the placebo response and effect
DESCRIPTION
The Placebo Response and Effect. Can be significant 30% or more in certain interventions An individual’s overall disease manifestation and treatment outcome is influenced by one’s beliefs, emotional and cognitive status and overall feeling of well-being - PowerPoint PPT PresentationTRANSCRIPT
The Placebo Response and Effect
Can be significant 30% or more in certain interventions
An individual’s overall disease manifestation and treatment outcome is influenced by one’s beliefs, emotional and cognitive status and overall feeling of well-being
The placebo response occurs in patients with Chronic pain, sensory processing Movement disorders and motor dysfunction Behavior and mental disorders Cognitive disorders
The Placebo Effect
The effect is linked to expectation of improvement, Pavlovian conditioning, and other mechanisms
Many neuromodulation studies have resulted in failures when the treatment outcome is compared to placebo Migraine, stroke, depression, Parkinson’s
gene infusion therapies Parkinson’s STN DBS study demonstrating
objective improvement in motor function with the DBS OFF and suggestion to patient being ON
Placebo Effect in Chronic Pain Neurochemical mechanisms
Endogenous opioid system implicated The affect can be blocked and reversed by
the μ-opioid antagonist (Naloxone) Higher concentrations of endorphins in
in the CSF Autonomic connections
Placebo analgesia is accompanied by reduced heart rate and decreased β- adrenergic responses
Placebos can also act on 5-HT-dependent hormone secretion
Pituitary and adrenal glands
4
Placebo and Brain Imaging
Increase in cerebral blood flow in the rostral anterior cingulate cortex
Similar outcome as with the administration of opioid receptor agonist (Remifentanil)
(Petrovic et al).
5
Placebo and Brain Imaging Modulation of the
Insular cortex, thalamus, sensory cortex Pre-frontal cortex, DLPFC, Orbitofrontal cortex
Similar regions are implicated in Chronic pain Anxiety, depression, behavior
Brain regions activated by noxious stimuli were diminished in placebo
Benedetti, Wager, Amanzino, Levine
6
Placebo and Study Trial Design Comparison to placebo control design
Is the placebo control itself been validated as a true control when there has been an intervention
The neuromodulation implant, the close follow-up monitoring and attention to patients can potentially alter the natural course of the disease and responsiveness
Need more studies comparing neuromodulation intervention to best medical management
Blinding strategies may need to be modified Cross over design Longer-term blinded evaluations How about a non-invasive placebo stimulator as
the next big thing in neuromodulation
7
Neuromodulation Patient Selection: The Disease
The Disease Complex disorders classified by a NAME However these are heterogeneous disorders with
pathophysiology, and clinical presentationMovement disorders, epilepsy, chronic pain, psychiatric and
cognitive disordersSubtypes and similar presentations are classified and
categorized under one disorders Dedicated team of specialists evaluating the patients to
verifyDiagnosis accuracy and chronicity Co-morbidity variablesTreatment resistance and severityPre-morbid functional status
Neuromodulation Patient Selection: The Chronic Refractory Condition
Chronic disease and disability What is considered a disability and how is that determined
Will that disability specifically improve with neuromodulation PD-Posture, writing, speech will not improve Is the motor disability worse than the pain
Often the most problematic and disabling element of the disease may not be congruent with the symptoms neuromodulation optimally treats
Does the neurological examination make sense and correlate with the anatomical lesion Severe tremor that stops with distraction Location of pain
Neuromodulation Patient Selection:When is the right time for Neuromodulation
When is the right time for neuromodulation implant What is a refractory patient What is an end stage patient
How many meds, how many procedures does the patient need to have before being an “appropriate” candidate
Is there a capacity and reserve in the neuronal network to allow for neuromodulation to work optimally
When do you consider neuromodulation intervention Early vs. late
Neuromodulation Patient Selection:Previous treatments
Previous history of response to medications or treatments is a positive predictor
Negative predictors A patient who gets worse with every procedure A patient whose pain migrates with each procedure Multiple procedures A patient had multiple complications and adverse events
with each procedure
Neuromodulation: Patient Selection Neuropsychological Screening
Psychiatric evaluationNo major untreated psychological factors
Pain
Stress
Depression
Limited/Loss of Abilities
• Axis I-depression, anxiety, OCD must be controlled and stable•Axis II—Caution--borderline personality• dependence or gain
Neuromodulation: Patient Selection Variables
Social elements Family and social support systems need to be in place Work situation Patient and family must be cooperative and motivated
Neuromodulation: Patient Selection Variables
Clear understanding of the procedure Benefits—SYMPTOMATIC and NOT A CURE Complications must be very clearly understood and repeated Realistic expectations about benefits need to be emphasized Motivated to get better Follow-up with therapy and neuromodulation implant adjustments
Neuromodulation: Patient Selection Variables
Adjunctive therapies are important Neuromodulation procedures is one part of an overall
integrated rehabilitation strategy Programming is complex and requires vigilance,
monitoring and expertise Disease fluctuations and progression need to be
considered Initiation of other therapies Social and occupational changes Adjustment to life change
Neuromodulation Patient Selection: Biomarkers
Biomarkers are important area of research and necessity to improve patient selection Imaging
Functional MRI, PET, EEG Blood test Genetic screening TMS Other physiological markers
16
Neuromodulation: Patient Selection Variables
Neuromodulation can be very effective and improve function and quality of life
However patient selection is: Not trivial Need to consider many variables Evaluation
Clear and detailed understanding of the patient Multidisciplinary team assessment Different time points
Team meetings to agree on selection, discussing the overall patient, social status, and follow-up care prior to performing actual procedure
17