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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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N. L.S.Potts andJ. R T.Davidson

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Delineating SOLYOM L, LEDWIDGE B, and SOLYOM C (1986) Phobia. Brit. 3. of Psychiat. 149: 464-470.

Social

SIITONEN L and JANE J Bowling Competitions.

Fluoxetine Treatment STERNBACH H (1990) of Clin. Psychopharmacol. $&(3):230.

of Social

Phobia.

J.

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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.

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