PRACTICAL PSYCHIATRY FOR PRIMARY CARE

1. PRACTICAL PSYCHIATRY FOR PRIMARY CARE THE MEDICAL MANAGEMENT OF MAJOR DEPRESSIVE DISORDER Hisam S. Goueli, M. D. Assistant Professor – Department of Psychiatry and Behavioral Sciences Emory University

2. MAJOR DEPRESSION BASICS • COMMON • second leading cause of worldwide disability • thirty-five percent meet criteria for depression • five to thirteen percent suffer from major depression • BURDEN • economic costs – absenteeism and presenteeism • medical costs – higher morbidity and mortality

3. MAJOR DEPRESSION BASICS • PRIMARY CARE VERSUS PSYCHIATRY • USPSTF and ACPM: category B • patient numbers – more than 50% • medical comorbidity • clinical outcomes • power of Family Medicine

4. MAJOR DEPRESSION DIAGNOSIS • DSM-IV-TR (2000) and DSM-V (2013) • two week history of change from baseline • depressed mood or anhedonia • four or more supporting criteria – suicide aside • not general medical condition or substance • not misdiagnosed for different psychiatric condition • significant distress or impairment

5. MAJOR DEPRESSION DIAGNOSIS • FREQUENCY: Single versus Recurrent • seventy-five to eighty-five percent are recurrent • two episodes spaced by 2 months • elimination of chronic modifier • SEVERITY: Mild, Moderate and Severe • COMPLEXITY: Psychosis and Catatonia • mood-congruent versus mood-incongruent • Three of twelve catatonic symptoms

6. MAJOR DEPRESSION TOOLS: DISEASE EDUCATION

7. MAJOR DEPRESSION TOOLS: DISEASE EDUCATION LOSS EXISTENTIAL STRESS RESILIENCE DEVELOPMENT BIOLOGICAL

8. MAJOR DEPRESSION TOOLS: DISEASE EDUCATION

9. MAJOR DEPRESSION TOOLS: DISEASE EDUCATION

10. MAJOR DEPRESSION TOOLS: DEFINITIONS

11. MAJOR DEPRESSION TOOLS: DEFINITIONS

12. MAJOR DEPRESSION TOOLS: INVENTORIES • BASIC TWO QUESTION SCREEN • down, depressed or hopeless • little interest or pleasure doing things • ADVANCED INVENTORIES • Beck Depression Inventory (BDI-II) • Patient Health Questionnaire-9 (PHQ-9) • Quick Inventory of Depressive Symptomatology – Self Report (QIDS-SR) • Reynolds Adolescent Depression Scale (RADS) • Geriatric Depression Scale (GDS)

13. MAJOR DEPRESSION TREATMENT: MEDICATION OVERVIEW • BIOLOGICAL TREATMENT DEVELOPMENT • first generation – increase concentrations • second generation – selective • third generation – combination • SECRET REGARDING ANTIDEPRESSANTS • Sequenced Treatment Alternatives to Relieve Depression (STAR*D)

14. MAJOR DEPRESSION: BRIEF SUMMARY • DIAGNOSIS OF MAJOR DEPRESSION • MAJOR DEPRESSION FIVE “R”s • response versus remission • relapse, reoccurrence and recovery • THE MONOAMINE HYPOTHESIS • serotonin and norepinephrine • monoamine deficiencies

15. MAJOR DEPRESSION TREATMENT: MEDICATION OVERVIEW

16. MAJOR DEPRESSION TREATMENT: MEDICATION OVERVIEW • FACTORS AFFECTING DECISION • prior response, family response and patient choice • medical and psychiatric comorbid conditions • cost • pharmacokinetics • gender, race and ethnicity • adherence and tolerability

17. MAJOR DEPRESSION TREATMENT: MEDICATION OVERVIEW • ANTIDEPRESSANT GUIDELINES • thirty percent placebo response • low initial dosages with methodical titration • reevaluate at 4 weeks • full therapeutic between 6 to 12 weeks

18. MAJOR DEPRESSION TREATMENT: MEDICATION OVERVIEW • ANTIDEPRESANT DURATION • minimum of 6-8 months after recovery • visits 1-3 months • slow taper over 2-3 months • long term management

19. MAJOR DEPRESSION TREATMENT: ENZYME INHIBITORS • MONOAMINE INHIBITORS • 3 available medications – phenelzine, tranylcypromine and isocarboxacid • most effective and most risky • fatal dietary restriction and drug interactions • STAR*D: incorporated at last stage

20. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION • SELECTIVE SEROTONIN (SSRIs) • SEROTONIN AND NOREPINEPHRINE (SNRIs) • TRICYCLIC ANTIDEPRESSANTS (TCAs) • ATYPICAL AGENTS

21. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION • SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) • six available choices • first line – replaced tricyclic antidepressants • STAR*D: 47% achieved remission

22. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION • SELECTIVE SEROTONIN SIMILARITIES • potent serotonin reuptake inhibition • side effect profiles – serotonin projections • SELECTIVE SEROTONIN DIFFERENCES • pharmacokinetics • cytochrome P450 profiles • secondary pharmacological characteristics • tolerability

23. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION

24. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION AKATHISIA, AGITATION and OBSESSIONS MOOD LIMBIC: ANXIETY GUT: CRAMPS and DIARRHEA APPETITE and EATING SEXUAL BEHAVIOR, VOMITTING and SLEEP

25. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION

26. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION • SELECTIVE SEROTONIN MANAGEMENT • maximum dosages – no fear dosing • adequate medication trials • side effect education – gastrointestinal and sexual • discontinuation – 20% per week reductions • serotonin withdrawal -- FLUSH

27. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION • SEROTONIN WITHDRAWL -- FLUSH • F: flu-like symptoms • L: lightheadedness and dizziness • U: uneasiness • S: sleep disturbances • H: headaches

28. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION • SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs) • 3 available choices • first or second line therapy – safer than TCAs • STAR*D: remission rates similar to SSRIs

29. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION NRI SNRI SRI

30. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION MOOD, INFORMATION PROCESSING and ATTENTION HEART: TACHYCARDIA ENERGY, FATIGUE and PSYCHOMOTOR TREMOR BLOOD PRESSURE

31. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION

32. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION • SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs) • activity depends on dose • maximum dosages – no fear dosing • adequate medication trials • side effect education – hypertension (3-13%) • pain syndromes – fibromyalgia and neuropathic pain

33. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION • TRICYCLIC ANTIDEPRESSANTS • 9 available agents • two major flavors – tertiary and secondary amines • replaced secondary to safety and tolerability • STAR*D: equal to mirtazipine

34. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION NRI CONSTIPATION, BLURRED VISION, DRY MOUTH and DROWSINESS WEIGHT GAIN and DROWSINESS TCA HIST MUSC SRI DIZZINESS and DECREASED BLOOD PRESSURE ALPHAS

35. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION • NORTRIPTYLINE – 25mg to 150mg • secondary amine – less affinity for alpha, histamine and muscarinic receptors • blood levels guide dose • low therapeutic index • caution populations – arrhythmias, sinus node dysfunction, conduction defects, dementia, suicidal patients and elderly

36. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION • ATYPICAL AGENTS • 3 available agents • two groups – norepinephrine and dopamine reuptake inhibitors (NDRIs) and mixed action • STAR*D: NDRIs remission similar to SSRIs • mixed action covered in anxiety lecture

37. MAJOR DEPRESSION TREATMENT: REUPTAKE INHIBITION

38. MAJOR DEPRESSION TREATMENT: NEGATIVE FEEDBACK INHIBITORS • MIRTAZIPINE – 7.5mg to 45mg • alpha-2 antagonist: cuts off the breaks • histimine blockade: sedation and weight gain • STAR*D: same as nortriptyline

39. MAJOR DEPRESSION TREATMENT: BASICS CONCLUSION • DIAGNOSIS OF MAJOR DEPRESSION • MAJOR DEPRESSION FIVE “R”s • response versus remission • relapse, reoccurrence and recovery • BASIC MEDICATION MANAGEMENT • selective serotonin • serotonin and norepinephrine • tricyclic antidepressants • atypical agents

40. MAJOR DEPRESSION ADVANCED:SWITCHING AND AUGMENTATION • IMPORTANCE OF REMISSION • eighty percent rule • obstacles to remission

41. MAJOR DEPRESSION ADVANCED:SWITCHING AND AUGMENTATION SWITCHING AUGMENTATION

42. MAJOR DEPRESSION ADVANCED:SWITCHING AND AUGMENTATION • SWITCHING • stop and start – MAOIs • dual tapering – third generation antidepressants • simultaneous switching – SSRIs • SWITCHING GROUND RULES • fifty percent response per SSRI • washout periods for MAOIs – 2 to 5 weeks

43. MAJOR DEPRESSION ADVANCED:SWITCHING AND AUGMENTATION • AUGMENTATION ADVANTAGES • decrease relapse • synergistic neurotransmitter effect • AUGMENTATION DISADVANTAGES • increase side effects • increase pharmacokinetic interactions • increase medication complexity and compliance

44. MAJOR DEPRESSION ADVANCED:SWITCHING AND AUGMENTATION • COGNITIVE-BEHAVIORAL AUGMENTATION • MEDICATION AUGMENTATION • S: stimulants • A: atypical antipsychotics • L: lithium • T: triiodothyronine (T3)

45. MAJOR DEPRESSION ADVANCED:SWITCHING AND AUGMENTATION • SOMATIC AUGMENTATION • Electroconvulsive Therapy (ECT) • Vagal Nerve Stimulators (VNS) • Trans Magnetic Stimulators (TMS) • Deep Brain Stiumlators (DBS)

46. MAJOR DEPRESSION ADVANCED:SWITCHING AND AUGMENTATION

47. MAJOR DEPRESSION ADVANCED:SWITCHING AND AUGMENTATION

48. MAJOR DEPRESSION ADVANCED:SWITCHING AND AUGMENTATION • STIMULANTS • increase dopamine and norepinephrine • patient selection • alertness and improved cognition • cautions • discontinuation

49. MAJOR DEPRESSION ADVANCED:SWITCHING AND AUGMENTATION • ATYPICAL ANTIPSYCHOTICS • serotonin2C receptor antagonism • patient selection • metabolic side effects and seizure risk • choosing an antipsychotic • discontinuation

50. MAJOR DEPRESSION ADVANCED:SWITCHING AND AUGMENTATION • LITHIUM • potentiates serotonergic activity • patient selection • response rates – onset and overall • practical family medicine evaluation and dosing • treatment failure – serum level 0.6 for 6 weeks