This one was fun. I was invited by Dr. Randalll Oliver, MD, Founder of the Oliver Heachache and Pain Clinic in Evansville, to present to an audience of primary care practitioners about how to use pysychiatric mediations ("psychopharmacology") in clinical practice. Along the way, I covered, ADHD and treatments, depression, anxiety, erectile dysfunction, hypoadrenia, and even touched on hypothyroidism. Although this presentation was in 2009, all of the drugs covered are stills in use, and, at times.... stupidly. This presentation deconstructs the intricacies of selecting and antidepressant, particularly in the SSRI class.

1. 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
Send in the Shrinks!
Know When to Hold’Em, When To
Fold’Em, and When to Start Thinking
A CME Presentation for the Oliver Pain Clinic CME
program ~ April 11, 2009 Evansville, Indiana

2. Louis B. Cady, M.D. – historical statement of
support, conflict of interests…
• Abbott Laboratories
• Bristol-Myers Squibb (Serzone)
• Celltech (Metadate CD)
• Cephalon (Provigil)
• Elli Lilly (Prozac)
• Forest Pharmaceuticals
(Celexa, Lexapro)
• Glaxo-SmithKline (Wellbutrin, Paxil)
• Janssen (Concerta, Reminyl)
• McNeil (Concerta)
• Pfizer-Roerig (Zoloft)
• Sanofi~aventis (Ambien)
• Sepracor (Lunesta)
• Searle Pharmaceutical (Ambien)
• Shire Pharmaceuticals (Adderall, Vyvnase)
• Takeda Pharmaceuticals (Rozerem)
• Wyeth-Ayerst (Effexor)
Note: There is no
commercial sponsor
for this talk this a.m.

3. H - 3
“There are two objects of medical education: to heal
the sick and to advance the science.”
- Dr. Charles H. Mayo, MD
“The glory of medicine is that it is always moving
forward, that there is always more to learn.”
- Dr. William J. Mayo

5. The CME Rules of Engagement
• My muzzle is off.
• The peer-reviewed medical literature is my
arbiter.
• Fair balance is key, unless there is only one
agent.
• I will stretch you and make you want to go
“check me out” in the literature.

6. How to Do It: The 6 Minute
Drill

7. A Psych work-up in 6 – 7 Minutes
• 1 Minute: background
• 1 Minute: “chief complaint”
• 2 Minutes: SSIGECAPS
– 3 “target symptoms”
– WORRY?
– TOO MUCH ENERGY?
• 1 Minute: medical differential: OSA,
thyroid, cardiac
• 1 Minute: explanation of medication
choice, titration issues
3

8. LOW ENERGY – frequently occurring with
depression. A “no duh,” KNOWN finding.
• People with depression
have LOW ENERGY….
So you….

9. Depression & Anxiety Dx in 1 Easy Lesson
DEPRESSION
SIG: E- CAPS!
• Sleep
• Sadness
• Interest loss
• Guilt
• Energy
• Concentration
• Appetite
• Psychomotor Sx
• Suicidal thinking
• Gen. ANXIETY D.O.
• Somatic Sx (“energy”,etc.)
• WORRY
• Irritability
• Concentration
• Keyed up
• Insomnia (“sleep”)
• Restlessness
SWICKIR is Quicker:
Worry + 3 = GAD (Baughman)
5of 9 with 1 of 2 x 2 weeks

10. Depression & LOW ENERGY in
One Easy Lesson
DEPRESSION
SIG: E- CAPS!
• Sleep
• Sadness
• Interest loss
• Guilt
• Energy
• Concentration
• Appetite
• Psychomotor Sx
• Suicidal thinking
OTHER FREQUENT CAUSES:
• Hypothyroidism
• Sub-syndromal or other
• Low DHEA
• Exhausted adrenals
– (can check with 4 cortisol
levels)
• Low testosterone
• Low micronutrients and
vitamins
• (low growth hormone)
5 of 9 with 1 of 2 x 2 weeks
w/o other causes!!!
MUST EXCLUDE OTHER
CAUSES, as well as treat for
presumptive diagnosis.

11. ADHD – A Family Practice Perspective
Montano, B – Un. Of CT Medical School Dept of Family Practice
• Adult prevalence rate 4.5%
• Most adult sufferers have not been properly
diagnosed or treated.
• They have at least one comorbid psych. d.o.
• This d.o. may offer the first clue of ADHD
• Comorbidities may confound the diagnosis.
• Use of available standardized rating scales
helpful.
• Primary caregivers encouraged to dx and tx.
J Clin Psychiatry. 2004;65 Suppl 3:18-21.

13. The FOUR FLAVORS OF ADHD, or…
314.00 ADHD Predominantly Inattentive
Type*
314.01 ADHD Predominant Hyperactive-
Impulsive Type*
314.04 ADHD, Combined Type
314.9 ADHD – Not Otherwise Specified
If it doesn’t wiggle, it doesn’t mean it’s
not hurting your productivity!

14. —Age—
Inattention
ADHD: Course of the Disorder
*
Loss of productivity
Tardiness, mistakes
Disorganization
Disruption of work flow

15. Kids and Adults – Differences in
INATTENTIVE domain
AS A CHILD:
• Difficulty sustaining
attention
• No follow through
• Cannot organize
• Loses important items
AS AN ADULT:
• Same – in meetings,
reading, paperwork
• Paralyzing
procrastination
• Slow, inefficient. Poor
time management
• Disorganized
Sources: DSM-IV (TR). APA 2000:85-93)
Weiss MD, Weiss JR. J Clin Psychiatry 2004;65(Suppl 3):27-37.

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

17. Adrenal Burnout

18. Scene of a Pharmacy. Late 15th century Fresco. Castle of Issogne, Valle d’Aosta,
Italy. (Pharmacy shows collection of herbs, ointments, oils, and rare substances.
“Mumia” was one of the most exotic!)

19. “Artistic genius” method

20. The “Do I feel
lucky?” method

21. The “Old-Timey” method and The Doc Cady
“Can’ts” of the TCA’s
Pee
Poop
Spit
Spurt
Focus
Think
 Stand up
 Stay awake
 Stay thin
ANTICHOLINERGIC/
ANTIMUSCARINIC
EFFECTS
Alpha-adrenergic
blockade
"Antihistamine"
effects
Paroxetine –
Paxil ® Paxil CR
® Pexeva ®

22. Why you don’t want anticholinergics
Difficulties with:
PEE
POOP
SPIT
SPURT (or equiv. !)
FOCUS
THINK
Related to
ANTICHOLINERGIC
EFFECTS

23. REMEMBER
1. A.D. Rx is given to
treat a LACK of
acetylcholine.
2. Why deliberately
give your patient
(old OR young)
something which
screws around with
cholinergic
neurotransmission?

24. Selecting Tricycyclics…

25. “2 P…
Or not 2 P…
That is the
interaction.”

26. “Drug-drug interactions”:
clinically relevant?!

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

28. S-citalopram
(escitalopram)
R-citalopram
Escitalopram: Benefits of the
Single Isomer
 Most selective SSRI: “more than
twice as selective” as citalopram
 More potent than citalopram in
vitro, lower effective dose
 Purified “active ingredient” of
citalopram
 Not therapeutically active
 Anti-H 1 adverse effects
 Pharmacokinetic effects –
Isomeric “ballast” with no
clinical benefit
Hyttel et al., 1992; Owens et al., 2001; von Moltke et al., 2001
“Celexa”

29. SSRI’s: Good News, Bad News
Clinical
usefulness
Rx-Rx
2nd order
Drug
Robust
2D6
NE
Prozac
Generally well-
tolerated
Neglible
DA
Zoloft
Sedation:
+/- benefits
2D6
Anti-CH!!
Paxil
Lexapro -
UNUSUALLY
CLEAN & powerful
Neglible
Anti-hist./
- nothing
CELEXA/
LEXAPRO
Occasionally
extremely
helpful
3A4 (mild)
-
Luvox (CR)

30. Other serotonin boosters of
significance
Clinical
usefulness
Rx-Rx
2nd order
Drug
“gold stand-
ard”- but TCA
2D6
5 HT
Imipramine
5HT + NE
(side effects!)
CLEAN
NE @
“inflection point”
Effexor
Sedation, weight
gain (may be a
good thing!)
None
5HT AND
NE
Remeron
LIMITED:
“Prozac with an
antidote”
3A4 (? fatal)
“SSRI” =
2ND; 5HT2
blocker = 1st
Serzone
PRISTIQ BALANCED CLEAN IDIOT PROOF!

32. Learning from the past: the role of
norepinephrine in medication therapy
[adapted by Cady from Richelson, Elliott. Pharmacology of antidepressants--characteristics
of the ideal drug. Mayo Clin Proc 1994;69:1069-1081]
385
286
67
7
3
0
0
0 100 200 300 400 500
Norpramin
Vivactil
Pamelor
Wellbutrin
Tofranil
Prozac
Zoloft
Ratio of blocking NE over 5-HT

33. A new wrinkle in medication therapy:
serotonin/norepinephrine
blocking potency ratio or..."Is the antidepressant well-
balanced?"
[adapted by Cady from Richelson, Elliott. Pharmacology of antidepressants--
characteristics of the ideal drug. Mayo Clin Proc 1994;69:1069-1081]
71
64
45
26
23
5
5
4
0 10 20 30 40 50 60 70 80
Luvox
Zoloft
Paxil
Desyrel
Prozac
Effexor
Anafranil
["Serzone"]
Selectivity for blocking uptake of 5-HT over NE

34. Know When to Fold’Em

35. Common sense ‘investing’ – in your
choice of medication
• Peter Lynch: “you should be able to explain in a
‘two minute pitch’ why you are buying a stock.”
• Warren Buffet: “You are neither right nor wrong
because the crowd disagrees with you. You are
right because your data and reasoning are
right.”
If you can’t explain to the medical
board what you’re doing, you
shouldn’t be doing it.

36. WAYS TO TELL YOU MAY BE
HEADED INTO TROUBLE
• Atypical antipsychotics – in ANYBODY that isn’t
clearly bipolar manic or schizophrenic.
– Use as “sleepers”
– Use for “anxiety”
• Alprazolam:
– Unless you choose to use it [off label] for infrequent
treatment of episodic panic attacks or severe anxiety
– Unless it is panic disorder
• Unless they have failed every other reasonable treatment

37. Further ways to head into trouble
• Combining medications in an off-label
manner: Strattera plus stimulant
• Using off-label medication without thorough
explanation, documentation of informed
consent, and appropriate charting.
– EXPLAIN THE POTENTIAL SIDE EFFECTS
• EXAMPLE: Trazodone and priapism

39. When to start THINKING

41. Top five reasons to start thinking
• Are you jamming a symptom into a
syndrome?
• Are you using the right tool for the job?
• Have you actually read the PI and are using
the medication responsibly?
• Are you “missing the medical” because of
the “head case” factor?
• Are you really a pessimistic, nihilistic,
practitioner?

42. 1) Jamming symptoms into syndromes.
• FATIGUE:
– Yes – it could be part of depression – “low
energy”
• Differential:
– Functional hypothyroidism (TSH doesn’t get it)
– OSA
– Post-viral fatigue
– IgG food sensitivities
– (Undisclosed family stress)

43. 2) Right tool for the job
• Buspirone - $4 - $10 at Walmart
– The only specific modern FDA approved anti-
anxiety agent.
– PI dosing is titrate up to 20 mg TID.
– Not “prn”
• Mood stabilizers for mood problems
• Antipsychotics for psychotic problems.
– Think about the potential for side effects!

44. 3) Read the PI? Example: Lamotrigine
• Rationale:
– Quote it and inspire confidence
– Enlist the patient in a therapeutic alliance.
– Forestall problems.
• Pay-offs:
– Maximum therapeutic “pay off” for this Rx trial.
– Avoid catastrophic reactions and malpractice
suits.

45. 4) Don’t “miss the medical”
• Frequent:
– Low thyroid
– “Viagra requests”
– Post-viral fatigue
– OSA
– Less than optimal DHEA

46. “But the doctor told me my thyroid
was fine.”
• 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.

47. Snoring and OSA – no laughing matter
• All adults:
– 2% of women; 4% of men
• Adults aged 30-60 years:
– 9-24% for men
– 4-9% for women
– Adults > 65 years: 65%
• Three biggest killers of
OSA sufferers:
– heart attacks
– Strokes
– Traffic accidents

48. Impotence: nature's way of saying,
"No hard feelings.”
• ABILITY goes…
• THEN desire……
• AND, there is no
known “Viagra
deficiency” in the
published literature.

49. Adrenal Burnout

50. 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]

51. 217 citations on “DHEA with
energy” – Jan 2006

52. 217 308 citations on “DHEA with
energy” – April 10, 2009

53. Signs & Symptoms of Adrenal Fatigue
• Difficulty getting up in a.m.
• Ongoing lethargy during the day.
• Continued fatigue not relieved by sleep.
• Craving for salt or salty foods.
• Increased effort to do daily tasks
• LESS PRODUCTIVE
• Decreased sex drive
• Decreased ability to handle stress.
• Light-headed when standing up quickly
• Increased recovery time for illness
• Generally less happy about life. THINK
CORTISOL!!

54. 5. NIHLISM ANYONE? Or…… Just how
bad do you think your patient is, anyway?
Are they really supposed to be THAT BAD?

55. “The Happy Hungarian”
Franz Lizst – 19th century traveling classical pianist rockstar.
Fathered children in his 70’s. (!!)

56. www.drlife.com

57. H - 57

59. Lymphocytes are used for Functional
Intracellular Analysis
www.spectracell.com

60. Nutrient Deficiencies and Previous
Supplementation
19%
Subjects showing no deficiency in norming studies by Spectracell
43%
Multiple deficiencies
with no previous
supplementation
38%
Multiple deficiencies with
PREVIOUS
SUPPLEMENTATION!

62. TESTOSTERONE
hormone replacement:
now in the peer-
reviewed medical
literature… even
psychiatry!

63. Wonderful things can happen with
adequate hormones!

64. • 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
Testosterone (Men)

65. – By age 70, 15% of men are
completely impotent; larger
percentage have considerably
decreased libido and fullness
of erection
– Correlation to decrease in
bioavailable testosterone
Testosterone (Men)

66. Hormone Lab Values
Age-Related Laboratory Normal Ranges
compared with
Optimal Ranges
Female
Lower
Normal
Lower
Optimal
Upper
Optimal
Upper
Normal
DHEA Sulfate (ug/dL) 12 350 500 379
Total Testosterone (ng/dL) 15 50 70 70
Free Testosterone (pg/mL) 0.6 7 10 8.5
Testosterone, % Free (%) 0.5 0.5 1.9 1.9

70. http://www.cadywellness.com/articles/age_
management_medicine.php
If your body was
a classic car….
How would you
treat it?!

71. Your Classic Car: Do you want “normal”
maintenance & aging, or “OPTIMAL”?!
“NORMAL”
OPTIMAL

72. “Age management
medicine” for automobiles
“Conventional medical
practice” for automobiles
No car lasts forever. We should
therefore take care of them if we want
to get the maximum mileage out of
them!
No car lasts forever. That’s life. Get
another one.
Paint fades and oil gets used up as the
car ages. We should do something
about it.
Paint fades and oil gets used up as the
car ages. This is a normal part of aging
and we should leave it alone.
It is a known fact that oil breaks down
with age, and is contaminated by
combustion products from the engine,
which results in more friction and wear
on the engine. We should do oil
changes every 3,000 miles to keep our
car in top shape.
It is a known fact that oil breaks down
with age, and is contaminated by
combustion products from the engine,
which results in more friction and wear
on the engine. This is just too bad. This
is the oil that came with the car. We
shouldn’t intervene. Just let the engine
seize!

73. There are fuel additives
we can use to keep our
cars burning cleaner and
preserve engines.
No fuel additives should
be used. They are
unnatural. Gas is all that
is required.
We should use optimal
quality of gas. Cheap gas
causes “pinging” which is
hard on the engine.
The quality of the gas is
irrelevant. Anything that
the motor will burn is
adequate.
We should take our car in
for preventive
maintenance before
anything breaks.
Preventive maintenance?
This is silly! Wait until
something breaks, then have
the car towed in so the
mechanic can really tell what
is wrong.

74. Doc Cady’s Genial Principles of
Pharmacotherapy with ANYTHING
•Always start LOW
• Modafanil: 1/8 [ONE-EIGHTH!!] of a 200 mg
tablet. ¼ tablet can produce REAL side effects.
• Lexapro – ¼ of a tablet
• For hormones: same principle. Check labs.
Don’t exceed physiologic norms (with
exception of selecting your “age range” for
your values.)

78. Personal collection
Louis B. Cady, M.D.

79. “For me, the practice of medicine has
opened the door to the greatest adventure in
life. Medicine is like a hallway lined with
doors, each door opening into a different
room, and each room opening
into another hallway,
again lined with doors.
Medicine is always
wonderful and never will
be finished.”
- Charles H. Mayo, M.D.

80. Thank you for your attendance.
Please see:
www.cadywellness.com/oliver for handouts.