Anticholinergic Burden: Clinical Reference Guide

⚠️ CRITICAL: Anticholinergic burden is CUMULATIVE. Multiple low-burden medications can produce high-burden effects (e.g., 1 + 1 + 1 = 3)

Anticholinergic Burden Scale by Medication Class

Class	Very Low (0)	Low (1)	Medium (2)	High (3)
Antidepressants	• Bupropion • Citalopram • Escitalopram • Fluoxetine • Fluvoxamine • Selegiline • Venlafaxine	• Desipramine§ • Mirtazapine • Sertraline • Trazodone	• Paroxetine	• Amitriptyline† • Clomipramine† • Doxepin† • Imipramine† • Nortriptyline† • Trimipramine†
Antipsychotics	• Brexpiprazole • Lumateperone • Lurasidone • Thiothixene • Ziprasidone	• Aripiprazole • Asenapine • Haloperidol • Iloperidone • Paliperidone • Risperidone	• Loxapine • Pimozide	• Amoxapine • Chlorpromazine • Clozapine • Fluphenazine • Olanzapine • Perphenazine • Prochlorperazine • Quetiapine* • Thioridazine
Other	Minimal anticholinergic activity	• Alprazolam • Clorazepate • Diazepam • Pramipexole	• Amantadine • Carbamazepine • Hydroxyzine‡ • Oxcarbazepine	• Benztropine • Diphenhydramine • Doxylamine

*Quetiapine's active metabolite (norquetiapine) has moderate-to-strong muscarinic receptor affinity (M1 Ki = 38.3 nM), contributing to anticholinergic effects at therapeutic doses (FDA label). Some scales classify quetiapine at lower levels; the ACB calculator and recent clinical data support a score of 3.
†Tricyclic antidepressants (TCAs) are among the most potent anticholinergic psychotropic medications. Amitriptyline has an anticholinergic equivalence (AE) of 8.99 using diphenhydramine as the reference standard (AE = 1). All listed TCAs, including the tertiary amines (amitriptyline, clomipramine, doxepin, imipramine, trimipramine) and the secondary amine nortriptyline, are classified as ACB score 3 in the ACB calculator, German Anticholinergic Burden Scale (GABS), and most validated scales.
§Desipramine is a secondary amine TCA with lower anticholinergic activity than tertiary amines. Most scales classify it as ACB 1–2. It causes significantly less salivation reduction than amitriptyline but retains meaningful anticholinergic properties; clinicians should monitor accordingly.
‡Clinical toxicology data suggest hydroxyzine produces fewer antimuscarinic effects than diphenhydramine in overdose (Simon & Heard, 2023). The FDA label lists only dry mouth as an anticholinergic adverse reaction. Some scales classify hydroxyzine as ACB 2–3.

Scale Variability: Anticholinergic burden scales vary significantly in how they classify individual medications. A 2026 systematic review found that approximately 74% of high-potency drugs are scored inconsistently across available scales, and no gold standard currently exists. Clinicians should interpret burden scores as estimates and consider pharmacological properties, patient-specific factors, and clinical context when making prescribing decisions.

Mortality Risk: High anticholinergic burden is associated with increased mortality in older adults with cognitive impairment (HR 1.15, 95% CI 1.03–1.29). This underscores the importance of routine burden assessment and deprescribing when clinically appropriate.

Anticholinergic Effects and Clinical Significance

Anticholinergic Effect	Clinical Significance
Dry Mouth	Tooth decay, gum inflammation, ulceration; poor dental hygiene increases risk for depression and dementia
Constipation	Bowel obstruction with potentially fatal paralytic ileus and sepsis
Urinary Retention	Urinary tract infections, renal or bladder damage
Dilated Pupils	Acute narrow-angle glaucoma, traffic accidents, falls
Impaired Accommodation	Inability to read fine print, functional impairment
Increased Heart Rate	Increased risk of cardiac arrest
Decreased Sweating	Hyperthermia, especially in hot environments
Decreased Bronchial Secretions	Mucous plugging of airways, worsens asthma and bronchitis
Cognitive Impairment	Poor memory and concentration, delirium, increased dementia risk

Essential Clinical Considerations

Time Course and Reversibility

Acute Effects: Peripheral effects (dry mouth, constipation) typically emerge within hours to days of initiation or dose increases.

Chronic Effects: Cognitive impairment may develop gradually over weeks to months.

Reversibility: Most effects are dose-dependent and reversible with dose reduction or discontinuation, though cognitive recovery may take weeks to months in elderly patients.

Drug Interactions and Potentiation

Non-psychiatric medications significantly contribute to anticholinergic burden:

• Antihistamines (diphenhydramine, hydroxyzine)
• Muscle relaxants (cyclobenzaprine)
• Urinary antispasmodics (oxybutynin, tolterodine)
• Antiemetics (scopolamine, promethazine)
• Sleep aids (doxylamine)

Critical: Always review complete medication list including over-the-counter medications.

Route of Administration Considerations

Oral: Standard dosing applies to burden scores

Transdermal: May have disproportionate systemic effects (e.g., scopolamine patches)

Intramuscular: Rapid onset, consider higher effective burden

Long-acting injections: Sustained anticholinergic exposure, difficult to reverse quickly

Special Populations

Elderly (>65 years): Increased sensitivity due to reduced cholinergic function and slower metabolism

Cognitive impairment: Even low-burden medications may cause significant deterioration

Polypharmacy: Common in geriatric psychiatry, requiring careful burden calculation

Management and Monitoring Recommendations

Baseline Assessment: Cognitive screening (MMSE, MoCA), bowel/bladder function, visual acuity
Regular Monitoring: Cognitive function every 3-6 months, especially in elderly patients
Environmental Precautions: Avoid heat exposure, ensure adequate hydration
Medication Review: Quarterly assessment of total anticholinergic burden including OTC medications
Tapering Strategy: Gradual reduction when possible, prioritize highest-burden medications
Patient Education: Signs/symptoms to report, importance of hydration, dental hygiene
Fall Prevention: Address visual impairment, orthostatic hypotension, cognitive effects
Constipation Management: Prophylactic bowel regimen for high-burden medications

Badre, N., & Geier, E. (2025). Anticholinergic equivalence in psychotropic medications: A guide for psychiatrists. Journal of Clinical Psychopharmacology. https://doi.org/10.1097/JCP.0000000000002073

Boustani, M., Campbell, N., Munger, S., Maidment, I., & Fox, C. (2008). Impact of anticholinergics on the aging brain: A review and practical application. Aging Health, 4(3), 311–320. https://doi.org/10.2217/1745509X.4.3.311

Brueckle, M. S., Thomas, E. T., Seide, S. E., et al. (2023). Amitriptyline’s anticholinergic adverse drug reactions: A systematic multiple-indication review and meta-analysis. PLoS ONE, 18(4), e0284168. https://doi.org/10.1371/journal.pone.0284168

Kiesel, E. K., Hopf, Y., & Drey, M. (2018). An anticholinergic burden score for German prescribers: Score development. BMC Geriatrics, 18, 239. https://doi.org/10.1186/s12877-018-0929-6

Lisibach, A., Benoist, V., Ceppi, M. G., Waldner-Knogler, K., Csajka, C., & Lutters, M. (2021). Quality of anticholinergic burden scales and their impact on clinical outcomes: A systematic review. European Journal of Clinical Pharmacology, 77, 147–162. https://doi.org/10.1007/s00228-020-02994-x

Pfistermeister, B., Tümena, T., Gaßmann, K. G., Maas, R., & Fromm, M. F. (2017). Anticholinergic burden and cognitive function in a large German cohort of hospitalized geriatric patients. PLoS ONE, 12(2), e0171353. https://doi.org/10.1371/journal.pone.0171353

Pistorio, S., Scotto di Tella, G., Canzanella, V., et al. (2025). Anticholinergic burden and behavioral and psychological symptoms in older patients with cognitive impairment. Frontiers in Medicine, 12, 1505007. https://doi.org/10.3389/fmed.2025.1505007

Pollock, B. G., Mulsant, B. H., Nebes, R., et al. (1998). Serum anticholinergicity in elderly depressed patients treated with paroxetine or nortriptyline. The American Journal of Psychiatry, 155(8), 1110–1112. https://doi.org/10.1176/ajp.155.8.1110

Simon, M., & Heard, K. (2023). Are antimuscarinic effects common in hydroxyzine overdose? A cohort analysis of antimuscarinic effects in hydroxyzine and diphenhydramine-poisoned patients. Clinical Toxicology, 61(5), 379–386. https://doi.org/10.1080/15563650.2023.2200575

Taylor-Rowan, M., Kraia, O., Kolliopoulou, C., et al. (2022). Anticholinergic burden for prediction of cognitive decline or neuropsychiatric symptoms in older adults with mild cognitive impairment or dementia. Cochrane Database of Systematic Reviews, 8, CD015196. https://doi.org/10.1002/14651858.CD015196.pub2

Vennard, O., Stewart, C., Tolia, M., Soiza, R. L., & Myint, P. K. (2026). Anticholinergic medication burden scales: A systematic review. Journal of the American Geriatrics Society. https://doi.org/10.1111/jgs.70352

Disclaimer: This chart is provided for educational purposes only and is not intended to substitute for professional clinical judgment, individualized patient assessment, or validated diagnostic instruments. PsychConcierge PLLC ("PsychConcierge.com") makes no guarantees regarding the accuracy, completeness, or applicability of this information to any specific patient scenario. Use of this resource does not establish a provider–patient relationship. All prescribing and deprescribing decisions should be made in consultation with licensed healthcare professionals. PsychConcierge PLLC and its affiliates disclaim all liability for outcomes associated with reliance on this content.