects can contribute nausea medications scopolamine, trimethobenzamide to agitation and Muscle relaxants and pain Cyclobenzaprine, meperidine, orphenadrine, phenyltoloxamine psychosis in medications Ulcer and acid reflux agents Cimetidine, glycopyrrolate, ranitidine dementia *Not a comprehensive list †Unknown whether CNS effects are important Source: Reference 5 erties—oxybutynin, ranitidine, and an un- suggests that dementia-related damage to known OTC sleep medication, which likely the cholinergic system leads to increased contains diphenhydramine or doxylamine— sensitivity to anticholinergics. that might contribute to her agitation. A cross-sectional study of 230 patients Patients with dementia are highly sen- with AD identified anticholinergic use as a sitive to the cognitive and psychiatric risk factor for psychosis (odds ratio 2.13, 95% adverse effects of anticholinergic medica- confidence interval, 1.03 to 4.43), after adjust- tions. In studies of patients with mild or ing for age and cognition.4 Among patients moderate Alzheimer’s dementia who re- receiving 2 or 3 anticholinergics, 69% had ceived the potent anticholinergic scopol- psychotic symptoms compared with 48% of amine, adverse effects included: those receiving 1 anticholinergic and 32% of • memory impairment those receiving no anticholinergics.4 Anticho- • restlessness linergic overdoses can cause psychotic symp- • disjointed speech toms and delirium. A subtle presentation of • motor incoordination delirium from prescribed anticholinergics • drowsiness may be confused with worsening dementia.1 • euphoria continued • agitation • hallucinations • hostility. For more information, go to Many of these effects worsened with CurrentPsychiatry.com increasing doses.2,3 Age-matched controls Seritan, anticholinergic experienced less severe memory impair- Current Psychiatry Current Psychiatry ment and no behavioral symptoms, which Vol. 9, No. 7 35 Savvy Psychopharmacology

When to discontinue Related Resources When diagnosing dementia it is important • Cancelli I, Beltrame M, D’Anna L, et al. Drugs with anticholinergic properties: a potential risk factor for to address other potential causes of cogni- psychosis onset in Alzheimer’s disease? Expert Opin Drug Saf. tive impairment, including medications. 2009;8(5):549-557. Approximately one-third of patients with • Meeks TW, Jeste DV. Beyond the black box: what is the role dementia receive anticholinergic drugs, for antipsychotics in dementia? Current Psychiatry. 2008;7(6): 50-65. which suggests that providers often do not • Centers for Education and Research on Therapeutics. recognize the potential for harm with these Anticholinergic pocket reference card. www.chainonline. medications.5 After patients receive acetyl- org/home/content_images/Anticholinergic%20Pocket%20 Card%20CLR%203_12_10.pdf. cholinesterase inhibitors (AChEIs)—which Drug Brand Names are used to enhance cognition in demen- Amitriptyline • Elavil Hyoscyamine • Cystospaz, tia patients—increased anticholinergic use Atropine • Sal-Tropine Levbid may follow, often to treat adverse effects of Azelastine nasal spray Imipramine • Tofranil AChEIs.5 This may negate the benefits of • Astelin Ipratropium • Atrovent Belladonna alkaloids Loxapine • Loxitane AChEIs and pose risk of further harm from • Donnatal Meclizine • Antivert the anticholinergics.1,5 Although any time Benztropine • Cogentin Meperidine • Demerol Clinical Point Brompheniramine Mepyramine • Anthisan is a good time to discontinue an inessential • Dimetane Methscopolamine • Pamine anticholinergic in a patient with dementia, Consider Carbamazepine • Carbatrol, Molindone • Moban discontinuing Tegretol, others Nortriptyline • Aventyl providers might consider screening for Carbinoxamine • Palgic Olanzapine • Zyprexa these drugs at the initial diagnosis, after anticholinergics if Chlorpheniramine Olopatadine nasal spray • Chlor-Trimeton • Patanase initiating a cholinesterase inhibitor or in- they are not essential Chlorpromazine • Thorazine Orphenadrine • Norflex creasing a dose, or if the patient develops Cimetidine • Tagamet Oxybutynin extended- psychotic or behavioral symptoms. to a patient’s health Clemastine • Tavist release • Ditropan XL or if safer alternatives Clidinium • Quarzan Paroxetine • Paxil For Mrs. J, ranitidine and oxybutynin Clomipramine • Anafranil Phenyltoloxamine likely were used to treat gastrointestinal are available Clozapine • Clozaril • Dologesic, Durayin, others Cyclobenzaprine • Flexeril Pimozide • Orap complaints and urinary frequency, which Cyproheptadine • Periactin Prochlorperazine are known adverse effects of AChEIs. Many Darifenacin • Enablex • Compazine Desipramine • Norpramin Procyclidine • Kemadrin OTC preparations for insomnia, respiratory Dexbrompheniramine Promethazine • Phenergan symptoms, and allergies contain older, anti- • Drixoral Propanthelin • Pro-Banthine Dexchlorpheniramine Protriptyline • Vivactil cholinergic antihistamines. Advise caregiv- • Polaramine Quetiapine • Seroquel ers of dementia patients about possible ad- Dicyclomine • Bentyl Ranitidine • Zantac verse effects of OTC medications to prevent Dimenhydrinate Scopolamine • Scopace • Dramamine Sertraline • Zoloft anticholinergic exposure. The Table (page 35) Diphenhydramine Solifenacin • VESIcare provides a partial list of medications thought • Benadryl, Sominex, others Thioridazine • Mellaril Docusate Sodium • Colace Tiotropium • Spiriva to have clinically significant anticholinergic Donepezil • Aricept Tolterodine • Detrol effects. Doxepin • Adapin Trihexyphenidyl • Artane Doxylamine • Aldex, Unisom, Trimethobenzamide • Tigan others Trimipramine • Surmontil ‘Pharmacologic debridement’ refers Flavoxate • Urispas Triprolidine • Actifed Glycopyrrolate • Robinul Trospium • Sanctura to tapering and discontinuing medications Hydroxyzine • Atarax that are no longer necessary or appropriate. Prescribers often are hesitant to discontinue Acknowledgements medications prescribed by other clinicians This work was supported by an Agency for Healthcare Research and Quality (AHRQ) Centers for Education and and may assume that a medication used Research on Therapeutics cooperative agreement #5 U18 long term has been tolerated and helpful. HSO16094. However, as patients age—particularly if Disclosure they develop dementia—their ability to tol- Dr. Carnahan receives grant/research support from the Agency for Healthcare Research and Quality. erate a medication can change. Patients with dementia also may have difficulty attribut- ing adverse experiences to medications and communicating these effects to providers. The sum of the evidence suggests that drugs Some medical providers may not recognize with anticholinergic effects can contribute to adverse psychiatric and cognitive effects of Current Psychiatry 36 July 2010 agitation and psychosis in dementia. the nonpsychiatric medications they pre- Savvy Psychopharmacology scribe because they do not have sufficient use of antipsychotics, which carry serious dementia expertise. Consulting with these risks for dementia patients.1 providers may help determine the risk-bene- fit considerations of these medications. References 1. Swanson KA, Carnahan RM. Dementia and comorbidities: Generally, anticholinergics should be dis- an overview of diagnosis and management. J Pharm Pract. continued if they are not essential to a pa- 2007;20:296-317. 2. Sunderland T, Tariot P, Murphy DL, et al. Scopolamine tient’s health or if safer non-anticholinergic challenges in Alzheimer’s disease. Psychopharmacology alternatives are available.5 Tapering may (Berl). 1985;87(2):247-249. 3. Sunderland T, Tariot PN, Cohen RM, et al. Anticholinergic be necessary to prevent adverse effects sensitivity in patients with dementia of the Alzheimer type and age-matched controls. A dose response study. Arch Gen from cholinergic rebound if a potent anti- Psychiatry. 1987;44(5):418-426. 5 cholinergic has been used chronically. The 4. Cancelli I, Valentinis L, Merlino G, et al. Drugs with anticholinergic properties as a risk factor for psychosis in first step in addressing Mrs. J’s agitation patients affected by Alzheimer’s disease. Clin Pharmacol is to discontinue the anticholinergic medi- Ther. 2008;84(1):63-68. cations and monitor her symptoms. This 5. Carnahan RM, Lund BC, Perry PJ, et al. The concurrent use of anticholinergics and cholinesterase inhibitors: rare event or pharmacologic debridement may avert the common practice? J Am Geriatr Soc. 2004;52:2082-2087.

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