Dr. Cady's update lecture for World Link Medical - August 17, 2012. Topics: use of hormones in functional medicine (and psychiatry) as well as "pedal to the metal" allopathic psychiatry.

2. Mental Health and Hormones: What in the
World do Hormones Have to Do with Current
Allopathic Psychiatry?
Louis B. Cady, MD – CEO & Founder – Cady Wellness Institute
Adjunct Professor – University of Southern Indiana
Adjunct Clinical Lecturer – Indiana University School of Medicine
Department of Psychiatry
Child, Adolescent, Adult & Forensic Psychiatry – Evansville, Indiana
This presentation is © Louis B. Cady M.D. and may not be reproduced or
used without permission. World Link Medical is authorized to
reprint/duplicate it for 2012 syllabi.
(c) 2012 Louis B. Cady, M.D. - all rights reserved

3. What our patients are telling us:

4. VISION: “We dramatically
transform the lives of our
patients and clients to levels of
peak physical and mental health,
supporting a lifetime of
maximum performance and
happiness.”

5. S
N
O
TI
C
A
BODY
D
IN
M

6. Critical area of concern for men &
women. Things that will make them:
• Tired &/or depressed
• Unable to cope
• “Mean”
• Stressed
• Deficient in libido or in the bedroom
• Demented

7. A Shrink meets the “anti-aging” crowd
• Patient “complaints” • Personal experience
• Loss of energy • Previous state:
• Loss of stamina “energy to burn”
• Loss of libido • “Snooze bar
• Weight gain syndrome”
• Loss of zest for life • “Piles syndrome”
• Loss of interest in career • “Why can’t I make
myself exercise?”
• “I’ve felt like I’ve been
aging since I was 35.” • Car wash MSE!

9. Interesting lab values – Cady – 3/11/03:
Lab Value Cenegenics Normal
a.m.glucose 87 mg/dl 65 – 85 65 – 109
Fasting insulin 3 u U/ml <5 <20
HgB A1C 4.9 % <5.1% < 6.0 %
Cholesterol 241 mg/dl <200 <200
Triglycerides 42 mg/dl <120 <150
Cor. Risk ratio 3.3 <4.0 Av = 5 – 6
Homocysteine 7.9 <8.0 5.4-11.4
DHEA-S 148 350 – 500 59 – 452

10. 4

11. Brain
Hypothalamus
Hypothalamus
Releasing
Releasing DHEA
Factors
Factors
Pituitary
ACTH LH & FSH Prolactin GH TSH
(breast)
Adrenal
Adrenal Testicles
Testicles Ovaries
Ovaries Liver
Liver Thyroid
Thyroid
Gland
Gland
Cortisol Testosterone Estrogen IGF-1 T3 & T4
DHEA Progesterone

12. Useful Target Symptoms in MDD
♦ Depressed mood 100%
♦ Reduced energy: 97%3
♦ Fatigue or loss of energy: 94%2
♦ Impaired concentration: 84%3
♦ Tiredness: 73%1
♦ Hypersomnia: 10%–16%4 (Insomnia)
1. Tylee et al. Int Clin Psychopharmacol 1999;14:139-151. 2. Maurice-Tison et al. Br J Gen
Pract 1998;48:1245-1246. 3. Baker et al. Comp Psychiatry 1971;12:354-65. 4. Horwath et
al. J Affect Disord 1992;26:117-25. 5. Reynolds and Kupfer. Sleep 1987;10:199-215.

13. “But the doctor told me my thyroid
was fine.”
• Can be “wnl” but suboptimal.
• TSH frequently only thing checked.
• Nothing known about Free T4 or Free T3.
• Free T4 can be converted to Reverse T3 under
stress (cortisol)
• Free T4 can be underconverted to T3.
• Can have normal levels (or slightly elevated
levels) of everything and have auto-immune
thyroid disease.

14. “the foot soldier” “the evil twin”

15. “Thyrotropin (Thyroid-Stimulating
Hormone or TSH). Measuring TSH is the
most sensitive indicator of
hypothyroidism.” (hunh?!)
http://www.umm.edu/patiented/articles/how_serious_hypothyroidism
Accessed: 9/5/2011

16. Se
CORTISOL
“the foot soldier” “the evil twin”

17. Yes, T-3 DOES get into the brain
(Transthyretin = carrier protein)
Or: The idiocy of T4 only thyroid treatment…
• Terasaki, T. and Pardridge, W.M.: Stereospecificity of triiodothyronine
transport into brain, liver, and salivary gland: role of carrier- and
plasma protein-mediated transport. Endocrinology, 121(3):1185-1191,
1987.
• http://www.kingpharm.com/uploads/pdf_inserts/Cytomel_PI.pdf.
• Mooradian, A.D.: Blood-brain transport of triiodothyronine is reduced in
aged rats. Mech. Ageing Dev., 52(2-3):141-147, 1990.
• Cheng, L.Y., Outterbridge, L.V., Covatta, N.D., et al.: Film
autoradiography identifies unique features of [125I]3,3'5'-(reverse)
triiodothyronine transport from blood to brain. J. Neurophysiol.,
72(1):380-391, 1994.
• Rudas, P. and Bartha, T.: Thyroxine and triiodothyronine uptake by the
brain of chickens. Acta Vet. Hung, 41(3-4):395-408, 1993.

18. Transthyretin (a systemic amyloid precursor)
may be protective for Alzheimer’s (Why?)
Li X et al. J Neurosci 2011 Aug 31;31(55):12483-90

19. LEVEL III RESULTS:
Per HDRS – 17, remission in:
15.9% on Li
24.7% on T3
Per QIDS-SR16, remission in:
13.2% on Li
24.7% for T3 *
* Fava & Covino: Augmentation/Combination Therapy in STAR*D Trial,
Medscape Psychiatry

22. • Early 20’s college student
• Weight gain, fatigue, brain fog
• Saw “numerous” MD’s asking for help
• Told “nothing is wrong with your thyroid;
your labs are fine.”

23. Fatigue from Adrenal Dysfunction - The
Worst Case Scensario:
Addison’s Disease

24. “Hypoadrenia”: The Adrenal Problem that most
conventionally trained physicians don’t know about.
• Non-Addison’s hypoadrenia
• Subclinical hypoadrenia
• Neurasthenia
• Adrenal neurasthenia
• Adrenal apathy
• Adrenal fatigue
• “Adrenal burnout”
• “Chronic fatigue syndrome”?!!

25. The state of adrenal exhaustion can
be determined
Early-stage Chronic Mid-stage Chronic End-stage (exhausted)
Stress Response Stress Response Chronic Stress
Response

26. DHEA – the critical hormone most
doctors never check
• Produced in the adrenal cortex
– Humans and primates are unique in secreting large
amounts
• Immune system booster
• Insulin regulator
• Energy increase – remarkable
• Boosts growth hormone
– 20% in men; 30% in women in one study
• [Yen, Morales Khorram – one year double-blind placebo
controlled crossover experiment – with 100mg DHEA]
• Antidepressant

28. The two “new ones” – 8/17/2012
- Opioid use has
increased.
- Concomitantly OPIAD
has increased.
- Testosterone and DHEA
are recommended.
-Corticotroph def = crucial
element of ant. Pituitary failure
-Dx with a.m. cortisol w/ stim
-TX with HC 20 mg per day,
divided doses.
-Tx determined by fatigue, BP,
BW, skin trophicity

29. Why isn’t adrenal fatigue diagnosed?
• Not severe enough to be an
emergency
• Symptoms can be attributed to other
things, including “just neurotic” or
“avoidant”
• “Functional medicine” testing not
typically done (& rarely is DHEA-S
checked)
• Modern medicine focuses on the
treatment of sickness, not “less than
optimal” function.
• “Bell Curve” paradigm

30. Neurobiological & neuropsychiatric effects
of DHEA & DHEAS [Maninger N et al. Front
Neuroendocrinology 2009]
• DHEA & DHEAS synthesized in adrenals
AND BRAIN.
• Biological actions of DHEA/DHEA-S:
– Neuroprotection
– Neurite growth
– Antagonistic effects on oxidants & glucocorticoids
• “accumulating data suggest abnormal DHEA
(S) concentrations in several neuropsychiatric
conditions.”

31. “Women’s issues”

32. The Glamorous Grandmother
• 4/8/11 – 80 yo returned to practice. No real
complaints. History of depression. On Pristiq.
– Daughter “handling her finances”
• 5/2/11 – “doing terrible.”
– TSH 3.84, Free T3 2.8 – on 50 MICROgrams T4
– Fasting BS 120; HgBA1C 6.5%
– Fasting insulin 36 (!!!) {3 – 25}
– Progesterone – 0.2 {0.2 – 1.4 follicular}
– Total testosterone 11
– DHEA-S = 25 MICROgrams/dL (!!)
• Age adjusted {10 – 90} . Cenegenics = {c. 500}
• Rouzier = {300 –females, 600 males}

33. G.G. - interventions 5/2/11 & Follow-up
• Interventions:
– DHEA – 25 mg SR q a.m.
– Progesterone 200 mg/cc, Topiclick – ¼ cc at
HS, then increase to ½ cc
– Testosterone – 8mg/cc Topiclick – 1/4cc
topically for one week, then ½ cc
– Referred to better MD for intervention with
AODM.
• 6/13/2011 – improvement in fatigue. Labs
rechecked.
• 7/11/2011 – “feeling wonderful”

34. G.G. – labs before and after
4/11/11 interventions 7/11/11 changes
TSH 3.84 Raise T4 from 0.01 (L) none
50 – 75 ug
FT4 1.16 “ 1.24 “
FT3 2.8 “ 3.3 “
Progesterone <0.2 100mg topical 0.9 None
HS
Testosterone 11 4mg topical 15 4 mg LABIAL
DHEA-S 25 25 mg SR n/a continue

35. The glamorous grandmother – post tune-up
9/28/2011 (permission granted to use photos & data) 01/26/2012

36. One destigmatizing notion:
Estrogen as MAOI
• Estrogen & Testosterone (!) decrease
MAO
– Luin, VN. Brain Res. 1975;86:273-306
• Platelet MAO levels inversely
correlated to estradiol levels
– Klaiber EL et al. Psychoneuroendo-
crinology. 1997 Oct;22(7):549-58.
• Estrogen decreases MAO-A & MAO-B
– Holschneider DP et al. Life Sci. 1998;63(3):155-60

37. Estrogen-related mood disorders –
reproductive life cycle factors.
Douma SL et al. Adv. Nursing Sci. 2005. 28 (4):364-375
• “Clinical recovery from depression
postpartum, perimenopause, and
postmenopause through
restoration of stable/optimal
levels of estrogen has been
noted.”

38. Symptoms of estrogen imbalances*:
 Hot flushes or flashes; night sweats
 Mood swings
 DEPRESSION, and/or anxiety, panic attacks
 “Concentration” issues: Memory, communication,
and attention span loss, “brain fog.” (Think:
“MORE MAO.”)
 Insomnia
 Weight gain – “appetite changes”
 SOMATIC symptoms : aches and pain
 General deterioration: Incontinence, digestive
disturbances, sensory function loss, aging skin . . .
thinning, wrinkles, sagging* Adapted from Whitney Gabhart, N.D.

39. The Case of the Crying Cleaner
• 1/11/12 - Symptoms:
– Crying/depressed = on
Citalopram
– Hot flashes
– Night sweats
• RX:
– Estradiol – 2 mg @HS
– Prometrium – 100 mg
@HS
– (continue citalopram)
• 1/15/12 – RESOLVED
• In 4 days!
Photo & data used with permission

40. Psychoactive Progesterone*
 Increases energy and libido
 Has a calming effect, acting like a
benzodiazepine to the brain (HS dosing)
 Enhances mood
 Balances blood sugar (appetite)
 Regulates fluid balance, sodium mineral balance
 Necessary for fertility
 Helps relieve menopausal symptoms
 Decreases risk of endometrial cancer and may help protect
against breast cancer, fibrocystic breasts, and
osteoporosis * Adapted from Whitney Gabhart, N.D.

41. Testosterone: The “sexist” bias against women
(e.g., “your loss of sex drive is just natural for
your age.”)
• Fall in the circulating testosterone and the adrenal
preandrogens most closely parallel increasing
age.
• Accelerated decrease occurs in the years
preceding menopause (like estrogen).
• Their loss affects: libido, vasomotor symptoms
(hot flashes), mood, well-being, bone structure,
and muscle mass.
– Burd, Bachmann. Androgen replacement in
menopause. Curr Womens Health Rep. 2001 Dec;
1(3):202-5.

42. The Case of “Pajama Mama”
• 41 yo MWF, mother of three, ref by therapist for worsening depression.
History of chronic headaches. Mild dep symptoms x 16 years.
• CC: “I think I need a good medication, and I need to stay on it.”
• In normal mood state until after birth of second child 14 years prior (@
age 27)
– Recalls “calling the doctor all the time” and ego-dystonic worries of
dropping her baby over a railing ACCIDENTALLY on the stairway
at home
• RX tried
– fluoxetine– “worked reasonably well”
– Amitryptline for headaches – “knocked me out”
– Alprazolam – had her first panic attack ON IT.
– Tried on duloxetine – no relief.
• Rx at presentation – fluoxetine 20 mg; topirimate 100 mg, sumitriptatn
as needed

43. The Case of “Pajama Mama” - treatment
• Fluoxetine gave sexual side effects. Stopped.
Escitalopram now at 15 mg. Trazodone 25 mg HS..
– Topirimate continued for migraines.
• Psychotherapy: focused on significant dependent
personality disorder and on controlling, overbearing, free-
spending, financially irresponsible husband.
– Increasing limit setting noted. Patient reading her bibliotherapy
assignments
• Escitalopram didn’t work. Back to fluoxetine. IgG Food
sensitivities found; diet restrictions instituted.
• 11/15/2011 – working professionally in her field, has gotten
graduate degree, but tired and wrung out. Exhausted at
end of day. Was tired on a cruise vacation almost all the
time. Went back to room to sleep. Forcing self to
exercise.

44. The Case of “Pajama Mama” – lab review
• TFT’S
– TSH 0.38 (L) {0.55 – 4.78}
– Free T4 1.05 {0.80 – 1.76}
– Free T3 2.9 {2.3 – 4.2}
– Reverse T3 199 {90 – 350}
• SEX HORMONES
– Total testosterone 11 {9 – 55}
– Free testosterone 1.3 {1.1 – 5.8}
– SHBG 60 {30 – 155}
– Progesterone 1.0 {0.2 – 1.4}
– Estradiol 67 {24 – 284}
• DHEA-Sulfate 55 {32 – 240}

45. This is what those labs “sound like”
• “I must be worse than I think I am, because my daughter made a comment about the members of her family. ‘Mom
likes her pajamas.’”
• “I’m frustated that I’m not doing great – I don’t know why. There should be no reason why I should think about the
way I feel, or wonder, ‘why don’t I want to get up?’ or ‘Why do I feel anxiety?’ I don’t have to give a speech. I don’t
have to do anything.”
• “I’ve done a lot of right things… I’ve done so many right things. I’ve taken my medicine like I’m supposed to. I’ve
tried to change my life and my thinking. I’ve done physical things [exercise] to try to help me.”

46. Pajama Mama – treatment and follow-up
• All psychotropics kept same
• Hormones added (11/15/2011):
– Testosterone – 10/mg/cc – ¼ cc labially daily -
increased to ½ cc (5 mg) labially per day.
– Amour thyroid – ¼ grain x 1 week, then ½ grain
– DHEA – 25 mg SR micronized daily in a.m.
• Still tired – 12/13/2011 –
– New RX: Hydrocortisone – 5 mg twice daily
added (a.m. and lunch)

47. PJ Mama – STABLE – 1/17/2012
• “I don’t have a hyperactive sense of energy, [but]
I’m no longer pajama mama [sic]. I just have the
energy to do what I’m supposed be doing, and
more, sometimes. But it’s not an odd, hyperactive
type thing.”
• Household budget now fixed and stable.
Increased limit setting with husband.
• “He has used anger to shut me down and shut me
out from day 1. He still uses anger, but instead of
me going away, he goes away. I don’t back
down.”

49. Fast food (low Zn) is bad for you.
• Fast food = high energy density = low essential
micronutrient density, ESPECIALLY ZINC
• Antioxidant processes are dependent on Zinc
• Fast food = severe decrease in antioxidant
vitamins and zinc, correlating with
inflammation in testicular tissue – with
underdevelopment of testicular tissue and
decreased testosterone levels

50. Testosterone (Men)
• Decline in male sex steroids not as
abrupt as menopause, but equally
debilitating
–Between 40 – 70, average male
loses:
• Nearly 2" of height
• 15% of bone density
• 10 – 20 pounds of muscle
• At 70 yoa, 15% completely
impotent

51. T vs Cognitive Function
Rosario ER. JAMA. 292(2004):1431-2

52. T vs Cognitive Function
• 400 independently living men, 40-80yo
– 100 in each age decade
– MMSE 21-30, average 28
– TT: 208-1141ng/dL; Bio-avail T 78-470ng/dL
• HIGHER T = better cognitive performance in
OLDEST AGE category
• Men with lowest 1/5 T = worse than men with
highest 1/5 T
• Highest Bio-available T more significant
than TT, age, intelligence level, mood,
smoking, and alcohol.
Muller M. Neurology. 64(2005):866-71

53. T vs Mood in men
• Study: 278 men, >45yo, followed 2 years
• Compared to eugonadal patients,
hypogonadal men w/TT <200ng/dL had
– 4-fold increase risk of depression
– Significantly shorter time to depression
diagnosis
• Depression risk inversely related to TT
w/statistical significance <280ng/dL
Shores MM, Arch Gen Psychiatry. 61(2004):162-7

54. Testosterone and “Prostate Cancer risk”
• Prostate CA found 2.15 & 2.26 times more
likely in lowest compared to highest tertile
of total and free testosterone
• “. . . there are several papers showing a
relationship between LOW testosterone
and prostate cancer. Specifically, low
testosterone has been associated with
high-grade tumors, advanced stage of
presentation, and worse prognosis.”
Morgentaler A. Eur Urol. 50(2006):935-9
Morgentaler A. Urology. 68(2006):1263-7

55. The Case of the Mismanaged
Executive - summary
• 42 year old male ADHD CEO. Background in
psychology. Now EXTREMELY stressed.
• “So tired I feel like I’m dying.” “Depressed.”
• Lab findings – low testosterone, despite multiple
pumps of Androgel per day managed by
endocrinologist (!). Low thyroid. Low DHEA.
• RX: Testosterone cypionate IM – 60 mg twice
weekly. DHEA – 50 mg SR. Armour thyroid – ½
grain.
• Clinical status: total resolution of symptoms in 3- 4
weeks. No antidepressant used.

56. Holistic Fun with Hormones
A synthesis…

57. 50’ish year old female, post-
menopausal, on no hormones
• On aggressive supplement regimen with
daily MVI and others
• Not ill
• Top rated medical care with previous labs
done
• Nothing identified as seriously abnormal
• “Just interested in having my hormones
checked.”

62. Treatment for this “normal” patient
1. Armour thyroid – ¼ grain for 1 week, then ½
grain. (Aiming for T3 in “high 3’s” or OPTIMUM)
2. DHEA – 25 mg SR micronized, compounded – in
a.m.
3. Progesterone – 50 mg SR compounded – at
night.
4. Testosterone – 3mg topical per day x 1 wk, then
6 mg. “Decrease dosing as needed for side
effects.”
5. Vitamin D – 5,000 IU twice daily x 3 weeks, then
decrease to one dose per day.
6. High potency liquid fish oil – 4 grams per day

64. What’s life like now?
• “it’s like the colors of the rainbow have gotten
more into the pink.”
• “My computer will survive – I use to ‘lose it’ over
my computer. I would swear obscenities.”
• “I’ve gotten into a zen like mode. Handling
everything that life can throw at me.”
• “It’s almost as if I’ve taken a pill or drug that jus
makes me handle everything that life is throwing at
me. I can roll with it.”
• “I’m not irritable any more. Time pressure has just
gone away.”

65. Key points
• A predominantly psychiatric view with
psychiatric interventions…
– Will not fix all symptoms
– Unlikely to get anybody else to do it for you,
either.
• STABILIZING THE BIOLOGICAL is critical
for full remission and total wellness when
hormones are not optimal.
• Holistic and integrated tx required.
• Yoking of thyroid, adrenal & sex steroids

66. HOW OBVIOUS DOES IT HAVE TO BE?
The Challenge of Empathic Listening
& CREATIVE THINKING
Ron Hunt lost an eye but suffered
no brain damage after a freak
accident with a large drill bit.
(ABCNEWS.com)

67. “Sit down before fact as
a little child,
be prepared to give up
every preconceived
notion,
follow humbly wherever
… nature leads,
or you shall learn
nothing.”
- Thomas H. Huxley

69. Pedal to the Metal Allopathic Psychiatry – or,
“How to Practice Like a Board Certified
Psychiatrist Without Being One”
Louis B. Cady, MD – CEO & Founder – Cady Wellness Institute
Adjunct Professor – University of Southern Indiana
Adjunct Clinical Lecturer – Indiana University School of Medicine
Department of Psychiatry
Child, Adolescent, Adult & Forensic Psychiatry – Evansville, Indiana
This presentation is © Louis B. Cady M.D. and may not be reproduced or used without
permission. World Link Medical is authorized to reprint/duplicate it for 2012 syllabi.
(c) 2012 Louis B. Cady, M.D. - all rights reserved

70. Relevance for your practice
• Don’t kill your patient with a drug-drug
interaction.
• Don’t diagnose someone as having “drug
problems” when they DON’T.
• Spot bad pharmacotherapy when you see it
and DO SOMETHING about it.
• If you prescribe psych meds – much greater
understanding of MOA’s.

71. Dangers with
Psychiatry/psychotropics
• Failure to diagnose
– (E.g “head case” and then they die of a medical problem)
• Failure to adequately treat
• Failure to prescribe accurately (Rx-rx interaction)
• Giving people side effects
• Using the wrong drug
• Ignorance about best options because “I always did it that
way.”
• Getting people addicted
• Practicing beyond your ability and expertise
• Violating black box warnings

72. *ACCURATE MEDICAL diagnosis a malpractice suit
Depression & Anxiety & “mood disorder due to a
in 1 Easy Lesson
general medical condition” AND r/o bipolar disorder
DEPRESSION Gen. ANXIETY D.O.
SIG: E- CAPS! •Somatic Sx (“energy”,etc.)
• Sleep •WORRY
• Sadness •Irritability
• Interest loss •Concentration
• Guilt •Keyed up
• *Energy •Insomnia (“sleep”)
• Concentration •Restlessness
• Appetite BEWARE BEWARE – “too much”
• Psychomotor Sx energy
• Suicidal thinking SWICKIR is Quicker:
Worry + 3 = GAD (Baughman)
5of 9 with 1 of 2 x 2 weeks

73. Comorbidity of Depression and
Anxiety
Disability % Patients
Disabled 3+ Days
GAD + MDD 33.7%
MDD/no GAD 19.45%
GAD/no MDD 16.9%
no GAD/no MDD 3.1%
0 5 10 15 20 25 30 35 40 45
Percent of Patients With ≥1 Disability Day in Past Month
Wittchen, Depress Anxiety, 2002

74. Where does ADHD come from?

75. Kids and Adults – Differences in
HYPERACTIVE domain
AS A CHILD: AS AN ADULT:
• Squirming, fidgeting • Work inefficiencies
• Cannot stay seated • Can’t sit through meetings
• Cannot wait turn • Cannot wait in line
• Runs/climbs excessively • Drives too fast
• Cannot play quietly • Self-selects very active job
• On the go/driven by motor • Cannot tolerate frustration
• Talks excessively • Talks excessively
• Blurts out answers • Makes inappropriate
• Intrudes, interrupts others comments
• Interrupts others
Sources: DSM-IV (TR). APA 2000:85-93)
Weiss MD, Weiss JR. J Clin Psychiatry 2004;65(Suppl 3):27-37.

76. Horrigan J, et al. Presented at 47th Annual AACAP Meeting:
October 24-29, 2000. New York, NY.

77. Persistence of ADHD Into Adulthood
• ADHD is a heterogeneous disorder associated with
considerable disability and comorbidity that, in many cases,
persists into adulthood1
– Some studies have found persistence as high as 36.3% 2
• Mood, anxiety, and substance use disorders are
the most common comorbid disorders in adults with ADHD 3
• Current prevalence of ADHD persistent into
adulthood 4.4%4
• Much of the treatment of adult ADHD can be based on
experience in treating children/adolescents5
1. Barkley et al. J Abnorm Psychol. 2002;111:279-289.
2. Kessler RC et al. Biol Psychiatry 2005 June;57(11):1442-51. [retrospective review of 3,197 14-44 yo
respondents in NCS-R]
3. Biederman et al. Am J Psychiatry. 1993;150:1792-1798. 4. Kessler et al. Am J Psychiatry. 2006;163(4):716-
23. 5. Dodson WW. J Clin Psychol. 2005;61:589-606.

78. Diagnostic Pearls - Cady
• How’s work?
– How has your employment history been?
• How’s your mood? Your marriage (relationship)?
• How was school for you?
• Are people nervous driving with you?
• Are there periods of time when you have too much
energy for no particular reason?
• Do you ever have to have a beer at the end of the day to
relax?
– [gently lead in to other substances, especially stimulants that
may have a CALMING effect]
– “Have you ever taken any of your child’s ADD Rx?” [or other
stimulants, energy drinks, diet pills, or cocaine]

79. Failure to adequately treat
1. “Begin with end in mind.” (Covey)
2. Start LOW – (rule of thumb – ½ what the
drug rep and package insert says!)
3. Go up to the maximum tolerated dosage,
with finesse.
– Tell them about “Goldilocks”
1. If it doesn’t work, add something
complimentary (that makes sense).

80. THE FACTS
• SSRI’s treat depression AND/OR anxiety
• Patients may INITIALLY need something else for daytime
anxiety or sleep.
• BZD’s of choice:
– clonazepam 1 mg tablets – ½ to 1 twice daily to three
times daily
– Diazepam – 5 mg =- ½ - 1 ½ twice daily to three times
daily
• (first pass and second pass effects)
• ANTIANXIETY RX (non BZD) – Buspirone, per package
insert. Push to 20 mg THREE TIMES DAILY or to the
point of maximum tolerability for 4 – 6 weeks AT THAT
DOSE.
– Start with 5 mg. Can use WITH SSRI’s

81. AVOID Alprazolam (Xanax ®)
• Addicting (and rapidly so)
• Can have seizures if rapidly withdrawn
(structurally similar to carbamazepine)
• MD’s shot over it.
• NOT an “anti-anxiety” medication
• NOT a sleeper.
• Even if they need a BZD for anxiety, it
doesn’t have to be Xanax.

82. Sleepers – my preferences
• Sleepers:
– Rozerem (brand) (a melatonin analog) – 8 (up to 16* mg) at
bedtime. VASTLY under-rated. May need to take 2 weeks before
adequate effect. (* off-label dose)
• Dual acting agent – homeostatic and circadian effects. 70x as potent
as melatonin.
– Trazodone (50 – 150mg ½ - 2 hrs before HS. (Note, off label
“unapproved.” Warn on priapism).
– Lunesta (brand) – 2 – 3 mg. Try samples. Have mouthwash on
hand. (Probably most predictable agent)
– Ambien 12.5 mg CR (brand) – legitimately lasts longer than
zolpidem. Probably not as effective as Lunesta.
– Zolpidem – generic. People get hooked on it.
• Paradigm: SYMPTOMATIC treatment – after
depression is stabilized, fade out the sleeper

83. Why treatment failures occur: too much or too little…
The REAL mechanism of action of SSRI’s
Animation © NEI, Inc. (Neuroscience Institute) and is used specifically with permission from
Stephen Stahl, MD, Ph.D.

84. Drug, drug...
who's got the
drug?

85. Depression/anxiety Rx:
• TCA
• Venlafaxine (Effexor)
• Duloxetine (Cymbalta)
• Mirtazapine (alpha 2)
• Desmethylvenlafaxine
(Pristiq)
& others….

86. Side Effects & Drug Interactions:
The Doc Cady “Can’t s” of the TCA’s
Pee
ANTICHOLINERGIC/
Poop ANTIMUSCARINIC
Spit EFFECTS
Spurt
Focus
Think
 Stand up Alpha-adrenergic
 Stay awake blockade
 Stay thin "Antihistamine"
effects

87. “Drug-drug interactions”
clinically relevant?!

88. Drug-drug interactions: chum for legal “sharks”

89. “Strattera [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]

90. Cytochrome p-450 2D6 inhibition measured as %
increase in “Desipramine AUC” – in vivo data
Critically important when
combining with other Rx
metabolized through 2D6
pathways
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

91. Some drugs metabolized through
cytochrome P-450 IID6 system
ADHD Antibiotics ANTI-PAIN
Amphetamines •TMP & SMX
STRATTERA CODEINE!
•Ampicillin
Analgesics •Erythromycin Bronchodilators
•Acetaminophen •Penicillin •Theophylline
•Aspirin •Tetracycline Cardiac
Antacids Antidepressants •Digoxin; digitalis
Antiarrthymics •TCA’s & “2P’s” Cough
•Procainamide, Antihistamines •Dextromethorphan
•Quinidine
Antihypertensives Diuretics
•Encainide
•Flecainide
Antipsychotics •Chlorthalidone
Anticonvulsant •Clozaril •Furosemide
•carbamazepine •Risperdal •HCTZ
•Zyprexa •Triamterine

92. The “not so selective” SSRI’s; how to
“Do yourself a favor.”
drug SSRI? 2nd order effects Side effects possible
Escitalopram Yes NOTHING (excess serotonin side
(Lexapro) now effects only)
generic
Sertraline (Zoloft) Yes Dopamine (1/3 as Agitation, nervousness;
potent as improved [ ]
amphetamine)
Citalopram Yes AntiH1 Sedation (note- FDA
(Celexa) lowered max dose to
40mg)
Paroxetine (Paxil) Yes Ach Doped up, TCA effects,
NOT “NRI” neurocognitive problems,
withdrawal. Sexual,
Prostate sxs
Fluoxetine Yes 5HT2C Agitation, appetite
(Prozac) suppression

93. New Agents, New Mechanisms
(agent) (MOA) Differentiating points
Venlafaxine (“IR” and XR) SSRI, NRI Nausea, GI side effects, sxl
(Effexor) dysfunction
Duloxetine (Cymbalta) SSRI, NRI Same. Better tolerated. For pain
w/ dep.
Desvenlafaxine (Pristiq) SSRI, NRI Better tolerated
Trazodone XR with 5HT2a/c
Contramid® (OLEPTRO) BLOCKER, mild
SSRI
Vilazodone (Viibryd) SPA, SSRI ONLY SPARI. Weaker “SSRI.”
Targets 5HT1A. Less sexual side
effects.
Bupropion (“XL” – not “NDRI” Possibility of anxiety & “wound
“SR”) (Wellbutrin) up.” Improved concentration.
Push to 450 mg. Seizures.

94. Duloxetine (Cymbalta) Versus
Escitalopram (Lexapro) and Placebo:
An 8-month, Double-Blind Trial in
Patients With Major Depressive
Disorder
Pigott et al., Curr Med Res Opin, 2007

95. Retardatio
Comparison of Escitalopram and Duloxetine:
HAMD (MMRM)
8-Month Trial
17
Maier
Subscales
Sleep
*
Somatization
Anxiety/
Total Score
*p<0.05
Pigott et al., Curr Med Res Opin, 2007

96. Comparison of Escitalopram and Duloxetine: 8-
Month Trial
Significantly Different Adverse Events (p<0.05 Duloxetine vs Escitalopram)
Percent of Patients
Pigott et al., Curr Med Res Opin, 2007

97. Comparison of Escitalopram and
Duloxetine: 8-Month Trial
Conclusions
• Remission rates for both escitalopram and duloxetine
continued to improve over time
• Significantly more escitalopram-treated patients
continued treatment compared to duloxetine-treated
patients
• Escitalopram showed significant improvement vs
duloxetine on the HAMD17 sleep subscale
• Compared to escitalopram, duloxetine significantly
increased pulse and systolic blood pressure
Pigott et al., Curr Med Res Opin, 2007

98. Two New Agents You Need to Know
• Extended release Trazodone
– NOT “son of Trazodone”
– Possibility of legitimate antidepressant effect with anti-
anxiety effect WITHOUT doping patient up.
– A “SARI” – serotonin antagonist reuptake inhibitor
• Vilazodone – the only SPARI available.
• How to appreciate:
– 5HT1A is receptor for antidepressant effect of serotonin
– 5HT2A and 5HT2 C: anxiety, sleep disruption, sexual
side effects.
– ANYTHING which works preferentially on 5HT1A is
GOOD!

99. XR Trazodone steady state dosing study
• (Levels done after 7
days steady state)
• 300 mg XR Traz
AUC comparable to
100 mg IR Traz tid
• Cmax 42% lower
than IR Trazodone
– Translation – it
doesn’t dope the
patient up.
Kramer, WG et al. Once-daily Trazodone: Overview of Pharmacokinetic Properties.
Poster – ACCP 38th Annual Meeting, San Antonio, TX 2005

100. XR Trazodone Food Effect Study
• PI says “take at night”
• CMax increase by 86%
(!!!) under fed conditions.
Peak is at 7 hours post
dose (with feeding).
• Note – this may lead the
enlightened prescriber to
vary the time of dosing.
Kramer, WG et al. Once-daily Trazodone: Overview of Pharmacokinetic Properties.
Poster – ACCP 38th Annual Meeting, San Antonio, TX 2005

101. Vilazodone – a SPARI (per Stephen Stahl, MD, Ph.D.) –
Serotonin Partial Agonist Reuptake Inhibitor
• Highly serotonergic. START LOW (5 mg).
• Because of 5HT1A agonism, LESS “SSRI” effect is
required.

102. ADHD Rx for frontline medicine
• Desiderata – get control, and keep it consistent for
predictable period of time
• Rules of thumb: don’t be guided on SIZE. START LOW.
“Know the Biederman max” for MPH and amphetamine.
• Recommendations (for children and adult):
– Focalin XR (Dexmethylphenidate XR) 5,10,15,20,30 and 40 mg
capsules)
• Rationale: MPH based. FAST. 8 – 10 hours. Can dose twice daily (off-
label), a.m. >pm. (can also start with ½ capsule)
– Vyvanse – (lisdexamfetamine [sic]) – 20,30,40,50,60,70 mg [= 7.5
– 30 mg] amphetamine equivalents. Lasts 12 – 14 hours. (Can
dissolve in water – per PI!).
– Kapvay/Intuniv – FDA approved in kids.
• Kapvay easier to use, better tolerated.
• Intuniv more potent, but more side effects (sedation)

103. Practicing beyond your ability (and knowledge) –
the second generation antipsychotics
• Definitions:
– Mood stabilizer – something that stabilizes mood
(Lithium, carbamazepine, VPA)
– Antipsychotic – something you give someone who is
PSYCHOTIC to get them UNPSYCHOTIC.
– Antidepressant – something for depression.
– “2nd generation antipsychotic (“SGA’s”) = S2/D2
blockers.”
• Can “stabilize mood” as well as function as antipsychotics
• Now some FDA approved for either add-on use or single agents
for “bipolar depression” (e.g., quietapine XR)

104. Know who you’re playing with
• SGA’s and WEIGHT GAIN (Cady experience)
– olanzapine/risperidone > quietapine>
aripiprazole/arsenapine> lurasidone/ziprasidone
• (Zyprexa/Risperdal>Seroquel> Abilify/Saphris> Latuda/Geodon)
• EXPENSIVE: $400 – $600 /per month
• All will work for mania. NONE are pure “mood stabilizers.”
Some make you fat.
• Some will work for depression but dope you up.
• Much less risky than 1st generation for tardive dyskinesia.
• Axiom: refine your psychopharmacology before going to
look for an SGA.
• If you have to use one (for bipolar or psychosis, Lurasidone
is probably most benign – 40 – 80 mg twice daily)

105. Cady recommendation for SGA’s in
primary care
• As little as possible.
• Do NOT use as primary mood stabilizers for bipolar disorder.
Use lithium (Type I) and/or VPA (Type I or II). (And check
levels and appropriate labs). Lamotrigine also a real option.
• Can use if single, or better yet, DOUBLE mood stabilizers
don’t work.
• Abilify (only “dopaminergic” SGA) probably best for
antidepressant augmentation.
– 2 – 4 or 5 mg is optimum dose for this. (Start with ½ of a 2
mg and go up)
– Onset is FAST when it happens.
• Olanzapine is most dependable for rapid onset and control of
manic episode, or agitation, or EXTREME PANIC & anxiety
(off label).. Lurasidone may be best tolerated.

106. “There are things
known and there are
things unknown, and
in between are the
doors.”
- Jim Morrison

107. Thanks for coming!
Sunset at CWI –by Louis B. Cady, M.D.

108. Contact information:
Louis B. Cady, M.D.
www.cadywellness.com
www.indianaTMS-cadywellness.com
Office: 812-429-0772
E-mail: lcady@cadywellness.com
4727 Rosebud Lane – Suite F
Interstate Office Park
Newburgh, IN 47630 (USA)