Transcript Document

Anxiety in practice
Diagnosis and management
1
What is ‘anxiety’?
A normal feeling: transient, disagreeable
emotional state, may be adaptive, signals
anticipated threat, initiates action.
A symptom: seen in wide variety of disorders,
A disorder: in which anxiety symptoms form a
dominant element.
2
How do the patients describe their
feelings of anxiety?
As an intense negative emotion, patients will use
words as –tense, panicky, terrified, jittery,
nervous, wound-up, apprehensive, worried etc.
Different symptoms of anxiety:
Somatic – subjective like twitching, tremors, hot
and cold flashes, sweating, palpitations, chest
tightness, difficulty swallowing, nausea,
diarrhoea, dry mouth, decreased libido etc.
Cognitive- hyper vigilance, poor concentration,
subjective confusion, fears of loosing control,
or going crazy, catastrophic thinking etc.
3
Behavioural symptoms-fearful expressions,
withdrawal, irritability, immobility,
hyperventilation etc.
Perceptual disturbance- depersonalization,
derealisation, hyperesthesia especially
hyperacusis.
4
A few terms:
Trait anxiety: lifelong pattern of anxiety as a
feature of temperament.
Free floating anxiety: persistently anxious mood
in which cause is unknown, and in which large
number of diverse thoughts and events trigger
and compound the anxiety.
Situational anxiety: only in relation to specific
occasions or external stimuli as in phobias.
Existential:being aware of its possible non-being
Ontic(fate and death),moral(guilt and
condemnation) and spiritual(emptiness and
meaninglessness)
5
Physical conditions presenting as
anxiety state
Medical diseases: brain tumours in temporal lobe
or 3rd ventricle region, stroke, migraine,
encephalitis, MS, epilepsy, Alzheimer's,
Parkinson's, Huntington's and Wilsons’
disease
Hypoxia, hypoglycemia, hyperthyroidism,
cushing’s syndrome, mitral valve prolapse.
Medications/drugs- cocaine, sympathomimetics
eg. Amphetamines, caffeine, lidocaine, alcohol
& sedative withdrawal.
6
Primary vs Secondary anxiety
Secondary anxiety as a response to an
underlying condition- a psychotic disorder,
depressions, substance related disorders.
Anxiety and depression: coexistence is
substantial,
Anxiety symptoms such as anxious mood and
irritability seen in majority of depressed
patients,
2/3 rd patients with Panic disorders will become
depressed in their life time.
7
Difference bt clinical anxiety and
depression.
Clinical anxiety
depression
Hypervigilance
Psychomotor retardation*
Severe sadness,
Perceived loss
Loss of interest- anhedonia
Hopelessness- suicidal*
Self depreciation*
Loss of libido
Early morning awakening*
Weight loss.
* strongest clinical markers of
depression.
Severe tension & panic
Perceived danger,
Phobic avoidance,
Doubt & uncertainty
Insecurity
Performance anxiety
8
Neurobiological mechanism of anxiety
Amygdala: ‘fear reaction’ in animal models,
nerve projections from amygdala
activates central autonomic nervous
system of brain– behavioural and
physiological manifestation of acute
anxiety.
Hypothalamus-pituitary- adrenal axis:
following early separation distress.
‘GAD: abnormal GABA in central BDZ
receptors.
9
‘Panicogens’: genetically predisposed and
traumatised by early separation distress
people respond with acute panic attack with
sod. Lactate infusion, co2, doxapram.
Hippocampus: neuronal degeneration
Glucocoticoid effects- explains memory
problems in PTSD.
10
Different anxiety disorders:
PANIC DISORDER AND AGORAPHOBIA: recurrent
panic attacks.
The panic attack : an episode of abrupt intense fear
that is accompanied by autonomic or cognitive
symptoms: palpitations, sweating, trembling or
shaking, sensations of shortness of breath or
smothering, feeling of choking, chest pain or
discomfort, nausea or abdominal distress, feeling
dizzy, unsteady, lightheaded, or faint,
derealization (feelings of unreality) or
depersonalization (being detached from oneself),
fear of losing control or going crazy,fear of dying,
paresthesias (numbness or tingling sensations),
chills or hot flushes
11
Phobic Anxiety Disorders
Agoraphobia
A. There is marked and consistently manifest fear
in, or avoidance of, at least two of the following
situations:
(1) crowds;
(2) public places;
(3) traveling alone;
(4) traveling away from home.
12
Phobic Anxiety Disorders
Agoraphobia
There is marked and consistently manifest fear in, or avoidance of, at least two of
the following situations:
(1) crowds;(2) public places;3) traveling alone;(4) traveling away from home.
B. At least two symptoms of anxiety in the feared situation
Autonomic arousal symptoms
(1) palpitations or pounding heart, or accelerated heart rate;(2) sweating; (3)
trembling or shaking;
(4) dry mouth (not due to medication or dehydration);
Symptoms involving chest and abdomen
(5) difficulty in breathing;(6) feeling of choking;(7) chest pain or discomfort;(8)
nausea or abdominal distress (e.g., churning in stomach);
Symptoms involving mental state
(9) feeling dizzy, unsteady, faint, or light-headed;(10) feelings that objects are unreal
(derealization), or that the self is distant or "not really here" (depersonalization);(11)
fear of losing control, "going crazy," or passing out;(12) fear of dying;
General symptoms
(13) hot flushes or cold chills;(14) numbness or tingling sensations.
13
SPECIFIC AND SOCIAL PHOBIAS:"phobia"
refers to an excessive fear of a specific object,
circumstance, or situation.
Both require the development of intense anxiety,
to the point of even situationally bound panic,
upon exposure to the feared object or
situation.
Also require that fear either interferes with
functioning or causes marked distress.
Finally, both conditions require that an individual
recognizes the fear as excessive or irrational
and that the feared object or situation is either
avoided or endured with great difficulty.
14
Obsessive-Compulsive Disorder:
Obsessions as defined by recurrent and
persistent thoughts, impulses, or images that
are experienced, at some time during the
disturbance, as intrusive and inappropriate and
that cause marked anxiety or distress,
Compulsions as defined by repetitive behaviors
(e.g., hand washing, ordering, checking) or
mental acts (e.g., praying, counting, repeating
words silently) that the person feels driven to
perform in response to an obsession, or
according to rules that must be applied rigidly.
15
PTSD
16
SUBSTANCE-INDUCED ANXIETY AND
ANXIETY DUE TO A GENERAL MEDICAL
CONDITION
prominent anxiety that arises as the direct result
of some underlying physiological perturbation.
clinically significant symptoms of panic, worry,
phobia, or obsessions emerge in the context of
prescribed or illicit substance use.
For example, panic attacks have been tied to
various medical conditions, including
endocrinologic, cardiac, and respiratory
illnesses.
17
Anxiety Disorder Not Otherwise Specified
This category includes disorders with prominent anxiety or
phobic avoidance that do not meet criteria for any specific
anxiety, disorder, adjustment disorder with anxiety, or
adjustment disorder with mixed anxiety and depressed
mood.
Examples include
1. Mixed anxiety-depressive disorder:
2. Clinically significant social phobic symptoms that are
related to the social impact of having a general medical
condition or mental disorder (e.g., Parkinson's disease,
dermatological conditions, stuttering, anorexia nervosa,
body dysmorphic disorder).
3. Situations in which the clinician has concluded that an
anxiety disorder is present but is unable to determine
whether it is primary, due to a general medical condition, or
substance induced.
18
GENERALIZED ANXIETY DISORDER: a pattern of
frequent, persistent worry and anxiety that is out of
proportion to the impact of the event or
circumstance that is the focus of the worry .
For example, while college students often worry
about examinations, a student who persistently
worries about failure despite consistently
outstanding grades displays the pattern of worry
typical of generalized anxiety disorder.
Patients with generalized anxiety disorder may not
acknowledge the excessive nature of their worry,
but they must be bothered by their degree of
worry.
This pattern must occur "more days than not" for at
least 6 months.
19
Case studies: 1
Ms. S. was a 25-year-old student who was referred for a psychiatric evaluation
from the medical emergency room at a larger university-based medical center.
Ms. S. had been evaluated three times over the preceding 3 weeks in this
emergency room.
Her first visit was prompted by a paroxysm of extreme dyspnea and terror that
occurred while she was working on a term paper. The dyspnea was
accompanied by palpitations, choking sensations, sweating, shakiness, and a
strong urge to flee. Ms. S. thought that she was having a heart attack, and she
immediately went to the emergency room.
She received a full medical evaluation, including an electrocardiogram (ECG) and
routine blood work, which revealed no sign of cardiovascular, pulmonary, or
other illness.
Although Ms. S. was given the number of a local psychiatrist, she did not make a
follow-up appointment, since she did not think that her episode would recur.
She developed two other similar episodes, one while she was on her way to visit a
friend and a second that woke her up from sleep. She immediately went to the
emergency room after experiencing both paroxysms, receiving full medical
workups that showed no sign of illness.-
20
Diagnosis:
Panic disorder:
21
Case study: 2
Mr. A. was a successful businessman who presented for
treatment following a change in his business schedule.
While he had formerly worked largely from an office
near his home, a promotion led to a schedule of
frequent out-of-town meetings, requiring weekly flights.
Mr. A. reported being "deathly afraid" of flying. Even the
thought of getting on an airplane led to thoughts of
impending doom as he envisioned his airplane
crashing to the ground.
These thoughts were associated with intense fear,
palpitations, sweating, clammy feelings, and stomach
upset. While the thought of flying was terrifying
enough, Mr. A. became nearly incapacitated when he
went to the airport. Immediately before boarding, Mr.
A. often had to turn back from the plane and run to the
bathroom to vomit.
22
Diagnosis:
Specific phobia.
23
Case study:3
Ms. B. presented for psychiatric admission after being transferred from a medical
floor where she had been treated for malnutrition.
Ms. B. had been found unconscious in her apartment by a neighbor. When brought to
the emergency room by ambulance, she was found to be hypotensive and
hypokalemic.
At psychiatric admission, Ms. B. described a long history of excessive cleanliness,
particularly related to food items.
She reported that it was difficult for her to eat any food unless it had been washed by
her three to four times, since she often thought that a food item was dirty. She
reported that washing her food decreased the anxiety she felt about the dirtiness
of food.
While Ms. B. reported that she occasionally tried to eat food that she did not wash
(e.g., in a restaurant), she became so worried about contracting an illness from
eating such food that she could no longer dine in restaurants. Ms. B. reported that
her obsessions about the cleanliness of food had become so extreme over the
past 3 months that she could eat very few foods, even if she washed them
excessively.
She recognized the irrational nature of these obsessive concerns, but either could not
bring herself to eat or became extremely nervous and nauseous after eating.
24
Diagnosis
OCD:
25
Case study:4
Mr. F. sought treatment for symptoms that he developed in the wake
of an automobile accident that had occurred about 6 weeks prior
to his psychiatric evaluation.
While driving to work on a mid-January morning, Mr. F. lost control of
his car on an icy road. His car swerved out of control into
oncoming traffic in another lane, collided with another car, and
then hit a nearby pedestrian. Mr. F. was trapped in his car for 3
hours while rescue workers cut the door of his car.
Upon referral, Mr. F. reported frequent intrusive thoughts about the
accident, including nightmares of the event and recurrent intrusive
visions of his car slamming into the pedestrian.
He reported that he had altered his driving route to work to avoid the
scene of the accident, and he found himself switching the
television channel whenever a commercial for snow tires
appeared. Mr. F. described frequent difficulty falling asleep, poor
concentration, and an increased focus on his environment,
particularly when he was driving.
26
Diagnosis:
PTSD
27
Case study: 5
Ms. X. was a successful, married, 30-year-old attorney who
presented for a psychiatric evaluation to treat growing
symptoms of worry and anxiety.
For the preceding 8 months, Ms. X. had noted increased worry
about her job performance. For example, while she had
always been a superb litigator, she increasingly found
herself worrying about her ability to win each new case she
was presented. Similarly, while she had always been in
outstanding physical condition, she increasingly worried
that her health had begun to deteriorate.
Ms. X. noted frequent somatic symptoms that accompanied
her worries. For example, she often felt restless while she
worked and while she commuted to her office, thinking
about the upcoming challenges of the day.
She reported feeling increasingly fatigued, irritable, and tense.
She noted that she had increasing difficulty falling asleep at
night as she worried about her job performance and
impending trials.-
28
Diagnosis:
GAD:
29
Generalized Anxiety Disorder
30
GAD: Content Overview
• GAD Background
— Epidemiology
— Burden of illness
— Treatment
— Diagnosis
• Pregabalin Pharmacokinetics
• Pregabalin in GAD
— Overview of clinical program
— Efficacy
— Tolerability and safety
31
GAD Epidemiology
General Population,
Primary Care Setting, and Comorbidities
32
GAD Symptoms: Prevalence Estimates
in the General Population
Prevalence (n=9282)
Duration of anxiety
symptoms (minimum)
Point (current)
1-year
Lifetime
1 month*
2.6%
5.5%
12.7%
3 months*
2.1%
3.9%
8.0%
6 months
(DSM-IV GAD)
1.8%
2.9%
6.1%
12 months
(DSM-IV GAD)
1.6%
2.2%
4.2%
*Anxiety symptoms fulfilling DSM-IV criteria for GAD, except for duration
Data from NCS-R (DSM-IV criteria), USA
Kessler et al. Psychological Med. 2005;35:1073-1082.
33
GAD: Lifetime Prevalence in the General
Population
10
All
9
Men
Women
% of population
8
7
6
5
4
3
2
1
0
Brazil
(n=1464)
Canada
(n=6261)
Data from surveys in 4 countries (DSM-III-R criteria)
Kessler et al. Psychol Med. 2002;32:1213-1225
The Netherlands
(n=7076)
USA
(n=5388)
All 4 samples
(n=20189)
34
Lifetime Prevalence of GAD in the
General Population by Age and Gender
Lifetime prevalence (%)
15
Women
All
Men
10
5
0
15–24
25–34
35–44
> 45
Age (years)
Data from NCS (DSM-III-R criteria), USA
Wittchen et al. Arch Gen Psychiatry 1994;51:355-364
35
Anxiety Disorders in Primary Care:
Point Prevalence Estimates
20
Point prevalence (%)
Lowest estimate
Highest estimate
15
11.8
10
8.5
7
5
3.7
3.1
2.6
1.5
2
0
GAD
Stein. J Clin Psychiatry. 2003;64(suppl 15):35-39
Panic disorder
Social anxiety
disorder
PTSD
36
Prevalence of GAD Symptoms in the
Primary Care Setting
40
35
All (n=17,739)
Men (n=7,274)
Women (n=10,465)
% of patients
30
25
20
15
10
5
0
GAD symptoms
1-4 weeks
Anxiety symptoms fulfilling DSM-IV for GAD criteria
Wittchen et al. J Clin Psychiatry. 2002;63(suppl 8):24-34
GAD symptoms
>6 months
(DSM-IV GAD)
37
GAD Symptoms Present Across the Age
Spectrum in Primary Care Setting
40
GAD DSM-IV diagnosis
*Anxiety symptoms
35
% of patients
30
25
6.8
5.6
7
6.6
6.6
20
2.7
2.4
3.1
19.8
19.3
19.5
60-69
70-79
80+
15
10
20.3
21.1
16-19
20-29
23.3
23.2
23.3
5
0
30-39
40-49
50-59
Age (years)
*Anxiety symptoms fulfilling DSM-IV GAD criteria, except for duration
Based on sample of n=17,739
Wittchen et al. J Clin Psychiatry. 2002;63(suppl 8):24-34
38
High Incidence of Comorbid Conditions
in GAD
60
GAD population (n=13,386)
Controls (n=89,971)
% of subjects
50
***P<0.01 vs. controls
***
40
***
30
20
***
***
***
10
***
***
0
GI
Disorders
GU
disorders
CV
disease
Chronic
pain (all)
Neuropathic
Major
pain only
Depressive
Disorder
Dysthymia
Condition
GI=gastrointestinal; GU=genitourinary, CV=cardiovascular
Data from medical claims databases 1999-2002
Data on file, Pfizer Inc. Brandenburg et al. ADAA 2005
39
Lifetime Prevalence of Comorbid Psychiatric
Disorders in Patients with GAD
Any other anxiety
disorder
58
Social phobia
34
Panic disorder
22
Any mood disorder
72
61
Major depression
Dysthymia
38
Substance abuse/
dependence
34
0
10
20
30
40
50
60
70
80
90
100
% of population with GAD
Data from international surveys in 4 countries (DSM-III-R criteria)
Subset of population with GAD
Kessler et al. Psychol Med. 2002;32:1213-1225
40
GAD Often Precedes the Development of
Other Psychiatric Disorders
Subset of those with GAD + comorbid disorder: GAD occurred first
Any other anxiety
disorder
25
22
Social phobia
16
Panic disorder
Any mood disorder
29
Major depression
21
Dysthymia
25
Substance abuse/
dependence
52
0
10
20
30
40
50
60
70
80
90
100
% of population with GAD
Data from international surveys in 4 countries (DSM-III R criteria)
Kessler et al. Psychol Med. 2002;32:1213-1225
41
GAD: Comorbidity, Presentation
and Course of Illness
42
GAD: A Common Comorbid Condition
• GAD is one of the most common conditions that occurs
comorbidly with other disorders
— 91% of patients with GAD have ≥1 additional diagnosis1
• GAD occurs comorbidly with many medical and psychiatric
conditions, including:
— Major depression1-4
— Chronic pain conditions4
— Panic disorder1-3
— Chronic fatigue syndrome2
— Social phobia1
— Gastrointestinal disease5
— Specific phobia1
— Irritable bowel syndrome2,5
— Post-traumatic stress disorder2
— Hypertension2
— Heart disease2
1. Sanderson. J Nerve Ment Dis. 1990;178:588-591
2. Stein. J Clin Psychiatry 2001;62(suppl 11):29-34; 3. Keller. J Clin Psychiatry 2002;63(suppl 8):11-16
4. Data on file Pfizer Inc; 5. Sareen et al. Depress Anxiety 2005;21:193-202
43
Physical Symptoms May Predominate
in GAD
• Aches, pains, soreness
• Insomnia (difficulty falling asleep)
• Symptoms of autonomic arousal
— Tachycardia, palpitations, sweating, tremor
• Gastrointestinal symptoms
— Nausea, diarrhea
• Other
— Dizziness, light-headedness
— Breathing difficulties
— Numbness, tingling
— Hot or cold flushes
Starcevic. Anxiety Disorder in Adults. Oxford University Press. 2005:102-140
Gorman. Clin Cornerstone. 2001;3(3):37-43
44
Most Patients with GAD do NOT Present
with Anxiety as the Primary Complaint
Only 13% had anxiety as primary complaint
60
% of patients with GAD
50
40
30
20
10
0
Anxiety
Somatic
illness/
complaints
Based on sample of n=17,739; 5.3% with GAD (DSM-IV)
Wittchen et al. J Clin Psychiatry. 2002;63(suppl 8):24-34
Pain
Sleep
disturbance
Depression
45
GAD: Often Not Recognized in Primary
Care
Mental
disorder
recognized
but GAD not
diagnosed
38%
34%
Specific GAD
diagnosis
28%
Mental
disorder not
recognized
Based on sample of n=17,739; 5.3% with GAD (DSM-IV)
Wittchen et al. J Clin Psychiatry. 2002;63(suppl 8):24-34
46
GAD Course of Illness
• Chronic
— Waxing and waning of symptoms1
— Low rates of remission over long term1,2
• Intermittent exacerbations
— Exaggerated response to stress1,3
• Symptom overlap with medical and psychiatric disorders3
— Many are undiagnosed4
• Episodes may be more persistent with age5
• Poorer outcomes in patients with psychiatric comorbidities6
1. Starcevic. Anxiety Disorder in Adults. Oxford University Press. 2005:102-140
2. Yonkers et al. Depress Anxiety. 2003;17:173-9; 3. Stein. J Clin Psychiatry 2003.64(suppl 15):35-39;
4. Wittchen et al. J Clin Psychiatry. 2002;63(suppl 8):24-34; 5. Wittchen et al. Arch Gen Psychiatry 1994;51:355-364;
6. Bruce et al. Am J Psychiatry. 2005;162:1179-87
47
Low Probability of Remission in GAD
Probability of full remission
1
0.9
0.8
Probability
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
1 (n=167)
2 (n=133)
3 (n=111)
4 (n=91)
5 (n=73)
Years since index episode
Full remission: PSR <3 for 8 weeks following index episode
HARP 5-year prospective study
Yonkers et al. Br J Psychiatry. 2000;176:544-549
48
Low Probability of Remission in GAD in
Men and Women
1
Probability of remission
P=0.24 test for gender difference
Men (n=48)
Women (n=119)
0.8
0.6
0.4
0.2
0
0
1
2
3
4
5
6
7
8
Years since index episode
Full remission: PSR <3 for 8 weeks following index episode
HARP 8-year prospective study
Yonkers et al. Depress Anxiety. 2003;17(3):173-179
49
GAD: Burden of Illness
50
GAD Patients in Primary Care: Difficulty
with Usual Activities in Past 4 Weeks
No difficulty
16%
Incapacitated
2%
Much difficulty
26%
Over 50% of
patients had at
least some
difficulty
A little difficulty
26%
Some difficulty
30%
Data from PCAP (n=142), USA
Maki et al. 2003. APA Presentation
51
Disability/Impairment* in GAD and/or
Major Depressive Episodes
100
% with disability/impairment
90
Due to somatic problems
Due to psychiatric problems
80
70
60
50
40
30
20
10
0
No GAD or Pure GAD
MDE
(n=666)
(n=16,023)
Comorbid Pure MDE
GAD/MDE
(n=772)
(n=278)
No GAD or Pure GAD
MDE
(n=666)
(n=16,023)
Comorbid Pure MDE
GAD/MDE
(n=772)
(n=278)
*Missing ≥ 1 day of work in previous month
MDE: major depressive episode
Based on primary care sample of n=17,739
Wittchen et al. J Clin Psychiatry. 2002;63(suppl 8):24-34
52
Work Impairment in GAD and Other
Chronic Conditions
Days work impairment in past month
14
12
Mean days
10
8
6
4
2
0
GAD
MDD
Hypertension
Arthritis
Data from Midlife Development in the US survey (MIDUS)
Work impairment based on work-loss days and work-cutback days
Kessler et al. 2001. In: Rossi AS, editor. Chicago: University of Chicago Press. pp403-426
Asthma
Diabetes
53
Patients with GAD Report Greater Work
Impairment than Patients with MDD
% with work days lost/impaired in past month
Average work days lost in past month
70
8
60
6
Work days lost
% of respondents
50
40
30
4
20
2
10
0
0
No GAD or
MDD (n=3764)
Pure GAD
(n=33)
Comorbid
GAD/MDD
(n=40)
Pure MDD
(n=344)
Wittchen et al. Int Clin Psychopharmacol. 2000;15:319-328
No GAD or
MDD (n=3764)
Pure GAD
(n=33)
Comorbid
GAD/MDD
(n=40)
Pure MDD
(n=344)
54
GAD is Associated with Quality of Life Impairment:
Mean SF-36 Scores in People with GAD and/or MDD
100
90
Mean SF-36 score
80
70
60
50
40
30
No GAD or MDD
Pure MDD
20
Comorbid GAD/MDD
Pure GAD
10
0
General
health
Physical
function
Physical
role
Bodily pain
Mental
health
P<0.05: GAD vs. no GAD or MDD for all domains.
P<0.05: GAD vs. MDD for general health, mental health, emotional role, vitality
Wittchen et al. Int Clin Psychopharmacol. 2000;15:319-328
Social
function
Emotional
role
Vitality
55
Increased Healthcare Utilization in GAD
Average number of visits in past year
24
Average number of visits/year
Primary care
Specialist (outpatient)
20
16
15
14
12
8
7
4
4
3
2
0
No GAD or MDE
Pure GAD
GAD + MDE
(n=16,023)
(n=666)
(n=278)
MDE: major depressive episode
Based on primary care sample of n=17,739
Wittchen. Depress Anxiety. 2002;16(4):162-171
56
Patients with GAD Have as Many Doctor
Visits as Patients with Depression
80
No GAD or MDE (n=16,023)
% of respondents
70
Pure GAD (N=666)
60
GAD + MDE (n=278)
50
Pure MDE (n=772)
40
30
20
10
0
4+ to PCPs
2+ to other specialists
Psychiatrist
Doctors visited in the past year
MDE: Major Depressive Episode
Wittchen et al. J Clin Psychiatry. 2002;63(suppl 8):24-34
57
Number of Concurrent Psychiatric
Disorders† in GAD Patients
Other anxiety
disorders
23
1.6
# of concurrent
disorders
24%
One
Two
Depressive disorders
27
Other anxiety and/or
depressive disorders
2
29%
34
0
10
Three or
more
9.7
20
30
40
1.2 45%
50
60
% of patients
GAD in German GP database
†Excluding GAD itself
N=3,340 GAD patients. Psychiatric disorder in the same year
IMS Mediplus Database German GP Analysis. Data on file, Pfizer Inc
58
Direct and Indirect Costs in GAD With
and Without Comorbidity
$2050/3 months
$1250/3 months
100%
90%
% of patients
80%
34
33
70%
60%
50%
25
42
40%
30%
20%
Work absenteeism
Outpatient services
Hospitalization
Medications
Diagnostic tests
35
21
10%
0%
GAD WITH comorbidity
(n=604)
GAD without comorbidity
(n=395)
Costs calculated as $(USA) in 1994 and expressed as equivalent value in 2007 $(USA)
Souêtre et al. J Psychosom Res. 1994;38:151-160
59
GP Visits and Referrals in 1 Year:
GAD Patients vs. Comparison Group
GP visits
100
# of visits
90
60
1
50
40
80
70
% of patients
3 or 4
2
70
# of referrals
3
2
**
67%
1
50
39%
40
30
20
20
10
10
0
0
Comparison
group
4+
60
30
GAD patients
Referrals by GP
90
>6
5 or 6
80
% of patients
100
GAD patients
Comparison
group
**P<0.001 GAD vs. comparison group
GAD in German GP database
N=3,340 in each group. Frequency in the year
IMS Mediplus Database German GP Analysis. Data on file, Pfizer Inc
60
GAD: Diagnosis
"Normal" worry vs. Generalized Anxiety Disorder (GAD)
“Normal” Worry:





Your worrying doesn’t get in the way
of your daily activities and
responsibilities.
You’re able to control your worrying.
Your worries, while unpleasant, don’t
cause significant distress.
Your worries are limited to a specific,
small number of realistic concerns.
Your bouts of worrying last for only a
short time period.
Generalized Anxiety Disorder:





Your worrying significantly disrupts
your job, activities, or social life.
Your worrying is uncontrollable.
Your worries are extremely upsetting
and stressful.
You worry about all sorts of things,
and tend to expect the worst.
You’ve been worrying almost every
day for at least six months.
61
Another GAD- Carrie’s story:
Carrie has always been a worrier, but it never interfered
with her life before. Lately, however, she’s been feeling
keyed up all the time.
She’s paralyzed by an omnipresent sense of dread, and
worries constantly about the future. Her worries make it
difficult to concentrate at work, and when she gets home
she can’t relax.
Carrie is also having sleep difficulties, tossing and turning
for hours before she falls asleep. She also gets frequent
stomach cramps and diarrhea, and has a chronic stiff
neck from muscle tension. Carrie feels like she’s on the
verge of a nervous breakdown.
62
Sound Familiar?
“I can’t get my mind to stop…it’s driving me
crazy!"
“He’s late - he was supposed to be here 20
minutes ago! Oh my God, he must have been
in an accident!”
“I can’t sleep — I just feel such dread … and I
don’t know why!”
63
Background: GAD Evolution as a Distinct
Diagnostic Entity is Relatively Recent
DSM-I (1952)
Anxiety reaction
DSM-II (1968)
Anxiety neurosis
DSM-III (1980)
GAD
(1-month duration)
Panic disorder
DSM-IV (1994)
GAD
(6-month duration)
Includes overanxious
disorder of childhood
Anxiety disorders
NOS
Rickels & Rynn. J Clin Psychiatry. 2001;62(suppl 11):4-12
64
Generalized Anxiety Disorder:
DSM-IV Diagnostic Criteria
•
•
•
•
•
•
Excessive anxiety and worry present most of the time for > 6 months
Difficult to control worry
Associated with (at least 3 items):
─ Restlessness
─ Being easily fatigued
─ Concentration difficulties
─ Irritability
─ Muscle tension
─ Sleep disturbance
Focus of anxiety and worry not confined to features of an Axis I disorder
Causes clincially significant distress or functional impairment
Not due to medication, illness, or substance abuse
DSM-IV-TR. APA 2000
65
Generalized Anxiety Disorder:
ICD-10 Summary
•
•
•
Anxiety is generalized and persistent and not associated with a particular
environmental circumstance (i.e. it is free-floating)
Anxiety present most days for at least several weeks at a time and usually
for several months
Symptoms should involve elements of:
─ Apprehension
• E.g. Worry about future, feeling “on edge”, difficulty concentrating
─ Motor tension
• E.g. Restlessness, fidgeting, tension headaches, trembling
─ Autonomic overactivity
• E.g. Light-headedness, sweating, tachycardia, epigastric discomfort
•
Must not meet full criteria for depressive episode, phobic anxiety disorder,
panic disorder, or obsessive-compulsive disorder
ICD-10, WHO 1992
66
DSM-IV and ICD-10 GAD Diagnostic
Criteria: Some Differences
DSM-IV
ICD-10
Diagnostic classification
Independent
category
Residual
category
Worry/anxiety symptom
Excessive anxiety
and worry
Persistent freefloating anxiety
≥6 months
Several months
Not essential
Must be present
Must be present
Not specified
Duration
Autonomic hyper-activity
and physical symptoms
Functional impairment
Rickels & Rynn. J Clin Psychiatry. 2001;62(suppl 11):4-12
Starcevic. Anxiety Disorder in Adults. Oxford University Press. 2005:102-140
67
Use of Published GAD Diagnostic
Guidelines
100
Psychiatrist
PCP
90
% using guidelnes
80
70
66
60
49
50
43
40
40
28
30
27
20
10
0
n=44
Germany
n=43
Italy
n=40 n=36
n=40 n=30
Spain
UK
• DSM-III and IV guidelines most commonly used
Data on file, Pfizer Inc
68
Guidance for Exploring a Suspected
Anxiety Disorder
Specific anxiety-related symptoms & impaired function
Also moderate/severe depression?
Yes
Treat
depression
No
Predominant symptom focus
Trauma
history &
flashbacks
Check for
PTSD
Obsessions

compulsions
Check for
OCD
Uncontrollable
worry in several
areas
Check for
GAD
Baldwin et al. J Psychopharmacol. 2005;19(6):567-596
British Association for Psychopharmacology
Intermittent panic/anxiety attacks and
avoidance
Fear of
social
scrutiny
Discrete/
object
situation
Check for
Social
Anxiety
Disorder
Check for
specific
phobia
Some uncued/
spontaneous
Check for
Panic Disorder
69
GAD: Disease and Management Issues
•
•
•
•
•
•
GAD lifetime prevalence ~5%
Comorbid disorders common
─ Common comorbidity of medical and psychiatric disorders
Usually chronic, relapsing-remitting course
─ Low probability of remission
─ Long-term treatment often needed
Sub-optimal recognition and diagnosis is common
─ Often presents as somatic complaint
Substantial quality of life and economic burden
Current treatments may have limitations
70
GAD Treatment
 Cognitive therapy (CBT): probably the most effective treatment.
 Counseling :
 Anxiety management courses : learning how to relax, problem
solving skills, coping strategies, and group support.
 Self help
You can get leaflets, books, tapes, videos, etc, on relaxation and
combating stress. They teach simple deep breathing techniques
and other measures to relieve stress, help you to relax.
71
Drug treatment for
GAD:
72
Rx Treatments For GAD
Antipsychotics 5%
Sedatives
11%
AEDs 3%
Antidepressants
38%
European data. IMS 4Q07
Benzodiazepines
43%
73
Evidence That Treating GAD Reduces
the Risk of Developing MDD
% developing depression
30
25
48% reduction: P<0.001
20
15
10
5
0
GAD untreated (n=99)
Data from NCS, USA. MDD: Major Depressive Disorder (DSM-III-R)
Hazard ratio =0.52 in patients who had taken psychotropic medication ≥4 times.
Goodwin et al. Am J Psychiatry. 2002; 159(11):1935-1937
GAD treated (n=120)
74
Current GAD Treatments:
Benzodiazepines
Advantages
Disadvantages
• Effective, mainly in somatic
symptoms1
•
Less effective for psychic
symptoms1
• Fast onset of action1
•
Dependence issues with
long-term use2,3
•
Withdrawal symptoms and
rebound anxiety2,3
•
Cognitive and psychomotor
impairment2
•
Drug-drug interactions
(CYP 3A4)2
• Reproducible response1
1. Gorman. J Clin Psychiatry. 2002;63(suppl 8):17-23
2. Nemeroff. J Clin Psychiatry. 2003;63(suppl 3):3-6
3. Chouinard. J Clin Psychiatry. 2004; 65(suppl 5):7-12
75
Current GAD Treatments:
SSRIs/SNRIs
Advantages
Disadvantages
•
Effective, mainly in psychic
symptoms1
•
Less effective for somatic
symptoms1
•
Reduce comorbid depressive
symptoms1
•
Variable patient response2
•
Delayed onset of action2
Low potential for abuse
•
Sexual dysfunction2
•
Weight gain1
•
Discontinuation symptoms2
•
Drug-drug interactions
(CYP 2D6)1
•
1. Raj & Sheehan. Generalized Anxiety Disorder. Martin Dunitz Ltd. 2002:137-152
2. Nemeroff. J Clin Psychiatry. 2003;63(suppl 3):3-6
76
Efficacy in Key Symptoms of GAD
Across Drug Classes
Benzo
TCAs
SSRIs &
SNRIs
Azapirones
α2δ ligand
<7 days
~3 weeks
~3 weeks
~3 weeks
<7 days
Psychic
symptoms
++
+++
+++
+++
+++
Somatic
symptoms
+++
+
+
+
+++
Associated
insomnia
+++
+
+
+
+++
Secondary
depressive
symptoms
+
+++
+++
++
++
Speed of
onset
+ Some efficacy, ++ Moderate efficacy, +++ Marked efficacy
Benzo: benzodiazepine, SSRI: Selective serotonin re-uptake inhibitor, SNRI: Serotonin-noradrenaline
re-uptake inhibitor; TCA: Tricyclic antidepressant. Not all classes approved for use in GAD in Europe.
Montgomery. Expert Opin. Pharmacother. 2006;7(15):2139-54
77
Tolerability and Safety Profiles Across
Drug Classes used in GAD
Benzo
TCAs
SSRIs &
SNRIs
Azapirones
α2δ ligand
+++
++
+/++
+
++
Weight gain
+
++
+
+
++
Sexual
dysfunction
0/+
+
++
+
0/+
0
+
+
+
0
Withdrawal
syndrome
+++
++
0/+/++
+
+
Risk of drug
interactions
++
++
0/+/++
+
0/+
Sedation/
psychomotor
impairment
GI sideeffects
0: minimum-to-none; + Some, ++ Moderate, +++ Marked
Benzo: benzodiazepine, SSRI: Selective serotonin re-uptake inhibitor, SNRI: Serotonin-noradrenaline
re-uptake inhibitor; TCA: Tricyclic antidepressant. Not all classes approved for use in GAD in Europe.
Montgomery. Expert Opin. Pharmacother. 2006;7(15):2139-54
78
Pregabalin: A new Approach
Advantages
Effective in somatic and psychic
symptoms1
Fast onset of action2
Effective in refractory patients3
Low abuse potential
Disadvantages
Less familiar with use in GAD
Potential rebound Anxiety on
withdrawal
Dizziness and somnolence main
AEs
Familiar molecule through other
indications
NO known PCK drug interactions
– easy to use
1. Montgomery . Expert Opin. Pharmacother. 2006; 7(15):2139-2154 (6 studies combined)
2. Herman et al. CINP 2008
3. Miceli et al. 2008
79
Thank you.
80