In this presentation, the third of three lectures Dr. Cady delivered in São Paulo, Brazil, Dr. Cady reviews the critical patterns of interactions with numerous frequently prescribed psychotropic medications (and others). Emphasis is given on how not to commit an obvious drug-drug interaction as well as avoiding more subtle ones. The focus then shifts to supplements: which ones are the best, which ones have mental health benefits, and how to avoid interactions between conventionally used supplements and psychiatric medications.
AORTIC DISSECTION and management of aortic dissection
"Killer Drugs & The Supplement Hall of Fame" - IMMH Brazil, 2015
2. “Killer Drugs & The Supplement
Hall of Fame”
Louis Cady, MD
CEO, Founder – Cady Wellness Institute
Newburgh, Indiana (US)
Indiana School of Medicine,
Dept. of Psychiatry
Brazil, 2015
3. Learning objectives
• Avoid killing/injuring patient with OBVIOUS
drug-drug interaction
– Become aware of more subtle interactions
– Identify some “fairly safe” medications for use
• Review key, basic concepts about groups of
vitamins, relevance of antioxidants, specific
minerals, and fish oil
• Will NOT review topics covered in other
lectures here, or advanced topics on
specific nutrients.
4. The BASICS
“Mr. Rohn, the
difference between
success and failure
in any endeavor is about a half-
dozen things.”
-Earl Shoaff
6. “Streaking”, or…..
Better Buckle Up!!!
• Definition: Streaking is the act of taking off
one's clothes and running naked through a
public place. [ref:
http://en.wikipedia.org/wiki/Streaking - accessed 09
02 2013]
• “In 1973, what the press called a ‘streaking
epidemic’ hit Stephen F. Austin State University in
Nacogdoches, TX, with streakers being seen in
residence halls, at football games and at various
other on-campus locations and events, including
Spring graduation.”
(Harvard-Yale game, 2006)
9. Two potential for interactions
1. PharmacoKINETICS – what the body does
to the drug
2. PharmacoDYNAMICS – what the drug(s)
do to the body.
10. The brain dead, almost too-obvious to
mention FATAL drug interaction
• MAOI with ANYTHING that boosts serotonin or
other catecholamines, e.g: nose spray,
pseudoephedrine hydrochloride, SJW, ANY anti-
depressant, or any of the following:
– Phenylpiperidine, opioids, meperidine, tramadol,
methadone, dextromethorphan, propoxyphene – all
appear to be weak SSRI’s.
• “Stealth MAOI’s”:
– Linezolid (Zyvox ®) - for vancomycin resistant
Enterococcus faecium infections, & MRSA
– Isoniazid (tuberculosis)
– Moclobemide (reversible MAO-A inhibitor – n/a in USA)
11. The similarly brain-dead “UN-interaction”
• 5HTP for precursor loading ALONG WITH
an SSRI, given reasonable doses, e.g.:
– Escitalopram – 20 mg + 50 and then 100 mg
5HTP, going up to as much as 300 mg per day
SLOWLY.
• (this is incredibly useful for antidepresssant “Poop-
out”)
• The STUPID, BRAIN DEAD way to create a
5HTP interaction:
– Fluoxetine 80 mg from a standing start, plus
300 mg 5HTP to wash it down with. DUMB.
12. “Strattera (atomoxetine)
[coupled with Prozac or Paxil]
has been great for our
admissions.”
-Dr. William Beute, MD
Pine Rest Campus Clinic
Grand Rapids, MI
April 21, 2004
[quoted with permission]
13. Cytochrome p-450 2D6 inhibition measured as %
increase in “Desipramine AUC” – in vivo data
Preskhorn, Alderman, et al. Pharmacokinetics of desipramine coadministered
with sertraline or fluoxetine. J. Clin Psychopharmacol 1994;14:90-98;
Escitalopram package insert - note – different source of data, but same method
Critically important when
combining with other Rx
metabolized through 2D6
pathways
17. The “not so selective” SSRI’s; how to
“Do yourself a favor.”
drug Clean?? 2nd
order effects Side effects possible
Escitalopram
(generic 3/2012)
Yes NOTHING (excess serotonin side
effects only)
Sertraline Yes Dopamine (1/3 as
potent as
amphetamine)
Agitation, nervousness;
improved [ ]
Citalopram Yes AntiH1 Sedation (note- FDA
lowered max dose to
40mg)
Paxil NO!! Anti-Chol.
NOT “NRI”
Doped up, TCA effects,
neurocognitive problems,
withdrawal. Sexual,
Prostate sxs
Fluoxetine NO!! 5HT2C Agitation, appetite
suppression
“Danger! Danger, Will Robinson!”
18. Side Effects & Drug Interactions:
The Doc Cady “Can’t s” of the TCA’s
Pee
Poop
Spit
Spurt
Focus
Think
Stand up
Stay awake
Stay thin
ANTICHOLINERGIC/
ANTIMUSCARINIC
EFFECTS
Alpha-adrenergic
blockade
"Antihistamine"
effects
20. New Agents, New Mechanisms
(agent) (MOA) Differentiating points
Venlafaxine (“IR” and XR)
(2D6)
SSRI, NRI Nausea, GI side effects, sxl
dysfunction
Duloxetine (2D6) SSRI, NRI Same. Better tolerated. For pain
w/ dep.
Desvenlafaxine (various)
Levomilnacipram (3A4)
SSRI, NRI Better tolerated
Trazodone XR with
Contramid®
5HT2a/c
BLOCKER, mild
SSRI
Vilazodone (3A4) SPA, SSRI ONLY SPARI. Weaker SSRI.
Targets 5HT1A. Less sexual side
effects.
Bupropion (“XL” – not
“SR”) (2B6)
“NDRI” Possibility of anxiety & “wound
up.” Improved concentration.
Push to 450 mg. (Seizure risk.)
21. …low levels of the antioxidant vitamins (Vitamins A, E, and C) may
increase risk for several chronic diseases. Most people do not
consume an optimal amount of all vitamins by diet alone.
Pending strong evidence of effectiveness from randomized trials, it
appears prudent for all adults to take vitamin
supplements.
22. “Inadequate intakes may result in chronic
metabolic disruption, including mitochondrial
decay.”
“[They] cause DNA damage, such as chromosome
breaks, in cultured human cells or in vivo.”
“triage theory
23. The Physicians’ Health Study II
• Take a multivitamin!
CONCLUSIONS: “Daily multivitamin
supplementation modestly but
significantly reduced the risk of total
cancer.” [HR 0.92, 95% CI, p=0.04]
25. 15,318 US adults in 3rd
National Health and Nutrition Examination
Follow-up study. (Different lifestyles and health risk factors were
accounted for in the study)
“serum alpha-carotene concentrations were
inversely associated with risk of death from all
causes, CVD, cancer, and all other causes[sic].”
27. Epidemiology of Vascular Ageing (EVA study)
Total plasma carotenoids are inversely related to mortality
(Akbaraly TN, et al Br J Nutr, Jan 2009)
• Study N=1389
– Age range = 59 – 71 years
– 9 years of duration with six waves of follow-up.
• Findings:
– “low total plasma carotenoid level was significantly
associated with all cause mortality in men but not in
women.
– 2.94X higher relative risk of mortality of being in lowest
quintile compared to highest quintile.
– “The present study suggests that total plasma
carotenoid levels could be a health indicator in
elderly populations.”
28. Conclusions from another study
• “It is concluded that
administration of antioxidants
could reduce the incidence of
brain tumors and probably other
types of cancer.”
• - Shewelta SA , Sheikh, BY Curr Drug Metab. 2011
Jul;12(6):587-93. (Dept.of Biosciences & Technology,
Alexandria University, Egypt.)
29. Lipid peroxidation, antioxidant status
& survival in institutionalized elderly
• Plasma MDA
predicted mortality
independently of all
other variables.
• B-carotene and
alpha tocopherol
were independently
associated with
survival. Huerta JM et al. Free Radical Research
2006, vol 40, no 6. pp 571-578.
30. Over 50% of the women in the Iowa study
lived longer than the average life
expectancy
38,000 White Women in Iowa
Early results showed women who used
C, D, E, and Calcium had significantly
lower rates of death
31. Meydani SN. Nutr Rev. 1993 Apr;51(4):106-9
“Recent studies have shown that supplementing the
elderly with single nutrients or mixtures of vitamins
and minerals at levels that exceed the
Recommended Dietary Allowances (RDAs)
significantly improves certain indices of the immune
response.”
“Recent studies have shown that supplementing the
elderly with single nutrients or mixtures of vitamins
and minerals at levels that exceed the
Recommended Dietary Allowances (RDAs)
significantly improves certain indices of the immune
response.”
32. Multiple lines lines of evidence indicate that
oxidative stress not only strongly participates in
an early stage of Alzheimer's disease prior to
cytopathology, but plays an important role in
inducing and activating multiple cell signaling
pathways that contribute to the lesion formations
of toxic substances and then promotes the
development of Alzheimer's disease.
33. Vitamins E & C Supplements Limit Oxidative
Brain Cell Damage, Cognitive Dysfunction
• Head, E, Christie L. (UC Irvine). Cognitive performance,
dementia and DNA/RNA oxidative damage in the oldest
old.” Poster 256 Oxidative Stress and Synaptic
Transmission, San Diego, 2007.
• “The two antioxidant vitamins were associated with
decreased oxidative damage to brain cells in the frontal
cortex. The researchers found that better cognitive
performances in elderly subjects is associated with lower
levels of oxidative DNA & RNA damage in the brain, and
that those taking multivitamins including vitamins E or C
tended to perform better on a test of global cognitive
ability.”
34. Adult ADHD and antioxidant status
Selek S et al. Evaluation of total oxidative status in adult attention deficit hyperactivity
disorder and its diagnostic implications. J. Psychiatry Research. 2012 Apr;46(4):451-5
• Blood samples obtained and total antioxidative status
(TAS), total oxidative status (TOS), and Oxidative Stress
Index(OSI) were determine at Harran University
Biochemistry Labs.
• ADHD group: TAS, TOS, and OSI were significantly higher
than controls.
– Adult ADHD was able to be predicted for TOS (Total
oxidative status) over 9.8575 umol H2)2/L level with 86% positive
predictive value and 100% negative predictive value.
• “In A-ADHD, oxidative balance in impaired.
High antioxidant levels may be
compensatory against the oxidant increase.”
35. “Antioxidants” & The State of the
Literature 9/8/2015
• “Antioxidant” with…
– ADHD - 124 citations
– Alzheimer’s dz - 4,703 citations
– Anxiety disorder - 491 citations
– Autism - 253 citations
– Bipolar disorder - 376 citations
– “clinical depression” 869 citations
– Fibromyalgia - 114 citations
– Schizophrenia - 852 citations
Surf on over to www.pubmed.gov and investigate!Surf on over to www.pubmed.gov and investigate!
36. “Antioxidants” with schizophrenia – a
taste of the literature
• Inflammation and schizophrenia: Alterations
in cytokine levels and perturbation in
antioxidative defense systems.
– Al-Asmari A, Khan MW. Hum Exp Toxicol.
2013 July 8
• The use of flavonoids in central nervous
system disorders.
– Grosso C, et al. Curr Med Chem. 2013 Jun 25
41. What the OAT showed…. (& “take home” points)
• DANGER of prescribing “one shot” B-vitamins
• B-vitamin COMPLEX recommended
• SERIOUS Vitamin C deficiencies exist.
– (This increases oxidative stress)
• Other nutrients & co-factors easily identified
!!!
Low riboflavin confirmed; very low (!!) Vit C; moderate CoQ10
42. The Effects of high dose B vitamins
on stress at work
• 3 month, double blind, placebo control, randomized study
– Measured: Personality, work demands, mood, anxiety, and strain
• The vitamin B complex treated
group reported significantly lower
personal strain and a reduction in
confusion and depressed/dejected
mood after 12 weeks.
Strough C et al. The effect of 90 day administration of a high dose vitamin B-
complex on work stress. Hum Psychopharmacol. 2011 Sept 8. doi
10.1002/hup.1229 (Swinburne University of Technology – Hawthorn, Victoria,
Australia.)
43. BRAIN SHRINKAGE…
Smith AD, Smith SM, de Jager CA, Whitbread P, et al. (2010) Homocysteine-Lowering by B Vitamins Slows the
Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS ONE
5(9): e12244. doi:10.1371/journal.pone.0012244
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012244
CONCLUSIONS: “The
accelerated rate of brain
atrophy in elderly with MCI can
be slowed by treatment with
homocysteine-lowering B-
vitamins.”
44. OK. It slows shrinkage. But are they sharper?
[deJager CA et al. Int J Geriatr Psychiatry. 2012 June;27(6):592-600]
“B-vitamins appear to slow cognitive and clinical
decline in people with MCI.”
45. “Micronutrient supplementation has a beneficial
effect on perceived stress, mild psychiatric
symptoms, and aspects of mood in apparently
healthy individuals. Supplements containing high
doses of B vitamins may be more effective in
improving mood states.”
46. The first groundbreaking study on use of a
vitamin to treat a mental disorder (B3)
• “Treatment of schizophrenia with nicotinic acid and
nicotinamide.”
– Hoffer A, et al. J Clin Exp Psychopath, 18:131-158.
Begun in 1952, published in 1957
• 30 schizophrenic patients
• Randomized to placebo, niacinamide, or niacin +other standard
treatments (ECT, barbiturate, psychotherapy)
– TX: 1 gram three times daily for 30 days (only)
– Then followed for 1 year.
• At one year: active treatment group had 80%
recovery rate compared to placebo (30%)
47. 1973 APA Hatchet Job on vitamins
• 1973 APA Task Force on Megavitamin and Orthomolecular
Therapy in Psychiatry
– Headed by Morris Lipton, MD – who was biased against.
• “… this Task Force considers the massive publicity which
they promulgate via radio, the lay press and popular books,
using catch phrases which are really misnomers like
‘megavitamin therapy’ and ‘orthomolecular treatment’ to be
deplorable.”
• Consequences:
– Inhibited any further exploration of nutrition/diet in schizophrenia
– Raised fears of academic retaliation, professional ostracism
• (& Flawed medical studies followed – with high dose
vitamins pushed to toxic levels (or used at ineffective
dosages), and not in healthy combinations.)
48. Canadian Psychiatric Association: “Statement
on Current Status of Megavitamin and
Orthomolecular Therapies, 1976”
“…recommends that
physicians do not use
these treatments except in
controlled clinical
investigations.”
49. • Irritability
• Apathy
• Anxiety
• Personality changes
• Depression
• Memory loss
• Dementia
• Subtle subclinical
cognitive impairment
• Hallucinations
• Violent behavior
Symptoms of B12 Deficiency
• Diminished sense of
touch and pain
• Clumsiness
• Weakness
• Pernicious anemia
• Chronic fatigue
• Tremors
• GI problems
• Peripheral neuropathy
Mental Physical
50. Your brain and B12
• If you are in the bottom 1/3rd
for B-12
levels….
• SIX TIMES increase risk of
brain volume loss (Odds ratio =
6.17, 95% CI)
– Vogiatzoglou A et al. Vitamin B12 status and
rate of brain volume loss in community-dwellers.
Neurology. 2008 Sep 9;71(11):826-32.
– (107 volunteers aged 61-87 years of age)
51. Vitamin B3 Restores Memory Loss
Associated with Alzheimer’s Disease
• Green K et al. (UC Irvine) “Oral Nicotinamide Treatment
Induces Ubiquitin-dependent degradation of phospho-tau
and restores cognitive function in a mouse model of
Alzheimer disease.” Poster 157, Nov 4 at Alzheimer’s
Disease and Other Dementias: Therapies II; San Diego
2007
• B3 given to rice BRED to develop plaques and tangles.
• Mice that received this had lower levels of phosphorylated
tau.
• “These findings suggest that Vitamin B3… might be a safe
and effective therapy for people with Alzheimer’s disease.”
52. B6 – appears helpful in autism
• Rimland, B et al. The effect of high doses of
vitamin B6 on autistic children: a double-blind
crossover study.” Am J Psychiatry. 1978
Apr;135(4):472-5
• 16 autistic children previously doing well on
B6 supplementation.
– Double blind – removal of B6 supplement and
replacement with placebo or continuation of B6
– “Behavior was rated as deteriorating
significantly during the B6 withdrawal.”
53. B6 with magnesium for ADHD
• “Improvement of neurobehavioral disorders in children
supplemented with magnesium-vitamin B6. I. Attention
deficit hyperactivity disorders.
– Mousain-Bosc M et al. Magnesium Res. 2006 Mar;19(1):46-52
• 40 children with symptoms of ADHD dosed with 6 mg/kg/d
of Magnesium and 0.6 mg/kg/d vit B6 for 8 weeks.
– Baseline – ADHD kids had significantly lower levels of RBC Mg than controls.
• TREATMENT:
– Mg-B6 regimen – led to significant increase in RBC Mg values.
– Hyperactivity and hyperemotivity/aggressiveness were reduced, and school
attention was improved.
• Withdrawal – when tx stopped, clinical symptoms re-
appeared in a few weeks together with drop in Ribcage
levels.
54. “B-vitamin deficiency” & The State of
the Literature September 8, 2015
• “B-vitamin deficiency” with…
– ADHD - 10 citations
– Alzheimer’s dz - 213 citations
– Anxiety disorder - 35 citations
– Autism - 27 citations
– Bipolar disorder - 23 citations
– “clinical depression” 103 citations
– Fibromyalgia - 5 citations
– Schizophrenia - 62 citations
Surf on over to www.pubmed.gov and investigate!Surf on over to www.pubmed.gov and investigate!
55. Just a “taste” of B-vitamin deficiency
with Schizophrenia
• Vitamin B12 deficiency masquerading as
clozapine-resistant psychotic symptoms in
schizophrenia
– Raveendranathan D, et al. J Neuropsychiatry Clin
Neurosci. 2013 Spring; 25(2):E34-5.
• Hyperhomocysteinemia & schizophrenia: case
control study.
– Mabrouk H, et al. Encephale. 2011 Sep; 37(4):308-13.
• Folate supplementation in schizophrenia: a
possible role for MTHFT genotype.
– Hill M, et al. Schizophr Res. 2011 Apr; 127(1-3):41-5.
57. - Selenium is one of the factors that may affect the risk of cognitive
decline. In selenium deficiency the brain remains selenium replete
the longest suggesting that Se plays an important role in brain
functions.
- Results from this study: “Low Se status is a risk factor for
cognitive decline even after taking into account vascular risk
factors
58. Special needs - Zinc
• Low Zinc- associated with low testosterone
– Per USDA, 60% of US men between 20 – 49
years of age do not get enough.
– N.B.: Do not supplement with > 50 mg daily
(can interfere with Cu+ metabolism)
• Tsai, E.C., Boyko, E.J., Leonetti, D.L., & Fujimoto,
W.Y. (2000). Low serum testosterone level as a
predictor of increased visceral fat in Japanese-
American men.
International Journal of Obesity and Related Metabolic Dis
24, 485-491
59. Correlation between serum testosterone level and
concentrations of copper and zinc in hair tissue
[Chang, CS et al. Biol Trace Elem Res. 2011 Dec; 144(1-3):264-71]
• 88 men 40 – 60 years of age.
• Serum testosterone measured in a.m.
• Copper and zinc levels quantified
• “subjects with normal testosterone had a
significantly higher Zn level compared to low
testosterone group (P=-.003)”
• “Normal testosterone is associated with a
higher Zn level.”
60. North America 85%
South America 76%
Asia 76%
Africa 74%
Europe 72%
Australia 55%
% Mineral depletion from the soil
during the past 100 years, by continent
Source: UN Earth Summit Report 1992
61. Magnesium! (from white paper by Greenblatt and Heim)
• Depleted in soil
• Nutrient depleted, calorie dense fast/processed food
• NHANES study (2005-2006) – 2/3rds of men and women
don’t get enough.
• First documented in 1921 – with 220/250 patients receiving
it benefited from it.1
• Confirmatory studies over last 50 years. 2,3,4
1. Weston PG. Magnesium as a sedative. Am J Psychiatry (1921) 22(1):637–8.
2. Jacka FN, Overland S, Stewart R, et al. Association between magnesium intake and
depression and anxiety in community-dwelling adults: the Hordaland health study. Aus
New Zealand J Psych (2009) 43(1):45-52.
3. Eby, G.A. 3rd, Eby KL. Magnesium for treatment-resistant depression: A review and
hypothesis. Medical Hypotheses(2010) 74(4):649-60.
4. Greenblatt, J. The Breakthrough Depression Solution. Sunrise River Press (2011)
62. Magnesium & The State of the
Literature September 8, 2015
• Magnesium with…
– ADHD - 47 citations
– Alzheimer’s dz - 149 citations
– Anxiety disorder - 76 citations
– Autism - 60 citations
– Bipolar disorder - 122 citations
– “clinical depression” 180 citations
– Fibromyalgia - 33 citations
– Schizophrenia - 96 citationsSurf on over to www.pubmed.gov and investigate!Surf on over to www.pubmed.gov and investigate!
64. • 493 schoolchildren, aged 7 – 9 years
from mainstream Oxfordshire schoosl,
selected for BELOW AVERAGE reading
performance.
• Lower DHA levels assoc. with:
– poorer reading ability
– Higher levels of parent rated oppositional
behavior & emotional lability
PLoS One. 2013 Jun 24;8(6):e66697. doi:
10.1371/journal.pone.0066697. Print 2013.
PLoS One. 2013 Jun 24;8(6):e66697. doi:
10.1371/journal.pone.0066697. Print 2013.
65. • 29 schoolchildren with ADHD vs. 43
without
• Callous-unemotional (CU) traits were
found to be significantly negatively
related to both eicosapentaenoic acid
(EPA), and total omega-3 in the ADHD
group.
Prostaglandins Leukot Essent Fatty Acids.
2013 Jun;88(6):411-8.
Prostaglandins Leukot Essent Fatty Acids.
2013 Jun;88(6):411-8.
66. • "Chronic deficiencies of certain minerals
such as zinc, iron, magnesium and iodine
and insufficient dietary intake of long-
chain polyunsaturated fatty acids may
have a significant impact on the
development and deepening of the
symptoms of ADHD in children.”
• Importance of DHA emphasized.
Konikowska K, et. al. Rocz Panstw Zakl Hig.
2012;63(2):127-34.
Konikowska K, et. al. Rocz Panstw Zakl Hig.
2012;63(2):127-34.
67. Top Targeted Supplements
(# of citations in PubMed
September 8, 2015)
• Gingko (3,516)
• S-adenosyl methionine [SAMe] (8,396)
• Curcumin (8,068)
• SJW – Saint John’s Wort (2,390)
• Panax Ginseng (5,302)
• Ashwaghanda (766)
• Deplin, EnLyte (by RX) = l-methylfolate
68. Gingko – color commentary
• 3,516 citations in PubMed as of September 8, 2015
• Cognitive enhancement:
– 34 outpatients with moderate cognitive impairments tx’ed with
standard extract of Ginkgo Biloba (EGb761) – 240 mg twice
daily . Significant improvement in attention, memory, orientation,
and visual-spatial/executive functions as well as anxiety and
depression.”
• Boiko AN et al. Zh Nevrol Psikhiatr Im S S Korsakova. 2013 –
“Possibilities of medical correction of moderate cognitive impairment.”
• In addition to cognitive effects:
– Might be useful in patient with early diabetic nephropathy .
Zhang L et al. Evid Based Complement Alternat Med. 2013
– Anti-inflammatory on osteoarthritis of knee. Chen YJ et al. J
Orthop Res. 2013 Mar 11.
69. EGb761 is used in most trials. Dosages: 80 –
720mg/day
Mechanisms of action: increasing cerebral blood flow,
antioxidant and anti-inflammatory effects, with
antiplatelet effects attributed to flavone and terpene
lactones.
“Possible interactions with MAOI’s, alprazolam,
haloperidol, warfarin, and nifedipine have been
reported.”
70. Clinically relevant interactions – Gingko
Curr Med Chem. 2011;18(31):4836-50. Chen, XW et al.
• Gingko may potentiate bleeding with
warfarin or aspirin
• increases blood pressure when combined
with thiazide diuretics
• has even led to a coma when combined
with trazodone
• induced mania if taken concomitantly with
phenelzine (MAOI)
71. New study – gingko/drug interactions may not be
as bad as thought
• Gingko leaf extracts (GLE’s) known to be taken regularly
by older people who are likely to use multiple other
drugs.
• IN VIVO studies in humans could not replicate preclinical
studies of high doses/concentrations of GLE that hinted
at both inhibition and induction of metabolic enzymes
and transporters.
• “At 240 mg/day, a clinically relevant interaction potential
of the standardized GLE EgB 761 could not be shown.”
• Doses higher than that led to weak induction of
CYP2C19 and weak inhibition of CYP3A4.”
Citation: Unger M. Pharmacokinetic drug interactions involving gingko biloba.
Drug Metab Rev. 2013 Aug; 45(3):353-85.
72. New study – gingko/drug interactions may not be
as bad as thought (conclusions)
• “THUS… the intake of the standardized GLE
Egb 761, together with synthetic drugs appears
to be safe as long as daily doses up to 240 mg
care consumed.”
• One caveat [from CADY] : this does not review the
potential for additive anticoagulant effects; it merely means
that gingko appears safe with everything else BESIDES
anticoagulants.
• Not for use with dual antiplatelet therapy or anti-coagulant
therapy.
Citation: Unger M. Pharmacokinetic drug interactions involving gingko biloba.
Drug Metab Rev. 2013 Aug; 45(3):353-85.
73. Gingko in Alzheimer’s disease
Ihl R. Effects of Gingko biloba extract Egb 761 ® in
dementia with neuropsychiatric features: review of
recently completed randomized, controlled trials. Int J
Psychiatry Clin Practice 2013 Jun 28.
• Review of four randomized, controlled trials investigating
efficacy of EGb761 in elderly patients with Alzheimer’s or
vascular dementia with neuropsychiatric features.
• N= 1,294 patients in this meta-analysis.
• These trials compared 120 mg twice daily or 240 mg daily
of EGb 761®.
– Three trials: EGb 761 vs. placebo
– One trial: Egb 761 vs. placebo with donepezil as an active control
74. Gingko in Alzheimer’s disease
Ihl R. 2013 ibidem
• “Patients treated with Egb 761 ® showed improvements of
cognitive performance and behavioural symptoms that
were associated with advances in activities of daily living
and a reduced burden to caregivers.”
– Placebo treated patients showed only minimal improvements.
– In each placebo controlled trial, Egb 761 ® was significantly
superior in all mentioned domains (p< 0.01)
– Note: in actively controlled trial, Egb 761 ® and donepezil (as well
as a combo of both drugs) had similar effects.”
• CONCLUSIONS: “The review supports the efficacy
of EGb 761 ® in age-related dementia with
neuropsychiatric features. The drug [sic] was safe
and well tolerated.”
75. “L-methylfolate: a Vitamin for your Monoamines”
[Stahl, SM Journ Clin Psych. Vol 69:9, Sept 2008 1352-1353]
Source: Stephen M. Stahl, MD, Ph.D., Neuroscience Education Institute
76. Law of mass action: “load the left side”
• L-tyrosine 500 –
1000 mg twice daily
– three times daily
• N-acetyl l-tyrosine
- 300 – 600 mg daily
to bid
• 5-HTP (w/ or w/o
P5P) – 50 – 100 mg
twice daily to three
times daily (start at
bedtime)
This technique is incredibly useful for
stimulant or antidepressant “poop-out”
This technique is incredibly useful for
stimulant or antidepressant “poop-out”
77. Nutraceutical “riffs”
• Randomized double-blind,
placebo controlled,
crossover
• 30 adults – ½ in each
group then crossed over
• 3 ingredients in active
– High potency
MVI/multimineral
– Fish oil (2.8 g, w/ 860
mg EPA + 580 mg
DHA)
– “BDN’s” – brain-
directed nutrients
• Outcome: rCBF &
MicroCog test
Amen, DG et al. Advances, Spring 2013 vol 27, no. 2, pp 24-33.
(loaded with references!)
Amen, DG et al. Advances, Spring 2013 vol 27, no. 2, pp 24-33.
(loaded with references!)
78. What was in the (deliberately lower dosed, synergistic)
brain enhancement supplement??
• In four capsules:
– Gingko – 80 mg
– Vinpocetine – 10 mg
– Phosphatidylserine – 67 mg (lower cortisol)
– Acetyl l-carnitine – 667 mg (elevate Ach levels)
– Huperzine – 100ug
• (primary cognitive enhancer; dosages within 200 –
400 mcg considered safe)
– N-acetyl cysteine 400 mg
• (as glutathione precursor)
80. Louis B. Cady, M.D. www.cadywellness.com
www.facebook.com/cadywellness www.tms-relief.com
Office: 812-429-0772 E-mail: lcady@cadywellness.com
4727 Rosebud Lane – Suite F ~ Interstate Office Park Newburgh, IN 47630 (USA)
TWITTER FEEDS: @LouisCadyMD @TMS4depression
Once more….
Where to “get the slides” -
Syllabus
www.slideshare.net/lcadymd
Cady Wellness Institute
app.
82. Neural inflammation/oxidative stress
in post-partum depression.
• Anderson G, Maes M. Journal of Neuropsychiatric Disease and
Treatment. 2013;9:277-87. E pub Feb 21 Postpartum depression:
psychoneuroimmunological underpinnings and treatment.
• Biological underpinnings reviewed:
– Tryptophan catabolites, indoleamine 2,3, dioxygenase, serotonin,
and autoimmunity mediates immuno-inflammation and oxidative
and nitrosative stress.
– It is suggested that the increased inflammatory
potential, decreased endogenous anti-inflammatory
compounds, together with decreased omega-3-poly-
unsaturated fatty acids causes an inflammatory
environment in the post-natal period.
– Melatonin recommended, as well as antidepressants and anti-
inflammatories.
83. H - 83
Vitamins – good for delinquents? (2000)
• DESIGN: stratified randomized, double-blind, placebo-
controlled trial with pretest and post-test measures of
antisocial behavior on school property.
• SETTINGS AND SUBJECTS: Two "working class," primarily
Hispanic elementary schools in Phoenix, Arizona.
– C. ½ the school population participated: 468 students aged 6 to 12
years.
• INTERVENTION: Daily vitamin-mineral supplementation at
50% of the U.S. recommended daily allowance (RDA) for 4
months versus placebo. The supplement was designed to
raise vitamin-mineral intake up to the levels currently
recommended by the National Academy of Sciences for
children aged 6 to 11 years.
Schoenthaler SJ, Bier ID. The effect of vitamin-mineral supplementation on
juvenile delinquency among American schoolchildren: a randomized, double-blind
placebo-controlled trial. Altern Complement Med 2000 Feb;6(1):7-17
84. H - 84
Results [Schoenthaler SJ, Bier ID. 2000, loc cit.]
• Of the 468 students randomly assigned to active or
placebo tablets, the 80 who were disciplined at least
once between September 1st and May 1st served as
the research sample.
• The 40 children who received active tablets were
disciplined, on average, 1 time each, a 47% lower mean
rate of antisocial behavior than….
• The placebo group of 40 children, who were
disciplined 1.875 times each (95% confidence
interval, 29% to 65%, p < .020).
• The children who took active tablets produced lower
rates of antisocial behavior in 8 types of recorded
infractions: threats/fighting, vandalism, being disrespectful, disorderly
conduct, defiance, obscenities, refusal to work or serve, endangering others,
and nonspecified offenses.
85. Conclusions [Schoenthaler SJ, Bier ID. 2000, loc cit.]
• “Poor nutritional habits in children that lead to
low concentrations of water-soluble vitamins
in blood, impair brain function and subsequently
cause violence and other serious antisocial
behavior.”
• “Correction of nutrient intake, either through a
well-balanced diet or low-dose vitamin-mineral
supplementation, corrects the low concentrations
of vitamins in blood, improves brain function and
subsequently lowers institutional violence and
antisocial behavior by almost half.”
86. PUFA’s & The State of the Literature
September 8, 2015
• Polyunsaturated fatty acids with…
– ADHD - 185 citations
– Alzheimer’s dz - 978 citations
– Anxiety disorder - 186 citations
– Autism - 106 citations
– Bipolar disorder - 219 citations
– “clinical depression” 492 citations
– Fibromyalgia - 34 citations
– Schizophrenia - 485 citations
Surf on over to www.pubmed.gov and investigate!Surf on over to www.pubmed.gov and investigate!
87. Omega-3’s with memory
• Yves Sauve, Ph.D. & colleagues
– University of Alberta
– Applied Physiology, Nutrition &
Metabolism 2012
• Lab models fed Omega-3 diet
had 30% higher levels of DHA
in hippocampus compared to
controls
• Appears to support the theory
that Omega 3 rich diet or dietary
supplementation may protect
memory.
88. “Antioxidants” & The State of the
Literature 9/1/2013
• “Antioxidant” with…
– ADHD - 91citations
– Alzheimer’s dz - 1,539 citations
– Anxiety disorder - 361 citations
– Autism - 178 citations
– Bipolar disorder - 294 citations
– “clinical depression” 762 citations
– Fibromyalgia - 95 citations
– Schizophrenia - 736 (!!) citations
Surf on over to www.pubmed.gov and investigate!Surf on over to www.pubmed.gov and investigate!
90. Top Targeted Supplements
(# of citations in PubMed 07 27 2013)
• Gingko (3,056)
• SAMe (7,713)
• Curcumin (5,848)
• SJW – Saint John’s Wort (2,138)
• Panax Ginseng (4,333)
• Ashwaghanda (576)
• Deplin, EnLyte (by RX) = l-methylfolate
91. “B-vitamin deficiency” & The State of
the Literature 9/1/2013
• “B-vitamin deficiency” with…
– ADHD - 2 citations
– Alzheimer’s dz - 44 citations
– Anxiety disorder - 5 citations
– Autism - 10 citations
– Bipolar disorder - 4 citations
– “clinical depression” 25 citations
– Fibromyalgia - none specifically
– Schizophrenia - 8 citations
Surf on over to www.pubmed.gov and investigate!Surf on over to www.pubmed.gov and investigate!
92. Magnesium & The State of the
Literature 9/1/2013
• Magnesium with…
– ADHD - 47 citations
– Alzheimer’s dz - 149 citations
– Anxiety disorder - 70 citations
– Autism - 53 citations
– Bipolar disorder - 119 citations
– “clinical depression” 163 citations
– Fibromyalgia - 29 citations
– Schizophrenia - 96 citationsSurf on over to www.pubmed.gov and investigate!Surf on over to www.pubmed.gov and investigate!
93. PUFA’s & The State of the Literature
9/1/2013
• Polyunsaturated fatty acids with…
– ADHD - 159 citations
– Alzheimer’s dz - 335 citations
– Anxiety disorder - 132 citations
– Autism - 80 citations
– Bipolar disorder - 189 citations
– “clinical depression” 432 citations
– Fibromyalgia - 31 citations
– Schizophrenia - 426 citations
Surf on over to www.pubmed.gov and investigate!Surf on over to www.pubmed.gov and investigate!
Notas del editor
In a flexible dose study evaluating the safety and efficacy of escitalopram in the treatment of panic disorder (with or without agoraphobia), outpatients were randomized to receive placebo, citalopram or escitalopram. There were approximately 120 patients per treatment group. Following a 2-week single-blind lead-in period, patients received 10 weeks of double-blind treatment. Treatment was initiated at a low dose (10 mg/day for citalopram and 5 mg/day for escitalopram) and then titrated after one week to 20 mg/day for citalopram and 10 mg/day for escitalopram. After week 4, dose could be increased to 40 mg/day citalopram and 20 mg/day citalopram. The Panic and Anticipatory Anxiety Scale (PAAS) and the Panic and Agoraphobia (P&A) scale were used to quantify panic attacks, anticipatory anxiety, and phobic avoidance.
Pernicious anemia – take note of pernicious – it sneaks up on you. Pernicious pathology
Chronic fatigue – frequently subsumed under fibromyalgia or “chronic fatigue syndrome”
Subtle subclincial cognitive impairment – can’t remember where you put your keys; can’t remember a face.