Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multi-Center Randomized Placebo-Controlled Clinical Trial Study of Citalopram for the Treatment of Agitation in Alzheimer's Disease
Brief Summary: The purpose of this study is to evaluate the safety and efficacy of citalopram for agitation in Alzheimer's dementia.


Options:
A: Inclusion criteria:

* Possible or probable Alzheimer's disease (National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria), with Mini-Mental State Exam (MMSE) score of 10-26 inclusive; MMSE scores above 26 in those who nevertheless meet criteria for AD may be allowed with Steering Committee approval on a case by case basis
* Clinically significant apathy for at least four weeks for which either 1) the frequency of apathy as assessed by the Neuropsychiatric Inventory (NPI) is 'Very frequently', or 2) the frequency of apathy as assessed by the NPI is 'Frequently' or 'Often' AND the severity of apathy as assessed by the NPI is 'Moderate' or 'Marked'
* A medication for apathy is appropriate, in the opinion of the study physician
* Provision of informed consent for participation in the study by patient or surrogate (if the patient is unable to provide informed consent) and caregiver
* Availability of primary caregiver, who spends greater than ten hours a week with the patient and supervises his/her care, to accompany the patient to study visits and to participate in the study
* Sufficient fluency, of both the patient and caregiver, in written and spoken English to participate in study visits, physical exams, and outcome assessments
* No change to AD medications within the month preceding randomization, including starting, stopping, or dosage modifications
* Treatment with stable doses of selective serotonin reuptake inhibitor antidepressants(SSRIs) is appropriate if stable for 3 months prior to randomization. Other psychotropics(with the exclusion of antipsychotics), if stable for 3 months, may be allowed only with Steering Committee approval on a case by case basis.

Exclusion criteria:

* Meets criteria for Major Depressive Episode, by Diagnostic Statistical Manual of Mental Disorder - IV (TR) criteria
* Clinically significant agitation /aggression for which either 1) the frequency of agitation /aggression as assessed by the NPI is 'Very frequently', or 2) the frequency of agitation /aggression as assessed by the NPI is 'Frequently' AND the severity of the agitation as assessed by the NPI is 'Moderate', or 'Marked'
* Clinically significant delusions for which either 1) the frequency of delusions as assessed by the NPI is 'Very frequently', or 2) the frequency of delusions as assessed by the NPI is 'Frequently' AND the severity of the delusions as assessed by the NPI is 'Moderate', or 'Marked'
* Clinically significant hallucinations for which either 1) the frequency of hallucinations as assessed by the NPI is 'Very frequently', or 2) the frequency of hallucinations as assessed by the NPI is 'Frequently' AND the severity of the hallucinations as assessed by the NPI is 'Moderate', or 'Marked'
* Treatment with psychotropic medications in the 2 weeks prior to randomization with the exception of approved treatments for dementia (ChEIs and memantine), selective serotonin reuptake inhibitor antidepressants, and trazodone (if used as an aid to facilitate sleep and not as an antidepressant); other psychotropics (with the exclusion of antipsychotics), if stable for 3 months, may be allowed only with Steering Committee approval on a case by case basis. Note that antipsychotics are expressly prohibited.
* Treatment with methylphenidate is contraindicated in the opinion of the study physician
* Failure of treatment with methylphenidate in the past for apathy after convincing evidence of an adequate trial as judged by study physician
* Treatment with a medication that would prohibit the safe concurrent use of methylphenidate such as monoamine oxidase inhibitors and tricyclic antidepressants
* Need for acute psychiatric hospitalization or is suicidal
* Uncontrolled hypertension (medication non-compliance or past 3 months with a diastolic reading of 105 as verified by compartment pressure of the rectus sheath (CPRS))
* Symptomatic coronary artery disease deemed to be significant by study physician at the time of screening
* Lack of appetite that results in significant unintentional weight loss as determined by the study physician in the last three months
* Significant communicative impairments
* Current participation in a clinical trial or in any study that may add significant burden or affect study outcomes
* Hyperthyroidism, advanced arteriosclerosis, symptomatic cardiovascular disease, serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or a family history of sudden death or death related to heart problems
* Glaucoma, pheochromocytoma, or known or suspected hypersensitivity to methylphenidate or its excipients
* Central Nervous System (CNS) abnormalities (e.g., cerebral aneurysm) and/or other vascular abnormalities such as vasculitis or pre-existing stroke, motor tics or a family history or diagnosis of Tourette's syndrome, seizures (convulsions, epilepsy), or abnormal EEGs
* Any condition that, in the opinion of the study physician, makes it medically inappropriate or risky for the patient to enroll in the trial
B: Inclusion Criteria:

1. Diagnosis of dementia of the Alzheimer type (DSM-IV Text Revision (TR) criteria)
2. Mini-mental state examination (MMSE) \>18, but \<29
3. Apathy Evaluation Scale (AES) score of more than 40
4. Ability to provide informed consent by either the patient or caregiver.
5. If subjects are being treated with antidepressants, they should be on a stable dose of antidepressants for at least two months prior to the enrollment into the study.
6. If subjects are being treated with cholinesterase inhibitors and memantine, they should be on stable dose of those medications at least four months prior to the enrollment into the study.

Exclusion Criteria:

1. Patient currently taking methylphenidate or hypersensitivity or prior significant adverse events with methylphenidate.
2. Patients currently taking Adderall (amphetamine mixed salts) or Dexedrine (dextroamphetamine sulphate) or any other amphetamine product.
3. Uncontrolled hypertension (BP \> 140/90) or tachycardia (100) at screening visit
4. Patients with frontotemporal dementia
5. Patients meeting criteria for Major Depressive Disorder on the Mini International Neuropsychiatric Inventory (MINI)
6. Patients with active psychosis as determined by MINI
7. Patients currently being treated with antipsychotics
8. History of uncontrolled seizure disorder
9. History of malignant hypertension, symptomatic cardiovascular disease, cardiomyopathy, known structural cardiac defect or medically unstable arrhythmias.
10. History of Tourette's syndrome or presence of motor tics
11. Patients with glaucoma
12. Patients taking monoamine oxidase inhibitors (MAOIs)
13. Patient taking clonidine
C: Inclusion criteria

* Probable Alzheimer's disease (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria), with Mini-Mental score of 5-28 inclusive
* A medication for agitation is appropriate, in the opinion of the study physician
* Clinically significant agitation for which either

  1. the frequency of agitation as assessed by the Neuropsychiatric Inventory (NPI) is 'Very frequently', or
  2. the frequency of agitation as assessed by the NPI is 'Frequently' AND the severity of the agitation as assessed by the NPI is 'Moderate', or 'Marked'
* Provision of informed consent for participation in the study by patient or surrogate (if necessary) and caregiver
* Availability of primary caregiver, who spends several hours a week with the patient and supervises his/her care, to accompany the patient to study visits and to participate in the study
* No change to Alzheimer's disease (AD) medications within the month preceding randomization, including starting, stopping, or dosage modifications

Exclusion criteria

* Meets criteria for Major Depressive Episode by Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV (TR)) criteria
* Presence of a brain disease that might otherwise explain the presence of dementia, such as extensive brain vascular disease, Parkinson's disease, dementia with Lewy bodies, traumatic brain injury, or multiple sclerosis
* Psychosis (delusions or hallucinations) requiring antipsychotic treatment in the opinion of the study physician
* Prolonged measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval)
* Treatment with citalopram is contraindicated in the opinion of the study physician
* Failure of past treatment with citalopram for agitation after adequate trial at a minimally accepted dose (greater than or equal to 20 mg/day)
* Treatment with a medication that would prohibit the safe concurrent use of citalopram, such as Monoamine oxidases (MAO) inhibitors
* Need for psychiatric hospitalization or suicidal
* Current participation in a clinical trial or in any study that may add a significant burden or affect neuropsychological or other study outcomes
* Current treatment with antipsychotics, anticonvulsants (other than dilantin), other antidepressants (other than trazodone, less than or equal to 50 mg per day at bedtime), benzodiazepines (other than lorazepam), or psychostimulants
* Any condition that, in the opinion of the study physician, makes it medically inappropriate or risky for the patient to enroll in the trial
D: Inclusion Criteria:

* Meets criteria for mild to moderate Alzheimer's disease (AD) with Mini-Mental State Examination (MMSE) score of 16-26 at Visit 1
* Modified Hachinski Ischemia Scale score of less than or equal to 4
* Geriatric Depression Scale score of less than or equal to 6
* A magnetic resonance imaging (MRI) or computerized tomography (CT) scan in the last 2 years with no findings inconsistent with a diagnosis of AD
* If female, must be without menstruation for at least 12 consecutive months or have had both ovaries removed

Exclusion Criteria:

* Is not capable of swallowing whole oral medication
* Has serious or unstable illnesses
* Does not have a reliable caregiver
* Chronic alcohol or drug abuse within the past 5 years
* Has ever had active vaccination for AD

Answer: C