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www.cadywellness.com
Louis B. Cady, MD – CEO & Founder – Cady Wellness Institute  Adjunct Professor – University of Southern Indiana Adjunct Cl...
“ Slumber not in the tents of your fathers.  The world is advancing.  Advance with it.” -  Giuseppe Mazzine
Topics we will cover in this talk <ul><ul><li>How it works </li></ul></ul><ul><ul><li>Safety and tolerability </li></ul></...
Depression & Anxiety & a malpractice suit in 1 Easy Lesson <ul><li>DEPRESSION SIG: E- CAPS! </li></ul><ul><li>Sleep </li><...
Comorbidity of Depression and Anxiety % Patients  Disabled 3+ Days 33.7% 19.45% 16.9% 3.1% Disability Wittchen,  Depress A...
“ Drug-drug interactions”  clinically relevant?!
Drug-drug interactions: chum for legal  “sharks”
“ Strattera  [coupled with Prozac or Paxil]   has been great for our admissions. ” -Dr. William Beute, MD Pine Rest Campus...
Cytochrome p-450 2D6 inhibition measured as % increase in  “Desipramine AUC” – in vivo data Preskhorn, Alderman, et al.  P...
Some  drugs metabolized through cytochrome P-450 IID6 system <ul><li>ADHD </li></ul><ul><ul><li>Amphetamines </li></ul></u...
“  A Trazodone product that actually WORKS for depression.” <ul><li>(Levels done after 7 days steady state) </li></ul><ul>...
XR Trazodone Food Effect Study <ul><li>PI says “take at night”  </li></ul><ul><li>CMax increase by 86% (!!!) under fed con...
Vilazodone – a  SPARI  (per Stephen Stahl, MD, Ph.D.) –  Serotonin Partial Agonist Reuptake Inhibitor <ul><li>Highly serot...
Major Depression Unmet Medical Needs
<ul><li>With each successive treatment failure, the landscape changes: </li></ul>Major Depression Current Treatment Landsc...
Adequate Treatment Is Difficult to Achieve Nemeroff (1996/1997)  Depress Anxiety ; Oquendo (2003)  J Clin Psychiatry ; Oqu...
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 & Covi...
“ Thyrotropin (Thyroid-Stimulating Hormone or TSH).  Measuring TSH is the most sensitive indicator of hypothyroidism. ”  (...
“ the foot soldier” “ the evil twin ” CORTISOL Se ?
Yes, T-3 DOES get into the brain  (Transthyretin = carrier protein ) <ul><li>Terasaki, T. and Pardridge, W.M.: Stereospeci...
 
 
STAR*D Study demonstrates that current treatment has limited effectiveness Trivedi (2006)  Am J Psychiatry ; Rush (2006)  ...
Likelihood of discontinuing treatment increases  with each new medication attempt Systemic   Drug Side Effects <ul><li>Wei...
Best Practices Treatment Guideline for Depression Based on 2010 APA guidelines and NeuroStar TMS Therapy® indication for u...
 
The Therapeutic Trifecta of Psychiatry: Shrinking Shocking or Drugging The  only three things you could do to a patient’s ...
A quick look back in history
&quot; The Shock Shop , Mr. McMurphy, might be said to do the work of the sleeping pill, the electric chair and the tortur...
Treating the Brain as an Electrochemical Target <ul><li>Brain activity can be altered: </li></ul><ul><ul><li>By PsychoTx <...
From Michael Farraday to today
Transcranial Magnetic Stimulation (TMS) <ul><li>The treatment coil produces 1.5 Tesla MRI-level field strength </li></ul><...
Per FDA Labeling: <ul><li>“ The NeuroStar* TMS System is indicated for the treatment of adult patients with Major Depressi...
ECT vs. TMS ECT TMS Anesthesia, LOC Yes No Induction of seizure Yes No Systemic effects Anesthetic drugs, increase HR none...
TMS Targeted Effects on Local and Distant Regional Blood Flow Nahas Z et al.  Brain Effects of TMS  Delivered Over Pefront...
Nahas Z et al.  Brain Effects of TMS  Delivered Over Pefrontal Cortex in Depressed Adults.  Journal of Neuropsychiatry and...
Targeted Effects on Mood Circuits in Brain  - aggregate SPECT of 12 patients after Left DLFC TMS: activation of fronto-cin...
TMS Therapy in Clinical Practice <ul><li>One TMS device FDA-cleared for the treatment of depression  </li></ul><ul><li>Non...
Recent TMS Literature Review <ul><li>Roughly 30 controlled clinical research studies to date </li></ul><ul><li>Most recent...
O’Reardon, JP, et al. (2007) Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depr...
<ul><li>No systemic side effects </li></ul><ul><li>No adverse effect on cognition </li></ul><ul><li>Most common adverse ev...
Contraindication <ul><li>TMS Therapy is contraindicated in patients with implanted metallic devices or non-removable metal...
Active research…
“ But my patients don’t know about this and aren’t asking for it….” <ul><li>“ It’s not the consumers’ job to know what the...
Perhaps the ability not only to acquire the confidence of the patient, but  to deserve it,  to see what the patient desire...
 
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Henderson depression update incl tms

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Dr. Cady presented this CME program on depression and TMS (Transcranial magnetic stimulation) to the medical staff of the Community Methodist Hospital in Henderson, KY on February 8, 2012. It reviews accurate diagnosis of depression, use of new medications, cautions on drug-drug interactions, and a review of the new development of TMS in the current treatments of 21st Century psychiatry.

Published in: Health & Medicine

Henderson depression update incl tms

  1. 2. www.cadywellness.com
  2. 3. 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 DEPRESSION: A CME REVIEW AND UPDATE ON TREATMENTS Presented to Henderson Community Methodist Hospital – Feb 8, 2012
  3. 4. “ Slumber not in the tents of your fathers. The world is advancing. Advance with it.” - Giuseppe Mazzine
  4. 5. Topics we will cover in this talk <ul><ul><li>How it works </li></ul></ul><ul><ul><li>Safety and tolerability </li></ul></ul><ul><ul><li>Where it fits in the “Treatment Algorithm” for Major Depression </li></ul></ul><ul><ul><li>New drugs </li></ul></ul><ul><ul><li>Unmet medical needs </li></ul></ul>TMS Major Depression
  5. 6. Depression & Anxiety & a malpractice suit in 1 Easy Lesson <ul><li>DEPRESSION SIG: E- CAPS! </li></ul><ul><li>Sleep </li></ul><ul><li>Sadness </li></ul><ul><li>Interest loss </li></ul><ul><li>Guilt </li></ul><ul><li>*Energy </li></ul><ul><li>Concentration </li></ul><ul><li>Appetite </li></ul><ul><li>Psychomotor Sx </li></ul><ul><li>Suicidal thinking </li></ul><ul><li>Gen. ANXIETY D.O. </li></ul><ul><li>Somatic Sx ( “ energy ”,etc.) </li></ul><ul><li>WORRY </li></ul><ul><li>Irritability </li></ul><ul><li>Concentration </li></ul><ul><li>Keyed up </li></ul><ul><li>Insomnia ( “sleep”) </li></ul><ul><li>Restlessness </li></ul>SWICKIR is Quicker: Worry + 3 = GAD (Baughman) 5of 9 with 1 of 2 x 2 weeks *ACCURATE MEDICAL diagnosis “mood disorder due to a general medical condition” AND r/o bipolar disorder BEWARE BEWARE – “too much” energy
  6. 7. Comorbidity of Depression and Anxiety % Patients Disabled 3+ Days 33.7% 19.45% 16.9% 3.1% Disability Wittchen, Depress Anxiety , 2002 Percent of Patients With ≥ 1 Disability Day in Past Month GAD + MDD MDD/no GAD GAD/no MDD no GAD/no MDD
  7. 8. “ Drug-drug interactions” clinically relevant?!
  8. 9. Drug-drug interactions: chum for legal “sharks”
  9. 10. “ 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]
  10. 11. Cytochrome p-450 2D6 inhibition measured as % increase in “Desipramine AUC” – in vivo data Preskhorn, Alderman, et al. Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine. J. Clin Psychopharmacol 1994;14:90-98; Escitalopram package insert - note – different source of data, but same method Critically important when combining with other Rx metabolized through 2D6 pathways
  11. 12. Some drugs metabolized through cytochrome P-450 IID6 system <ul><li>ADHD </li></ul><ul><ul><li>Amphetamines </li></ul></ul><ul><ul><li>STRATTERA </li></ul></ul><ul><li>Analgesics </li></ul><ul><ul><li>Acetaminophen </li></ul></ul><ul><ul><li>Aspirin </li></ul></ul><ul><li>Antacids </li></ul><ul><li>Antiarrthymics </li></ul><ul><ul><li>Procainamide, </li></ul></ul><ul><ul><li>Quinidine </li></ul></ul><ul><ul><li>Encainide </li></ul></ul><ul><ul><li>Flecainide </li></ul></ul><ul><li>Anticonvulsant </li></ul><ul><ul><li>carbamazepine </li></ul></ul><ul><li>ANTI-PAIN </li></ul><ul><ul><li>CODEINE! </li></ul></ul><ul><li>Bronchodilators </li></ul><ul><ul><li>Theophylline </li></ul></ul><ul><li>Cardiac </li></ul><ul><ul><li>Digoxin; digitalis </li></ul></ul><ul><li>Cough </li></ul><ul><ul><li>Dextromethorphan </li></ul></ul><ul><li>Diuretics </li></ul><ul><ul><li>Chlorthalidone </li></ul></ul><ul><ul><li>Furosemide </li></ul></ul><ul><ul><li>HCTZ </li></ul></ul><ul><ul><li>Triamterene </li></ul></ul><ul><li>Antibiotics </li></ul><ul><ul><li>TMP & SMX </li></ul></ul><ul><ul><li>Ampicillin </li></ul></ul><ul><ul><li>Erythromycin </li></ul></ul><ul><ul><li>Penicillin </li></ul></ul><ul><ul><li>Tetracycline </li></ul></ul><ul><li>Antidepressants </li></ul><ul><ul><li>TCA ’ s & “ 2P ’ s ” </li></ul></ul><ul><li>Antihistamines </li></ul><ul><li>Antihypertensives </li></ul><ul><li>Antipsychotics </li></ul><ul><ul><li>Clozaril </li></ul></ul><ul><ul><li>Risperdal </li></ul></ul><ul><ul><li>Zyprexa </li></ul></ul>
  12. 13. “ A Trazodone product that actually WORKS for depression.” <ul><li>(Levels done after 7 days steady state) </li></ul><ul><li>300 mg XR Traz AUC comparable to 100 mg IR Traz tid </li></ul><ul><li>Cmax 42% lower than IR Trazodone </li></ul><ul><ul><li>Translation – it doesn’t dope the patient up. </li></ul></ul>Kramer, WG et al. Once-daily Trazodone: Overview of Pharmacokinetic Properties. Poster – ACCP 38 th Annual Meeting, San Antonio, TX 2005
  13. 14. XR Trazodone Food Effect Study <ul><li>PI says “take at night” </li></ul><ul><li>CMax increase by 86% (!!!) under fed conditions. Peak is at 7 hours post dose (with feeding). </li></ul><ul><li>Note – this may lead the enlightened prescriber to vary the time of dosing. </li></ul>Kramer, WG et al. Once-daily Trazodone: Overview of Pharmacokinetic Properties. Poster – ACCP 38 th Annual Meeting, San Antonio, TX 2005
  14. 15. Vilazodone – a SPARI (per Stephen Stahl, MD, Ph.D.) – Serotonin Partial Agonist Reuptake Inhibitor <ul><li>Highly serotonergic. START LOW (5 mg). </li></ul><ul><li>Because of 5HT1A agonism, LESS “SSRI” effect is required. </li></ul>
  15. 16. Major Depression Unmet Medical Needs
  16. 17. <ul><li>With each successive treatment failure, the landscape changes: </li></ul>Major Depression Current Treatment Landscape Trivedi (2006) Am J Psychiatry; Rush (2006) Am J Psychiatry; Fava (2006) Am J Psychiatry; McGrath (2006) Am J Psychiatry High Low Adverse Events Long-Term Durability Efficacy Responsive Resistant Treatment Effectiveness <ul><ul><li>Likelihood of long-term durability of benefit declines </li></ul></ul><ul><ul><li>Intolerance due to adverse events worsens </li></ul></ul><ul><ul><li>Likelihood of benefit from the next option diminishes </li></ul></ul>OUTCOME
  17. 18. Adequate Treatment Is Difficult to Achieve Nemeroff (1996/1997) Depress Anxiety ; Oquendo (2003) J Clin Psychiatry ; Oquendo (1999) Am J Psychiatry . <ul><li>Adequacy of treatment has been estimated to be as low as 18%, regardless of agent used </li></ul><ul><li>The ratio of inadequate-to-adequate treatment attempts is 4:1 </li></ul>… adequate treatment in depression is the exception, not the norm Adequate Dosage Adequate Duration Poor tolerability Lack of adherence to recommended treatment Lack of efficacy Medical and Psychiatric Comorbidities Factors contributing to inadequate treatment include:
  18. 19. 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 LEVEL III RESULTS:
  19. 20. “ 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_000038_6.htm Accessed: 9/5/2011
  20. 21. “ the foot soldier” “ the evil twin ” CORTISOL Se ?
  21. 22. Yes, T-3 DOES get into the brain (Transthyretin = carrier protein ) <ul><li>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. </li></ul><ul><li>http://www.kingpharm.com/uploads/pdf_inserts/Cytomel_PI.pdf . </li></ul><ul><li>Mooradian, A.D.: Blood-brain transport of triiodothyronine is reduced in aged rats. Mech. Ageing Dev ., 52(2-3):141-147, 1990. </li></ul><ul><li>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. </li></ul><ul><li>Rudas, P. and Bartha, T.: Thyroxine and triiodothyronine uptake by the brain of chickens. Acta Vet. Hung , 41(3-4):395-408, 1993. </li></ul>Or: Why is T3 reasonable for depression?
  22. 25. STAR*D Study demonstrates that current treatment has limited effectiveness Trivedi (2006) Am J Psychiatry ; Rush (2006) Am J Psychiatry ; Fava (2006) Am J Psychiatry ; McGrath (2006) Am J Psychiatry
  23. 26. Likelihood of discontinuing treatment increases with each new medication attempt Systemic Drug Side Effects <ul><li>Weight Gain </li></ul><ul><li>Constipation </li></ul><ul><li>Diarrhea </li></ul><ul><li>Nausea </li></ul><ul><li>Drowsiness </li></ul><ul><li>Insomnia </li></ul><ul><li>Decreased Libido </li></ul><ul><li>Nervous Anxiety </li></ul><ul><li>Increased Appetite </li></ul><ul><li>Decreased Appetite </li></ul><ul><li>Fatigue </li></ul><ul><li>Headache/ Migraine </li></ul><ul><li>Abnormal Ejaculation </li></ul><ul><li>Impotence </li></ul><ul><li>Sweating </li></ul><ul><li>Tremor </li></ul><ul><li>Treatment Discontinuation Side Effects </li></ul><ul><li>Weakness </li></ul><ul><li>Dry Mouth </li></ul><ul><li>Dizziness </li></ul>Trivedi (2006) Am J Psychiatry ; Rush (2006) Am J Psychiatry ; Fava (2006) Am J Psychiatry ; McGrath (2006) Am J Psychiatry ; Neuronetics, Inc. (data on file)
  24. 27. Best Practices Treatment Guideline for Depression Based on 2010 APA guidelines and NeuroStar TMS Therapy® indication for use. Adapted from: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3 rd Edition, APA (2010) Unmet Medical Needs
  25. 29. The Therapeutic Trifecta of Psychiatry: Shrinking Shocking or Drugging The only three things you could do to a patient’s brain…
  26. 30. A quick look back in history
  27. 31. &quot; The Shock Shop , Mr. McMurphy, might be said to do the work of the sleeping pill, the electric chair and the torture rack. It's a clever little procedure, simple, quick, nearly painless it happens so fast, but no one ever wants another one. Ever.”
  28. 32. Treating the Brain as an Electrochemical Target <ul><li>Brain activity can be altered: </li></ul><ul><ul><li>By PsychoTx </li></ul></ul><ul><ul><li>Chemically (eg, via drugs) </li></ul></ul><ul><ul><li>Electrically (eg, via ECT or TMS) </li></ul></ul><ul><li>Drug action is anatomically diffuse and systemic </li></ul><ul><li>ECT is generalized and electro-chemical </li></ul><ul><li>TMS is focused, non-invasive and non-systemic </li></ul>Pizzigalli (2011) Neuropsychopharmacology Amygdala Ventromedial Prefrontal Cortex Prefrontal Cortex Anterior Cingulate Gyrus
  29. 33. From Michael Farraday to today
  30. 34. Transcranial Magnetic Stimulation (TMS) <ul><li>The treatment coil produces 1.5 Tesla MRI-level field strength </li></ul><ul><li>Magnetic field pulses to 2-3 cm. depth; induces small current. [Faraday – Inductive Coupling] </li></ul><ul><li>Current depolarizes neurons locally and precisely. Neurotransmitters released LOCALLY, and circuits fire. </li></ul>Faraday (1839) Experimental Research in Electricity . Vol 1; Barker (1991) J Clin Neurophysiol ; Barker (1985) Lancet
  31. 35. Per FDA Labeling: <ul><li>“ The NeuroStar* TMS System is indicated for the treatment of adult patients with Major Depressive Disorder (MDD) who have failed to receive satisfactory improvement from one prior antidepressant medication at or above the minimal effective dose and duration in the current episode…” </li></ul>* CME explanatory note – the brand name is used because this is the only currently FDA approved treatment fot TMS.
  32. 36. ECT vs. TMS ECT TMS Anesthesia, LOC Yes No Induction of seizure Yes No Systemic effects Anesthetic drugs, increase HR none Treatment schedule 3X/ week (8 -15 tx) Daily, M-F, six weeks (30 tx) Rapidity of onset 2 – 3 treatments 2 – 3 weeks Mechanism of action SEIZURE. Massive NT release; rise in sz threshold Reactivation of neural circuits. Precise, LOCAL release of NT’s. Side effects Memory loss, confusion Essentially none (mild HA 1 st week) Psychosocial impact can’t work Drive to and from tx’s, work improved After-effects Mild (usually transient) memory loss None. Pro-cognitive Insurance coverage Almost always Rare. Improving
  33. 37. TMS Targeted Effects on Local and Distant Regional Blood Flow Nahas Z et al. Brain Effects of TMS Delivered Over Pefrontal Cortex in Depressed Adults. Journal of Neuropsychiatry and Clinical Neurosciences 2001:13:459-460.
  34. 38. Nahas Z et al. Brain Effects of TMS Delivered Over Pefrontal Cortex in Depressed Adults. Journal of Neuropsychiatry and Clinical Neurosciences 2001:13:459-460.
  35. 39. Targeted Effects on Mood Circuits in Brain - aggregate SPECT of 12 patients after Left DLFC TMS: activation of fronto-cingulate brain circuit <ul><li>Kito, S, Fujita, K, Koga, Y. (2008) Changes in Regional Cerebral Blood Flow After Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex in Treatment-Resistant Depression. J Neuropsychiatry Clin Neurosci 20(1) :74-80. </li></ul>TMS Coil L L R R
  36. 40. TMS Therapy in Clinical Practice <ul><li>One TMS device FDA-cleared for the treatment of depression </li></ul><ul><li>Non-invasive and non-systemic </li></ul><ul><li>Scalp discomfort or headache = most common side effect. </li></ul><ul><li>Outpatient procedure </li></ul><ul><li>37 minute treatment, M-F, for 4-6 weeks </li></ul><ul><ul><li>(no LOC, no sedation, no cognitive clouding) </li></ul></ul><ul><li>Observed therapy facilitates adherence with treatment </li></ul>
  37. 41. Recent TMS Literature Review <ul><li>Roughly 30 controlled clinical research studies to date </li></ul><ul><li>Most recent meta-analysis (Slotema, et al, 2010): </li></ul><ul><ul><li>Included analysis of 34 studies involving 1,383 patients </li></ul></ul><ul><ul><li>Estimated standardized effect size = 0.55 (P < 0.001) </li></ul></ul><ul><ul><li>Conclusion: “…rTMS deserves a place in the standard toolbox of psychiatric treatment methods, as it is effective for depression…and has a mild side effect profile….” </li></ul></ul><ul><li>Slotema, CW, Blom, JD, Hoek, HW, Sommer, IEC. (2010) Should we expand the toolbox of psychiatric treatment methods to include repetitive transcranial magnetic stimulation (rTMS)J Clin Psych 71(7) :873-84. </li></ul><ul><li>Schutter, DJLG. (2009) Antidepressant Efficacy of High-Frequency Transcranial Magnetic Stimulation Over the Left Dorsolateral Prefrontal Cortex in Double-Blind Sham-Controlled Designs: A Meta-Analysis. Psychol Medicine , 39 :65-75. </li></ul>
  38. 42. O’Reardon, JP, et al. (2007) Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: A Multi-Site Randomized Controlled Trial. Biol Psychiatry 62 :1208-1216.
  39. 43. <ul><li>No systemic side effects </li></ul><ul><li>No adverse effect on cognition </li></ul><ul><li>Most common adverse event associated with treatment was scalp pain or discomfort </li></ul><ul><ul><li>< 5% of patients discontinued due to adverse events </li></ul></ul><ul><li>No seizures were reported during studies. </li></ul><ul><li>The estimated risk of seizure with NeuroStar in clinical use is <0.003% per treatment  exposure, and 0.1% per patient exposure. </li></ul><ul><li>Long term safety demonstrated in 6 months follow-up </li></ul>Current TMS Therapy: Safety Overview Janicak, et al. J Clin Psychiatry , 2008; Janicak, et al. Brain Stimulation , 2010.
  40. 44. Contraindication <ul><li>TMS Therapy is contraindicated in patients with implanted metallic devices or non-removable metallic objects in or around the head </li></ul><ul><li>Dental implants are fine. </li></ul>
  41. 45. Active research…
  42. 46. “ But my patients don’t know about this and aren’t asking for it….” <ul><li>“ It’s not the consumers’ job to know what they want.” </li></ul><ul><li>- Steve Jobs </li></ul>
  43. 47. Perhaps the ability not only to acquire the confidence of the patient, but to deserve it, to see what the patient desires and needs, comes through the sixth sense we call intuition, which in turn comes from wide experience and deep sympathy for and devotion to the patient , giving to the possessor remarkable ability to achieve results. ...William J. Mayo, 1935

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