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 transcript:

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

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

acute 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

serotonin transporter MAO SEROTONIN IS DESTROYED Stahl S M, Essential Psychopharmacology (2000)

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

Stahl S M, Essential Psychopharmacology (2000)

5HT1D Stahl S M, Essential Psychopharmacology (2000)

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

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

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

alpha 2 hetero receptor serotonin neuron Stahl S M, Essential Psychopharmacology (2000)

norepinephrine serotonin alpha 1 receptor Stahl S M, Essential Psychopharmacology (2000)

norepinephrine serotonin alpha 1 receptor Stahl S M, Essential Psychopharmacology (2000)

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

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

5HT2A Stahl S M, Essential Psychopharmacology (2000)

Serotonin Pathways Raphe Nucleus Stahl S M, Essential Psychopharmacology (2000)

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

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

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

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

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

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

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

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

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

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

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

substance P release pain and swelling substance P release Stahl S M, Essential Psychopharmacology (2000)

= 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 Stahl S M, Essential Psychopharmacology (2000)

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

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

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

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

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

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

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 Stahl S M, Essential Psychopharmacology (2000)