Download to read offline
![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](https://image.slidesharecdn.com/sendintheshrinks-231214185340-abd212eb/75/SEND-IN-THE-SHRINKS-2009-Oliver-CME-seminar-32-2048.jpg)
![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](https://image.slidesharecdn.com/sendintheshrinks-231214185340-abd212eb/75/SEND-IN-THE-SHRINKS-2009-Oliver-CME-seminar-33-2048.jpg)
![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](https://image.slidesharecdn.com/sendintheshrinks-231214185340-abd212eb/75/SEND-IN-THE-SHRINKS-2009-Oliver-CME-seminar-36-2048.jpg)
![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]](https://image.slidesharecdn.com/sendintheshrinks-231214185340-abd212eb/75/SEND-IN-THE-SHRINKS-2009-Oliver-CME-seminar-50-2048.jpg)
![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.)](https://image.slidesharecdn.com/sendintheshrinks-231214185340-abd212eb/75/SEND-IN-THE-SHRINKS-2009-Oliver-CME-seminar-74-2048.jpg)
Uploaded byLouis Cady, MD
SEND IN THE SHRINKS - 2009 Oliver CME seminar
Dr. Louis B. Cady presents an overview of psychiatric evaluations and medication management, emphasizing the importance of accurate diagnosis and appropriate treatment strategies. The document discusses various psychiatric disorders, their symptoms, and treatment options, particularly focusing on ADHD and antidepressant therapies, while highlighting the significance of individualized care and informed decision-making. Cady also addresses the potential pitfalls in prescribing practices and the need for ongoing education in medical practice.
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SEND IN THE SHRINKS - 2009 Oliver CME seminar
- 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 “Thereare 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 Rulesof 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 DoIt: The 6 Minute Drill
- 7. A Psych work-upin 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 & AnxietyDx 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 & LOWENERGY 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 – AFamily 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 FLAVORSOF 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 ofthe 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.
- 18. Scene of aPharmacy. 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.
- 20. The “Do Ifeel lucky?” method
- 21. The “Old-Timey” methodand 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’twant anticholinergics Difficulties with: PEE POOP SPIT SPURT (or equiv. !) FOCUS THINK Related to ANTICHOLINERGIC EFFECTS
- 23. REMEMBER 1. A.D. Rxis given to treat a LACK of acetylcholine. 2. Why deliberately give your patient (old OR young) something which screws around with cholinergic neurotransmission?
- 24.
- 25. “2 P… Or not2 P… That is the interaction.”
- 26.
- 27. Drug-drug interactions: chumfor legal “sharks”
- 28. S-citalopram (escitalopram) R-citalopram Escitalopram: Benefits ofthe 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 boostersof 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 thepast: 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 wrinklein 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 toFold’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 TELLYOU 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 tohead 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 startTHINKING
- 41. Top five reasonsto 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 symptomsinto 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 toolfor 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 thePI? 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 “missthe medical” • Frequent: – Low thyroid – “Viagra requests” – Post-viral fatigue – OSA – Less than optimal DHEA
- 46. “But the doctortold 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 wayof saying, "No hard feelings.” • ABILITY goes… • THEN desire…… • AND, there is no known “Viagra deficiency” in the published literature.
- 49.
- 50. DHEA – thecritical 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 citationson “DHEA with energy” – April 10, 2009
- 53. Signs & Symptomsof 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” FranzLizst – 19th century traveling classical pianist rockstar. Fathered children in his 70’s. (!!)
- 56.
- 57.
- 59. Lymphocytes are usedfor Functional Intracellular Analysis www.spectracell.com
- 60. Nutrient Deficiencies andPrevious 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 inthe peer- reviewed medical literature… even psychiatry!
- 63. Wonderful things canhappen with adequate hormones!
- 64. • Decline inmale 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 age70, 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-RelatedLaboratory 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 bodywas 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” forautomobiles “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 fueladditives 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 GenialPrinciples 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, thepractice 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 foryour attendance. Please see: www.cadywellness.com/oliver for handouts.