American Psychiatric Association Council on Aging

1. American Psychiatric AssociationCouncil on Aging Neuropharmacological Drug Products Psychophamacological Drugs Advisory Committee Psychiatric and Behavioral Disturbances Associated with Dementia Food and Drug Administration March 9, 2000

2. American Psychiatric Association • Presenters • Christopher C. Colenda, MD, MPH • Chair: Council on Aging • Jacobo Mintzer, MD • Chair: Committee on Ethnic Minority Elderly

3. Behavioral and Psychological Symptoms of Dementia • The above term does not define a specific clinical entity for purposes of drug development • The central question for the committee is whether there is sufficient scientific evidence that specific psychiatric symptoms are fundamental manifestations of the Alzheimer’s disease, and thus warrant drug development or indication

4. Conceptual Model of Disease Latency Induction Promotion Expression Clinical Detection of the Disease (Onset of Signs and Symptoms) Initiation of Pathological Process Initiation of the Etiological Process Outcome of the Disease Kleinbaum, Kupper, Morgenstern: Epidemiological Research. 1982; pp 21-22.

5. Criteria Used to Assess Available Evidence Supporting a Causal Interpretation Hill AB: Principles of Medical Statistics. 1971

6. Circadian-Rhythm Disturbances(Sleep-Wake Disturbances)

7. Psychosis Due to DAT Hill AB: Principles of Medical Statistics. 1971

8. Benefits of Establishing Appropriate Targets for Pharmacological intervention • Psychoactive drugs are widely used in DAT • “Off label” use expose patients to severe side effects without evidence of possible benefit • Labeling will provide information on therapeutic targets and safety information specific to the targeted population

9. Benefits of Establishing Appropriate Targets for Pharmacological intervention • The establishment of specific labeling will provide with a strong incentive for the development of safer and more effective compounds to treat these difficult psychiatric syndromes

10. Conclusion • Psychiatric syndromes are part of the core manifestation of DAT • There is enough scientific evidence to support the labeling for psychosis, alteration in circadian rhythm and depression as valid targets for pharmacological intervention in DAT • Other psychiatric syndromes should be considered as scientific evidence becomes available