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Getting the Most of Antidepressants RVU 05-03-2014

Getting the Most of Antidepressants RVU 05-03-2014. Larry O. Sanders, MD Diplomate of the American Board of Psychiatry and Neurology. Goals. Screening the Primary Care population for Mental Disease. First Line and Second Line Treatment of MDD.

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Getting the Most of Antidepressants RVU 05-03-2014

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  1. Getting the Most of AntidepressantsRVU 05-03-2014 • Larry O. Sanders, MD • Diplomate of the American Board of Psychiatry and Neurology

  2. Goals • Screening the Primary Care population for Mental Disease. • First Line and Second Line Treatment of MDD. • Evidence that more than Major Depression is Involved. • When to Refer to Mental Health.

  3. In US, Major Depression is aCommon Medical Illness

  4. Why Treat Depression? • Disability • Morbidity- Depression makes existing somatic conditions worse. (Inflammatory Factors) • Mortality- Psychiatric patients die up to 20years earlier than average. Most Common reason is Cardiovascular Disease! • Second is Suicide.

  5. Inflammatory Factors, 1 • Major Depression Increases • Inflammatory Factors, • Worsening the Prognosis of • Somatic Illness

  6. Inflammatory Factors, 2 • Somatic Illnesses • Increase • Inflammatory Factors, • Worsening the Prognosis of • Major Depression

  7. Depression and Atherosclerotic Disease. • Major Depression carries 4X Riskof developing a Myocardial Infarction! Anda 1993, Barefot, et. Al. 1996, Pratt 1996 • MIs comorbid with MDD are 5X More likely to be Fatal.Anda 1993 • 16.5% Mortality Risk@ 6 months following Acute MI if also Depression vs 3% if not Depressed.Frasure-Smith 1993 • Major Depression carries same Risk Factor for developing an MI, as Cigarette Smoking!

  8. Major Depression5 Symptoms, 2 Weeks, >50% each day (pneumonic “Sige Caps”) • Mood* • Sleep • Interest* • Guilt or Hopelessness • Energy • Concentration • Appetite • Psychomotor • Suicidal/Homocidal Ideation *Depressed Mood or Anhedonia must be present

  9. Nature vs Nurture • MDD is strongly genetic, with well over 100 genes involved. • However, the largest risk for developing MDD as an adult is losing a parent before age 12. • Many Environmental, Psychological and Sociological factors can effect it. 10

  10. Medical Disease can appear as Major Depressive Disorder • Many Medical Diseases can appear as MDD. R/O: • Hypothyroidism • Anemia, both Microcytic and Macrocytic • Any inflammatory Disease • Hyperparathyroidism (even slightly elevated Ca++ may be important) • Various Vitamin deficiencies, including: D, B12, B6, Folate, etc. • Vitamin D deficiency seems more common since the use of high SPF Sunscreens. 11

  11. Other (Free) Scales • PHQ 2 Screener • ( Very brief. I don’t encourage its’ use). • Zung Depression Rating Scale • QIDS-SR • Quick Inventory Depressive Symptomatology (Self Report) • CUDOS • Clinically Useful Depression Outcome Scale

  12. Treat to Remission!Sub-Syndromal Depression = Relapse One or more Symptoms 7 months until Relapse! No Symptoms Months Well Judd 1998

  13. Symptoms and Circuits • Advocated by • Stephen M. Stahl, MD

  14. Circuit

  15. When a Brain Circuit, when overstimulated or under-stimulated, it will produce certain symptoms.(adapted from Steven Stahl, MD)

  16. Each Symptom, regardless of the disease, comes from the Same Circuit Malfunction!(adapted from Steven Stahl, MD)

  17. Symptoms & Circuits • By Knowing Which Symptom is related to which Circuit, • and by Knowing How Each Medication Effects Each Circuit • You can Logically Deduce Which Medication Will Best Treat Most Mental Conditions. • (adapted from Steven Stahl, MD)

  18. 3 Major Circuits Contributing toMental Illness

  19. Circuits Serotonin

  20. Circuits Serotonin Norepinephrine

  21. Circuits Serotonin Norepinephrine Dopamine

  22. SymptomsAssociated with theseCircuits

  23. Symptoms associated with Serotonin • Serotonin helps us “Cope”. • If Serotonin is too Low: Irritable, Anxious, Easily Overwhelmed, Hopeless, Suicidal, “poor sense of Well-being” • If Serotonin is too High: Serotonin Syndrome; Agitation, Fasciulations, Hyperthermia, Vital Sign Disturbance, leading to stupor, come then death. [Although pharmacists warn of this, neither I nor any Psychiatric Colleagues have ever seen this condition. So it appears to be very rare.]

  24. Symptoms associated with Norepinephrine • Norepinephrine is like “Adrenaline”. • If Norepinephrine too Low: Anergy, Immediate Memory Impaired, Psychomotor Retardation. • If Norepinephrine too High: Irritable, Agitation, Insomnia. (Similar Symptoms to Low Serotonin).

  25. Symptoms associated with Dopamine • Dopamine provides Interests/Desire, mentally. (Dopamine has other physical functions as well). • If Dopamine too Low: Apathy, Dementia, Muscle • If Dopamine too High: Hedonism, Psychosis, Mania

  26. Symptoms & Circuits Serotonin Mood* Emotion Cognitive Function Norepinephrine Dopamine

  27. Symptoms & Circuits Serotonin Suicidal/Homicidal Frustration, “Sense of Well Being” Obsession, Sleep, Guilt or Hopelessness Mood* Emotion Cognitive Function Norepinephrine Dopamine

  28. Symptoms & Circuits Serotonin Suicidal/Homicidal Frustration, “Sense of Well Being” Obsession, Sleep, Guilt or Hopelessness Mood* Emotion Cognitive Function Energy Alertness Psychomotor Working Memory Norepinephrine Dopamine

  29. Symptoms & Circuits Serotonin Suicidal/Homicidal Frustration, “Sense of Well Being” Obsession, Sleep, Guilt or Hopelessness Mood* Emotion Cognitive Function Energy Alertness Psychomotor Working Memory Desire Interest* Norepinephrine Dopamine

  30. Symptoms & Circuits Serotonin Suicidal/Homicidal Frustration, “Sense of Well Being” Obsession, Sleep, Guilt or Hopelessness Irritability Anxiety Mood* Emotion Cognitive Function Energy Alertness Psychomotor Working Memory Desire Interest* Norepinephrine Dopamine

  31. Symptoms & Circuits Serotonin Suicidal/Homicidal Frustration, “Sense of Well Being” Obsession, Sleep, Guilt or Hopelessness Irritability Anxiety Mood* Emotion Cognitive Function Energy Alertness Psychomotor Working Memory Desire Interest* Concentration Motivation Norepinephrine Dopamine

  32. Symptoms & Circuits Serotonin Suicidal/Homicidal Frustration, “Sense of Well Being” Obsession, Sleep, Guilt or Hopelessness Appetite Aggression Sex Irritability Anxiety Mood* Emotion Cognitive Function Energy Alertness Psychomotor Working Memory Desire Interest* Concentration Motivation Norepinephrine Dopamine Slaby and Tancradi 2002, Stahl 2004

  33. Symptoms, Circuits & Medications

  34. 5HT1a 5HT1a

  35. Classes of Antidepressants • SSRIs • SNRIs, NaSSI • SDRIs • NDRIs (mechanism of Wellbutrin not fully understood) • DRIs, DAgs • NRIs – (not very effective). • (MOAIs, not covered here, are powerful Antidepressants; but carry HTN risk with certain foods and/or meds and Serotonin Syndrome with SRIs.)

  36. Suicidality vs Suicide • An ironic fact about Antidepressant use is that Suicidality risk (thoughts, not death) increases transiently, BUT SUICIDE (DEATH) risk DECREASES in patients less than 24 y.o.! (expound)

  37. Medications Effecting PrimarilySerotonin

  38. SSRIs • “Multi Action” – ssri, 5HT1a, 1b, 3, & 7. • Vortioxetine (Brintellix). • “Dual Action”- SSRI & 5HT1a. • Vilazadone (Viibryd). • “Single Action”– SSRI. • Escitalpram (Lexapro). • Fluoxetine (Prozac). SSRI + bits of others. • “Half Action” - Racemic mixture, half active. • Cilatopram (Celexa).

  39. Symptoms, Circuits & Medications-Trade Names Larry O. Sanders, MD c 2002, 2014 “Multi Action”- Brintellix 5-20mg “Dual Action” - Viibryd 10-40mg “Single Action”- Lexapro 10-20mg Prozac 20mg “Half Action” - Celexa 40mg SSRI Serotonin Suicidal/Homicidal Frustration, “Sense of Well Being” Obsession, Sleep, Guilt or Hopelessness Appetite Aggression Sex Irritability Anxiety Mood* Emotion Cognitive Function Energy Alertness Psychomotor Working Memory Desire Interest* Concentration Motivation Norepinephrine Dopamine

  40. Medications effecting Both Serotonin and Norepinephrine

  41. SNRIs • Levomilnacipram (Fetzima) 1:2 S:N • Duloxetine (Cymbalta) 9:1 S:N • Desvenlafaxine (Pristiq) 15:1 S:N • Venlafaxine(Effexor) 30:1 S:N • At low dose is SSRI. At high dose SNRI. Strong W/D issues! • {Paroxetine (Paxil) 20-40mg} • Weight gain, Fatigue, Strong W/D issues!

  42. Symptoms, Circuits & Medications-Trade Names Larry O. Sanders, MD c 2002, 2014 “Multi Action”- Brintellix 5-20mg “Dual Action” - Viibryd 10-40mg “Single Action”- Lexapro 10-20mg Prozac 20mg “Half Action” - Celexa 40mg SSRI Fetzima 40-120mg Cymbalta 60mg Pristiq 50-100mg Effexor 75-375mg (Paxil) 20mg Serotonin SNRI Suicidal/Homicidal Frustration, “Sense of Well Being” Obsession, Sleep, Guilt or Hopelessness Appetite Aggression Sex Irritability Anxiety Mood* Emotion Cognitive Function Energy Alertness Psychomotor Working Memory Desire Interest* Concentration Motivation Norepinephrine Dopamine

  43. NaSSAIndirectly elevates Norepinephrine (Noradrenaline) and Serotonin • Mirtazapine (Remeron) • Sedating, increases appetite and weight gain.

  44. Symptoms, Circuits & Medications-Trade Names Larry O. Sanders, MD c 2002, 2014 “Multi Action”- Brintellix 5-20mg “Dual Action” - Viibryd 10-40mg “Single Action”- Lexapro 10-20mg Prozac 20mg “Half Action” - Celexa 40mg SSRI Fetzima 40-120mg Cymbalta 60mg Pristiq 50-100mg Effexor 75-375mg (Paxil) 20mg Serotonin SNRI Suicidal/Homicidal Frustration, “Sense of Well Being” Obsession, Sleep, Guilt or Hopelessness Remeron 30-45mg (Indirect ^ S & N) Appetite Aggression Sex Irritability Anxiety Mood* Emotion Cognitive Function Energy Alertness Psychomotor Working Memory Desire Interest* Concentration Motivation Norepinephrine Dopamine

  45. Medications Effecting Norepinephrineand Dopamine

  46. NDRI • Bupropion (Wellbutrin) 300-450mg • IR. Not Well Tolerated. • SR. Lasts 12 hours. • XL. Lasts 24 hours.

  47. Amphetamines • Terminal Releasers and • Reuptake Inhibitors of Norepinephrine and Dopamine

  48. Symptoms, Circuits & Medications-Trade Names Larry O. Sanders, MD c 2002, 2014 “Multi Action”- Brintellix 5-20mg “Dual Action” - Viibryd 10-40mg “Single Action”- Lexapro 10-20mg Prozac 20mg “Half Action” - Celexa 40mg SSRI Fetzima 40-120mg Cymbalta 60mg Pristiq 50-100mg Effexor 75-375mg (Paxil) 20mg Serotonin SNRI Suicidal/Homicidal Frustration, “Sense of Well Being” Obsession, Sleep, Guilt or Hopelessness Remeron 30-45mg (Indirect ^ S & N) Appetite Aggression Sex Irritability Anxiety Mood* Emotion Cognitive Function Energy Alertness Psychomotor Working Memory Desire Interest* Concentration Motivation Norepinephrine Dopamine NDRI NRI Wellbutrin 300-450mg Amphetamines 10-30mg b.i.d.

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