Transcript JK, 2009

Treatment of
anxiety disorders
MUDr. Jiřina Kosová
Psychiatric Centre Prague,
3. MF UC
Anxiety disorders
(a little bit sadly)
Life-time prevalence
of anxiety
dis. – above
30% !
Life-time
prevalence
in population
studies
Insufficiently
and/or low diagnose, inadequate
(NCS a ECA)
14
treatment
– less than 1 of 5 patients has correct
13,3%
Reasons
problems with dg
treatment
! (Kasper,of
2006)
12
5%
of pat.
in primary(62%;
care 33,5%
came with
- High
comorbidity
with psychiatric
10
problem,
BUT above 40% of further patients fulfills
depression)
dg.-criteria for MD
!!! (depression, anxiety)
7,8%
8
(Ansseau
et al., 2004)
- Insufficient
awareness (attention)
Consequences
– general
chronicity,
 quality of life,  risk
6
5,1%
- Uncertainty
of
practitioners
of TS
4
3,5%
- Relative
lack of research
Price
- 48 milliards
€ in 28 European countries;
2,5%
- (Witchen
in 2spiteaof
frequent
(more often
Jacobi,
2005; benzo
Baldwin prescription
at al., 2005)
than AD and/or pst !!! (Kasper, 2006)
0
Only 2 of
5 patients
SAD
PTSD asymptomatic
GAD
PD after 12
OCDyears
(Tyrer et al., 2004)
Comorbidity – example of SP
Depression
37 %
Dysthymia
15 %
Isolated
phobias
38 %
Panic dis.
11 %
Agoraphobia
23 %
SOCIAL
PHOBIA
GAD
13 %
PTSD
16 %
Avoidant
pers.dis.
58 %
Alcohol
24 %
Treatment - when ?
 intensity of symptoms,
recent onset, association
with some stressful life
event, degree of
functional failure; – need
not specialized treatment
(advantage of AD over
placebo is not clear !!!)
(for ex. Huppert et al., 2004)
severity, persistence of
symptoms, comorbidity, 
functional failure,
concomitant medication,
+ medical history; - TREAT!
depressive symptoms –
always AD !!!
Let him be, it's O.K. Just wait as soon
as he'll push off the bottom.
Treatment of anxiety disorders
Both pharmacotherapy and psychotherapy
effective
CBT has big ES in GAD, PD, SP, PTSD,
children anxiety disorders (accessibility
and/or knowledge of methods, trained
therapists !!!)
SSRI, SNRI
TCA, IMAO
BZD, anticonvulsants, antipsychotics
SSRI and venlafaxine
Effective; good tolerability, - 1st choice
AE: initial increase of tension,
nervousness, insomnia, nausea; sexual
dysfunctions
Withdrawal syndrome
After initiation/increase - careful monitoring
In venlafaxine – ECG, BP; usually not in
patients with heart disease, hypertension,
elektrolyt. disbalance (CSM, 2004; NICE, 2008)
TCA and IMAO
Because of AE – only in non-responders, or
during bad tolerance of 1st choice medication
Cardio- a CNS toxicity
NOT in high TS risk
Withdrawal syndrome
Very limiting pharmacologic interactions
Ami, Imi
Phenelzine – PD, SP
BZD
from 60th; 1970 – increase of GABA
transmission; lately – identification of specific
bonding places, or some ligands
In 80 % prescribing by general practitioners
Only in 10 % it is regular!!!
Very popular – treacherous successfulness –
e.g. in GAD 65 - 75 %,  HAMA by 29 - 69%;
PD, SP,…+ effect in the first week already
control studies – early signif. effect x placebo;
only unimportant differences between individual
BZD
Benzodiazepines - AE and risks
sedation, motoric deficits - 1,45 - 2,4x higher risk of
accidents contributing to death or emergency care
5-10 % of accidents – in association with BZD; in 43 - 65 %
found alcohol + BZD (Thomas, 1998)
203 pat.,
6-y concentration,
follow-up study,
cognitive
(attention,
implicit in
andsevere
explicit
mental
disorders
+ drug
abuse
memory)
- signif.
disturbance
in memory
tests after 3,5-years of
alprazolam treatment
– a43%
had
(Kilic
spol., 1999)
prescribed BZD, but – higher
score
of symptoms,
lower
quality
of life)
paradox
reactions
- aggression,
anxiety,
restlessness
(Brunette
et al.,
2003)
abusus
– mental
and
physical dependence, tolerance
Into anxiety
our therapy comes more than 60 %
rebound
Useof
in late
graviditywith
 neonatal
hypotonia,
withdrawal
patients
BZD (BZD
„safer“
than
syndrome
in newborns
AD– from
patients out of view!!!)
BZD are released to milk – known sedation and hypothermia
in nurslings (Bernstein, 1995)
Another options
Antipsychotics
AE, little of studies, different efficacy,
augmentation in OCD
Anticonvulsive drugs (except of BZD)
GAD, SP; non-responders, intolerance of AD
tolerance, dependence ???
(Ashton and Young, 2003)
Pregabaline +, Tiagabine –
Agomelatine !!!
(Stein a spol., 2008)
Treatment of panic disorder
Demands: quick response, disappearance of
attacks, decrease of total and anticipation
anxiety, elimination of avoidant behavior,
increase of skills, quality of life, decrease of
vulnerability to relapse, long-term effect,
maintenance after end of the treatment, zero
dependence, good tolerability, little AE, low
price, easy use, compliance (Starcevic,2004)
SSRI, CBT, (BZD), IMAO, TCA – effective in the
acute and/or long-treatment (Sheehan, 2002)
CBT !!!
Therapy of PD
1st choice: CBT (event. short dynamic pst) or
SSRI (8-12 weeks)
Good efficacy (including comorbid symptoms),
tolerability;
2nd choice: TCA
effectiveness, reliability, low price
Resistance: combination with pst;
augmentation; change of AD (venlafaxin; IMAO
– in comorbid atypical depression, or SP)
(high-potent BZD – in the beginning only, in
combination with AD)
M-analysis: Boyer 1995; Janicak 1999; Otto et al., 2001
Treatment of GAD
Psychotherapy, pharmacotherapy effective
SSRI (paroxetine, escitalopram), venlafaxin,
TCA, BZD, buspiron, hydroxyzine – effective
in short/long-term treatment
anticonvulsants
CBT
Short dynamic pst
Combination of CBT with medication (AD): nonsignificant difference between CBT alone – or the
combination CBT + medication
BUSPIRON
Azapirone, partial agonist of 5-HT1A receptors, slight affinity
to D2; no interactions with GABA-BZD receptor complex
Effective in both – mental and somatic anxiety symptoms
in comorbid diagnoses (depression, alcohol addiction)
minimal risk of dependence; low evidence about overdose
Low AE profile; occurrence of AE is not dependent on age,
or on duration of treatment
Slow onset in comparison with BZD
AE (against placebo): dizziness (64 % x 12 %), nausea
(34 % x 13 %), somnolence (19 % x 7 %), headache,
nervousness, dry mouth
rare cases of „psycho toxicity“ (psychosis, mania, panic
attacks); or neuromuscular toxicity (dystonia, dyskinesia)
0 data about its use in gravidity, lactation
Hydroxyzine
Antagonist of H1 receptors, M, 5-HT2
(+ little affinity to 1 and D2)
Effective in GAD, early onset, dose 50
mg/day (up to 150 mg/day)
Usually without sedation, dependence,
or memory disturbances; refines sleep
Good at: irritability, anxiety anticipations,
lack of concentration
The most frequent AE: somnolence (28
% x 14 %), dry mouth, weight increase
Futher possibilities
Pregabaline (structural analog of GABA)
Tiagabine (selective inhibitor of GABA
reuptake)
Kava-kava extract
Agomelatine
Psychoterapy in GAD
CBT – (Deacon and Abramowitz, 2004)
3 M-analyses (Borkovec and Whisman, 1996; Gould et
al., 1997; Weston and Morrison, 2001) demonstrated
the effectively of CBT – ES 1,01; 0,91; 2,09
resp.
Other specific PST
Psychoanalysis, group dynamic pst (Durham et al.,
1994; Crits-Christoph et al., 1996)
Relaxation
Biofeedback
Summary – treatment of GAD
1st choice in uncomplicated, mild - moderate,
without comorbidity: PST (CBT, group, short
dynamic); in severe, chronic, with comorbidity combination
1st pharmacological choice: paroxetine,
escitalopram či venlafaxin (8-12 weeks)
2nd choice: TCA, buspiron, hydroxyzine, (BZD),
anticonvulsants
Refractory: augmentation; change of AD,
combinations of drugs
Maintenance treatment – many years !
Acc.to: Barlow et al., 1997; Bourin and Lambert, 2002; Huppert and
Sanderson, 2003; Deacon and Abramowitz, 2004
Recommended dosages in OCD
Drug
Acute treatment
Maintenance
Start
(mg/day)
Average
(mg/day)
Maximal
(mg/day)
Average
(mg/day)
25
150-200
250
150
sertralin
50
50-200
200
50-200
fluvoxamin
50
150-200
300
150
paroxetin
10-20
40-60
60
40
fluoxetin
10-20
20-60
80
20-40
citalopram
10-20
20-60
60
20-40
venlafaxin
75
150-225
225
150-225
clomipramin
by Hollander, Simeon, Gorman, 1999)
Neurosurgery in OCD
(by Rasmussen and Eisen, 1997)
Procedure
effect
cingulotomia
56 %
67 %
61 %
50 %
capsulotomia
limbic leucotomy
tractotomy
under ncl. caudatus
(Gamma knife)
(40 - 50 %)
Souhrn - léčba OCD
1.volba u mírné: KBT
1.volba u stř.těžké až těžké: SSRI + KBT
2.volba: Klomipramin + KBT
Rezistence: jiné SRI, augmentace (NL);
kombinace, i.v. SSRI, rTMS, ECT,
neurochirurgie
Therapy of social phobia
PST, pharmacotherapy effective
We decide by the severity, intensity of avoidant behavior,
comorbidity, history, previous therapy, cooperation of patient
Drugs
SSRI (paroxetin, escitalopram, sertralin, fluvoxamin),
IMAO, RIMA, BZD, anticonvulsants, beta blockers, venlafaxin)
Comparison – meds x CBT – the same eff.
108CBT
studies;
SSRI or BZD
Combination of meds and
– in long-term
most(Feldman
effective;
perspective perhaps CBT better
and Rivas-
1st choice SSRI (good at
Other PST
fear, avoidance, somatic
symptoms, increase
Interpersonal
social functions,
Psychodynamic – case-reports
uncontrolled
study: ability to
work,
decrease
relapses
78 % of
patients improved
Vasquez, 2003)
(Lipsitz et al., 1999)
Summary – treatment of SP
1st choice in mild, uncompl.: CBT group
(event. interpersonal pst; treining of social skills)
1st choice in general., comorbid: SSRI
(paroxetin, sertralin, fluvoxamin, escitalopram) +
CBT, event. support
2nd choice: IMAO, RIMA, BZD
Resistance: combination of drugs with pst;
augmentation; change of AD (venlafaxin;
gabapentin, bupropion)
Performance anxiety – beta blockers
Mixed anxiety-depressive disorder –
treatment possibilities
SSRI
SNRI
IMAO
TCA
Mixed anxiety
depressive
disorder
RIMA
BZD
PSYCHOTHERAPY
CBT
Supportive psychotherapy in mixed
anxiety - depressive disorder
vyslechnutí pacienta, empatie
informace o poruše
povzbuzení a posílení naděje na vyléčení a vysvětlení
možnosti léčby
informace o způsobu léčby, medikaci a životosprávě
včetně
plánování aktivit
edukace o tělesných příznacích
ujasnění souvislostí stresujících událostí, změn nebo
problémů
v životě s rozvojem a udržováním poruchy
systematické přepracování katastrofických myšlenek a
scénářů
nácvik relaxace
podpora adaptivních způsobů řešení problémů v životě
Specific (isolated) phobias
Exposition in vivo (gradual or flooding overflow)
Exposition in imagination
5 – 10 sessions  effect in 80 – 90 % of
patients !!!
Training of muscle relaxation
One special problem – phobia from blood
(decrease of BP !!)
Treatment of PTSD
Prevention (acute intervention!)
Therapy aim against core symptoms PTSD
(reminiscences,Relative
avoidance
from reminding
little of pharmacol.
studies
impulses, lack Good
of positive
efficacy -emotions,
fluox., parox., hyper
sertralin,arousal)
phenelzin
efficacy-TCA
(except functioning,
for veterans)
and secondaryModerate
symptoms
(disturbed
Partially
effectivecomorbidity,
– trazodon, nefazodon
impaired stress
tolerance,
relations)
EMDR
buspiron – decrease of arousal
• Mood
Controversial
attitudes
(Hollander
and Simon, 2003)
PST
stabilizers
– irritability,
impulsiveness
• gabapentin
Better than –relaxation
(Carlson
et al., 1998)
improvement
of sleep
Hypnóza
drugs
• Avoid
5 years
catamnestic
study – symptoms)
originally improved
(hard
withdrawal
• BZD
Vysoká
hypnabilita
veteránů
veterans
after EMDR
– new worsening
At
least
partial
effect
between
4-8 week
- good
Hypnosis
• V et
porovnání
účinnější
(Macklin
al., 2000)s čekáním (WL)
Duration
(Brom
of maintenance
aofspol.,
1989)
treatment
not clear
–
•
Better
effect
CBT
after
acute
treatment,
and
EMDR (Eye-movement
and reprocessing)
min.
mdesensitization
• 12
after
3RIZIKO
m
too – může vést k těžkému
stavu
(Spiegel,
(Bourin
and 1988)
Lambert, 2002)
(Devillydissociativnímu
and Spence, 1999)
Psychotherapy in PTSD
CBT – expositional confrontation with anxious
memories, situations; cognitive
restructuration; training of adaptation and
handling of anxiety
Supportive pst (calming and education,
safety), psychodynamic pst, groups,
family pst (in all we reconstructed the
trauma, lead to abreaction)
Short-term dynamic pst – 2 contr. studies
(Brom and Kleber, 1989; Brom et al., 1989)
Summary – treatment of PTSD
1st choice in mild (without comorbidity):
specific pst
1st choice in „more serious“: SSRI (sertralin,
paroxetin)+pst
2nd choice: symptomatic therapy – trazodon or
gabapentin to improve of sleep; thymoprofylactic
drugs to decrease of irritability, buspiron to
reduction of hyper arousal
Resistence: another SSRI, augmentation (TCA,
thymopropfylactic drug, buspiron, AP),
combination
(start with low dosages; don't use BZD!)
By: Bourin and Lambert, 2002; Deacon and Abramowitz, 2004
Pharmacotherapy – start
Before – talk to patient about every
advantages and handicaps
Analyze mainly patient worries (AE)
SSRI – 1st choice
BZD – effect, but risks
Monitoring of initial AE (AD), gradual start
Monitoring of AE during the end (AD, BZD)
Some other drugs - TCA, IMAO, AP, AK –
individual judgment
To reach of clinical response in
initial treatment
Use 4-6 weeks (older patients longer)
If after 4th week no response (et least 20%
reduction in symptomatology) – probability of the
subsequent improvement is low (20%)
1st step: recheck dg., and optimize the dosages
Control: pharmacokinetic factors, plasmatic
levels, non-psychiatr. meds, physical and
laboratory examinations, coexisting
psychosocial stressors
In case of insufficient response
30 – 50 % of pat. - inadequate treatment response
the main pharmacological strategies
(there is not sufficiently enough info about
superiority of some)
1. Change for AD from other pharmacological
group
2. Change for AD from same pharmacological
group
3. combination
4. augmentation
5. wait
Risk of relapse after treatment
discontinuation
Generally – ¼ of patients after acute
phase and discontinuation of treatment
relapse in first two month
Significantly higher risk of relapse –
patients with residual symptoms after
acute phase
Recommendation for
maintenance treatment
All patients – maintenance phase min. 6
months after full remission, pro „worse“
min. 1 year, for serious OCD – life-time
Minimally 2 years in case of next risks
factors:  duration, repeating,  severity,
comorbidity
Dose of AD in the maintenance phase is
the same
Stop - slowly (tappering) – to prevent
withdrawal syndrome
. Treatment of anxiety - summary
1st choice in mild disorders – psychotherapy (shortterm CBT), supportive, self-help, monitoring
1st choice in more serious – pharmacological – SSRI
(event. SNRI), drugs + pst (CBT)
2nd choice – TCA, long-term CBT program (group);
change of meds., combination, augmentation
BZD only short-term
Education
Monitoring, and running care about AE
Pharmacotherapy, and CBT - compatible, without
interferences mutually
CBT added to meds – better outcomes than
medication alone
Summary - recommendations
Acute phase 6-12 weeks (older patients longer), in
case of insufficient response – check up dg., and
dosages, co-existing psychosocial stressors; and next:
1. Change AD – other pharmacological group
2. Change AD – same pharmacological group
3. combination
4. augmentation
5. wait
Extremely high risk of relapse !!!
Maintenance treatment min. 1 year after we reach a
full remission, for serious OCD - lifetime
Dose of AD in the maintenance treatment – the same!
End – slowly (tappering) – to prevent withdrawal
syndrome
Thank you
for your attention
Eat each morning
one frog, and
there could not
be nothing worse
for the rest of the
day!