Post on 11-Jan-2016
AFFECTIVE DISORDERSLONG-TERM TREATMENT OF
DEPRESSION
PROF. MUDr. JIŘÍ RABOCH
1.LF UK A VFN
PRAHA
AFFECTIVE DISORDERSin the history
• 4. b.c. Hippokrates - melancholy, mania• 1899 Kraepelin manic depressiv psychosis• 1953 Kleist, Leonhard - unipolar x bipolar
depression
Paradigms of depression and its treatment
duration treatment
start of 20th cent. long-term long-term
1960 - 1970 short-term short-term
1980 - 1990 long-term long-term
1990 long-term short- and long-term
(Hirschfeld, R.M.A.,1998)
THE GLOBAL BURDEN OF DISEASE
Ch.J.L.MURRAY, A.D.LOPEZ, 1997
HARVARD SCHOOL OF PUBLIC HEALTH
WORLD HEALTH ORGANISATION
WORLD BANK
DALY - Disability Adjusted Life Years
DALY = YLL + YLD
YLL - Years of Life Lost
YLD - Years Lived with Disability
% DALY OF NEUROPSYCHIATRIC DISORDERS IN VARIOUS PARTS OF THE WORLD
0
5
10
15
20
25
30
DALY
mark.ec.
form.soc.
lat.Am.
China
Asia
Med.Sea
subsah.Afr.
Disability Adjusted Life Years Murray a Lopez, 1997
10 MAIN CAUSES OF DEATHestablished market economies
0
2000
4000
6000
8000
10000
12000
14000
16000
YLL
IHD
CVD
traf.acc.
lung canc.
selfinf. Inj.
perinat.
resp.inf.
congenit.
colon ca.
stom. Ca.
Years of Life Lost Murray a Lopez, 1997
10 MAIN CAUSES OF DISABILITIES established market economies
0100020003000400050006000700080009000
10000
YLD
depr.
alcohol
osteoart.
dementia
sch
bp
CVD
OCD
traf.acc.
diabetes
Murray a Lopez, 1997Years Lived with Disability
DALY (%)world
1. Respiratory infections 8,2
2. Diarhoea 7,2
3. Perinatal conditions 6,7
4. Major depression 3,7
5. IHD 3,4
6. CVD 2,8
7. Tuberculosis 2,8
8. Measles 2,7
9. Traffic accidents 2,5
10. Congenital anomalies 2,4
Murray a Lopez, 1997
DALY (%) established market economies
1. 9,9
2. Major depression 6,1
3. CVD 5,9
4. Traffic accidents 4,4
5. Alcohol use 4,0
6. Osteoarthritis 2,9
7. Trachea, bronchus, lung cancers 2,9
8. Dementias 2,7
9. Self-inflicted injuries 2,3
10. Congenital anomalies 2,2
Murray a Lopez, 1997
DALY (%) established market economies age 15 -
441. Major depression 12,3
2. Alcohol use 8,9
3. Traffic accidents 8,5
4. Schizophrenia 5,0
5. Self-inflicted injuries 4,2
6. Bipolar disorder 3,7
7. Drug use 2,9
8. OCD 2,7
9. Osteoarthritis 2,7
10. Violence 2,4Murray a Lopez, 1997
DALYformerly socialist countries
0
500
1000
1500
2000
2500
depr.male depr.female dem.male dem.female
1990
2000
2010
2020
Murray a Lopez, 1997
LIFE-TIME PREVALENCE (%)NCS
TOTAL Men Women
Affective disorders
17,1 12,7 21,7
Anxiety disorders 24,9 19,2 30,5
Dependencies 26,6 35,4 17,9
Non-affektive psychoses
0,7 0,6 0,8
Mental disorders 48,0 48,7 47,3
Kessler, 1994
0
10
20
30
40
50
60
70
80
90
100
0 5 15 25 35 45 55 65 75
AGE OF ONSET OF DEPRESSION
CU
MU
LA
TIV
E F
RE
QU
EN
CY
Cumulative frequency of depression according to the decade of birth and the age at the start of the disease
ECA study
1955+
1945-19541935-1944
1925-1934
1915-1924
1905-1914
1905
Wittchen et al., 1994
FIRST OUT-PATIENT PSYCHIATRIC EVALUATION DURING A YEAR
(2 450 106 EVALUATIONS)
DIAGNOSIS 1994 2003 CHANGES (%)
ORGANIC DISORDERS 27 421 45 083 64,4
DEPENDENCIES 31 097 34 484 10,9
SCHIZOPHRENIA 33 805 37 987 12,4
AFFECTIVE DISORDERS 37 915 79 215 108,9
NEUROTIC DISORDERS 103 577 158 168 52,7
CHILDRENS MENTAL DISORDERS
23 460 21 162 -9,8
TOTAL 307 877 419 175 36,2
ÚZIS 2005
13
28
43
52
5962
66 6871
74 7580 81 82 82
87
0
20
40
60
80
100
0,5 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
CUMULATIVE FREQUENCY OF RELAPSES OF DEPRESSION
(378 patients with depressive disorder)
years
Cu
mla
tive
fre
qu
ency
(%
)
Rothschild, A. J., 1999)
LONG-TERM COURSE OF DEPRESSION
bez suic.
úvahy suic.
suicidium
2/3 suicidal ideas
7 – 15 % commits suicide
Keller a Sadock, 1991
NUMBER OF COMMITED SUICIDES/100 000
0
10
20
30
40
50
60
70
80
Rus. Hun Franc. ČR GB Gree.
male
female
WHO 2000
0
5
10
15
20
25
30
35
67 70 73 76 79 82 85 88 91 94 97 0
MUŽI
ŽENY
COMITTED SUICIDESCZECH REPUBLIC
/100 000
ÚZIS 2003
CZECH REPUBLIC
2002 - COMMITED SUICIDES 1483 (1 173 men a 310 women)
ÚZIS 2003
FACTORS INFLUENCING THE COURSE OF DEPRESSION
• GENETIC RISK• AGE AT THE START OF DEPRESSION (<25, 60<)• NUMBER OF PREVIOUS EPIZODES AND THEIR LENGTH• REZIDUAL SYMPTOMS• COMORBIDITY• FEMALE GENDER• PSYCHOSOCIAL SITUATION (PARTNER)• BIOLOGICAL FACTORS – SLEEP PATTERN, HHA ACTIVITY
PHASES OF DEPRESSION TREATMENT
(Kupfer, 1991)
time
Depre
ssio
n inte
nsi
ty
acute continuing maintenance
DEPRESSION TREATMENT OPTIONS
• ANTIDEPRESSANTS, OTHER DRUGS • PSYCHOTHERAPY (KBT, IPT)• OTHER BIOLOGICAL METHODS
ECT
rTMS
PHOTOTHERAPY
SLEEP DEPRIVATION
VNS, DBS
PHASES OF DEPRESSION TREATMENT
(Kupfer, 1991)
time
Depre
ssio
n inte
nsi
ty
acute continuing maintenance
FINISHING THE CONTINUING TREATMENT PHASE
• 4 – 9 MONTHS OF EUTHYMIA• NOT FULFILLING THE CRITERIA FOR
MAINTENANCE TREATMENT• THE PATIENT IS ASKING FOR
• DISCONTINUATION SYNDROM – TCA, SSRI WITH SHORT-TERM ELIMINATION HALF-TIME
• SLOWLY DECREASING THE DAILY DOSAGE - 25 % DD PER MONTH
PHASES OF DEPRESSION TREATMENT
(Kupfer, 1991)
time
Depre
ssio
n inte
nsi
ty
acute continuing maintenance
MAINTENANCE THERAPY
Number of previous epizodes Clinical characteristics biological characteristics
- 3 or more previous suicide sleep pattern epizodes farmacoresistency - one previous epizode psychotic depression HHA activity with special clinical somatic features characteristics difficult psychosocial
situationdouble depression
Maixner a Greden, 1998
MAINTENANCE TREATMENT(LONG-TERM)
• WHAT ANTIDEPRESSANT
• WHAT DOSAGE
• HOW LONG
WHAT ANTIDEPRESSANT?
MAINTENANCE TREATMENT(LONG-TERM)
• LITHIUM• CLASSICAL ANTIDEPRESSANTS• IMAO, RIMA• SSRI• OTHER MODERN
ANTIDEPRESSANTS
0
0,2
0,4
0,6
0,8
1
0 10 20 30 40 50 60 70 80 90 100 110
weeks
RESUTLTS OF MAINTENANCE TREATMENT WITH IMIPRAMINE IN 4. AND 5. YEARS IN
COMPARISON WITH PLACEBO
(Kupfer, D.J., et al., 1992)
p<0,006
Imipramin (n=11)
Placebo (n=9)
Cu
mu
lativ
e f
req
ue
ncy
of
pa
tien
ts in
re
mis
sio
ni
SSRIs – inhibition of P450 microsomal enzymes
enzyme citalopram fluoxetine fluvoxamine paroxetine sertraline
CYP1A2 - - +++ - -CYP2D6 + +++ - +++ +CYP3A3/4 ? + ++ - -CYP2C19 ? ++ +++ ? -
? data lacking - no capacity
+ minor capacity ++ less potent
+++ most potent
(Edwards, J.G. a Anderson, I., 1999
POTENTIALLY SERIOUS DRUG INTERACTIONS OF SSRIs
all antikoagulancia zvýšený antikoagulační efekt(warfarin, kumaroly)
all antidepresivaIMAO serotoninergní syndrom(nižší pravděpodobnost u reverzibilních preparátů)Tricyklika zvýšená hladina některých tricyklik
fluoxetine antiarytmikaflecainid zvýšená plasmatická koncentrace
fluoxetine antikonvulziva snižování záchvatového prahufluvoxamine carbamazepin zvýšené plazmatické hladiny
phenytoinall antihistaminika
terfenadin zvýšené riziko arytmiíall lithium CNS toxicitaall sumatriptan CNS toxicitafluoxetinefluvoxamine klozapin zvýšená plazmatická hladina klozapinufluoxetine haloperidol zvýšená plazmatická hladina haloperidoluall ritonavir zvýšení koncentrace SSR1fluvoxamine theophyllin zvýšená plazmatická hladina theophyllinufluoxetine selegilin CNS excitace, hypertenzeall tramadol zvýšené riziko konvulzí
(Edwards, J.G., Anderson, L, 1999)
MAINTENANCE DEPRESSION TREATMENT
• SSRIs > CLASSICAL ANTIDEPRESSANTSSIMILAR EFFECT BETTER TOLERABILITY COMORBID DISORDERS ONCE A DAY DOSAGE
LOW INTOXICATION LETHALITY
• ANDERSON, 1998
HOW LONG?
0,00
0,20
0,40
0,60
0,80
1,00
0 52 104 156 208 260 312 364 416 468 520 572 624 676 728 780
weeks
pat
ien
ts in
rem
issi
on
Recurrences in 105 patients with major depression after 5 years-remission
(Mueller, T.I., et al., 1999)
WHAT DOSAGE?
DOSAGES OF ANTIDEPRESSANTS IN MAINTENANCE TREATMENT OF
DEPRESSION
• IMIPRAMINE – 3-YEARS FOLLOW-UP – 100 mg - 70 % RELAPSES
200 mg - 30 % RELAPSES (FRANK et al., 1993)
• CITALOPRAM 20 i 40 mg EFFECTIVE IN CONTINUING TREATMENT (MONTGOMERY et al., 1993)
• DECREASING THE DOSAGE OF CITALOPRAM FROM 40 TO 20 mg 2-YEARS FOLLOW-UP – 50 % RELAPSES (FRANCINI et al.,1999)
COMPLIANCE
• STRATEGIES FOR IMPROVING
PATIENT – PHYSICIAN RELATIONSHIP
EDUCATIONADEQUATE FARMAKOTHERAPY
Haddad, 2000
PSYCHOFARMACOLOGICAL THERAPY ONLY 13,4 % OF PEOPLE WITH DEPRESSIVE SYMPTOMS (!!!)
0
10
20
30
40
50
%
% 46 13 12 6 2 20
anxiol.antidep
r.hypn. neurol. other ns
Vaněk, Raboch, Vaněk, 2000