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Unipolar Depression (Treatment (SSRI (side effects (sexual dysfct (up to…
Unipolar Depression
Treatment
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mild-moderate > antidepressants and psychotherapy equal efficacy; severe - antidepressants alone better than therapy alone
mechanisms: blocking reuptake, blocking receptors, altering second messengers, gene expression, glial cells, inflammation
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SSRI
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Paxil causes weight gain, anticholinergic s/s
side effects
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Paroxitine (Paxil) - abrupt stopping causes BAD withdrawal - electrical sensation, flu-like s/s
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nafazadone
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good for chronic pain, normalizes sleep
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venlafaxine: block reuptake of 5HT, NE, DA; more side effects and really bad withdrawal
mirtazepine - no reuptake effects, 5HT antagonist and alpha-2: very sedating, weight gain (good for depression in cachectic cancer patients)
duloxetine (NE, 5HT reuptake inhibitor): may help w/ chronic pain
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Neurobiology
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CRF: pitu releases ACTH -- influences adrenal to release cortisol (which downregs hypothalamus and pitu)
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imaging
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amygdala hyperactivity, limbic system - high arousal state
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systemic factors: increased inflamm (CRP, TNF), gene expression off, default mode network
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Psychological etiology
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interpersonal theory: unresolved grief, disputes, transitions, social skill deficits
cognitive theory: global negative assumptions, negative cognition, catastrophic, self-fulfilling prophecies
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Major Depressive Episode
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incidence - men 4-10%, women 10-25%
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depends on impaired FUNCTION, not just sadness
Non-pharm tx
ECT: most effective, fewest side effects, turns on neuroprotective genes
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5HT-DA interaction
5HT acting on 5HT2 blocks DA activity - Parkinsonism possible w/ SSRIs (also psychosis, anxiety)
more difficult to integrate motion: stumbling, postural swaying
5HT3 receptor in brainstem - increased dopamine release leading to nausea (5HT3 blockers - odansetron)