2 & 3 together hormones, allopathic psychiatry


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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.

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  • Depressed mood is the most commonly cited symptom in major depressive disorder. Studies have shown that fatigue and reduced energy are nearly as common as depressed mood. As many as 94%-97% of patients may experience reduced energy and fatigue, while 73% may complain of tiredness. Impaired concentration is also common and occurs in as many as 84% of patients. Hypersomnia, or excessive sleepiness as opposed to physical weariness, is less common and occurs in 10%-16% of patients.
  • Addison ’s disease, like so many medical conditions, has a history of being ignored, hidden, and misunderstood.  It is a rare disease that affects about one in every 100,000 Americans and is usually diagnosed around age forty. 
  • These symptoms correlate to decrease in bioavailable testosterone
  • RIA (in-house after diethylether extraction) Total testosterone - T (RIA) 208-1141ng/dL, average 536+/-153ng/dL Bioavailable testosterone - BT (calculated) 78-470ng/dL, average 236+/-63ng/dL
  • Hypogonadal if TT < 200ng/dL or FT < 0.9ng/dL
  • Both MDD and GAD are associated with considerable functional impairment and disability. Comorbid depression and GAD tends to result in greater levels of disability as measured by the proportion of patients who report 1 or more days of disability in a 30-day period. Patients experience diminished functioning both at work and socially, with many reporting moderate or severe social disability. Reference Wittchen HU. Generalized anxiety disorder: prevalence, burden, and cost to society. Depress Anxiety . 2002;16:162-171.
  • ADHD is a heterogeneous disorder associated with considerable disability and comorbidity that, in many cases, persists into adulthood. 1 Mood, anxiety, and substance use disorders are the most common comorbid disorders in adults with ADHD. 2 ADHD in adults is more prevalent than once thought. The National Comorbidity Survey found the estimated lifetime prevalence of ADHD in adults to be 8.1%. 3 According to DSM-IV criteria, adults diagnosed with ADHD must have had childhood onset and persistent and current symptoms, although allowance is made for partial remission. 4 Due to the great syndromatic continuity between childhood and adult ADHD, much of the medication management of adults with ADHD can be based on the experience gained from treating children and adolescents. 5 Barkley RA, Fischer M, Smallish L, Fletcher K. The persistence of attention-deficit/hyperactivity disorder into young adulthood as a function of reporting source and definition of disorder. J Abnormal Psychol. 2002;111:279-289. Biederman J, Faraone SV, Spencer T, et al. Patterns of psychiatric comorbidity, cognition, and psychosocial functioning in adults with attention deficit hyperactivity disorder. Am J Psychiatry . 1993;150:1792-1798. Kessler RC, Berglund P, Demler O, Jin R, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry . 2005;62:593-602. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 4th ed. ( DSM-IV  ). Washington, DC: American Psychiatric Association; 1994:78-85. Dodson WW. Pharmacotherapy of adult ADHD. J Clin Psychol . 2005;61:589-606.
  • 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.
  • Duloxetine versus escitalopram and placebo: an 8-month, double-blind trial in patients with major depressive disorder. Curr Med Res Opin. 2007 Apr 27;
  • Overall effects of treatment of depression were assessed by the HAMD 17 total score using MMRM analysis. Treatment effects related to the somatic symptoms associated with depression were assessed by the anxiety/somatization subscale that consists of HAMD 17 items 10 (psychiatric anxiety), 11 (somatic anxiety), 12 (gastrointestinal-related symptoms), 13 (general somatic symptoms), 15 (hypochondriasis), and 17 (insight). The sleep subscale (HAMD 17 items 4, 5, and 6) was used to assess the treatment effects on insomnia (initial, middle, and terminal). The Maier subscale measures the core symptoms of depression and comprises HAMD 17 items 1 (depressed mood), 2 (feelings of guilt), 7 (work and activities), 8 (retardation), 9 (agitation), and 10 (psychic anxiety). The impact of treatment on energy and interest levels was evaluated by the retardation subscale: HAMD 17 items 1 (depressed mood), 7 (work and activities), 8 (retardation), and 14 (genital symptoms). After 8 months of treatment, duloxetine (60-120 mg/day) and escitalopram (10-20 mg/day) showed similar efficacy on HAMD 17 total and subscale scores, except the sleep subscale. On the HAMD 17 sleep subscale, escitalopram was significantly more efficacious than duloxetine (p<0.05). Rates of remission were not significantly different between escitalopram and duloxetine over the 8-month course of the study (50% vs 47%; respectively). Because so few patients on placebo (n=15) completed the entire 8-month study, the power to detect a difference between placebo and active treatments after 8 weeks was significantly decreased and very likely to be insufficient. Reference Pigott TA, Prakash A, Arnold LM, Aaronson ST, Mallinckrodt CH, Wohlreich MM. Duloxetine versus escitalopram and placebo: an 8-month, double-blind trial in patients with major depressive disorder. Curr Med Res Opin . 2007;23(6)1303-1318.
  • This slide shows the adverse events that were significantly different between escitalopram and duloxetine. Nausea, dry mouth, vomiting, yawning, and night sweats were reported at a significantly higher rate with duloxetine than with escitalopram, whereas only migraine was more frequently reported in the escitalopram group than in the duloxetine group. References: Pigott TA, Prakash A, Arnold LM, Aaronson ST, Mallinckrodt CH, Wohlreich MM. Duloxetine versus escitalopram and placebo: an 8-month, double-blind trial in patients with major depressive disorder. Curr Med Res Opin . 2007;23(6)1303-1318.
  • Throughout this 8-month extension study, escitalopram and duloxetine showed similar efficacy on all study measures except on the HAMD 17 sleep subscale. On the HAMD 17 sleep subscale, escitalopram was significantly more efficacious than duloxetine. Remission rates between escitalopram and duloxetine were not significantly different and both treatments lead to continued improvement over time. Significantly more escitalopram-treated patients continued treatment compared to duloxetine-treated patients, and duloxetine treatment led to an increase in both pulse and systolic blood pressure. References: Pigott TA, Prakash A, Arnold LM, Aaronson ST, Mallinckrodt CH, Wohlreich MM. Duloxetine versus escitalopram and placebo: an 8-month, double-blind trial in patients with major depressive disorder. Curr Med Res Opin . 2007;23(6)1303-1318.
  • 2 & 3 together hormones, allopathic psychiatry

    1. 1. 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, IndianaThis 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
    2. 2. What our patients are telling us:
    3. 3. 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.”
    4. 4. S N O TI CA BODYD IN M
    5. 5. 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
    6. 6. 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!
    7. 7. Interesting lab values – Cady – 3/11/03:Lab Value Cenegenics Normala.m.glucose 87 mg/dl 65 – 85 65 – 109Fasting insulin 3 u U/ml <5 <20HgB A1C 4.9 % <5.1% < 6.0 %Cholesterol 241 mg/dl <200 <200Triglycerides 42 mg/dl <120 <150Cor. Risk ratio 3.3 <4.0 Av = 5 – 6Homocysteine 7.9 <8.0 5.4-11.4DHEA-S 148 350 – 500 59 – 452
    8. 8. 4
    9. 9. 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 GlandCortisol Testosterone Estrogen IGF-1 T3 & T4DHEA Progesterone
    10. 10. 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 GenPract 1998;48:1245-1246. 3. Baker et al. Comp Psychiatry 1971;12:354-65. 4. Horwath etal. J Affect Disord 1992;26:117-25. 5. Reynolds and Kupfer. Sleep 1987;10:199-215.
    11. 11. “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.
    12. 12. “the foot soldier” “the evil twin”
    13. 13. “Thyrotropin (Thyroid-StimulatingHormone or TSH). Measuring TSH is themost sensitive indicator ofhypothyroidism.” (hunh?!) http://www.umm.edu/patiented/articles/how_serious_hypothyroidism Accessed: 9/5/2011
    14. 14. Se CORTISOL“the foot soldier” “the evil twin”
    15. 15. 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]3,35-(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.
    16. 16. 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
    17. 17. 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
    18. 18. • 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.”
    19. 19. Fatigue from Adrenal Dysfunction - TheWorst Case Scensario: Addison’s Disease
    20. 20. “Hypoadrenia”: The Adrenal Problem that mostconventionally trained physicians don’t know about.• Non-Addison’s hypoadrenia• Subclinical hypoadrenia• Neurasthenia• Adrenal neurasthenia• Adrenal apathy• Adrenal fatigue• “Adrenal burnout”• “Chronic fatigue syndrome”?!!
    21. 21. The state of adrenal exhaustion can be determinedEarly-stage Chronic Mid-stage Chronic End-stage (exhausted) Stress Response Stress Response Chronic Stress Response
    22. 22. 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
    23. 23. 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
    24. 24. 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
    25. 25. 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.”
    26. 26. “Women’s issues”
    27. 27. 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}
    28. 28. 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”
    29. 29. G.G. – labs before and after 4/11/11 interventions 7/11/11 changesTSH 3.84 Raise T4 from 0.01 (L) none 50 – 75 ugFT4 1.16 “ 1.24 “FT3 2.8 “ 3.3 “Progesterone <0.2 100mg topical 0.9 None HSTestosterone 11 4mg topical 15 4 mg LABIALDHEA-S 25 25 mg SR n/a continue
    30. 30. The glamorous grandmother – post tune-up9/28/2011 (permission granted to use photos & data) 01/26/2012
    31. 31. 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
    32. 32. 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.”
    33. 33. 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.
    34. 34. 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
    35. 35. 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.
    36. 36. 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.
    37. 37. 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
    38. 38. 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.
    39. 39. 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}
    40. 40. 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.”
    41. 41. 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)
    42. 42. 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.”
    43. 43. 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
    44. 44. 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
    45. 45. T vs Cognitive Function Rosario ER. JAMA. 292(2004):1431-2
    46. 46. 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
    47. 47. 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
    48. 48. 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
    49. 49. 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.
    50. 50. Holistic Fun with HormonesA synthesis…
    51. 51. 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.”
    52. 52. Treatment for this “normal” patient1. 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
    53. 53. 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.”
    54. 54. 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
    55. 55. 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)
    56. 56. “Sit down before fact asa little child,be prepared to give upevery preconceivednotion,follow humbly wherever… nature leads, or you shall learnnothing.”- Thomas H. Huxley
    57. 57. 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, IndianaThis presentation is © Louis B. Cady M.D. and may not be reproduced or used withoutpermission. World Link Medical is authorized to reprint/duplicate it for 2012 syllabi. (c) 2012 Louis B. Cady, M.D. - all rights reserved
    58. 58. 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.
    59. 59. 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
    60. 60. *ACCURATE MEDICAL diagnosis a malpractice suit Depression & Anxiety & “mood disorder due to a in 1 Easy Lesson general medical condition” AND r/o bipolar disorderDEPRESSION 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
    61. 61. 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
    62. 62. Where does ADHD come from?
    63. 63. Kids and Adults – Differences in HYPERACTIVE domainAS 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.
    64. 64. Horrigan J, et al. Presented at 47th Annual AACAP Meeting:October 24-29, 2000. New York, NY.
    65. 65. 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.
    66. 66. 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]
    67. 67. Failure to adequately treat1. “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).
    68. 68. 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
    69. 69. 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.
    70. 70. 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
    71. 71. Why treatment failures occur: too much or too little… The REAL mechanism of action of SSRI’sAnimation © NEI, Inc. (Neuroscience Institute) and is used specifically with permission fromStephen Stahl, MD, Ph.D.
    72. 72. Drug, drug...whos got the drug?
    73. 73. Depression/anxiety Rx: • TCA • Venlafaxine (Effexor) • Duloxetine (Cymbalta) • Mirtazapine (alpha 2) • Desmethylvenlafaxine (Pristiq) & others….
    74. 74. 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
    75. 75. “Drug-drug interactions” clinically relevant?!
    76. 76. Drug-drug interactions: chum for legal “sharks”
    77. 77. “Strattera [coupled withProzac or Paxil] has beengreat for our admissions. ” -Dr. William Beute, MD Pine Rest Campus Clinic Grand Rapids, MI April 21, 2004 [quoted with permission]
    78. 78. Cytochrome p-450 2D6 inhibition measured as % increase in “Desipramine AUC” – in vivo data Critically important when combining with other Rx metabolized through 2D6 pathwaysPreskhorn, Alderman, et al. Pharmacokinetics of desipramine coadministeredwith sertraline or fluoxetine. J. Clin Psychopharmacol 1994;14:90-98;Escitalopram package insert - note – different source of data, but same method
    79. 79. Some drugs metabolized through cytochrome P-450 IID6 systemADHD Antibiotics ANTI-PAINAmphetamines •TMP & SMXSTRATTERA CODEINE! •AmpicillinAnalgesics •Erythromycin Bronchodilators•Acetaminophen •Penicillin •Theophylline•Aspirin •Tetracycline CardiacAntacids Antidepressants •Digoxin; digitalisAntiarrthymics •TCA’s & “2P’s” Cough•Procainamide, Antihistamines •Dextromethorphan•Quinidine Antihypertensives Diuretics•Encainide•Flecainide Antipsychotics •ChlorthalidoneAnticonvulsant •Clozaril •Furosemide•carbamazepine •Risperdal •HCTZ •Zyprexa •Triamterine
    80. 80. The “not so selective” SSRI’s; how to “Do yourself a favor.”drug SSRI? 2nd order effects Side effects possibleEscitalopram Yes NOTHING (excess serotonin side(Lexapro) now effects only)genericSertraline (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 sxsFluoxetine Yes 5HT2C Agitation, appetite(Prozac) suppression
    81. 81. New Agents, New Mechanisms(agent) (MOA) Differentiating pointsVenlafaxine (“IR” and XR) SSRI, NRI Nausea, GI side effects, sxl(Effexor) dysfunctionDuloxetine (Cymbalta) SSRI, NRI Same. Better tolerated. For pain w/ dep.Desvenlafaxine (Pristiq) SSRI, NRI Better toleratedTrazodone XR with 5HT2a/cContramid® (OLEPTRO) BLOCKER, mild SSRIVilazodone (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.
    82. 82. Duloxetine (Cymbalta) VersusEscitalopram (Lexapro) and Placebo:An 8-month, Double-Blind Trial in Patients With Major Depressive Disorder Pigott et al., Curr Med Res Opin, 2007
    83. 83. RetardatioComparison 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
    84. 84. Comparison of Escitalopram and Duloxetine: 8- Month TrialSignificantly Different Adverse Events (p<0.05 Duloxetine vs Escitalopram) Percent of Patients Pigott et al., Curr Med Res Opin, 2007
    85. 85. Comparison of Escitalopram and Duloxetine: 8-Month TrialConclusions• 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
    86. 86. 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!
    87. 87. 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
    88. 88. 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
    89. 89. 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.
    90. 90. 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)
    91. 91. 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)
    92. 92. 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)
    93. 93. 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.
    94. 94. “There are thingsknown and there arethings unknown, andin between are thedoors.”- Jim Morrison
    95. 95. Thanks for coming! Sunset at CWI –by Louis B. Cady, M.D.
    96. 96. 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)