Prevent drug-drug interactions with cholinesterase inhibitors
Avoid adverse events when prescribing medications for patients with dementia.
Antipsychotics. Nearly one-half of AD patients experience delusions, often in the middle stage of the disease, and many are prescribed second-generation antipsychotics (SGAs) to control delusions, hallucinations, sundowning, agitation, or aggression. Concomitant use of AChEIs and antipsychotics may increase the risk of extrapyramidal symptoms by disrupting the acetylcholine/dopamine balance in the striatum.5
In AD patients taking donepezil and risperidone, case reports describe parkinsonian syndrome and rigidity with immobility, which resolved after the antipsychotic was discontinued.5,11 When rivastigmine and risperidone were coadministered, however, no clinically relevant adverse interactions were noted in a 20-week, open-label trial of 65 patients with AD, 10 with vascular dementia, and 10 with both.17
The FDA has warned of increased risk of death when SGAs are used to treat behavioral disturbances in dementia patients. In a recent meta-analysis of 15 placebo-controlled trials, cognitive tests scores worsened when AD patients took aripiprazole, olanzapine, quetiapine, or risperidone. A significant risk for cerebrovascular events was seen, especially with risperidone, although no clear causal relationship was established.18 Falls, injury, and syncope were not increased, and patients with less severe dementia, outpatients, and those selected for psychosis were less affected. Thus, provide careful follow-up and avoid long-term unwarranted antipsychotic use in AD patients.
Highly anticholinergic FGAs such as chlorpromazine are not recommended for AD patients (Table 4).
Antidepressants. Up to 30% of AD patients experience major depression.19 SSRIs are the antidepressants most often used to treat depression and anxiety in AD patients.
Citalopram, escitalopram, or venlafaxine are good choices for patients with AD because of minimal CYP inhibitory activity.4 Fluvoxamine, fluoxetine, and paroxetine inhibit CYP 2C9, through which warfarin and some other drugs with a narrow therapeutic index are metabolized.6
Herbal supplements. Ginkgo biloba and huperzine A (Chinese club moss) are the herbal supplements used most commonly by dementia patients. Ginkgo inhibits platelet aggregation and can cause bleeding complications, with or without concomitant antiplatelet or anticoagulant therapy such as aspirin, warfarin, and NSAIDs. Enzyme induction of CYP 2C19 by ginkgo, leading to subtherapeutic levels of anticonvulsants, has been implicated in a report of fatal seizures. Huperzine A is a natural cholinesterase inhibitor and should not be combined with AChEIs because of the risk of additive adverse effects.10
Related resources
- Jacobson SA, Pies RW, Greenblatt DJ. Handbook of geriatric psychopharmacology. Washington, DC: American Psychiatric Publishing; 2002.
- Sandson, NB. Drug-drug interaction primer. Washington, DC: American Psychiatric Publishing; 2007.
- Amantadine • Symmetrel
- Amitriptyline • Elavil
- Amoxapine • Asendin
- Aripiprazole • Abilify
- Atropine • Sal-Tropine
- Benztropine • Cogentin
- Bethanechol • Urecholine
- Biperiden • Akineton
- Bupropion • Wellbutrin
- Buspirone • BuSpar
- Carbamazepine • Tegretol
- Celecoxib • Celebrex
- Chlorpheniramine • Chlor-Trimeton
- Chlorpromazine • Thorazine
- Cimetidine • Tagamet
- Citalopram • Celexa
- Clomipramine • Anafranil
- Clozapine • Clozaril
- Cyclobenzaprine • Flexeril
- Cyproheptadine • Periactin
- Dextromethorphan • Benylin, Delsym, others
- Dicyclomine • Bentyl
- Digoxin • Lanoxin
- Diphenhydramine • Benadryl
- Disopyramide • Norpace
- Donepezil • Aricept
- Doxepin • Adapin, Sinequan
- Duloxetine • Cymbalta
- Escitalopram • Lexapro
- Erythromycin • E-Mycin
- Fluconazole • Diflucan
- Fluvoxamine • Luvox
- Fluoxetine • Prozac
- Galantamine • Reminyl, Razadyne
- Haloperidol • Haldol
- Hydroxyzine • Vistaril
- Hyoscyamine • Anaspaz, Levbid, Levsin
- Imipramine • Tofranil
- Itraconazole • Sporanox
- Lamotrigine • Lamictal
- Levodopa/carbidopa • Sinemet
- Lithium • Eskalith, Lithobid
- Lorazepam • Ativan
- Meclizine • Antivert
- Memantine • Namenda
- Mirtazapine • Remeron
- Nefazodone • Serzone
- Neostigmine • Prostigmin
- Olanzapine • Zyprexa
- Oxazepam • Serax
- Oxybutynin • Ditropan
- Paroxetine • Paxil
- Pimozide • Orap
- Promethazine • Phenergan
- Protriptyline • Vivactil
- Pyridostigmine • Mestinon
- Quetiapine • Seroquel
- Ranitidine • Zantac
- Risperidone • Risperdal
- Rivastigmine • Exelon
- Scopolamine • Scopace
- Sertraline • Zoloft
- Succinylcholine • Anectine
- Temazepam • Restoril
- Thioridazine • Mellaril
- Tolterodine • Detrol
- Trazodone • Desyrel
- Trihexyphenidyl • Artane
- Valproate • Depakote
- Venlafaxine • Effexor
- Warfarin • Coumadin
- Ziprasidone • Geodon
- Zolpidem • Ambien
The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
