Transcript Clinical Controversies in Complementary and Alternative

Complementary and Integrative
Medicine in Psychiatry
Sian Cotton, PhD
Associate Professor
Departments of Family Medicine and Pediatrics
Director, UC Center for Integrative Health and Wellness
Objectives
1. Definitions and Brief History
- Complementary and Alternative Medicine (CAM)
- Integrative Medicine (IntM)
2. Rates and Predictors of Use of IntM
3. Latest evidence for IntM Approaches for Mood
Disorders, Anxiety, Substance Use, ADHD
4. IntM Resources
5. Ongoing IntM initiatives at UC College of Medicine
The History of CAM
Complementary
Medicine
1980s
Alternative
Medicine
1990s
National Center for
Complementary and
Alternative
Medicine (NCCAM)
Eisenberg
NEJM
1991
Office for the Study
of Unconventional
Medical Practices
1993
1997 1998
IntM fellowship
Dedicated to exploring CAM
Practices
Practices
not
not
generally
generally
recognized
recognizedbyby
Office
of
Alternative
in the
context
of rigorous
of Arizona
1 inUniversity
3 community;
Americans
use
CAM
medical
medical
community;
used
used
inwith
place of
Medicine
science and disseminating
conventional
conventional
medicine
medicine
research findings
Cohen et al., 2007; http://nccam.nih.gov/health/whatiscam/ Rakel, (2007). Eisenberg et al. (1993).
2000s: Integrative Medicine
“Combines
treatments from
conventional medicine and CAM
for which there is some highquality evidence of safety and
effectiveness”
http://nccam.nih.gov/health/whatiscam/; Rakel (2007).
NCCAM Classifications
 NCCAM Classifications:
1.Natural Products (e.g., herbs and supplements)
2.Mind-Body Medicine (e.g., yoga and acupuncture)
3.Manipulative and Body-Based Practices (e.g.,
chiropractic and massage)
4.Other CAM Practices (e.g., Reiki and traditional Chinese
medicine)
 Definition of CAM constantly changing
The practice of integrative medicine: A legal and operational guide, Cohen et al., 2007;
http://nccam.nih.gov/health/whatiscam/; Rakel (2007). Eisenberg et al. (1993).
Tenets of Integrative Medicine
Relationship-centered
care
Creates an optimal
healing environment
Removes barriers to
activate innate healing
response
Uses natural, less
invasive interventions
before costly, invasive
ones when possible
Engages mind, body,
spirit, and community
Healing is always
possible, even if
curing is not
Rakel (2007). Integrative Medicine. Philadelphia: Saunders Elsevier.
Integrative Medicine Use
Rates of IntM Use in American Adults
(1990-2007)
% of Adults Using CAM
45
40
35
30
25
20
15
10
5
0
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
Year
Barnes, PM, Bloom, B, and Nahin, R. CDC National Health Statistics Report #12. CAM use among adults and children, United States, 2007,
December 2008 ;Eisenberg, D., Davis, R., Ettner, S., Appel, S., Wilkey, S., Van Rompay, M. (1998). Trends in alternative medicine use in the
U.S., 1990-1997: Results of a follow-up national survey. JAMA, 280(18), 1569-1575
IntM Use by Age - 2007
Barnes, PM, Bloom, B, and Nahin, R. CDC National Health Statistics Report #12. CAM use among
adults and children, United States, 2007, December 2008.
IntM Use by Race/Ethnicity in Adults- 2007
Barnes, PM, Bloom, B, and Nahin, R. CDC National Health Statistics Report #12. CAM use among
adults and children, United States, 2007, December 2008.
10 Most Common IntM Therapies Among Adults2007
Barnes, PM, Bloom, B, and Nahin, R. CDC National Health Statistics Report #12. CAM use among adults and children,
United States, 2007, December 2008.
Diseases/Conditions For Which IntM Is Most
Frequently Used Among Adults – 2007
Barnes, PM, Bloom, B, and Nahin, R. CDC National Health Statistics Report #12. CAM use among adults and children,
United States, 2007, December 2008.
Why Do People Use IntM?
• Relieve symptoms of diseases and chronic illnesses
• Relieve side effects associated with conventional
medical treatments
• Increase perceived control over own health
• Support a holistic health philosophy
• Improve overall health
Barnes, et al. CDC National Health Statistics Report #12. CAM use among adults and children, US, 2007
Costs of IntM Use
Total = $33.9 billion
• $22 billion (64%) self-care
• $11.9 billion (35.2%)
practitioner visits
• Compared to 1997
− Increase from $20 billion
− Majority of costs from
self-care rather than
practitioners
Relaxation
therapies
0.6%
Practitioner Costs
35%
Homeopathic
Medicine
9%
Natural Products
44%
Yoga, tai chi,
qigong
12%
Nahin et al. (2009). Costs of complementary and alternative medicine (CAM) and frequency of visits of CAM
practitioners: United States, 2007). National Health Statistics Report, 18, 1-16.
Evidence of Integrative
Medicine for Psychiatric
Conditions
Does Integrative Medicine Work?
Grading the Evidence
 Grade A: Best evidence
 Grade B: Moderate evidence
 Grade C: Least evidence
Rakel (2012). Integrative Medicine. Philadelphia: Saunders Elsevier
Is Integrative Medicine Safe?
Grading the Potential Harm

Grade 3: Most harm
 Potential to result in death or permanent disability

Grade 2: Moderate harm
 Potential to cause reversible side effects, or interact
negatively with other therapies

Grade 1: Least harm
 Little, if any, risk of harm
Rakel (2012). Integrative Medicine. Philadelphia: Saunders Elsevier
For example...
C3A1
little
evidence,
risk
of potential
serious
B2
== some
= good
evidence,
evidence,
some
little
risk of harm
harm
harm
Rakel (2012). Integrative Medicine. Philadelphia: Saunders Elsevier
Integrative Medicine for Mood
Disorders
Unipolar Depression: IntM

According to NIMH, 17% of adults and 11% of adolescents have a lifetime
prevalence of Major Depressive Disorder; 54% using IntM (2001)
Rating
Integrative Medicine Technique
A1
• Psychotherapy, often combined with pharmaceuticals
A2
• St. Johns wort, 900mg daily 3 equal doses
• Pharmaceuticals (SSRIs and newer antidepressants)
B1
• Exercise most days, engage in social activities
• Eliminate caffeine, simple sugars, eat whole foods
• Phototherapy, 30-60 minutes of bright light
B2
• Fish oil (1-6g daily)
• Vitamin B complex and folic acid (400mcg-1mg)
• SAMe (start 200mg 1-2X titrate up to 1600mg daily)
Rakel, 2012; Kessler et al., 2011; Pratt & Brody, 2008
Unipolar Depression: Botanicals
A
St. John’s Wort
• Hypericum perforatum plant
• Proposed mechanism of action related to inhibition of
serotonin, dopamine, and noradrenaline reuptake
• Monotherapy (300 mg TID)
• Cochrane review of 29 trials (N = 5489)
– 18 compared to placebo; 17 compared to antidepressants
• Superior to and just as effective as standard antidepressants for mild/mod
depression
• Fewer side effects than standard antidepressants
• Use caution with OCs, warfarin, antiretrovirals
Linde, Berner, Kriston 2009; Rakel, 2012
2
Unipolar Depression: Supplements
B
SAMe
• S-Adenosylmethionine, major methyl donor
– Involved in metabolism of neurotransmitters
• Adjuvant or monotherapy; 200mg 1-2x/day; titrate up
• Review of 14 placebo controlled studies; AHRQ report
− More effective than placebo for mild (effect size = .64) and
moderate (effect size = .48) but not severe depression
− Comparable to antidepressants
− Relatively free of side effects
− Weak methodological designs: low power, no long term
outcomes
Carpenter, 2011; Rakel, 2012
2
Unipolar Depression: Supplements
Folic Acid and B Vitamins
• Vitamin B complex 100 as augment to antidepr.
– B6 low levels in depressed pts (part. women on OCs)
• 2009 Cochrane review of 3 trials (N = 247)
− With conventional treatment: folate significantly reduced
depressive symptoms (2.65 points; 95% CI = .38 to 4.93)
− Monotherapy folate: no significant benefit (n=96)
− No problems with safety or acceptability
• 2008 meta-analysis of 6 open-labels and 2 RCTs
− Concluded that depr pts with low or normal folate levels
could benefit from folate supplementation
Rakel, 2012; Morris et al., 2008; Taylor et al., 2004
B
2
Unipolar Depression:
Nutrition/Supplements
Omega-3 Fatty Acids
• Supplement or nutrition
‒ EPA or EPA/DHA in combination best (1-6g)
‒ 2-3 servings/week of herring, mackeral, wild salmon or
sardines (veg: flaxseed/walnuts)
• Meta-analysis of 10 double-blind RCTs (N = 329)
‒ Significant improvements: effect size = .61, p = .003
– Dosage did not affect efficacy (<1g to > 4g)
– Heterogeneity between studies, publication bias
Rakel, 2012; Lin et al,. 2007
B
2
Mindfulness and Psychotherapy
• Mindfulness-Based Cognitive Therapy (MBCT and MBCTC): 8-11 week group therapy aimed at reducing
maladaptive links between negative thoughts and moods
• Mindfulness-Based Stress Reduction (MBSR): 8-week
group therapy focused on mindfulness techniques for
stress reduction
• Dialectical Behavior Therapy (DBT): 32-week group
therapy with four separate modules, only mindfulness is
used throughout all
• Acceptance and Commitment Therapy (ACT):
psychotherapy approach focused on values clarification
and increasing psychological flexibility
Sears, Tirch, & Denton, 2011
Types of Mindfulness Activities
• Body scan: guiding the participant in noticing bodily
sensations and the cognitive and emotional reactions to the
sensations without attempting to change the sensations
themselves
• Sitting meditation: guided silent meditation bringing
awareness to the thoughts, feelings, and sensations
experienced
• Walking meditation: slow, deliberate, and attentive walking
while bringing awareness to the experience
• Mindful movement: including yoga-type exercises , Tai Chi,
Qigong, dance guided in a manner that allows the participant
to slowly and methodically explore the sensory, emotional,
and cognitive realms of the experience
Sears, Tirch, & Denton, 2011
Unipolar Depression: Mindfulness
Mindfulness-Based Cognitive Therapy
• Systematic review of 4 studies
‒ 3: MBCT plus usual care better than usual care alone in
reducing relapse in patients with > 3 depr. episodes (32% vs.
60%, p = .0003)
‒ 1: MBCT with graduated d/c of medication showed similar
1-year relapse rates as continued medication
‒ Small N’s; methodological limitations
• Meta-analysis of 6 RCTs (N=593) of adults with recurrent
depression in remission
‒ Significantly reduced risk of relapse (43%) for >3
depressive episodes, but not fewer episodes
‒ As effective as anti-depressants in 2 studies
Chiesa et al., 2011; Hofman et al., 2010; Piet, 2011
Unipolar Depression: Mindfulness
Mindfulness-Based Stress Reduction
• Meta-analysis of 10 RCTs: d = .54, p < .0001 in
improving mental health symptoms, including depressive
symptoms
• Meta-analysis of 39 studies, (n=1,140), including
depression
– Pre-post effect size estimate .59 for depr (.97 if depr/anx)
• Meta-analysis of 19 RCTs: g = .49, p < .01
– Depression, anxiety and chronic pain
Grossman 2004; Reibel et al., 2011; Hoffman et al., 2010; Kabat-Zinn, 1982
Unipolar Depression: Acupuncture
Cochrane review and meta-analysis
• 30 studies (N = 2,812)
• Proposed mechanism: may alter NT levels (Western)
• Acupuncture appeared to perform as well as medication
with reducing the severity of depression and is relatively
safe
• Insufficient evidence that acupuncture was more
effective than sham acupuncture, or non specific
acupuncture
• Small sample sizes, problems with randomization and
blinding, lack of follow-up, heterogeneity of tx
Smith et al., 2010
Unipolar Depression: Mind-Body Medicine
Relaxation Skills
• 1/2 have tried mind-body exercises, 2/3 found helpful
• Cochrane review of 15 studies of progressive muscle
relaxation, guided imagery, autogenic training, etc.
– Greater reductions in self-reported depressive
symptoms as compared to wait-list control (95% CI: 0.94 to -.24)
– Fewer reductions in self-reported depressive
symptoms than CBT (95% CI: .14 to .62)
– Relaxation as first-line treatment in stepped-care
approach
Jorm et al., 2009; Pilkington et al., 2005
Bipolar Disorder: Dietary Supplements
• Review based mostly on unipolar depression studies
– Too few studies in bipolar patients (with exception of Omega-3s)
• Two RCTs of Omega-3s in bipolar
– Significant improvements in depressive symptoms and global
functioning over a 12-week period as compared to placebo
– No significant difference between groups in a study of rapid cycling
bipolar disorder
– Proposed mechanisms: similar to lithium or Valproate, or may alter
neuronal membrane fluidity
– Well-tolerated; few side effects
– Additional studies needed to clarify role; optimal dosing; use during
depressive or manic phase; issues of purity of marketed
supplements
Andreescu et al., 2008
Bipolar Disorder: Dietary Supplements
• St John’s wort: Mixed / Inconsistent results
–
–
–
–
–
–
No studies specifically in bipolar
37 RCTs depressive disorder compared to placebo or antidepr
Potentially minimal benefits for mild/moderate symptoms depr
Comparable benefits to conventional antidepressants
More efficacious than fluoxetine but no different than placebo
Potential to induce mania (several case reports); Adverse drug
interactions
– Can be recc for bipolar with mild/mod symptoms – monitor for mania
• SAMe: More research needed
– Potential to induce mania or hypomania (case reports)
– Questions re dosing; efficacy and assess risk of mania
Andreescu et al., 2008
Bipolar Disorder: MBCT
• RCT of 95 adults: treatment as usual (TAU) vs. TAU+MBCT
– MBCT associated with reductions in anxiety symptoms (Mpost =
40.65 MBCT vs. 44.19 TAU)
– MBCT not associated with reductions in depressive symptoms, time
to manic relapse, total number of manic episodes, or mood severity
at 12-month follow-up
• RCT among adults with residual depressive symptoms
– MBCT associated with increased mindfulness, fewer depressive
symptoms, less attentional difficulties, better emotion regulation,
and greater psychological well-being, positive affect, and
psychosocial functioning post-treatment and at 3-month follow-up
• Electroencephalography (EEG) study of 21 adults
– MBCT associated with decreased activation of non-relevant
information processing during attentional tasks
Perich et al., 2012; Deckserbach et al., 2012; Howells et al., 2012
Integrative Medicine for
Anxiety
Anxiety
o
According to NIMH, 29% of adults and 25% of adolescents have
a lifetime prevalence of anxiety disorder; 57% using IntM (2001)
Rating
Integrative Medicine Technique
A1
• Nutrition (e.g,. Omega3s – 2-3 servings or 1000mg flaxseed oil;
reduce or eliminate caffeine/alcohol)
• Regular physical activity
• Psychotherapy, relaxation training
A2
• Vitamin B6
• Pharmaceuticals (SSRIs, anxiolytics)
B1
• Increase social connections
• Vitamin B 100 complex with folic acid (400mcg daily)
B2
• Folic acid
• Valerian extract
• Kava (50-70mg TID)
Rakel, 2012; www.nimh.nih.gov
Anxiety: Botanicals
• Kava (Piper methysticum) (50-70mg TID)
– Pulverized roots of pepper plant
– Mechanism of action not determined though proposed
benzodiazepines
• 12 double blind RCTs (N = 700)
– 7 trials showed HAS scale reduction in favor of Kava
– Minimal, transient side effects reported
• Avoid in pregnancy, Parkinson’s, liver
problems, other sedative medications
• Long term safety data needed
• Large sample size trials needed
Rakel, 2012; Pittler, 2010
B
2
Anxiety: Botanicals
Valerian
• Valeriana officinalis plant
‒ Most trials with sleep disturbance rather than anxiety
– Used in Europe for over 1000 years as sedative
– Not suitable for acute anxiety; may take several weeks
• Cochrane review
– Only one RCT met criteria for inclusion: 4-week pilot study (N =
36) comparing valerian with placebo and diazepam
– Found no difference in placebo/valerian groups; no difference in
valerian/diazepam groups (HAM-A scores); all well tolerated
– Insufficient evidence to draw conclusions on efficacy/safety
• Less rigorous studies found reductions in anxiety symptoms
• Dosage: 150-300mg morning and 300-600mg evening for mild to
moderate anxiety
Rakel, 2012; Miyasaka, 2009
B
2
Anxiety: Acupuncture
• Since 2004, 10 RCTs and 2 non-RCTS
‒ Variable quality of evidence
‒ Large variety in methodology (points used, number of points
used in a session, duration of sessions, frequency of
treatment and duration of treatment program)
• 3 recent trials with GAD
‒ Acupuncture vs drug treatment over 4-6 weeks
‒ Similar effects reported but variable quality studies
• While generally safe, use of acupuncture for anxiety
remains unclear
Pilkington, 2010
Anxiety: Mindfulness
• Mindfulness-Based Therapy (e.g., MBCT, MBSR)
‒ 2010 Meta-analysis
‒ 39 studies (n=1,140)
‒ Average pre-post effect size (Hedge’s g = 0.67), higher
when anxiety and depression
‒ Effect sizes robust, maintained at follow-up, unrelated to
tx duration
• Potential mechanisms of action
‒ Physiological arousal viewed as transient – lower distress
‒ Neurobiological level / neuroimaging studies showing
structural changes in brain
Hofman, Sawyer, Witt, & Oh, 2010; Krisanaprakornkit, 2009
Integrative Medicine for
Substance Use Disorders
Substance Abuse

2011: 56.8 mill smokers; 16.7mill alcohol dep/abuse; 4.2mill marijuana
abuse
Rating
Integrative Medicine Technique
A1
• Acupuncture (5 needles in ear several times week; NADA)
• 12-Step Programs (spirituality and social support)
A2
• Pharmaceuticals (Alcohol: Clonazepam, Tobacco: Zyban)
B1
• Meditation, biofeedback, hypnosis, guided imagery, yoga
• Spiritual connection or practice
• Culturally specific interventions (e.g., Native Americans)
B2
For associated anxiety/insomnia:
• Valerian (300-450mg TID or 400-900mg before sleep)
• Kava kava (100mg TID)
• St John’s Wort (300mg TID; 450-600mg 2X day depr)
• Kudzu (TCM; 1.2g 2Xday)
Rakel, 2012; www.drugabuse.gov
Integrative Medicine for
Attention Deficit Hyperactivity
Disorder (ADHD)
ADHD


3-10% of school-aged children; 2.5% prevalence in adults
In children, 12-64% report using IntM for ADHD
Rating
Integrative Medicine Technique
A1
• Improve diet, correct deficiencies, avoid dehydration
• Vigorous activity 30min daily
• Regularly monitor and support family
B1
• Regular meals with low glycemic index
• Avoid artificial sweeteners, preservatives (with sensitivities)
• Social support; parent training; family communication
B2
• Pharmaceutical management
C1
• Massage therapy
• Stress management and emotional self-management
C2
•
Sleep: Melatonin (.3-3mg before bed)
Rakel, 2012; Weber and Newmark, 2009
Resources
Books
Finding the Evidence
 www.pubmed.org
 www.nccam.nih.gov
 http://nccam.nih.gov/health/providers
 Medline Plus Complementary and Alternative Medicine
www.nlm.nih.gov/medlineplus/complementaryandalternative
medicine.html
 www.umassmed.edu/cfm/index.aspx
UC Center for Integrative
Health and Wellness
Consortium of Academic Health Centers for
Integrative Medicine
1999 – Duke U, Harvard U, Stanford
U, UCSF, U Arizona, U Maryland, U
Mass, U Minnesota
2000 – Albert Einstein/Yeshiva U,
Georgetown, Thomas Jefferson U
2002 – UTMB, U Pittsburgh,
U Washington, U Penn, U Hawaii,
UMDNJ, U Michigan, Columbia
2003 – UCLA, OHSU, U Calgary,
George Washington U
2004 – U Connecticut, U New
Mexico,
UCI, Wake Forest, U Alberta
2005 – Laval U, UNC-Chapel Hill,
U Wisconsin
2006 – U Colorado, U Kansas,
U Vermont, May Clinic, Stanford, Yale
2007 – Vanderbilt, McMaster, Johns
Hopkins
2008 – Boston U, Northwestern U,
Ohio State
2009 – U Cincinnati, U IL-Chicago
2010 – U Chicago, U Iowa
2011 – Mount Sinai, UT MD
Anderson, Aurora Healthcare,
Cleveland Clinic, Tufts U
2012- Allina Health
60
CAHCIM
50 51
50
40
36
28
30
39
42
44
46
31
23
19
20
10
0
8
11 11
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
http://www.imconsortium.org
Current Initiatives at UC COM
 To develop and sustain a premier Center for Integrative Health
and Wellness at the UC COM
 Horizontal integration with Centers for Excellence / Programs
Clinical
• Interdisciplinary, focus
on optimizing wellness
• Multiple clinical locations
with IntM physicians,
psychologists, therapists;
group space
•Women’s Health Ctr
• Barrett Ctr
• Collaborate with CCHMC;
community IntM
practitioners
Current Initiatives at UC COM
 To develop and sustain a premier Center for Integrative Health
and Wellness at the UC COM
 Horizontal integration with Centers for Excellence / Programs
Clinical
• Interdisciplinary, focus
on optimizing wellness
• Multiple clinical locations
with IntM physicians,
psychologists, therapists;
group space
•Women’s Health Ctr
• Barrett Ctr
• Collaborate with CCHMC;
community IntM
practitioners
Education
• Curriculum integration;
4th year elective
• Develop Medical Student
Scholars Program in IntM
• Eventual resident and
fellowship IntM training
• Faculty IntM grand
rounds/ seminars
Current Initiatives at UC COM
 To develop and sustain a premier Center for Integrative Health
and Wellness at the UC COM
 Horizontal integration with Centers for Excellence / Programs
Clinical
• Interdisciplinary, focus
on optimizing wellness
• Multiple clinical locations
with IntM physicians,
psychologists, therapists;
group space
•Women’s Health Ctr
• Barrett Ctr
• Collaborate with CCHMC;
community IntM
practitioners
Education
• Curriculum integration;
4th year elective
• Develop Medical Student
Scholars Program in IntM
• Eventual resident and
fellowship IntM training
• Faculty IntM grand
rounds/ seminars
Research
• Develop strong portfolio
of federal and foundation
sponsored IntM projects
• Comparativeness
effectiveness studies of
IntM model to usual care
with national CAHCIM
network
• Examine sustainable
models of IntM care
UC Integrative Medicine Research
• Multi-site RCT examining Progressive Muscle Relaxation (PMR)
for seizure frequency reduction in adults with stress-related
epilepsy (Privitera)
• Neurofunctional Changes Associated with Mindfulness Based
Cognitive Therapy (MBCT) for Anxiety Symptoms in Youth at
Risk for Bipolar Disorder (Delbello/Cotton/Sears)
• School-based RCT examining feasibility and efficacy of a
breathing retraining intervention, as compared to an
education control, in African-American adolescents with
persistent asthma (Cotton)
• Omega-3 FA vs placebo for 12 weeks in children/adolescents
with depression and at least one bipolar I parent, fMRI pre/post (Delbello/McNamara)
Thanks!
[email protected]