Escitalopram for Agitation in Alzheimer's Disease

Prior treatment

• Contraindication to treatment with escitalopram as determined by a study physician, such as recent (30 days) use of monoamine oxidase inhibitors (MAOIs) or potential participant is hypersensitive to escitalopram or citalopram or any inactive ingredients
• Prior failed treatment attempt with citalopram or escitalopram for agitation after adequate trial, at minimally accepted dose

Other illness

• Has major depression, as indicated by major depressive episode (MDE) in the past 90 days (meeting the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) criteria)
• Presence of another brain disease that fully explains the dementia, (e.g., extensive brain vascular disease, Parkinson's disease, dementia with Lewy bodies, traumatic brain injury, or multiple sclerosis)
• Indication for psychiatric hospitalization or acute suicidality, in the opinion of the study physician
• Any condition that, in the opinion of the study physician, makes it medically inappropriate or risky for the potential participant to enroll in the trial
  • if the QTcB is determined while the rhythm is paced, 50 ms is subtracted from the calculated value. The study cardiologist must confirm eligibility in this scenario.

Lab values

• Abnormal corrected QT interval using Bazett's formula (QTcB)\*\* as determined on enrollment ECG (defined as \> 450 ms for men and \> 470 ms for women)
• Recent (30 days) presence of severely reduced renal function (as identified by a Glomerular filtration rate (GFR) clearance \< 30 mL/min) or reduced hepatic function

Other

• Residence in a skilled nursing or Long-Term Acute Care (LTAC) facility
• Recent (\< 7 days) changes in antipsychotics, anticonvulsants, or psychosis (delusions or hallucinations) requiring a new or change in antipsychotic treatment (in the opinion of the study physician)
• Current treatment (within 7 days) with any of the following:
  • antidepressants (other than trazodone, ≤ 100 mg per day at bedtime)
  • benzodiazepines (other than lorazepam), or
  • psychostimulants
• Recent (\< 14 days) changes in Dextromethorphan/quinidine, prazosin, and pimavanserin
• Recent (\< 14 days) use of medical marijuana
• Current participation in a clinical trial or in any study that may add a significant burden or affect neuropsychological or other study outcomes
• Significant communicative impairments that would affect participation in a clinical trial

• Alzheimer's dementia diagnosed clinically by the National Institute on Aging (NIA) and the Alzheimer's Association (AA) (2011 NIA/AA criteria)
• Mini-Mental State Examination Telephone (MMSET) score of 3-20 inclusive
• Meets the International Psychogeriatric Association (IPA) provisional criteria for agitation in cognitive disorders
• Clinically significant agitation/aggression as assessed by the Neuropsychiatric Inventory (NPI) for which either:
  • The frequency is 'Very frequently,' or
  • The frequency is 'Frequently' AND the severity is 'Moderate' or 'Marked'
• Provision of informed consent for participation in the study by both caregiver and participant (or, if participant is unable to provide informed consent, with surrogate consent and participant assent)
• Availability of a caregiver who spends at least several hours per week with the participant, supervises his/her care, is willing to accompany the participant to study visits, and is willing to participate in the study
• Stable (for ≥ 7 days) dosing of antipsychotics for agitation or psychosis, if being used at all
• A medication for agitation is appropriate, in the opinion of the study physician