Depression

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Depression
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Depression

• Known as a Mood/Affective Disorder
• Affect emotions
• Major Types
• Bipolar
• Unipolar
• Seasonal Affective Disorder

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Depression

• Unipolar (major depression)
• Most common affective disorder
• 19 million Americans/year (17)
• 11 million clinical major depression
• 15 parasuicide
• Most effectively treated

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Depression
Unipolar (major depression) Problems with
diagnosis Both a mental disorder normal mood
state
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Depression
Reactive-Exogenous triggered by an obvious event
Endogenous No trigger No obvious event
Duration Intensity
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• Anhedonia (experience pleasure)
• Weight gain or loss
• Hypersomnia, insomnia
• Fatigue, loss of energy
• feelings of worthlessness guilty
• difficulty concentrating

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Clinical Depression
(5 symptoms)
(2 symptoms)
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• Genetic Risk
• Concordance rate of 68 in monozygotic
• Concordance rate of 15 dizygotic
• Family member 10 tx more likely

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

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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
• -Healthyno effect of diet or cocktail
• PET shows prefrontal cortex trypto less

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Evidence in Support

• Antidepressants Work!..so, monoamine
• agonists
• Monoamine Antagonist depression
• ex Reserpine (Rauwolfia serpentina)
• 100s years ago used to
• calm insanity
• treat hi BP 15 got depressed

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Evidence Refuting the Monoamine Hypothesis

• Antidepressants Workin 80 of the
• clinical population
• whats 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
• effectalthough in the brain

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Treatment Biochemical Therapies
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Antidepressants

• Monoamine Oxidase Inhibitors (MAOIs)
• Tricyclics
• Selective Monoamine Reuptake
• Inhibitors (SSRIs)

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Monoamines?
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Monoamines

• Catecholamines Norepinephrine
• Indolamines Serotonin

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• Monoamine Oxidase Inhibitors (MAOIs)

- MAOIs block the enzyme monoamine oxidase -
MAO breaks down monoamines into inactive
metabolites
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MAOIs

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

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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)
  

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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

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Tricyclics
Called tricyclics because chemical
structure Includes 3-ring structure 2 benzene
rings 1 central seven membered ring
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Tricyclics
works by preventing presynaptic reuptake
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Tricyclics
1st tricyclic Imipramine (Tofranil) serend
ipity! - 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
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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

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Second Generation Selective Serotonin Reuptake
Inhibitors (SSRIs) Atypical Antidepressants
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SSRIs Block Reuptake
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• 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)

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• SSRIs (SertralineZoloft, ParoxetinePaxil
• (Fluvoxamine Luvox, CitalopramCelexa)
• 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)