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SOCIAL PHOBIA: BIOLOGICAL ASPECTS AND PHARMAcOTHERAPY NICHOLAS Department
L.S. POTTS and JONATHAN R.T. DAVIDSON
of Psychiatry, Duke University Durham N.C.. U.S.A.
Medical
Center
(Final form , June 1991) Contents 1. 2. 3. 4. 5. 6. 7. a. 9. 9.1 9.2 9.3 9.4 9.5 10.
Abstract Introduction Defining Social Phobia Epidemiology Genetics Biological Markers Provocation Tests Thyroid Function Dopaminergic Theory Pharmacotherapy MAOI'S Other Antidepressants Beta-Blockers Benzodiazepines Other Medications Conclusions References
032
636 636 637 638 638 638 639 639 640 640 641 641 642 642 642 643
Abstract Potts, Nicholas L.S. and Jonathan R.T. Davidson: Social Prog. NeuroBiological Aspects and Pharmacotherapy. Psychopharmacol. & Biol. Psychiat. 1992, 16(5): 635-646.
Phobia:
1.
the anxiety disorders Social phobia is one of until recently, had not been thoroughly investigated.
that
2.
Social phobia is a relatively common appears to have a genetic basis.
that
3.
There are certain physiological aspects of social phobia that separate it from the other anxiety disorders.
4.
Support for a dopaminergic abnormality related to social phobia is supported by investigation studies and pharmacotherapy.
5.
There are a number of studies reporting treatment of social phobia with medications.
Kewords: tricyclic
benzodiazepines, antidepressants,
anxiety
disorder
success
in
the
genetics, monoamine oxidase inhibitors, social phobia.
Abbreviations: cerebrospinal fluid (CSF), mitral valve prolapse oxidase inhibitors (MAOI), tricyclic anti(MvP), mono-amine depressant (TCA), Thyroid stimulating hormone (TSH), thyrotropin releasing hormone (TRH). 635
N. L.S.Potts and J. R T. Davtdson
636
1.
The
DSM-III
disorders that
manual
troduction
separated
social
phobia
from other
in 1980 and listed it as an individual a
time
vast
amount
of research
has
been
anxiety Since
illness. aimed
at
further
understanding
the biology of social phobia and how it differs from
other anxiety
disorders.
This research has been partly
finding biological
markers
concentrating
possible
on
specific for this disorder, pharmacological
aimed at
as well as
agents
which
may
The purpose
alleviate the symptoms associated with this disorder. of this review article is to integrate the biological
research
this
explain
anxiety
disorder
aetiopathophysiology
into
phobia is
persistent
fear
which
can
help
by
Definins Social Phobia DSM-III-R
defined by an
individual
of
criteria
being
as
exposed
to
scrutiny by others and that he or she may do something, a way that will be embarrassing I or III disorder such situations
on its
and provide a brief basis for pharmacotherapy. 2.
Social
a model
is related
or enduring
or humiliating, to the fear,
a
possible or act in
(ii) no other axis
(iii) either
them with intense
(i)
avoiding
anxiety,
and
(iv)
this fear is recognized by the patient as excessive or unreasonable (DSM-III-R, There phobia.
such
lavatory.
clinical
subtypes
as
The
public
speaking
or
of
social
fear of a specific
urinating
in
a
public
The other is a group with a pervasive fear of almost all
interactions
Heimberg phobia
distinct
to be two
The first group has a well demarcated
situation, social
1986).
appear
(DSM-III-R 1986; Pollard
and Henderson
1988;
et al 1990). patients
in the
of something
first
have a simple phobia rather humiliation themselves.
or
physical
rather
symptoms
identical to the generalized
circumscribed
than
of
this
physical subtype
do not
they fear harm are
to also
subtype.
In the other group, the generalized only fears performance type
a well
These patients
than a social phobia, because
embarrassment
The
group have
like public speaking.
subtype, the individual
situations, but
most
not
social situations,
They also differ in that they are e.g., meeting new people. frequently associated with an avoidant personality disorder, which can make rates.
treatment Moreover,
different.
more
difficult
and inhibit
long-term
success
the treatment of the two subtypes appears to be
These criteria are summated in Table 1.
Sod
687
phobia
Table Diagnostic
1
Criteria
for Social
A.
A persistent fear of one or more situations (the social phobic situations) in which the person is exposed to possible scrutiny by others and fears that he or she may do something or act in a way that will be humiliating or embarrassing.
B.
If an Axis 111 ox another in A is unrelated to it.
C.
During some phase of the disturbance, exposure phobic stimulus (or stimuli) almost invariably immediate anxiety response.
D.
The phobic anxiety.
E.
The avoidant behaviour interferes with occupational functioning or with usual social activities or relationships with others, or there is marked distress about having the fear.
F.
The person recognises unreasonable.
G.
If the person is under 18, the disturbance criteria for Avoidant Disorder of Childhood
situation(s)
Axis
I disorder
is avoided,
that
his
is present,
or her
fear
(DSM-III-R,
large
States
(Meyers
et al 2.0%
and
be almost for
Canada,
Studies phobia
the
with
(Raguram
and
average
age
of
is
et
symptoms
al
it from
anxiety
disorders,
et
1983;
development depression
al of
1986;
of 1.4%
for men
in
social former,
1.3%
for
prevalence
found
that et
15-20
years
old,
and
associated
social
and
with
to
and
2.0%
patterns,
as
well
and
Social
1985a) as
of social
patients than
other
1985).
The
phobia
also
phobia, like
unremitting and to
The
1983).
class
social
disorders.
al
al
Nordlund
to run a chronic, et
50-60%
Amies
Persson
anxiety
Liebowitz
cases.
to be
lifetime
out
of The
1970;
educational
tends
avoidance
in some
prevalence
prevalence the
rate
have
(Marks between
other
carried
1985).
of anxiety
other
the
month found
populations
differentiate
(Amies
or
does not meet the or Adolescence.
studies,
found
six
latter
males
onset
(Solyom
physical
intense
is excessive
of the population.
an incidence
from a higher
to come
phobics
are
the
Bhide
of clinical
patients
have
1.3-2.0%
found
1986),
for women;
identical
women
tend
and
epidemiologic
to be approximately
men
with
Evidemiolocy
community-based
United
phobia
fear
1986) 3.
Two
the
to the specific provokes an
or is endured
--
the
Phobia
leads
course to
alcoholism
the and
N.L.S.PottsandJ.RT.Davidson
4. When
Genetics
Torgerson
using the Norwegian twin registry, (1979)‘ 95 monozygotic and twins he Sound the dizygotic
compared monozygotic
twins showed certain
a significantly
concordance
such
situations,
as
in
strangers
or being observed while writing, working,
Reich and Yates
social
higher
distress
eating
or trembling.
(1988a) reported social phobics had significantly
more relatives with this disorder, compared to relatives to have a higher
relative
incidence of social phobia than normal controls.
relatives
of generalized
of panic
There was a trend for social phobic relatives
disorder patients. In addition,
for with
of social phobics
have
a lower
incidence
anxiety disorder, panic disorder, and alcohol abuse
to panic
disorder
probands.
Perugi
et al
(1990) found
similar results in his family studies of anxiety disorder patients. 5. There
are now
abnormalities
Bioloaical Markers
numerous
that
studies
help
anxiety disorders,
and
pathophysiology
social
of
that
separate also
demonstrate
social
shed
phobia
light
phobia.
The
on
most
biological from
the common
physical
symptoms of social phobia include blushing, palpitations, or trembling, and sweating. Dizziness, lightheadedness, ears, weakness impending
in limbs, difficulty
doom
features
or
of panic
social phobics al 1988).
doing
breathing,
something
disorder,
are
crazy,
and fear of either
which
significantly
are
less
prominent
frequent
in
(Solyom et al 1986; Liebowitz et al 1985a; Yates et (26.7%) had echocardiogram
(Chaleby 1988), compared with 4.17% prevalence
evidence
patients
also reported
(Gorman et al 1985).
by Benca
et al
of MVP
in epidemiological
(Markiewicz et al 1976) of the general population
in panic disorder was
shaking
ringing in
Another area of research from Saudi Arabia found 8 of 30
social phobic patients studies
other
possible
and 50%
This association
(1986) in relation
successful
treatment with imipramine. 6. Papp
et al
reproduce under
stress.
eight-fold, one
(1988)
elevated
of
infused
the serum
to
social phobic levels
seen
(Dimsdale and Moss 1980). belief that,
epinephrine
catecholamine
serum
Although
Tests in
subjects
levels
observable The
phobics
seen in
epinephrine
subjects. in
social
levels
they were only able to produce
eleven
correspond
Provocation
to
subjects increased
anxiety
in
levels infused did public
speaking
These results are consistent
during
with the
although elevated serum catecholamines are associated
Socialphobia
639
with anxiety I they do not trigger anxiety, but rather are a consequence of it. In 15 social phobic patients, lactate infusions only produced one case of panic (Liebowitz et al 1985b), compared to 50% or greater of panic patients (Liebowitz et al 1985c; Pitts and McClure 1967; Liebowitz et al 198813). Gorman et al (1988) studied ventilatory physiology of pstients with anxiety disorders and found that three out of three social phobic patients had panic after inhaling air with 7% CO,. Of panic disorder patients, only six of nine showed the same response. Some of the differences mentioned above appear in Table 2. Table 2 Differences in Social phobia and panic Disorder Common_Symptoms
blushing palpitations tremor sweating
dizziness ligheadedness weakness fear of impending
MVP (Gorman,etal 85)
26.7% tfhaleby 88)
50% panic
Lactate Infusion 85~)
69% (Liebowitz 85b)
k-50% (Liebowitz
doom
7,
Thyroid Function
Thyroid function tests, i.e., T3, T4, free T4, TSH and incidence of anti-thyroid antibodies, are within normal ranges in social However, after an phobia patients (Tancer et al 199Oa). injection of TFIH,Tancer et al (1990b) noted social phobics had greater mean arterial and systolic pressure a significantly response to TRH than either panic disorder patients or normal controls. The relevance of the latter two studies is difficult to specify except that they further distinguish social phobics from other anxiety disorder patients. This effect, seen at one minute after injection, had disappeared by six minutes. 8.
ponamineraic Theorv
studies implications regarding the Treatment carry aetio-pathophysiology of social phobia. Mikkelsen et al (1981) reported 15 cases of social phobia, school phobia and work avoidance developing in Tourette's disorder patients treated with low dose haloperidol, a dopamine receptor blocking agent. Indirect evidence to support a dopaminergic theory comes from studies that show improvement in social phobias when using MAOI'S, which are known to act as dopamine agonists. This concept is supported by the fact that MAOI's that have a greater dopamine
N.L.S.Potts andJ. R.T.Davidson
640
agonist
effect
phobics
(Gittleman-Klein
Mikkelsen
are more effective and Klein,
in treating
social
1971 and 1973; Rapoport
and
1978).
Cooper dopamine
than TCA's
et al
(1986) were able to quantify
effect
tricyclic
in patients
antidepressants.
correlation
of
on MAOI's
this enhanced
compared
to
patients
King et al (1986) reported
cerebrospinal
fluid in
(CSF)
dopamine
levels
and
extraversion
pharmacological
evidence supporting a dopaminergic hypothesis comes
(Goldstein
1987)
and
other
phobics.
to successfully phobic
Further
treat social phobia
disorders
These results are summarized
1981).
social
on
a positive
self-reported
from a study using clonidine
16
CNS
(Hoehn Saric
et al
in Table 3.
Table
3
Studies Supporting Dopaminergic Theory A.
Haloperidol induced social phobia in 15 patients with Tourettes (Mikkelson,et al 81)
B.
Effectiveness of MAOI's dopamine agonist effect (Gitelman-Klein and Klein 71 and 73)
C.
Effectiveness of clonidine in social phobia patients 87)
D.
Direct correlation between Csf dopamine and extraversion in social phobia patients (King, et al 86) 9.
9.1
are numerous
There
such
examined
the
role
of
(MAOI'S)
as
Most of these
MAOI's, but
certain
Liebowitz
et
al
(1984,
efficacy
of phenelzine
placebo
in
reducing
studies
more recent
benzodiazepines,
The best studied antidepressant
buspirone.
have
shown
is superior to imipramine, interpersonal
sensitivity
involve
ones have
f luoxetine,
is phenelzine.
198533, 1988a)
the
discussing
available
reports
of social phobia.
anti-depressants,
by
Pharmacotheraoy
Mono Amine Oxidase Inhibitors
pharmacotherapy
(Goldstein
and
Studies that
the
atenolol, at doses
and of
Liebowitz's findings suggest that patients with a 45-90mg/day. generalized form of social anxiety derive greater benefit from phenelzine than atenolol, but patients with a more circumscribed social phobia do as well with atenolol as they do with phenelzine. Gelernter phenelzine therapy. reasonable
et
al
over
(in press) alprazolam,
Tranylcypromine, results
have found superior efficacy for placebo and cognitive behavioral another MAOI,
with one study reporting
62% (Deltito and Stam 1989).
has demonstrated
improvement
rates
of
641
Social phobia
Recent
using
studies
moclobemide, inhibit
type
15 patients
A
report
with
as
they
carry
found
a higher
that
study,
effective
in
by Versiani
treating
12 of
clinical
substantial
Liebowitz
(van Vliet et al 1990).
an unpublished
moclobemide
showed
phobia
brofaromine
(198923) reported phenelzine
Moreover,
from the Netherlands
social
with
improvement found
Both of
MAOI's that reversibly and preferentially
A MAO-2 receptors.
margin.
and
brofaromine
to treat social phobia, have been reported.
these are new reversible safety
MAOI's,
new
the
et al,
social
that
phobia
as
in a small open clinical trial.
Other Antidenressants
9.2
Both
imipramine
phenelzine sensitivity Zitrin
and amitriptyline
in reducing
et
social
in depression al
Sternbach
(1990),
successful
treatment
no double-blind,
a
lower
symptoms
efficacy
and
than
interpersonal
(Liebowitz et al 1984; Nies et al 1983;
Two studies,
1983).
have
phobic
have
Deltito
reported
and
clinical
Stam
(1989)
anecdotes
on
of a few cases of social phobia.
placebo controlled
and the
However,
study has yet been reported.
Beta-Blockers
9.3
An array
of studies
in
mostly
conducted
have been with
patients
performance
using
beta-blockers, social
related
anxiety.
Falloon et al (1981) conducted the first placebo controlled
study
using
could
find
a beta-blocker no difference
This study,
between
however,
diagnostic
criteria,
have focused studied,
Their
study
drug therapy and behavioral from
a
small
sample
and lack of normal controls.
on performance except
social phobia.
suffered
the diagnosis
determined, Liebowitz
to treat
anxiety.
for research
by Liebowitz
poor
Other studies
In the patient
of social phobia had
therapy.
size,
populations
not been clearly et al
(1988a),
by
(1989a), and by Gorman et al (1985).
It is worth mentioning
the other studies, however,
as seven out
of ten showed a marked reduction in performance anxiety in over 50% of patients Jane
(Gottschalk
1976; James
et al 1974; Krishnan
et al 1977; Brantigan
1974; Siitonen
et al 1982; Neftel
and
et al
1982; Krope et al 1982; Hartley et al 1982; James et al 1983; Desai et al 1983). 1989a)
that
These lend support to Liebowitz's patients
phobia benefit
with a well
circumscribed
from treatment with beta-blockers.
findings form
of
(1988a, social
N.L.S.PotAsandJ.RT.Davidson
642
9.4
Benzodiazeoines
In 1984, a study to evaluate the efficacy of diazepam phobic
patients
compared et al,
showed
it was significantly
in social
less effective
to clomipramine in reduction of sy'mptomatology (Gelernter With the introduction of alprazolam for the
in press).
treatment
it was not long before it was tried
of panic disorder,
Besides one paper describing four social phobics
in social phobia. who
that
improved on alprazofam
(Lydiard et al 1988), there have been
two open trials with alprazolam
and one controlled
study.
In both open trials all patients experienced a reduction When the medication
symptoms. returned
was ceased, however,
in their
all patients
to pre-treatment levels of anxiety (Reich et al 1989; The one double blind study found that only
Reich and Yates 1988b). 38% of social reports,
phobics
Like
improved with alprazolam.
any improvement
during the study disappeared
the other two months
after the medication was discontinued
(Gelernter et al, in press).
Munjack
reduction
within
et al
(1990) found
a rapid
two weeks with clonazepam
compared
in symptomatology
in the majority
of subjects,
as
to four weeks before a reduction of symptoms was seen in
the best of the phenelzine
and atenolol studies
(Liebowitz
et al
198813; Liebowitz 1989b; Gelernter et al, in press; Deltito and Stam 1989). 9.5
Other Medications
Schneier
et
(1990),
al
patients,
discovered
or very much
that
an
open
buspirone
60%
of
trial of
patients
15 were
using
the
social rated
improved on the Clinical Global Impression
new
phobic as much Scale at
The use of clonidine in social phobia has been discussed
week 12.
by Goldstein,
who presented
blushing not responsive but
in
anxiolytic
non-benzodiazipine
a case of social phobia
to propanolol,
phenelzine,
with
severe
or alprazolam,
which responded rapidly and effectively to clonidine (Goldstein
1987).
Clonidine
may be helpful in social phobia
as blushing
is
reported by patients to be one of the most common physical symptoms of social phobia
(Solyom et al 1986; Liebowitz et al 1985a; Reich
and Yates et al 198833). 10. Social prevalence
phobia
is
a
Conclusions
common
anxiety
disorder
with
similar
rates among males and females.
from the other anxiety disorders
Social phobia differs in symptomatology as well as in
associated biological abnormalities.
Recent evidence suggests that individuals who develop social phobia are genetically predisposed.
socialphobia
Related to this genetic predisposition is a dopaminergic model to explain social phobia. This model is supported by a number of dopamine abnormalities seen in patients with social phobia and by Pharmacological treatment of this pharmacotherapy studies. disorder offers promising results with a number of new agents on the horizon that may provide more effective as well as safer treatment options.
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Fluoxetine Treatment STERNBACH H (1990) of Clin. Psychopharmacol. $&(3):230.
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and reprint requests should be addressed to:
Dr. N. Potts P.0, BOX 3812 Duke University Medical Center Durham NC 27710 U.S.A.
of of