1.  Disorders of mood ◦ found throughout history  unipolar or major depression  bipolar or manic depression

2.  Depression ◦ over 10% with ~ 5% (11,000,000) suffering from a depressive episode in any given year ◦ untreated - 25 - 30% will attempt or commit suicide ◦ 2X greater prevalence in women than men ◦ estimated only ~ 50% receive specific treatment

4.  Genetics ◦ concordance rates:  fraternal twins - 20% concordance  monozygotic or identical twins - 50% concordance

5.  Neurochemical Theory ◦ monoamine theory: ◦ supportive data 1. Reserpine 2. Drugs used to treat depression increase activity of NE and/or 5HT neurons

6.  Pharmacologically ◦ drugs have been available for ~ 40+ years ◦ two categories of drugs emerged about the same time; tricyclic antidepressants and MAO inhibitors ◦ more recently SSRIs have taken over the market ◦ Even more recently SNRI (ex. Effexor® or venlafaxine)

8.  Blocks reuptake of NE and 5HT  very widely used  fairly significant side effects ◦ effects on other NT ◦ sedation, weight gain

9.  mechanism of action: block the enzyme that breaks down excess NE and 5HT  proved as effective (if not more so) than traditional tricyclics or SSRIs  not used as first level txt due to risk of adverse side effects- related to diet

10.  Alters the metabolism of amino acid tyramine ◦ foods high in tyramine include: aged cheeses, wine, smoked fish, yeast products ◦ consumption of these can result in a hypertensive crisis:  severe headaches, heart palpitations. Flushing, nausea, vomiting, stroke ◦ very long 1/2 life (2 weeks)

11.  Fluoxetine (Prozac) - first introduced in US in 1988  SSRIs have a more favorable side effect profile than earlier antidepressants  relatively safe (esp in OD situations)  some controversy…... – increased risk of suicide – especially in kids

12. (Celexa)

13. US FDA Updated in 2007- Black box warnings…..

14.  SNRI – serotonin and norepinephrine reuptake inhibitors

15. Norepinephrine and dopamine reuptake inhibitor Bupropion (Wellbutrin) Serotonin and norepinephrine reuptake inhibitors Duloxetine (Cymbalta) Venlafaxine (Effexor)

16.  Some patients do not respond well to first treatment  most take 3 - 4 weeks to exert significant therapeutic effects ◦ what does this suggest?

17. 1. ECT - electroconvulsive therapy ◦ may cause the most rapid change in receptor density 2. Sleep deprivation ◦ many sleep abnormalities associated with endogenous depression  reduced SWS, increased stage 1, increased REM

18. 3. Phototherapy - Seasonal Affective Disorder

19.  Shifts between manic and depressive states  Treatment: ◦ Lithium – extremely toxic!

20.  introduced in 1990’s to treat bipolar  possible mechanism?