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Treatment of Behavioral Symptoms in Alzheimer's Disease

This study has been completed.
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
New York State Psychiatric Institute Identifier:
First received: January 23, 2001
Last updated: May 23, 2016
Last verified: February 2012

The optimal strategy for the treatment of behavioral complications in patients with probable Alzheimer's disease (AD) remains unclear.

The objective of this study is to evaluate the risk of relapse following discontinuation of haloperidol in patients with Alzheimer's disease (AD) with psychosis or agitation who respond to it.

In Phase A of this study, AD outpatients with behavioral complications receive 20 weeks of open haloperidol treatment with an oral dose of 1-5 mg daily, titrated individually to achieve the optimal trade-off between efficacy and side effects. Responders to Phase A participate in Phase B, a 24-week continuation trial in which patients are randomized to continuation haloperidol or placebo.

The primary outcome is the time to relapse of psychosis or behavioral disturbance.

Condition Intervention Phase
Alzheimer's Disease
Drug: Haloperidol-Haloperidol
Drug: Haloperidol-Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of Behavioral Symptoms in Alzheimer's Disease

Resource links provided by NLM:

Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • For the primary hypothesis, the primary endpoint is time to relapse. [ Time Frame: 0-24 weeks in Phase B ]

Secondary Outcome Measures:
  • Severity of target symptoms at the end of Phase A as a predictor of relapse [ Time Frame: 0-24 weeks in Phase B ]
  • Severity of Brief Psychiatric Rating Scale psychosis and hostile suspiciousness factor scores [ Time Frame: 0-20 weeks in Phase A and 0-24 weeks in Phase B ]
  • MMSE and Blessed Functional Activity Scale [ Time Frame: 0-20 weeks in Phase A and 0-24 weeks in Phase B ]

Enrollment: 44
Study Start Date: January 1999
Study Completion Date: December 2004
Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Haloperidol-Haloperidol
Haloperidol for 20 weeks followed by haloperidol for 24 weeks
Drug: Haloperidol-Haloperidol
Haloperidol open label flexible dose 1-5 mg daily for 20 weeks followed by haloperidol double-blind 1-5 mg for 24 weeks
Other Name: Haldol
Placebo Comparator: Haloperidol-Placebo
Haloperidol for 20 weeks followed by placebo for 24 weeks
Drug: Haloperidol-Placebo
Haloperidol open-label flexible dose of 1-5 mg for 20 weeks followed by placebo double-blind for 24 weeks
Other Name: Haldol

Detailed Description:

The study involves two phases. Outpatients with AD who meet inclusion/ exclusion criteria enter Phase A, the 20 week open acute treatment phase that uses a flexible dose regimen of haloperidol 1-5 mg daily. Haloperidol is started at an oral dose of 1 mg daily, with subsequent dose titration in 1 mg increments until the optimal dose is reached, i.e., optimal trade-off between efficacy and side effects. At the end of Phase A, patients who do not meet criteria for clinical response exit the protocol and is treated openly with alternative medications.

Phase A responders enter Phase B, a 24-week random assignment, placebo-controlled, continuation trial. Randomization is stratified by the severity of dementia and by the presence of psychosis. Half the patients are randomized to haloperidol (continuing at the same dose as at the end of Phase A), and the other half are randomized to placebo. Patients who relapse during Phase B exit the protocol and receive open treatment.

In Phase A, patients are followed at 0, 2, 4 weeks and every 4 weeks thereafter until 20 weeks. In the discontinuation trial, Phase B, patients are followed at 0, 1, 2, 4, week time points and every 4 weeks thereafter until 24 weeks. If a patient shows signs of relapse, the patient is brought in for more frequent visits, regardless of the stage of the protocol.


Ages Eligible for Study:   50 Years to 95 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Meets DSM-IV criteria for dementia either sex, age 50-95 years
  • Meets NINCDS-ADRDA criteria for probable Alzheimer's disease
  • Meets Folstein Mini-Mental State Exam score of 5-26, inclusive
  • Intellectual impairment reported for at least six months
  • Availability of family member who has had direct contact with the patient for an average of at least once every week during the three months prior to study entry
  • Has current symptoms of psychosis or agitation. Criteria for "psychosis" requires the presence of delusions and/or hallucinations identified by the Columbia University Scale for Psychopathology in Alzheimer's Disease (CUSPAD) and a minimum Brief Psychiatric Rating Scale (BPRS) psychosis factor score of at least 4 (moderate severity) on one of the following two items: These two items comprise the psychosis factor, excluding the item for conceptual disorganization. Agitation is defined as a score of greater than 3 (present at least 10 days per month) on one or more of the CERAD Behavioral Rating Scale for Dementia items for agitation, purposeless wandering, verbal aggression or physical aggression.
  • Free of psychotropic medication for at least two weeks prior to study entry, or able to tolerate medication washout for this period.
  • Informed consent by patient and family member, as per IRB procedures at New York State Psychiatric Institute.

Exclusion Criteria:

  • Acute unstable medical condition, delirium, alcohol or substance abuse or dependence within the past 1 year
  • Clinical evidence of stroke, other dementias including vascular or Lewy body or frontotemporal dementia, multiple sclerosis, Parkinson's disease, Huntington's disease, tardive dyskinesia
  • Diagnosis of a psychotic disorder antedating the onset of dementia
  • Antipsychotic medication usage during 4 weeks prior to study entry
  • Contraindication to the use of haloperidol
  Contacts and Locations
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Please refer to this study by its identifier: NCT00009217

United States, New York
New York State Psychiatric Institute
New York, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
National Institute of Mental Health (NIMH)
Principal Investigator: Davangere Devanand, M.D. Columbia University College of Physicians and Surgeon
  More Information

Additional Information:
Responsible Party: New York State Psychiatric Institute Identifier: NCT00009217     History of Changes
Obsolete Identifiers: NCT00000183
Other Study ID Numbers: #4051R
R01MH055735 ( US NIH Grant/Contract Award Number )
Study First Received: January 23, 2001
Last Updated: May 23, 2016

Keywords provided by New York State Psychiatric Institute:
Alzheimer's disease

Additional relevant MeSH terms:
Alzheimer Disease
Psychotic Disorders
Mental Disorders
Psychomotor Agitation
Behavioral Symptoms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Neurologic Manifestations
Psychomotor Disorders
Neurobehavioral Manifestations
Signs and Symptoms
Haloperidol decanoate
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists processed this record on May 25, 2017