Placebo Effects – Clinical Data
John M. Kelley, PhD
Associate Professor, Endicott College
Deputy Director, Program in Placebo Studies, Harvard Medical School
Staff Psychologist, Massachusetts General Hospital
Overview of Goals
1. Demonstrate that the placebo effect is powerful
2. Show that the placebo effect can be decomposed
into separate factors
3. Show that these placebo effects are active not only
when placebos are administered but also when
active treatments are delivered.
4. Describe a method by which placebo effects might
be harnessed in medical and psychiatric treatments
Beecher (1955). JAMA, 59, 1602-1606
Hrobjartsson (2014). NEJM, 344(21), 1594-1602
Components of the Placebo Response
• Regression to the mean
• Natural history of the disorder
• Change in life circumstances (diet, exercise,
social support, stress reduction, rest)
• Other psychological or physical treatments
• Placebo effect
Kaptchuk (2008). BMJ, 336, 998-1003.
Placebo Acupuncture Needle
Placebo Acupuncture Needle
Needle Set Up
Placebo Needle
Streitberger (1998). The Lancet, 352, 354-365.
Genuine Needle
Design
• 262 patients with IBS
• Randomized to 3 treatment groups:
(1) Waitlist control (N=87)
(2) Limited placebo acupuncture (N=88)
(3) Augmented placebo acupuncture (N=87)
• 3-week trial, 2 treatments per week
Outcomes at 3-week end point
©2008 by British Medical Journal Publishing Group
Kam-Hansen (2014). Science Translational Medicine, 6, 218ra215
Treatment Conditions
• Within-subjects experiment in 66 migraine patients
• 7 migraines attacks treated in random order as follows:
• No Treatment
• Told Placebo, Given Placebo
• Told Uncertain, Given Placebo
• Told Drug, Given Placebo (deception)
• Told Placebo, Given Drug (deception)
• Told Uncertain, Given Drug
• Told Drug, Given Drug
3 x 2 Design
Two factors crossed with each other:
Labeling (expectancy)
- “Placebo”
- “Drug or Placebo”
- “Drug”
Pill Type
- Active Drug (Maxalt)
- Inactive Placebo
First Proposal for Open-Label Placebo
Walter Brown, MD:
“Among less severely depressed patients … the placebo
response rate is close to 50% and often indistinguishable
from the response rate to antidepressants … I propose that
the initial treatment for selected depressed patients should
be four to six weeks of placebo. Patients so treated should
be informed that the placebo pill contains no drug but that
this treatment can be helpful.”
Brown (1994). Neuropsychopharmacology, 10(4), 265-269.
Rationale for Placebo Efficacy
Clinicians explained that placebos are inactive substances like a
sugar pill, which contain no medication. They also noted that:
(1) In RCTs, placebo response often rivals response to active
treatment;
(2) Classical conditioning is a possible mechanism for
automatic self-healing;
(3) Placebo-treated patients who are more compliant have
better outcomes; and
(4) Positive expectations increase placebo effects, but it is OK
to have doubts.
Clinicians delivered the rationale in a natural and supportive
manner that allowed for questions and answers.
Kaptchuk (2010). PLOS ONE, 5(12), e15591
Design
•
•
•
3-week trial of open-label placebo in 80 IBS patients
Prior to randomization all patients were given a rationale for
why placebos might be effective :
(1) The placebo effect is powerful in RCTs
(2) The body can automatically respond to placebos
(3) A positive attitude is helpful but not essential
(4) Taking the pills faithfully is essential
Patients were randomly assigned to either:
(1) Open-Label Placebo Pill, twice daily (N=43)
(2) No Treatment Control (N=37)
Kelley (2012). Psychotherapy and Psychosomatics, 81:312–314
Design
•
•
•
20 MDD patients recruited for a 4-week trial
Prior to randomization all patients were given the persuasive
rationale for why placebos might work that included
(1) The placebo effect is powerful
(2) The body can automatically respond to placebos
(3) A positive attitude is helpful but not essential
(4) Taking the pills faithfully is essential
Patients were randomly assigned to either:
(1) Open-Label Placebo Pill, twice daily (N=11) for 4 weeks
(2) Waitlist Control (N=9) for 2weeks, followed by 4 weeks
of Open-Label Placebo
Improvement by Group at 2 Weeks
Measure
HamD-17
QIDS
SDQ
Waitlist
-0.67±4.00
-0.22±2.44
1.38±10.77
Open-Label
1.64±4.52
2.27±3.88
3.70±18.98
d
.54
.77
.15
p
.26
.13
.75
Note: All values are means ± SD. Positive scores indicate
improvement.
Ham-D-17 Improvement at 2 Weeks
2
1
0
-1
Waitlist
Control
Open
Placebo
Improvement after 4 Weeks of Placebo
Measure
HamD-17
QIDS
SDQ
Pre
18.00±4.94
14.85±2.68
146.94±19.71
Post
14.75±6.61
12.10±4.34
138.75±27.65
Change
3.25±6.01
2.75±3.84
9.89±15.71
Note: All values are means ± SD. Positive scores indicate
improvement.
d
.57
.76
.34
p
.03
.005
.02
Pre-Post Ham-D Scores (N=20)
20
18
16
14
12
10
8
6
4
2
0
18.0
14.8
Baseline
4 Weeks
Criticisms of Open-Label Placebo
•
•
Are we testing open-label placebo or are we testing the
rationale?
Isn’t generalization limited to patients who are willing to take
open-label placebos?
Where do we go from here?
• Larger 2-arm trial of open-label placebos vs. waitlist
control
• 3-Arm trial
• Waitlist control
• Open-Label Placebo
• Open-Label Drug
Thank you for your attention!
My Principal Collaborators
• Ted Kaptchuk
• Irving Kirsch
• Tony Lembo
• Maurizio Fava
• Rami Burstein