[Neurobiology and pharmacotherapy of social phobia].
L'Encéphale. 2004-09-01; 30(4): 301-313
DOI: 10.1016/s0013-7006(04)95442-5
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Aouizerate B(1), Martin-Guehl C, Tignol J.
Author information:
(1)Service de Psychiatrie d’Adultes, (Professeur Tignol) Université
Victor-Segalen Bordeaux 2, Centre Hospitalier Charles-Perrens, Centre Carreire,
121, rue de la Béchade, 33076 Bordeaux.
Social phobia (also known as social anxiety disorder) is still not clearly
understood. It was not established as an authentic psychiatric entity until the
diagnostic nomenclature of the American Psychiatric Association DSM III in 1980.
In recent years, increasing attention among researchers has contributed to
provide important information about the genetic, familial and temperamental
bases of social phobia and its neurochemical, neuroendocrinological and
neuroanatomical substrates, which remain to be further investigated. Up to date,
there have been several findings about the possible influence of variables,
including particularly genetic, socio-familial and early temperamental (eg
behavioral inhibition) factors that represent risk for the later development of
social phobia. Clinical neurobiological studies, based on the use of exogenous
compounds such as lactate, CO2, caffeine, epinephrine, flumazenil or
cholecystokinin/pentagastrin to reproduce naturally occurring phobic anxiety,
have shown that patients with social phobia appear to exhibit an intermediate
sensitivity between patients with panic disorder and control subjects. No
difference in the rate of panic attacks in response to lactate, low
concentrations of CO2 (5%), epinephrine or flumazenil was observed between
patients with social phobia and normal healthy subjects, both being less
reactive compared to patients with panic disorder. However, patients with social
phobia had similar anxiety reactions to high concentrations of CO2 (35%),
caffeine or cholecystokinin/pentagastrin than those seen in patients with panic
disorder, both being more intensive than in controls. Several lines of evidence
suggest specific neurotransmitter system alterations in social phobia,
especially with regard to the serotoninergic, noradrenergic and dopaminergic
systems. Although no abnormality in platelet serotonin transporter density has
been found, patients with social phobia appear to show an enhanced sensitivity
of both post-synaptic 5HT1A and 5HT2 serotonin receptor subtypes, as reflected
by increased anxiety and hormonal responses to serotoninergic probes. Platelet
5HT2 receptor density has also been reported to be positively correlated to
symptom severity in patients with social phobia. During anticipation of public
speaking, heart rate was elevated in patients with social phobia compared to
controls. Norepinephrine response to the orthostatic challenge test or to the
Valsalva maneuver was also greater in patients with social phobia. While normal
beta-adrenergic receptor number was observed in lymphocytes, a blunted response
of growth hormone to clonidine, an a2-adrenergic agonist, was reported. This
suggests reduced post-synaptic a2-adrenergic receptor functioning related to
norepinephrine overactivity in social phobia. Decreased cerebrospinal fluid
levels of the dopamine metabolite homovanillic acid have also been observed.
There are relatively few reports of involvement of the adrenal and thyroid
functions in social phobia, and all that has been noted is that patients with
social phobia show an exaggerated adrenocortical response to a psychological
stressor. Recent advances in neuro-imaging have contributed to find low striatal
dopamine D2 receptor binding or low dopamine transporter site density in
patients with social phobia. They have also demonstrated the involvement of the
cortico-limbic pathways, including the prefrontal cortex, hippocampus and
amygdala, which show an increased activity in different experimental conditions.
These brain regions have extensively been reported to play an important role in
the cognitive appraisal in determining the significance of environmental
stimuli, in the emotional and mnemonic integration of information, and in the
expression of contextual fear-conditioned behaviors, which might be disrupted in
the light of the phenomelogical aspects of social phobia. A substantial body of
literature based on case reports, open and placebo-controlled trials, has now
clearly examined the efficacy of major classes of psychotropic agents including
monoamine oxidase inhibitors, beta-blockers, selective serotonin reuptake
inhibitors and benzodiazepines in social phobia. Until recently, irreversible
non-selective monoamine oxidase inhibitors, of which phenelzine was the most
extensively evaluated, were considered as the most efficacious treatment in
reducing the symptomatology associated with social phobia in 50-70% of cases
after 4 to 6 weeks. However, side effects and dietary restrictions limit their
use. This led to the development of reversible inhibitors of monoamine oxidase
A, for which careful dietary monitoring is not required. Moclobemide has been
the most widely studied but produced unconvincingly therapeutic effects on
social phobic symptoms. To date, selective serotonin reuptake inhibitors may be
considered as a reasonable first-line pharmacotherapy for social phobia. There
is growing evidence for the efficacy of the selective serotonin reuptake
inhibitors fluvoxamine, fluoxetine, citalopram, paroxetine and sertraline. They
have beneficial effects with response rates ranging from 50 to 80% in social
phobia. It has been recommended that the treatment period should be extended at
least 6 months beyond the early improvement achieved within the first 4 to 6
weeks. The overall advantages include tolerability with a low risk of adverse
events. The benzodiazepines clonazepam and alprazolam have also been proposed
for the treatment of social phobia. Symptomatic relief occurred in 40 to 80% of
the cases with a relatively rapid onset of action within the first two weeks.
Untoward effects, discontinuation-related withdrawal symptoms and abuse or
dependence liability constitute major concerns about the use of benzodiazepines,
so they should be reserved for cases unresponsive to the safer medications cited
above. Beta-blockers such as atenolol and propanolol have commonly been employed
in performance anxiety, decreasing autonomic symptoms (eg, tachycardia, sweating
and dry mouth). However, they are not effective in the generalized form of
social phobia. Other pharmacologic alternatives seem helpful for the management
of social phobia, including venlafaxine, gabapentin, bupropion, nefazodone or
augmentation with buspirone. Preliminary studies point to promising effects of
these agents. Larger controlled clinical trials are now needed to confirm their
potential role in the treatment of social phobia.
DOI: 10.1016/s0013-7006(04)95442-5
PMID: 15538306 [Indexed for MEDLINE]