sat seminar a - powerpoint (dr. john so) (160526 for printing) · 2016. 7. 5. · •efficacy...
TRANSCRIPT
Clinical Updates
Management of Anxiety Disorders
John So - Psychiatrist
foreword
• Six Persimmons 《六柿圖》
• Muqi Fachang 牧谿法常
• after Zen meditation
•mindfulness
• other trends of psychotherapy
• other modalities of treatments
• by evidence or impression?
general
• anxiety disorders
• normal emotion � disorders
•becoming disabling
•reducing quality of life
• characteristics
•different types
•prone to have co-morbidities
•prone to be chronic
general
• drugs
• benzodiazepine
• antidepressant (SSRI SNRI)
• others
•other antidepressants
•other agents
BZ
• benzodiazepines
• rapid symptomatic relief
•efficacy
• pooled analysis showed less risk
of treatment discontinuation due
to lack of efficacy as compared to
placebo (Martin JL et al, 2007)
BZ
• benzodiazepines
• rapid symptomatic relief
•efficacy
•recommendation
• only for severe, disabling or
extremely distressing anxiety
• dependence, withdrawal risks
• lowest effective dose
• shortest period (maximum 4/52)
• caution with substance misuse
BZ
• benzodiazepines
• rapid symptomatic relief
• real world…
•over-prescription
• Harvard / Brown
Anxiety Research Project (HARP)
• naturalistic, longitudinal, multisite
study of adults with anxiety
disorders (Benítez CI et al, 2008; Vasile RG
et al, 2005)
• psychiatric setting
BZ
• benzodiazepines
BZ
• benzodiazepines
BZ
• benzodiazepines
• rapid symptomatic relief
• real world…
•over-prescription
• Harvard / Brown
Anxiety Research Project (HARP)
• Clonazepam 1.6mg
• Alprazolam 2.0mg
• Lorazepam 2.8mg
• Diazepam 13.0mg
BZ
• benzodiazepines
• rapid symptomatic relief
• real world…
•over-prescription
•“should not be denied”
• “a very small number of patients
with severely disabling anxiety
may benefit from long-term…
benzodiazepine” (12th Maudsley
Guidelines, 2015) (Tan KR et al, 2011)
(Tan KR et al, 2011)
SSRI / SNRI
• SSRI antidepressant
• efficacious first-line drug
•“broad spectrum”
•short and long term
•generally well tolerated
(Baldwin D et al, 2014)
SSRI / SNRI
• SSRI antidepressant
• efficacious first-line drug
• SNRI antidepressant
• venlafaxine and duloxetine
•short and long term for GAD
• venlafaxine
•acute treatment and relapse
prevention in panic disorder
(Baldwin D et al, 2014)
SSRI / SNRI x GAD
• SSRI / SNRI x GAD
• dosing
•1 / 2 normal starting dose
• some have initial worsening of
anxiety (Scott A et al, 2001)
SSRI / SNRI x GAD
• SSRI / SNRI x GAD
• dosing
•1 / 2 normal starting dose
•titration upwards
• normal dosage as tolerated
• predictors: severity and duration
of symptoms, (neuroimaging?)
• response within 6 weeks,
continues to increase over time (Ballenger JC, 2004, Baldwin DS et al, 2006, 2011)
SSRI / SNRI x GAD
• SSRI / SNRI x GAD
4th
wee
k
SSRI / SNRI x GAD
• SSRI / SNRI x GAD
• dosing
•1 / 2 normal starting dose
•titration upwards
•at least 1 year treatment
• optimal duration undetermined(Baldwin DS et al, 2014, Davidson JR et al, 2010)
• longer continuation treatment (Baldwin DS et al, 2011)
R
GAD Rx responders
treatment
placebo
(Baldwin DS et al, 2011)
SSRI / SNRI x GAD
• SSRI / SNRI x GAD
• dosing
•1 / 2 normal starting dose
•titration upwards
•at least 1 year treatment
• optimal duration undetermined(Baldwin DS et al, 2014, Davidson JR et al, 2010)
• longer continuation treatment (Baldwin DS et al, 2011)
SSRI / SNRI x GAD
• SSRI / SNRI x GAD
• dosing
•1 / 2 normal starting dose
•titration upwards
•at least 1 year treatment
• optimal duration undetermined
• longer continuation treatment
• may prevent depression; drug tx
NOT associated with depression (Goodwin RD & Gorman JM, 2002)
SSRI / SNRI x GAD
• SSRI / SNRI x GAD
• dosing
• drug choice (Baldwin D et al, 2011b)
•Fluoxetine
• probably most effective
•Sertraline
• probably best tolerated
Rank Responsereduction of
HAM-score ≥ 50%
Remissionfinal
HAM-A score ≤ 7
Withdrawalfor
adverse events
1 Fluoxetine Fluoxetine Sertraline
2 Lorazepam Escitalopram Pregabalin
3 Duloxetine Venlafaxine Fluoxetine
4 Sertraline Paroxetine Paroxetine
5 Paroxetine Sertraline Tiagabine
6 Pregabalin Duloxetine Venlafaxine
7 Venlafaxine Tiagabine Escitalopram
8 Escitalopram N/A Duloxetine
9 Tiagabine N/A Lorazepam
(Baldwin D et al, 2011b)
(Baldwin D et al, 2011b)
Efficacy of drug
treatments for GAD:
systematic review and
meta-analysis.
Systematic review of RCT:
3249 citations
46 randomised controlled trials
27 with sufficient or appropriate data
(Baldwin D et al, 2011b)
Efficacy of drug
treatments for GAD:
systematic review and
meta-analysis.
Systematic review of RCT:
3249 citations
46 randomised controlled trials
27 with sufficient or appropriate data
Primary Bayesian probabilistic mixed
treatment meta-analyses allowed
pharmacological treatments to be
ranked for effectiveness for each
outcome measure, given as
percentage probability of being the
most effective treatment.
(Baldwin D et al, 2011b)
(i.e. less withdrawal for adverse events)
SSRI / SNRI x GAD
• SSRI / SNRI x GAD
• dosing
• drug choice (Baldwin D et al, 2011b)
•Fluoxetine
• probably most effective
•Sertraline
• probably best tolerated
SSRI / SNRI x GAD
• SSRI / SNRI x GAD
• dosing
• drug choice (Baldwin D et al, 2011b)
•Fluoxetine
•Sertraline
•please note…
• unpublished data, sponsorships,
publication bias, methodology…
• GAD highly variable, racial
disparities…
SSRI / SNRI x others
• SSRI / SNRI x panic disorder
• dosing (12th Maudsley Guidelines, 2015)
•1 / 2 normal starting dose
•titration upwards
• bottom antidepressant range
• paroxetine may need higher dose
• response as long as 6 weeks
SSRI / SNRI x others
• SSRI / SNRI x panic disorder
• dosing (12th Maudsley Guidelines, 2015)
•1 / 2 normal starting dose
•titration upwards
•at least 8 months
• optimal duration undetermined (Rickels K & Schweizer E, 1998)
• evidence of benefit for at least 3
years (Choy Y et al, 2007)
SSRI / SNRI x others
• SSRI / SNRI x panic disorder
media
n
1.17 yr
media
n
5.67 yr
SSRI / SNRI x others
• SSRI / SNRI x panic disorder
• dosing (12th Maudsley Guidelines, 2015)
• drug choice
•SSRI first line
•clonazepam augmentation
• may lead to more rapid
response, but not greater overall
response (Pollack HM et al, 2003)
• BZ controversies (Davidson JR, 2004, NICE
Guidelines CG113, 2011)
SSRI / SNRI x others
Disorder DosingResponse
(week)
Minimum
(month)
GADhalf starting dose
titrate to normal dose6 12
Panic
Disorder
half starting dose
titrate to normal dose6 8
Social
Phobia
standard dose
titration may not be required8 12
OCDhigher licensed dose
but standard dose may suffice10 to 12 12
PTSDlower starting dose
high dose often required8 to 12 6
(12th Maudsley Guidelines, 2015)
etc
• other antidepressants
• TCA
•efficacy
• efficacious in some anxiety
disorders
• more side effects (Baldwin DS et al, 2014)
•clomipramine augmentation
• OCD cases (Koran LM et al, 2007)
etc
• other antidepressants
• agomelatine
•melatonergic and serotonergic
• MT(1), MT(2), 5-HT(2C) receptors
•efficacy
• efficacious in GAD, RCT vs
placebo, fu 12 weeks and 6
months (Stein DJ et al, 2008, 2012)
• less sexual or withdrawal side
effects; liver function monitor (Baldwin DS et al, 2014)
Results of AMSPa Drug Surveillance Program(Friedrich ME et a, 2016)
TCA &
Tetra
SSRI
Results of AMSP **a Drug Surveillance Program(Friedrich ME et a, 2016)
Arzneimittelsicherheit in der Psychiatrie
in-patients on antidepressants
(from 1993 to 2011)
n = 184 234
DILI = 149 (0.08%)
etc
• other antidepressants
• mirtazapine (Baldwin DS et al, 2014)
•NorAdrenergic and Specific
Serotonergic Antidepressant
•efficacy
• limited and inconsistent
evidence
• probably less frequent sexual
dysfuction
etc
• other antidepressants
• bupropion (Baldwin DS et al, 2014)
•noradrenergic, dopaminergic
•efficacy
• non-specific anxiolytic effect,
pilot study support
• concomitant BZs are necessary (Coplan JD et al, 2015)
etc
• other antidepressants
• TCA
• agomelatine
• mirtazapine
• bupropion
etc
• other agents
• pregabalin
•Ca channel α2δ subunit ligand
•efficacy
• efficacious in GAD (Baldwin DS et al,
2015, Pollack MH, 2009)
• initial dose 150mg
• comparable onset with BZ;
abrupt stop may cause rebound
anxiety and seizures (12th Maudsley
Guidelines, 2015)
etc
• other agents
• quetiapine
•atypical antipsychotic
•efficacy
• efficacious in GAD, acute
treatment, relapse prevention (Maneeton N et al, 2016, Katzman MA et al, 2011)
• dose from 50 to 150 or 300mg
• low acceptability and tolerability,
generally for non-response cases (Baldwin DS et al, 2011)
etc
• other agents
• buspirone
•azapirone anxiolytic
• 5-HT1A, 5-HT2A, D2, α1-
adrenergic and α2-adrenergic
receptors
•efficacy
• efficacious in GAD, not superior
to BZ, not as acceptable as BZ (Chessick CA et al, 2006)
etc
• other agents
• hydroxyzine
•1st generation antihistamine
•efficacy
• efficacious in GAD, also tolerable,
may be as effective as
chlordiazepoxide or buspirone
(noting study limits) (Guaiana G et al,
2010)
etc
• other agents
• flupentixol-melitracen (Wang L et al, 2015)
•“Deanxit”
•efficacy
• chronic somatic diseases
associated anxiety symptoms
• RCT response rates favouring
addition to sertraline to lower
anxiety for first two weeks
• potential tardive dyskinesia risk
etc
• other agents
• flupentixol-melitracen (Wang L et al, 2015)
drug
• SSRI / SNRI
• fluoxetine
• sertraline
• other
antidepressants
• TCA
• agomelatine
• mirtazapine
• bupropion
• benzodiazepine
• other
agents
• pregabalin
• quetiapine
• buspirone
• hydroxyzine
• flupentixol-
melitracen
anxiety disorders
• drug treatments
• noting other modalities
• generally, SSRI first line
• temporarily, BZ coverage
• response around 6 to 12 weeks
• prone chronic and co-morbid
anxiety disorders
• drug treatments
• limits
• evidence issues
•access to data, publication bias,
methodology limits
• cultural and biological differences
•side effects and withdrawals
• “guideline” issues
anxiety disorders
• drug treatments
• limits
• inherent issues
• anxiety disorders
•highly variable
•prone chronic and co-morbid
•residual symptoms and
resistant cases
Reference
• 12th Maudsley Guidelines (2015). The Maudsley Prescribing Guidelines in
Psychiatry, 12th Edition. April 2015, Wiley-Blackwell.
• Baldwin D et al (2011b). Efficacy of drug treatments for generalised
anxiety disorder: systematic review and meta-analysis. BMJ. 2011 Mar
11;342:d1199.
• Baldwin DS et al (2006). Escitalopram and paroxetine in the treatment of
generalised anxiety disorder: randomised, placebo-controlled, double-
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• Baldwin DS et al (2011). Evidence-based pharmacological treatment of
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