1. Depression

2. Depression Known as a Mood/Affective Disorder Affect = emotions
Major Types
Bipolar
Unipolar
Seasonal Affective Disorder

3. Depression Unipolar (major depression) Most common affective disorder
19 million Americans/year (17%)
11 million clinical & major depression
15% parasuicide
Most effectively treated

4. Depression Unipolar (major depression) Problems with diagnosis…
Both a mental disorder & normal mood
state

5. Depression Duration & Intensity Reactive-Exogenous triggered by an
obvious event
Endogenous
No trigger
No obvious event
Duration & Intensity

6. Anhedonia (experience pleasure)
Weight gain or loss
Hypersomnia, insomnia
Fatigue, loss of energy
feelings of worthlessness guilty
difficulty concentrating

7. Clinical Depression
(5 symptoms)
(2 symptoms)

10. 

12. Concordance rate of 68% in monozygotic
Genetic Risk
Concordance rate of 68% in monozygotic
Concordance rate of 15% dizygotic
Family member = 10 tx more likely

15. Theories of Depression

16. Most Dominant Theory of Depression
Monoamine Hypothesis of Depression
Depression is associated with an
under activity at serotonergic and
noradrenergic synapses
(Indolamines & catecholamines)

17. Evidence in Support
- CSF of depressed pt suicidal
low levels of 5HIAA
-Post Mortem
brains from depressed pt (prefontal)
above avg # of 5HT & Norepi
receptors upregulation
Post Mortem Suicide
low 5HT
low Norepi

18. Tryptophan depletion in depressed
Evidence in Support
Tryptophan depletion in depressed
pt (Delgado, 1990)
Put on Low Trypto. Diet (salad, corn, gelatin)
Then, amino ccid cocktail (no trypto.)…so hi
other amino acids
Trypto. Dropped! = relapse
-Healthy…no effect of diet or cocktail
…PET shows prefrontal cortex trypto less

19. Evidence in Support
Antidepressants Work!..so, monoamine
agonists
Monoamine Antagonist = depression
ex: Reserpine (Rauwolfia serpentina)
100’s years ago used to
calm insanity
treat hi BP = 15% got depressed

20. Antidepressants Work…in 80% of the clinical population
Evidence Refuting the Monoamine Hypothesis
Antidepressants Work…in 80% of the
clinical population
…what’s up with the other 20%???
-“Lag Time”
time it takes a drug to work in the
brain vs the time we see a behavioral
effect  3 to 4 weeks to see behave
effect…although in the brain

21. Treatment – Biochemical
Therapies

22. Antidepressants Monoamine Oxidase Inhibitors (MAOIs) Tricyclics
Selective Monoamine Reuptake
Inhibitors (SSRIs)

23. Monoamines?

24. Monoamines
Catecholamines: Norepinephrine
Indolamines: Serotonin

25. Monoamine Oxidase Inhibitors (MAOIs)
- MAOIs block the enzyme
monoamine oxidase…
- MAO breaks down monoamines
into inactive metabolites

26. MAOIs: Iproniazid (eye-pron-eye-a-zid) First antidepressant (1957)
- originally marketed as rocket fuel
- TX for TB
A flop!…serendipity intervened

27. MAOIs: Isocarboxazid Phenelzine Tranylcypromine Side effects:
hypertension (BP): headaches, sweating,
nausea, vomiting
Side effects represent drug interaction
drug X food
Tyramine – cheese, wine, licorice, raisins
MAO breaks down tyramine= too much
 intracranial hemorrage (stroke)

28. MAOIs: “Cheese Effect” Pharmacist G.E.F. Rowe
wife was being treated with MAOI
headaches after eating cheese
Blackwell et al
found that cheese causes a large
increase in BP without MAO
increase in tyramine indirectly acts on sympathetic release of Norepi

29. Tricyclics Called tricyclics because chemical structure
Includes 3-ring structure – 2 benzene rings &
1 central seven membered ring

30. Tricyclics
works by preventing presynaptic reuptake

31. Tricyclics 1st tricyclic: Imipramine (Tofranil) serendipity!
- Synthesized in 1948 as an antihistamine
- Used in Schizophrenia – no help with psychosis but less depressed
Side effects: (safer than MAOI)
- block histamine receptors: produces drowsiness
- block acetylcholine receptors: dry mouth, difficulty
urinating
- Na+ Channels: heart irregularities

32. Tricyclics Appear to work better with: - Early morning awakenings
- Loss of appetite
- Weight loss
Morning depression heightened
Contraindicated for Bipolar depression  can trigger the mania

33. Second Generation: Selective Serotonin
Reuptake Inhibitors (SSRIs)
“Atypical” Antidepressants

34. SSRIs: Block Reuptake

35. SSRIs
Just Like the tricyclics but selective to
block serotonin uptake
Fluoxotine (Prozac)
-first on the market in 1980s
-most prescribed
-not more effective in tx depression
* fewer dangerous side effects
* effective in a wide range of
affective problems lack of self-
esteem, fear of failure, OCD,
Binge eating & purging (Bulimia)

36. SSRIs (Sertraline:Zoloft, Paroxetine:Paxil
(Fluvoxamine: Luvox, Citalopram:Celexa)
Side Effects:
SSRIs do not effect:
MAO – little risk of hypertension
Do not worry about food interaction
However side effect:
nervousness
25% nausea-10% nausea (Prozac & Zoloft)
Priapism (trazadone) - protracted & painful penile
erection
Social anxiety disorder, PTSD, Panic disorder, OCD)
ALSO: Selective Norepi Reuptake Inhibitors
(Reboxetine)