Related Experiment Video
Updated: Nov 30, 2025
03:37
Self-Administration of Drugs in Mouse Models of Feeding and Obesity
Published on: June 8, 2021
4.9K
Towards safer risperidone prescribing in Alzheimer's disease
Suzanne Reeves1, Julie Bertrand2, Hiroyuki Uchida3
1Division of Psychiatry, University College London, UK.
The British Journal of Psychiatry : the Journal of Mental Science
|November 12, 2020
Summary
This study found that optimal dosing of risperidone for Alzheimer's disease psychosis depends on age and cognitive function. Adjusting doses based on individual drug clearance can help avoid side effects like extrapyramidal symptoms (EPS).
Area of Science:
- Pharmacology
- Geriatric Medicine
- Neuroscience
Background:
- Current guidelines for treating psychosis, agitation, and aggression in Alzheimer's disease (AD) recommend the lowest possible antipsychotic dose but lack specific dosing information.
- Antipsychotic medications are frequently used in AD, but optimal dosing strategies to balance efficacy and side effects remain unclear.
Purpose of the Study:
- To investigate the pharmacokinetic profiles of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) in Alzheimer's disease patients.
- To determine the relationship between these pharmacokinetic profiles and the occurrence of treatment-emergent extrapyramidal side effects (EPS).
- To simulate optimal dose adjustments for risperidone based on individual patient characteristics.
Main Methods:
- Utilized data from the Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease study (NCT00015548).
- Developed a statistical model to describe the concentration-time course of risperidone and 9-OH-risperidone.
- Employed logistic regression to associate pharmacokinetic biomarkers with EPS and simulated dose adjustments.
Main Results:
- Identified an age-related decrease in risperidone clearance and reduced renal elimination of 9-OH-risperidone, leading to slower active moiety clearance in 22% of patients.
- Higher trough concentrations of 9-OH-risperidone and active moiety, along with lower Mini-Mental State Examination (MMSE) scores, were significantly associated with EPS.
- Model-based predictions indicated optimal risperidone doses ranging from 0.25 mg/day to 1 mg/day, varying by age and MMSE score, with alternate-day dosing suggested for individuals with slower clearance.
Conclusions:
- Findings support the need for age- and MMSE- score-based dose adjustments for risperidone in Alzheimer's disease patients.
- A single concentration-to-dose ratio measurement can effectively identify patients with slower drug clearance, enabling personalized dosing strategies.
- Optimized dosing can potentially mitigate the risk of extrapyramidal side effects in this vulnerable population.
Related Concept Videos
01:15Drug Dosing: Geriatric Patients
119
Elderly individuals encompass a diverse population with varying degrees of age-related physiological changes. Defining the elderly presents challenges, as the geriatric population is often arbitrarily categorized as individuals older than 65. However, many individuals in this group lead active and healthy lives, with an increasing number surpassing 85 years and falling into the older elderly category. Physiological changes associated with aging impact performance capacity and homeostatic...
119
01:22Alzheimer's Disease: Treatment
604
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
604
01:08Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
94
Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
94
01:27Pharmacodynamics in Geriatric Patients: Effects of Age
104
Age-related pharmacokinetic changes are extensively documented, but understanding age-related pharmacodynamic alterations is relatively limited. This knowledge gap can be partly attributed to the complexity of developing appropriate measures of drug responses compared to bioanalytical methods for determining drug concentrations.Most information regarding age-related differences in human pharmacodynamics originates from cross-sectional studies. However, these studies assume that observed mean...
104
01:28Drug Therapy
170
The advent of drug therapy has profoundly shaped modern mental health care, providing targeted treatments for a range of psychological disorders. Psychotherapeutic drugs, classified into antianxiety, antidepressant, and antipsychotic medications, address symptoms across anxiety disorders, mood disorders, and schizophrenia. While these medications have transformed patient outcomes, they require careful management due to their potential side effects and limitations.
Antianxiety Medications
Antianxiety Medications
170
01:22Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Absorption
111
As individuals age, their body's physiology evolves, affecting drug pharmacokinetics. The most apparent changes occur in the gastrointestinal tract, where an increase in gastric pH, a delay in gastric emptying, and a reduction in gastrointestinal motility are observed. Remarkably, these changes do not substantially modify the absorption of orally administered drugs, particularly those absorbed via passive diffusion.Transdermal drug delivery emerges as a highly viable method for older adults due...
111