The CDC recently released guidelines regarding the use of opioid medications in the treatment of chronic pain. The CDC recommends that clinicians should consider nonpharmacologic therapies like medical foods as a first line therapy to safely and effectively treat chronic pain.
2. 2www.tmedpharma.com
• 100 Million Americans Affected
• Almost 35% of the US Population
• $635 Billion a Year in Costs
• By 2029, 20% of the US
Population will be 65 Years or
Older
The Epidemic of
Chronic Pain in America
3. Persistent Pain Lasting Longer than 12 weeks
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Defining Chronic Pain
A Disease of the Nervous System
A Maladaptive Physiologic Response
8. 8www.tmedpharma.com
Chronic Back Pain Altering Amino
Acid Metabolism
0
5
10
15
20
25
30
35
Arginine Serine Histidine Tryptophan
mg%ofProtein
CBP Change in Blood Concentration of Amino Acids2
Day 1
Day 28
Normal
N=25
Patients with chronic pain syndromes have documented deficiencies of certain
amino acids.1 Patients with chronic low back pain commonly present with lower
levels of the amino acids required for producing pain modulating neurotransmitters
compared to healthy subjects.
2
1. Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Wall K. Serum amino acids in fibrositis/fibromyalgia syndrome. J Rheumatol Suppl 1989;19:158-163
2. Shell, et al., “A Double-Blind Controlled Trial of a Single Dose Ibuprofen and an Amino Acid Medical Food Theramine for the Treatment of Low Back Pain; Publication pending, 2010.
9. 9www.tmedpharma.com
Expanding and Augmenting
Chronic Pain Treatments with
Medical Foods
Medical Foods work through a
different pathway from drugs,
addressing the distinct
physiologic and metabolic
needs of chronic pain.
Manipulation vs. Creation
10. 10www.tmedpharma.com
Nutritional Requirements
of Pain Syndromes
The altered metabolic processes
associated with pain syndromes require
additional amounts of 1-2 :
• Arginine Nitric Oxide
• Choline Acetylcholine
• GABA GABA
• Glutamine Glutamate, GABA, Glutathione
• Histidine Histamine
• Tryptophan Serotonin
• Serine d-Serine
1. Wurtman RJ. Nutrients affecting brain composition and behavior. Integr
Psychiatry 1987;5:226-238.
2. Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Wall K. Serum amino acids in
fibrositis/fibromyalgia syndrome. J Rheumatol Suppl 1989;19:158-163.
11. 11www.tmedpharma.com
Amino Acid Concentrations Affect the
Ability of the Nervous System to Regulate Pain
Choline Acetylcholine Potentiates NO and
Serotonin
Inhibits NMDA
receptor activity
Tryptophan 5-HTP Serotonin
Inhibits Substance
P and NMDA
receptor activity
Decreases Pain
Signals in CNS
Serine d-Serine Regulates NMDA
receptor activity
Sensitizes opioid
receptors
Arginine Nitric Oxide
Inhibits afferent
pain signals in
CNS
Vasodilator and
opioid activator
Histidine Histamine
Stimulates
production of
glucocorticoids
Modulates
inflammation
GABA GABA
Inhibits NMDA
receptor activity
Dampens Pain
Signals
12. 12www.tmedpharma.com
Medical Foods for the Dietary
Management of Pain and Osteoarthritis
Product NAME Manufacturer Indication
Theramine® Targeted Medical Pharma Clinical Dietary Management of
Pain Disorders and Inflammatory
Conditions
Limbrel® Primus Pharmaceuticals Clinical Dietary Management of
the Metabolic Processes of
Osteoarthritis
Trepadone® Targeted Medical Pharma Clinical Dietary management of the
altered metabolic processes
associated with pain and
inflammation related to joint
disorders. (JD)
Percura™ Targeted Medical Pharma Clinical dietary management of the
altered metabolic processes
associated with pain, inflammation
and loss of sensation due to
peripheral neuropathy.
13. 13www.tmedpharma.com
Theramine®
for the dietary management of pain disorders and inflammatory conditions
“Naproxen and an Amino Acid Medical Food
Theramine for the Treatment of Low Back
Pain” American Journal of Therapeutics 2010.
Double-blind,
multicenter,
randomized 3 arm
trial conducted at
independent facilities
in the USA with 129
subjects over 28
days.
44% reduction in back
pain over 28 days.
65% reduction in back
pain when combined
with low dose naproxen
17% reduction in CRP
“Reduction in Pain and Inflammation
Associated with Chronic Low Back Pain with
the use of the Medical Food Theramine”
American Journal of Therapeutics 2014.
Double-blind,
multicenter,
randomized 3 arm
trial conducted at
independent facilities
in the USA with 122
subjects over 28
days.
41% reduction in back
pain over 28 days.
62% reduction in back
pain when combined
with low dose
ibuprofen
24% reduction in IL-6
14. 14www.tmedpharma.com
Limbrel®
for the clinical dietary management of the metabolic processes of osteoarthritis
“Safety, efficacy and acceptability of flavocoxid
(Limbrel®) compared with naproxen in subjects with
osteoarthritis of the knee: A Pilot Study”
Osteoarthritis and Cartilage Vol. 15.
Double-blind
randomized trial
conducted at facilities
in Russia with 103
subjects for 30 days.
Significant reduction in
the signs and symptoms
of knee OA.
Equivalent efficacy to
500mg naproxen in
controlling the signs and
symptoms of OA
“ Efficacy and safety of flavocoxid, a novel
therapeutic, compared with naproxen: a
randomized multicenter controlled trial in subjects
with osteoarthritis of the knee.” Advances in
Therapy, 2010.
Double-blind,
multicenter
randomized trial
conducted at
independent facilities
in the USA with 220
subjects for 12
weeks.
90% of subjects
responded
positively
Equivalent efficacy
to 500mg naproxen,
with far fewer UGI
and renal AEs
15. 15www.tmedpharma.com
Comprehensive Pain
Management with Medical Foods
Reduce: Adjunct Therapy
Poly-pharmacy, drug dose, and
treatment duration
Replace: Standalone Therapy
Ineffective or dangerous drugs
Restore:
Amino acid, nutrient and
neurotransmitter levels, minimizing
co-morbidities of chronic pain
16. 16www.tmedpharma.com
Medical Foods as an Adjunct to
Low Dose Analgesics
2.95
-44
-65
-80
-60
-40
-20
0
20
Percent(%)
Reduction of Pain – Roland Morris Index
Naproxen Theramine Both
p<0.05
n=126
0.73
-50.3
-63.1-70
-60
-50
-40
-30
-20
-10
0
10
Percent(%)
Reduction of Pain - Roland-Morris Index
Ibuprofen n = 43 Theramine n = 41 Combination n = 38
p<0.01
Optimize Drug Dosages
Minimize Attenuation
Reduce Harmful Side
Effects
Improve Clinical
Outcomes
17. 17www.tmedpharma.com
Benefits to Providers and
Pharmacists
•Generally Recognized as Safe Ingredients
•Most Side Effects Comparable to Placebo
•FDA Regulation and Oversight
•Non-Addictive
Safety Profile
•Supported by Multiple Double Blind Efficacy Studies
•Individual Ingredient Efficacy
•Fills the Treatment Gap that Drugs Cannot
•Replacement/Adjuct Therapy for High Risk Narcotics & NSAIDs
Efficacy Profile
•Encapsulated for Easy Use
•Improved Tolerability
•No Serious Side Effects
Adherence and
Compliance
18. 18www.tmedpharma.com
Benefits to Patients and
Caregivers
•Comparable to and More Effective than NSAIDs
•Compliment to or Replacement for Narcotic Analgesics, SSRI, SNRI
•Reduces Pain and Inflammation
Alternative
Therapy
•Non-Addictive
•Non-Sedative
•Addresses Underlying Metabolic Demands of Pain Disorders
Natural
Therapy
•Physician Oversight
•No Serious Side Effects
•Over 15 years of Professional Clinical Use
Safe &
Effective
19. 19www.tmedpharma.com
Understanding the
Market Potential
30 billion OTC tablets
sold annually in the
USA
70 million annual
NSAID prescriptions
in the USA
127 Million annual
narcotic prescriptions
in the USA
100 million
Americans with from
chronic pain
27 Million people
with OA in USA
76 Million Baby
Boomers in the USA
16,500 NSAID
Related Deaths
Annually
16,651 Deaths Due
to Rx Narcotics in
2010
Patients 65
and older
should not
take NSAIDs
20. 20www.tmedpharma.com
The Future of Pain
Management
• Pain
• Inflammation
• Co-morbidities
• Poly-pharmacy
• NSAIDs
Reduce
• Amino Acids and
Neurotransmitters
depleted by disease
• Dangerous and
Addictive Drugs
• Ineffective Therapies
Replace
• Nervous System
Function
• Pain Control
• Daily Function
• Homeostasis
Restore
Lynette Add Notes Here
Common drugs do not address many of these issues and can exacerbate them.
Affect of Chronic Back Pain Pain on Brain Morphology.
Given that normal whole-brain gray matter atrophy is 0.5% per year of aging and that atrophy caused by CBP is 5–11%, the magnitude of brain gray matter atrophy caused by CBP is equivalent to 10 –20 years of aging. However, this analogy only holds for the overall magnitude, because the regional specificity of atrophy in CBP is distinct from that seen with aging
Patients with CBP showed 5-11% less neocortical gray matter volume than control subjects. The magnitude of this decrease is equivalent to the gray matter volume lost in 10-20 years of normal aging. The decreased volume was related to pain duration, indicating a 1.3 cm3 loss of gray matter for every year of chronic pain. CBP is accompanied by brain atrophy and suggests that the pathophysiology of chronic pain includes thalamocortical processes.
Data from a double blind , multicenter study published in the American Journal of Therapeutics indicates the relationship between CBP and amino acid deficiency.
Drugs treat the symptoms of pain and do not address the underlying physiologic, metabolic and cellular changes that result from chronic pain. In many cases drugs can exacerbate the symptoms of a disease by depleting neurotransmitters and their receptors. Ex. Benzodiazapines
Ex. SSRI depleting serotonin without replacing tryptophan
Medical Foods provide the nervous system with the cellular tools/fuel it needs to mitigate pain and inflammatory signals
Example Continued:
Decrease in Choline means decreased parasympathetic autonomic nervous system activity due to pain disorder. Decrease in choline causes increased creatine phosphokinase and alanine transaminase, and must be addressed.
Administration of choline increases production of acetylcholine which reduces transmission of pain signals and inhibits proinflammatory cytokines and substance P release without noxious side effects related to harmful drugs
Nociception or pain signaling are propagated and mitigated by a series of chemical and electrical processes involving amino acids, nutrients and neurotransmitters. Amino acid deficiencies in Chronic pain patients can lead to complex pain conditions such as hyperalgisia and allodynia. Because the nervous system is using the same amino acids and neurotransmitters to operate multiple systems, patients with chronic pain often suffer from other co-morbiditiess such as sleep disorders and depression.
In addition to a variety of open label and post market studies Theramine has been the subject of 2 double blind studies.
In addition to a variety of open label and post market studies Theramine has been the subject of 2 double blind studies.
The risk of adverse events increases with the number of medications prescribed, and the number of medications prescribed increases with age.
In multiple clinical trials the co-administration of a low dose drug and a medical food have proven to be effective at treating symptoms and improving clinical outcomes without dangerous side effects.
Providers and pharmacists have a natural, clinically effective tool that they can educate patients about. A medication that works as a standalone and as an adjunct therapy. A complimentary therapy that helps manage a disease without harmful side effects. Since many side effects are dose dependent, MF can help a provider have flexibility in his/her dosing of a drug.
Addressing the distinct nutritional requirements of a patient suffering from chronic pain is a vital part of COMPREHENSIVE pain mgmt. Offering patients a non-sedative, non-addictive pain management option that can be an adjunct to current pain regimes or used as a standalone medication is often well received.
Offer pateints better or comparable efficacy without the dangerous side effects.
70 million prescriptions and more than 30 billion over-the counter tablets sold annually in the United States alone
107,000 patients are hospitalized annually for nonsteroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) complications and at least 16,500 NSAID-related deaths occur each year among arthritis patients alone. The figures of all NSAID users would be overwhelming, yet the scope of this problem is generally under-appreciated.”