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DEPRESSION NORMAL MOOD RECOVERY OR REMISSION EPISODE OF DEPRESSION TIME 6 - 24 months 5-1 Stahl S M, Essential Psychopharmacology (2000)

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Presentation on theme: "DEPRESSION NORMAL MOOD RECOVERY OR REMISSION EPISODE OF DEPRESSION TIME 6 - 24 months 5-1 Stahl S M, Essential Psychopharmacology (2000)"— Presentation transcript:

1 DEPRESSION NORMAL MOOD RECOVERY OR REMISSION EPISODE OF DEPRESSION TIME 6 - 24 months 5-1 Stahl S M, Essential Psychopharmacology (2000)

2 DEPRESSION NORMAL MOOD RESPONSE 5-2 Stahl S M, Essential Psychopharmacology (2000)

3 acute 6 - 12 weeks continuation 4-9 months maintenance 1 or more years REMISSION RECOVERY DEPRESSION NORMAL MOOD 100% 5-3 Stahl S M, Essential Psychopharmacology (2000) TIME

4 5-4 Stahl S M, Essential Psychopharmacology (2000) acute 6 - 12 weeks continuation 4-9 months maintenance 1 or more years TIME DEPRESSION NORMAL MOOD RELAPSE RECURRENCE

5 5-5 Stahl S M, Essential Psychopharmacology (2000) DEPRESSION NORMAL MOOD MANIA HYPOMANIA MIXED EPISODE

6 12 months DEPRESSION NORMAL MOOD RAPID CYCLING 5-6 Stahl S M, Essential Psychopharmacology (2000)

7 2+ years DEPRESSION NORMAL MOODDYSTHYMIA 5-7 Stahl S M, Essential Psychopharmacology (2000)

8 6 - 24 months 2+ years DEPRESSION NORMAL MOOD DYSTHYMIA PARTIAL RECOVERY DOUBLE DEPRESSION 5-8 Stahl S M, Essential Psychopharmacology (2000)

9 5-9 Stahl S M, Essential Psychopharmacology (2000) 8 weeks DEPRESSION NORMAL MOOD 67% RESPONDERSMEDICATION medication started 33% NON- RESPONDERS

10 5-10 Stahl S M, Essential Psychopharmacology (2000) 8 weeks DEPRESSION NORMAL MOOD 33% RESPONDERSPLACEBO placebo started 67% NON- RESPONDERS

11 5-11 Stahl S M, Essential Psychopharmacology (2000) DEPRESSION NORMAL MOOD 50% continue response PLACEBO SUBSTITUTION antidepressant treatment placebo 50% relapse

12 5-12 Stahl S M, Essential Psychopharmacology (2000) DEPRESSION NORMAL MOOD 90% continue response DRUG CONTINUATION antidepressant treatment 10% relapse

13 MAO enzyme destroying neurotransmitter monoamine neurotransmitter NORMAL STATE -- no depression MONOAMINE HYPOTHESIS 5-13 5-14 Stahl S M, Essential Psychopharmacology (2000) DEPRESSION -- caused by neurotransmitter deficiency

14 Increase in neurotransmitters causes return to normal state MAO inhibitor blocks the enzyme from destroying monoamine neurotransmitter reuptake pump blocked by antidepressant 5-15 5-16 Stahl S M, Essential Psychopharmacology (2000)

15 NE (norepinephrine) tyrosine transporter TYR TOH DOPA DDCDA DBH NOREPINEPHRINE IS PRODUCED 5-17 Stahl S M, Essential Psychopharmacology (2000)

16 NOREPINEPHRINE IS DESTROYED COMT destroys NE norepinephrine transporter MAO 5-18 Stahl S M, Essential Psychopharmacology (2000)

17 NOREPINEPHRINE RECEPTORS presynaptic alpha 2 autoreceptor postsynaptic alpha 2 receptor postsynaptic beta 1 receptor alpha 1 receptor 5-19 Stahl S M, Essential Psychopharmacology (2000)

18 terminal alpha 2 autoreceptor somatodendritic alpha 2 autoreceptor 5-20 Stahl S M, Essential Psychopharmacology (2000)

19 NE occupying somatodendritic autoreceptor causes a decrease in firing and a decrease of NE release 5-21 Stahl S M, Essential Psychopharmacology (2000) NE

20 NE occupying terminal alpha 2 receptor halts release of NE 5-22 Stahl S M, Essential Psychopharmacology (2000) NE

21 Norepinephrine Pathways Locus Coeruleus 5-23 Stahl S M, Essential Psychopharmacology (2000)

22 beta 1 receptor 5-24 Stahl S M, Essential Psychopharmacology (2000) DepressionFrontal 1

23 alpha 2 receptor Frontal 2Attention 5-25 Stahl S M, Essential Psychopharmacology (2000)

24 5-26 Stahl S M, Essential Psychopharmacology (2000) Limbic EmotionsAgitation Energy Level

25 5-27 Stahl S M, Essential Psychopharmacology (2000) CerebellumTremor

26 5-28 Stahl S M, Essential Psychopharmacology (2000) Spinal CordBlood Pressure

27 5-29 Stahl S M, Essential Psychopharmacology (2000) HeartTachycardia

28 5--30 Stahl S M, Essential Psychopharmacology (2000) BladderUrinary Retention

29 tyrosine transporter TOH TYR DOPA DDC DA (Dopamine) DOPAMINE IS PRODUCED 5--31 Stahl S M, Essential Psychopharmacology (2000)

30 COMT destroys NE dopamine transporter MAO DOPAMINE IS DESTROYED 5--32 Stahl S M, Essential Psychopharmacology (2000)

31 DOPAMINE RECEPTORS presynaptic autorecptor D1 D2D3 D4 D5 dopamine transporter 5--33 Stahl S M, Essential Psychopharmacology (2000)

32 5HT (Serotonin) SEROTONIN IS PRODUCED tryptophan transporter TRY-OH 5HTP AAADC Tryptophan 5--34 Stahl S M, Essential Psychopharmacology (2000)

33 serotonin transporter MAO SEROTONIN IS DESTROYED 5--35 Stahl S M, Essential Psychopharmacology (2000)

34 SEROTONIN RECEPTORS alpha 2 hetero receptor 5HT1D autoreceptor 5HT1A serotonin transporter 5HT2A 5HT2C 5HT35HT4 5HTX 5HTY 5HTZ 5--36 Stahl S M, Essential Psychopharmacology (2000)

35 5--37 5-38 Stahl S M, Essential Psychopharmacology (2000)

36 5HT1D 5--39 5-40 Stahl S M, Essential Psychopharmacology (2000)

37 5--41 Stahl S M, Essential Psychopharmacology (2000)

38 5--42 Stahl S M, Essential Psychopharmacology (2000)

39 norepinephrine serotonin alpha 2 hetero receptor serotonin neuron 5--43 Stahl S M, Essential Psychopharmacology (2000)

40 alpha 2 hetero receptor serotonin neuron 5--44 Stahl S M, Essential Psychopharmacology (2000)

41 norepinephrine serotonin alpha 1 receptor 5--45 Stahl S M, Essential Psychopharmacology (2000)

42 norepinephrine serotonin alpha 1 receptor 5--46 Stahl S M, Essential Psychopharmacology (2000)

43 brake accelerator Locus Coeruleus NE-5HT Interactions 5--47 Stahl S M, Essential Psychopharmacology (2000)

44 serotonin neuron presynaptic alpha 2 autoreceptor postsynaptic alpha 2 hetero receptor presynaptic alpha 2 autoreceptor alpha 1 receptor norepinephrine neuron 5--48 Stahl S M, Essential Psychopharmacology (2000) 5HT accelerator 5HT brake

45 5HT2A 5--49 5-50 Stahl S M, Essential Psychopharmacology (2000)

46 Serotonin Pathways Raphe Nucleus 5--51 Stahl S M, Essential Psychopharmacology (2000)

47 5--52 Stahl S M, Essential Psychopharmacology (2000) Frontal CortexMood

48 5--53 Stahl S M, Essential Psychopharmacology (2000) Basal Ganglia OCD Akathisia/ Agitation

49 5--54 Stahl S M, Essential Psychopharmacology (2000) LimbicAnxiety

50 5--55 Stahl S M, Essential Psychopharmacology (2000) HypothalamusAppetite/bulimia

51 5--56 Stahl S M, Essential Psychopharmacology (2000) Sleep CentersInsomnia

52 5--57 Stahl S M, Essential Psychopharmacology (2000) Spinal CordSexual Dysfunction

53 5--58 Stahl S M, Essential Psychopharmacology (2000) Brainstem Vomiting Center Nausea and vomiting

54 5--59 Stahl S M, Essential Psychopharmacology (2000) GutGI cramps/Diarrhea

55 Monoamine Receptor Hypothesis of Depression Normal functioning Decrease in NT Receptors up- regulate due to lack of NT 5--60 5-61 6-62 Stahl S M, Essential Psychopharmacology (2000)

56 5--63 Stahl S M, Essential Psychopharmacology (2000) BDNF gene Stress BDNF

57 5--64 Stahl S M, Essential Psychopharmacology (2000) Apoptosis

58 substance P release pain and swelling substance P release 5--65 Stahl S M, Essential Psychopharmacology (2000)

59 = substance P hypothalamus amydala and limbic areas dopamine centers norepinephrine centers Neurokinin Hypothesis of Emotional Malfunctioning Corollary: Blockng the Appropriate Neurokinin Receptor will Reduce Emotional Distress 5--66 Stahl S M, Essential Psychopharmacology (2000)

60 substance P Neurokinin A (NK-A) Neurokinin B (NK-B) ArgProLysGln Phe GlyLeuMetNH2 GlyLeuMetNH2 GlyLeuMetNH2 Val SerAspThrLysHis AspPheHisMetAsp 5--67 Stahl S M, Essential Psychopharmacology (2000)

61 PPT-A gene PPT-A mRNA signal peptidase endoplasmic reticulum converting enzyme substance P NK-1 receptor 5--68 Stahl S M, Essential Psychopharmacology (2000) PPT-A spliced mRNA PPT-A protein PT-A

62 PPT-A gene PPT-A mRNA signal peptidase endoplasmic reticulum converting enzyme substance P NK-1 receptor 5--69 Stahl S M, Essential Psychopharmacology (2000) PPT-A spliced mRNA PPT-A protein PT-A

63 PPT-A gene PPT-A mRNA signal peptidase endoplasmic reticulum converting enzyme substance P NK-1 receptor PPT-A spliced mRNA 5--70 Stahl S M, Essential Psychopharmacology (2000) PPT-A protein PT-A

64 PPT-A gene PPT-A mRNA signal peptidase endoplasmic reticulum converting enzyme NK-A NK-2 receptor 5--71 Stahl S M, Essential Psychopharmacology (2000) PPT-A spliced mRNA PPT-A protein PT-A

65 PPT-A gene PPT-A mRNA signal peptidase endoplasmic reticulum converting enzyme NK-A NK-2 receptor PPT-A spliced mRNA 5--72 Stahl S M, Essential Psychopharmacology (2000) PPT-A protein PT-A

66 PPT-B gene PPT-B mRNA PPT-B protein signal peptidase endoplasmic reticulum PT-B converting enzyme NK-B NK-3 receptor PPT-B spliced mRNA 5--73 Stahl S M, Essential Psychopharmacology (2000)


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