Kaplan

1
?????????? ?????????

• ????? 10
• 15-16.3.04
• ???? ????
• ?????? ???????????
• ?????????? ??-????

2
??????, ???????, ???????
??? ?????? ?? ??????? ??????? ????? ??????
???????? ?????
15-10 ?? ??????? ??????? ????? ?? ??????
Kaplan Sadock, 1991WPA/PTD Educational Program
on Depressive Disorders
3
"??????? ????" ?? ??? ???????, ?????? ?? ?????
??? ???? ??????

• Population studied 3,007 adults in New Haven
• Follow-up period 15 months
• Main findings
• 4.3 times more deaths in depressed
• None from suicide
• Increased risk same for physically healthy and
  not healthy
• None were treated for depression
• Cause of death
• 63 cardiovascular
• 22 cancer
• 15 other (most pulmonary)

Bruce NL, Leaf PJ. AJPH 198979(6)
4
?????? ??? ????????????? ???? ?????...

• ??? ????? ????? ????, ?? ??????? ?????? ??
  ??????? ??? ??????? ??????? ?? ?????? ????? ????,
  ?? ?????? ???? ??? ????? ?? ???? ??? ???? ?????,
  ??? ?????????, ?????? ??????? ??? ("???? ?????")
• ?????? ?????, ?? ?? ????? ????? ?????? ????????
  ????? ???? ???? ?????? ????? ?? ???????
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  ??? ????? ??????? ?? ???, ???? ?????????????????
  ????? ??? ?? ????? ?? ???
• ??? ?????? ??? ??? ???? ?????? ??? ???????

5
????? ?? ???????
??????????

• ???? ???? ??????? ?
• ?????????? ?????? ?? ????
• ??????????????? ?????? ?? ????
• ?????? ????, ???????? ???????, ?????? ??????
  ??-?????

"???"
"???"
???????????????
6
????? ?? ???????
??????????

• ??????????? ????? Top-Down, ????? ?????? ???????
  ???????? ?? ??????? ??? ?????? ??????? ?????? ??
  ????? ???? ???, ???????? ??????
• ???????????????? ????? Bottom-Up, ????? ???? ??
  ????? ???? ???????? ?????? ?????? ??? ??????
  ?????? ??????? ??? ?? ???

"???"
"???"
???????????????
7
??????????, ?????? ?????? ????

• ??? ?????? ????? ???? ?????? ?????????? ??
  ?????????? ?? ????? ????? ????? ???? ?? ???, ??
  ?????? ???????? ??? ???? ??????? (??????? ??????
  ???, ?????? ???, ???? ???)
• ??? ?????? ????? ???? ?????? ?????????? ??
  ?????????? ?? ??? ???? ????? ????, ?????
  ????????? ??????? ?????? ????? ????, ????? ?????
  ???? ?????? ??????? ????, ???? ???? ????? ???,
  ?????? ?????

8
??????????, ?????? ?????? ????

• ?????? ??????????? ??????? ?? ????? ????? ?? ????
  ???? ???????? ????? ???????? (E)
• ?????????? ???? ?????????? Top-Down ???? ??????
  ????? ????? ?????? ?????? ????, ???? ????? ??????
  ??? ???? ????? ????
• ????? ??? ??????????????? ?????????? Bottom-Up
  ????? ?????? ????? ?? ?????? ???? ???
• ????? ??? ?????? ???????????, ??????, ?? ??????
  ?? ????? ???? ???? ??????????? ??? ????? ????
  ??????? ????? ????? ???? ????? ?? ????? ????? ??
  ???? ??? ???? ???

9
?????? ??????? ????????? "????"

• ????? ?-SSRIs ????? ??????? ?????? ????? ??
  ????????? ???? ??? ?????? ????? ???????? ???
  (Peter Kramer - Listening to Prozac)
• ?? ???? ??????? (????? ???? ?????? ?? ?? ?? ????
  ??????) ??????????? ????? ????? ??????, ????
  ??????? ?????? ?????? ?? ????? ????????? ????
• ???? ???? ??? ??????, ?????? ??? ??? ??? ???????
  ???? ???? ????? ????? ?????? ???? ?????? ????
  ?????? ??????? ????
• ?????? ?? ?????? ?? ?????????? ?? ????? ????
  ?????? ??????? ?????, ??? ????? ??????? ?? ?? ???
  ???? ???????? ???? ???? (Keller et al., NEJM 2000)

10
?????? ??? - ?????????????

• ????? ??????? ??? (Major Depressive Disorder)
  ???? ??? ??? ?? "???? ????? ???????" ???
  ?????-??? ??? ?????? ??????
• ?? ???, ?????? ?????? ???????? ??? ??????? ????
  ?????? ?? ??? ??????? ?????? ????? ????
• ?????, ?????? ?????? ???? ???????? ??? ???????
  ??????? ???????? ?????? ????? ????
• ??? ?? ???? ??????? ???? ??????? ???????? ?? ????
  ?? ??????? ?????? ????????? (???????????
  ?????????) ???? ?????? ?????? ???????
• ??? ???? ?? ?????? ????? ??????????? ??????
  ??????? ???????

11
?????? ??? - ?????????????

• ??????? ???????????? ????????? ??????? ?????? ???
  ????? ??? ?????? ?????? (state, not trait)
• ?????? ????????? ?? ???????? ???????????? ??????
  ?? ????? ?????
• ???????????
• ?????? ???? ????? ?????? ????? ???
• ???? ????? ?? ?????? ??????????? ????? ????
  ???????
• ??? ??????? ?????? ?? ??? ??? ???????????? ????
  ??? ???????
• ??? ??? ???????????? ?????? ???? ?????? ????

12
?????? ???????????? ????
13
?????? ??? - ????????????????

• ???????? (5-HT)
• ?????? ???? ????? ?????? ????? ???
• ????? ????? ?????? ???? ????? ???, ?? ?? ????
• ??????? ???? 5-HT2 ?- 5-HT1a ?? ???????? ?????
  ???????
• ???????????????? ????? ?????? ??? ??????? ???????
• GABA?
• Dopamine ? ?
• CRF ? (???? ???? ?? PTSD ???????? ???????)

14
?????? ????????? ????
15
?????? ?????????
16
???????? ????????? ???????
?????? MAO ???? ????????? ???????
????????? ??????? (??????????? ?????????)
???? ????? ??? ??????
?????? ?????? (reuptake pump) ????? ?????????
??????? ??? ????-???????, ?? ??? ?????
17

• ???????? ????????? ???????
• ????????? ?? ?????? ?????? ??????

???? ?????? ???????? ?/?? ??????????? ??????
???????? ????? ????? ???? ?????, ???-?????
18
Monoamine Receptor Hypothesis of Depression??????
?????
Decrease in NT
19

• ????? ????? ?? ??????????? ?????????

5-HT
NE
Anxiety Irritability
Energy Interest
Impulse
Mood, Emotion, Cognitive Function
Sex
Appetite
Motivation
Aggression
Drive
DA
20
??? ?????, ??????? ???? ???? ?????
Normal Mood
40 Recovery
20 Dysthymia or Partial Recovery
40 Stay Depressed
Depression
1 year
21
?????? ?????? ??????(Antidepressants)

• ??? "?????? ??????" ??? ???? ???? ?? ???????
  ?????? ?? ?????? ?? ???? ????, ????? ????, ?????
  ???????-???????, ?????????, ?????? ????? ??????
  ?????? ?????, ????? ???????? ??? ??????
• ?????? ??????? ????? ??????? ?????? ?????? ???,
  ??????? ?SSRIs ??????? ?????? ???? ???? ???????
  ?????? ??? ??? ??? ???????? ?????? ???????
  ???????? ???????? ???? ???? ????? ????? ??
  ?????????

22
?????? ?????? ??????? ?????? ??????

• ?????? ?????? ????? ????? ?????? ??????? ??????
  ???? ????? ?????? ?????? ??? ????? ?????? ?????
  ???????
• ?????? ?????, ????? ???, ??????? ???
• ???? ?????? ?????? ??? ??? ???? (????? ??? ???
  ???????? ????????????? ?? ?????? ???? ?????
  ????????? ???)
• ?????? ????? ????? ??? ??? ???? ????? ??????, ???
  ??? ????? (?????? ?????? ?????? ??????? ???????
  ????? ??? ??? ???)
• ???? ???, ?????? ???????? ?????? ?? ????????
  ??????? "??"

23
????? ????? ????? ??????

• ?????? ??????? ????? ??????? ?????? ????? ??
  ?-?????? ?????? ???? ???? ?? ????
• ??? ???? ????? ?? ?????? ???
• 1) ?????? ?????? - ???? ????? ?????, ?? ?????
  ????????
• 2) ?????? ?????? ?????? ??????? ????-??????, ????
  ????? ?????? ??????? ???? ?? ??????? ??????
  ?????? ????
• 3) ???????? ?? ???????? ????????? ??????? ?????
  ????? ???? ?? ?????? ???? ??????, ???? ??????
  ??????? ??????? ?????????? ?? SNRIs

24
????????? ?????? ?????? ?????? ?????? (???????
??????????? ????)

• "??? ??? ?????" ?????? ?????? ???? ???????? ???
  ????????
• ????? ????? ????? ??????? ?????? ?????? ???????
  ???, ???????? ?? ?????? ????? ??
• ?????-?? ??????? ????? ?????? ??? ?????
• ????? ?????? ?????? ??? ???? (?? ???? ?????)
• ????? ?? ??? ????? ??? ???? (???? ????? ????
  ???????)

25
??????? ?????? ?? ?????? ?????? ??????

• ?? ??????? ?????? ??????? ??????? ?????? ????
  ?????? ????? ????? ????????? ?/?? ????????????
  ?????? ????????
• ?????? ??????????, ?????????? ??????? ?????? ??
  ???????? ??????? ???????? ???????????? ????? ???
  ????-???????
• ????? ???? ?- SSRIs ?????? ?? ?????? ?????
  ???????? ????? ??? ????-???????
• ????? ???? ? MAOIs ?????? ?? ?????? ?????
  ????????, ??????????? ??????? ??? ????-???????
  (??? ??????????? ????)

26
????? ?????? ??????? ?????? ????

• SSRIs
• ?????, ??????, ?????? (fluoxetine)
• ?????? (sertraline)
• ??????, ????? (paroxetine)
• ???????, ?????, ??????? (citalopram)
• ??????? (fluvoxamine)
• SNRIs
• ?????? (venlafaxine)
• ????? (milnacipran)
• NRIs
• ??????? (reboxetine)
• MAOIs
• ????? (phenelzine)
• ??????, ???????? (moclobemide)

• Tricyclics / Tetracyclics
• ???????, ???????? (imipramine)
• ???????, ?????? (clomipramine)
• ?????? (amitriptyline)
• ?????? (desipramine)
• ??????, ???????? (maprotiline)
• ????? (doxepin)
• ????????? (trimeprimine)
• ?????? ?????
• ???????, ????? (trazodone)
• ??????? (nefazodone)
• ????? (mirtazapine)
• ????????, ??????? (mianserin)
• ????? (bupropion)

27
Selective Serotonin Reuptake Inhibitors
(SSRIs)(???? ????? ?????)

• ??????? ?????? ????? ??????? ??????-???, ???
  ?????? ????? ?????????, ???? ???????, ??????
  ??????? ??? ?????? ?????? ?????? ?????, ?????? ??
  ???? ????? ?????? ????? ???? ?????? ????, ??????
  ????? ???', ????? ??????? ???? ?? ??????
• ??????? ?????? ????? ??????, ?????? ?????-???
  ?????? ????, ???? ????
• ??????? ????? 60-20 ?? ????, ??????? 100 ??
  ????, ?????? 20 ?? ????, ??????? 40-20 ?? ????

28
Listening to Prozac
????? ???? ??????? ?????? SSRI ????? ????? ??????
??????? ?? ???? ??? ?????? ?????? ???? ?? ???????
????? ??? ??? ???? ??? ??? ???? ?????? ?????
29
Tricyclic Antidepressants (TCAs)

• ??????? ?????? ?????, ???? ???? ???? ?????? ???,
  ???? ?????
• ??????? ???????, ?????? ????? ??????????????,
  ?????? ????? ??????????, ?????? ????? ?? ?????,
  ?????? ????? ???, ??????? ???? ??????-???
  (?????? ??????? ?? ?????? ??????????)
• ??????? ??????? 200-100 ?? ????,
  ??????? 300-100 ?? ????

30
?????? ??????? ??????? ????? ? TCAs

• ????? ????
• ????? ????
• ????? ??????
• ???? ????????????
• ????????
• ????? ?????? ????? ????????
• ?????? ????
• ????? ?????? (???? ? 50 ????? ?????? ???? ?
  TCAs ?? ??? ?? ????? ????)
• ???-???
• ??????-??? ?? ?????-???
• ??? ??? ???? ???? ????? ????

??????? ???????
31
?????? ???????? ?????? ??????? ???
Normal Mood
Medication Started
67 Responders
33 Nonresponders
Depression
8 weeks
32
????? ?????
8 weeks
33
???? ?????? ?????? ???? ?????? ????? ????
10 relapse
34
???????? ?????? ????,?? ??????? ??? ???
???????????? ?? ?????? ??? ????

• 50 ?? ???? ???? ??????? ??????? ??? ???? ???????
  ???????? ????? ????? ?????
• ?? ???? ????? ????? ???????, ???????? ????????
  ????? ?? ??????
• 50 ???? ??????? ???????? ???
• 70 ???? ??? ????????
• 90 ???? ???? ????????

35
??????? ?????? ?? ????? ?????? ?????

• ????? ???? ?? ???
• ???? ?? ???? ???????? ?? ?????? ???
• ????? ?? ???
• ??? ???????? ?? ?????? ??? ??? -
• ???????? ??????? ?? ????? ??-??????
• ???????? ?? ???? ?? ??????? ???? ??? ?????? ??
  ????? ????
• ??? ????? ?????? ??????? (??????? ?????? ???? ???
  20)
• ??? ????????? ??????
• ???? ???? ????? ??? ??????? ????? ????? ????????

36
FIVE-YEAR OUTCOME FOR FULL-DOSE MAINTENANCE
THERAPY OF RECURRENT DEPRESSION
Imipramine (n11)
p0.006
Placebo (n9)
Patients with no recurrence during a 3-year,
full-dose maintenance trial were randomized to 2
years of imipramine or placebo.
Kupfer et al. Arch Gen Psychiatry 199249769
37
????? ?? ?????????? ?? ???????? ????????????
????? ??????

• ???? 6-5 ?????? ?? ????? ????? ????
• ?? ?????? ????? ?? ???????? ?? ?????
• ????? ???? ????, ?? ?????? ?????
• ????? ?????? ????? ????? ?????
• ????? ?????? ?????? -
• ?????? ????
• ????? ??????

38
??????? ?????? ???????????? ????? ??????

• ??????, ?????? ?? ????? ??????????
• ?????? NRI /TCA ? SSRI ?? ????
• ?????? ??????
• ?????? ??????? ????? ????? (T3, T4)
• ????? ???? ?/?? ????? ????

39
?????? ???? ????? (ECT)

• ????? ????? ? 30, ???? ????? ?? ??? ????????
  ??????? ??????? ??? ????????? ????? ????? ????
  ??????? ???? ???? ???????
• ???? ?? ?????? ???? ??????? ???????? ???? ??????
• ???? ???? ?????? ????? ??? ???? ????
• ??? ?? ??? ????? ????????, ??? ??????? ????? ???
  ??????
• ???? ??? ?? ????? ?? ?????? ??? ?????

40
?????? ???? ????? (ECT)

• ????? ?????? ??????? ??? ????? ??????? -
• ????? ??? (???? ?? ????), ??"? ?? ????? ?? ??
  ????? ???
• ????? ???? (?????? ?????), ???? ????? ??????, ??
  ????? ????? ??? ?????
• ????? ?????? ???? ???????? ????? ???? ??????
  ????? ???? ??? ????? ??-????, ?? ?? ????? ????
  ????? ??????? (Sackheim et al., 2000)

41
?????? ???? ????? (ECT)

• ???? ?????? ????? ?????? ????? ??????? ????
• ????? ???? ?? ???? ???? ???? ?? ?? ????? ????
  ???? ?????
• ????? ?????? ?? ?????? ????? ????? ???? ????? ???
  ??????? ??????? ?? ???????
• ????? ????????, ???? ??????-?????? ???????
• ???? ????? ???? ??????? ??????? ?????? ????, ???
  
• "??? ???? ???, ????? ?? ?????"

42
??????? ?????? ???? ?????

• ?????? ????-???? (??????? ???? ????? ?? ????????
  ???????)
• ???? ????? ????? ??????
• ???????-??? ??????? (????? ?????)
• ???? ????? ????? ???????? ?????? ?? ????? ???????
  ?????? ??????

43
?????? ??????? ????????????

• "?????? ?????" ?????? ??? ???? ?????, ??????,
  ????? ??? ??, ????? ?????
• ?????? "??" ?? ????? ?????
• "?????? ??????" ??? ????? ?????? ???? ?????
  ?????? ????? ??????? ????, ???? ?????
• ??? ?????? ??????? ????? ?????? ?????? ??????
  ?????? ?????, ???? ???? ??? ????? ??? ????? ?????
  ?????? ??, ????? ????? ?? ????? ??? ?????

44
?????? ??????? ????????????

• ??? ?????? ?????? ???? ???????, ??? ????? ????
  ???????? ???? ???
• ??? ???? ?? ????? ?? ???? ?????? ??????? ?? ?????
  ????? ????? (???????????????), ???? ??????
  ?????? ?????? ????? ?????
• The price of freedom is eternal vigilance("????
  ????? ??? ????? ????? ?? ?????")

45
"????" ????? ??????

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  ??????? ??? ?? ????? ??????? ???????. ????? ????
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  ????? ?? ???? ????? ?? ?????? ???. ??????
  ???????, ?????? ??? ?????. ??? ?? ??? ????. ???
  ????????."

46
"????" ????? ????

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  ???? ????, ???? ????? ????? ??????? ????."