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18 Cards in this Set

  • Front
  • Back
Major Depression Epidemiology
-Lifetime Risks
-Duration of untreated episodes
-Risk of recurrence and hypothesized biological correlate
-10% LTR for men
-20% LTR for women
-Average untreated episode: 9-12 months
-2/3 of all cases are recurrent. 50% after 1 episode, 80% after 2, 90% after 3.
-R.o.R. may reflect kindling effect in limbic system
Etiology of Major Depression
-Stress-diathesis model
-Final common biological pathway
-Response to failure
-Response to success
-interplay between biological vulnerability and environmental stressors

-Dysregulation of limbic system/monoamine pathways. (5HT, NE, and DA)

-Personal, permanent and pervasive

-Impersonal, transient, and specific
Diagnostic criteria for MDD
-4 domains of symptoms
-X of these 2
-X of 9 others
-Symptom duration
-Symptom consequences
-Exclusion criteria
-Departure from normal mood, psychomotor activity, cognitive functioning, and vegetative features.

-Depressed Mood and/or Loss of interest or pleasure

-change in appetite, weight or sleep; fatigue; poor concentration; psychomotor agitation or retardation; worthlessness or guilt; suicidal thoughts; etc

-Must last >2 weeks
-Must cause marked distress or functional impairment

-Cannot be caused by substance or general medical condition. Doesn't meet criteria for mixed episode (mania copresent).
SSRI
-Example
-Proposed mechanism
-Common Side Effects
-Dangerous rare side effects
Ex: Fluoxetine

-??Downregulation of 5-HT1A??
-??Increased BDNF??

Common side effects
*Sexual dysfunction (5-HT2)
*Nausea, diarrhea, other GI (5-HT3)
-appetite changes
-headaches
-insomnia
-initial anxiety, but subsides

Dangerous Side Effects
-Serotonin syndrome: agitated and confused, autonomic hyperactivity, and motor tremors.
SNRI
-Two drugs
-Differences in dosage effects and one special usage
-4 major side effects
Venlafaxine: first SSRI, then NRI as dose increases; slight DRI at high dose.

Duloxetine: Both SSRI and NRI at low doses. Used for neuropathic pain.

-HTN, insomnia, constipation, and sweating
NDRI
-Major benefits/uses
-Major side effects
Buproprion

Major benefits/uses
- less weight gain, smoking cessation, possibly improve SSRI sexual dysfunction

Major side effects
-seizure risk in bulemics, insomnia, tremor, dry mouth, odd tastes.
SA(S)RI
-Key difference from SSRI side effects
-1 drug no longer used: Mechanism and side effect
-1 drug still used: Mechanism and side effect
Both are more sedating and have less sexual dysfunction because of 5-HT2C block.

Nefazodone: SSRI, 5-HT2C antagonist, and alpha-1 antagonist. However, liver toxicity.


Trazodone: SSRI, 5-HT2C antagonist, H1 antagonist, and alpha-1/2 antagonist. Used for its sedative properties. Rare Priapism!
NASSA/NSA
-Action
-Receptors affected and their effects
Mirtazapine: Noradrenergic serotinergic antagonist

Antagonist for the following receptors:
-5-HT2a: antidepressant effects
-5-HT2c: anxiolytic, sedative, reduced sexual dysfunction
-5-HT3: less nausea
-Alpha-2: increased NE and 5-HT output
-H1: sedation and weight gain
MAOI
-Reversible?
-Which enzymes?
-Diet
-Side effects
-Severe side effects
-Irresversible inhibitors
-MAO-A--> NE metabolism
-MAO-B--> DA metabolism
-Tyramine in diet can lead to HTN
-Side effects: hypotension/orthostasis, antocholinergic (constipation, dry mouth, urinary retention), CNS (headaches, weakness, tremor), weight gain, impotence
-Severe: coma, seizure, death from OD
TCA
-Two groups
-Secondary biochemical effects
-Common Side effects
-Metabolism
-NRI and SNRI

-H1 antagonist
-alpha-1 antagonist
-M1 antagonist
-ion channel blocking.

-Anticholinergic side effects
-cardiovascular
-CNS: sedation, confusion, tremor, seizures
-Other: weight gain, impotence, mania in BP patients

-P450 metabolism

-1 week overdose can be lethal
-Very cheap drugs
Major Depression: Remission
-Remitters
-Responders
-Remission: patient no longer meets criter for MDD, is asymptomatic/minimally symptomatic and has functional improvement

-Responders have symptomatic improvement, but remain majorly functionally impaired
-3X risk of relapse
Duration of antidepressant therapy
- First MDE: 12 months
- >or=2 MDE: maintenance treatment
- >3 MDE: lifelong
Maintenance Therapy
-Prevent recurrence
-Continue >or= 4 months
-Same dose/drug as acute therapy
-Duration, 2 episode cycles
-Slowly taper over 3-6 months
Neurotransmitter: 5-HT
-Origin
-Excess receptor stimulation side effects for 5HT-2 and 5HT-3
-Originates in Raphe Nucleus

Excess 5-HT2: sexual dysfunction and insomnia

Excess 5-HT3 (?4?): Nausea, diarrhea, appetite
Neurotransmitter: DA
-Origin
-Excess D2 Blockade side effects
-Substantia Nigra

-Excess D2 Blockade: EPS, flattened affect, slowed cognition, increased prolactin
Neurotransmitter: NE
-Origin
-Excess Alpha-1 Blockade side effects
-Locus Ceruleus

-Alpha-1 Blockade: dizziness, hypotension, drowsiness, sexual dysfunction
Neurotransmitter: ACh
-Origin
-Excess receptor inhibition side effects
-??
-Anticholinergic (antimuscarinergic??) : blurred vision, dry mouth, constipation, difficulty urinating, confusion/delirium
Neurotransmitter: Histamine
-Origin
-Excess H1 Blockade side effects
-Hypothalamus
-H1 Blockade: sedation, weight gain, hypotension