Pharmacotherapy For Social Anxiety Disorder in Adults

Pharmacotherapy for social anxiety disorder in adults - UpToDate 09/10/23, 23:20
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Pharmacotherapy for social anxiety disorder in adults

author: Murray B Stein, MD, MPH
section editor: Peter P Roy-Byrne, MD
deputy editor: Michael Friedman, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2023.

This topic last updated: Jun 06, 2022.
INTRODUCTION
Social anxiety disorder (SAD), also known as social phobia, is a condition marked by
extreme fear of situations that involve possible scrutiny by others. The individual is
concerned that embarrassment or humiliation will result, and so they avoid such
situations or endures them with intense anxiety.
SAD is a prevalent condition, estimated to affect between 4 and 10 percent of the adult
United States population over a 12-month period. SAD typically begins in childhood or
adolescence and, untreated, can be associated with the subsequent development of
major depression, substance use disorder, and other mental health problems. The
disorder can be associated with extensive functional impairment and reduced quality of
life [1].
This topic addresses the pharmacologic treatment of SAD. Discussed separately are
epidemiology, pathogenesis, clinical manifestations, and diagnosis of SAD; psychotherapy
for SAD; and fears and specific phobias in children. (See "Social anxiety disorder in adults:
Epidemiology, clinical features, assessment, and diagnosis" and "Social anxiety disorder in
adults: Psychotherapy" and "Overview of fears and phobias in children and adolescents".)
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APPROACH TO TREATMENT
Our approach to selecting among treatments for social anxiety disorder, including the use
of pharmacotherapy and psychotherapy, is discussed separately. (See "Approach to
treating social anxiety disorder in adults".)
TYPES OF SOCIAL ANXIETY DISORDER
In the transition from the American Psychiatric Association’s Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition (DSM-IV) to DSM-5, the subtypes of
generalized and nongeneralized social anxiety disorder (SAD) were replaced by SAD and
SAD, performance only, respectively [2]. The guidance that follows applies to SAD.
Pharmacotherapy for performance-only SAD is discussed separately, later in the topic.
(See 'Social anxiety disorder, performance only' below.)
MONOTHERAPY
Several classes of drugs are used to treat social anxiety disorder (SAD), including selective
serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors
(SNRIs), monoamine oxidase inhibitors (MAOIs), and benzodiazepines. Pharmacologic
treatment is quite different for the performance-only version of SAD compared with the
general form of SAD (known prior to DSM-5 as nongeneralized and generalized SAD).
Whenever pharmacotherapy is prescribed for SAD, it is good clinical practice to

recommend to the patient that they enter previously feared social situations to “test out”
the effects of the medication and to learn that these situations are safe and can be
tolerated. Although there are no research data to support this claim, there is some reason
to believe that those patients who do the most “practicing” and “expanding of their social
horizons” while on medication are the ones who have the best longer-term outcomes.
Selective serotonin reuptake inhibitors — A meta-analysis of seven trials that compared

SSRIs with placebo in a total of 896 patients with SAD found that SSRIs resulted in greater
symptom reduction compared with placebo and had a moderate effect size [3]. SSRIs are
the best studied and the most commonly prescribed of the medication treatments for SAD
[4]. The SSRI paroxetine was the first medication to receive approval from the Food and
Drug Administration (FDA) in the United States for SAD [5].
As an example, a clinical trial randomly assigned 183 patients with SAD to receive
paroxetine (20 to 50 mg) or placebo for 11 weeks. Patients receiving paroxetine were
more likely to be “much improved” or “very much improved” at the end of treatment with
paroxetine compared with patients on placebo (55 versus 24 percent). The mean score on
the Liebowitz Social Anxiety Scale was reduced in the paroxetine group compared with the
placebo group (39 versus 17 percent).
The clinical effects of SSRI treatment for SAD typically require four to six weeks to have a
significant impact; maximal benefit can require as long as 16 weeks [6]. Patients should be
encouraged to “try out” the medication by engaging in social situations that typically
result in anxiety and to report back about their response. One of the first indications of
response is the patient’s report of feeling less “self-conscious” in typical social situations.
Higher doses of SSRIs typically result in better outcomes, so the dose is usually pushed to
the maximum tolerated by the individual (unless an excellent response is attained at a
lower dose, at which point the dose would be held there to ascertain stability of the
response).
Although some SSRIs have been more extensively studied than others in the treatment of
SAD, there is no evidence of superiority of one SSRI over another. As examples:
● Paroxetine can be started at 10 mg/day taken orally and increased to a therapeutic

dose of 20 mg/day after a few days. If the patient does not respond after a six-week
trial, the dose can be increased in 10 mg increments every few weeks to a maximum
of 60 mg/day.
● Sertraline can be started at 50 mg/day taken orally and, if the patients does not
respond after six weeks, can be increased in 50 mg increments every few weeks to a
maximum of 250 mg/day.
Common side effects of SSRIs include restlessness, agitation, headache, diarrhea, nausea
and insomnia. SSRIs also cause sexual dysfunction in as many as 50 percent of patients.
(See "Selective serotonin reuptake inhibitors: Pharmacology, administration, and side
effects" and "Sexual dysfunction caused by selective serotonin reuptake inhibitors (SSRIs):
Management".)
Many of the side effects can be reduced or avoided by starting the medication at lower
doses and increasing it gradually. See table for standard and lower initial doses as well as
the range of therapeutic doses for SSRIs ( table 1).
Serotonin-norepinephrine reuptake inhibitors — Although less well studied than the

SSRIs, the SNRI venlafaxine extended release appears to be equally effective for SAD on
the basis of a comparable effect size compared with various SSRIs in meta-analysis [7-10].
As an example, a clinical trial randomly assigned 440 patients with SAD to treatment with
venlafaxine (75 to 225 mg daily extended release), paroxetine (20 to 50 mg daily), or
placebo [8]. After 12 weeks, response rates were similar in the venlafaxine and paroxetine
groups, both of which were superior to placebo (59 and 63 versus 36 percent response,
respectively). Medication discontinuation rates were similar with venlafaxine and
paroxetine, but adverse events leading to a reduction in dosage were more common with
venlafaxine (16 versus 8 percent).
Venlafaxine can be started at 37.5 mg/day taken orally and increased to a dose within the
therapeutic range, between 75 and 225 mg/day ( table 1). SSRI recommendations
regarding gradual titration, trial duration, and dose increases apply to SNRIs as well.
The most common side effects of venlafaxine are nausea, dizziness, insomnia, sedation,
and constipation. Venlafaxine may cause elevations in blood pressure. Though usually
small, the increases can be significant in some patients. The medication should be
avoided in patients with hypertension, and blood pressure should be monitored during
use. (See "Serotonin-norepinephrine reuptake inhibitors: Pharmacology, administration,
and side effects".)
There are no published data from controlled trials on the use of another marketed SNRI,
duloxetine, in the treatment of SAD.
Monoamine oxidase inhibitors — The MAOIs have the longest track record of use for
SAD, having been essentially the only pharmacotherapy available (though never FDA
approved) for SAD prior to the advent of the SSRIs. However, side effects and dietary
restrictions limit their use. MAOIs are generally reserved for SAD refractory to other
treatments. Some practitioners feel that MAOIs are more effective than SSRIs or SNRIs,
though no comparative efficacy trials have been conducted to substantiate this belief.
(See "Monoamine oxidase inhibitors (MAOIs): Pharmacology, administration, safety, and
side effects".)
Several randomized trials have found that phenelzine is an efficacious treatment for SAD,
with approximately one-half of patients responding with a clinically significant reduction
in symptoms [3]. A 2010 randomized trial that included a phenelzine arm found a
response rate of 54 percent for phenelzine compared with 33 percent for placebo [11].
Phenelzine is typically started at 15 mg once or twice daily, and increased to a total dose
of 60 to 90 mg/day based on response. It can take four to six weeks for a response to
occur, and longer for maximal response to be attained.
MAOIs cause inhibition of the MAO enzyme. Irreversible MAOIs, such as phenelzine, are
incompatible with certain foods and medications (eg, cheese, aged meats, alcohol, over-
the-counter cold preparations). A potentially fatal hypertensive reaction can occur if users
of MAOIs consume food containing tyramine; thus, use of irreversible MAOIs must be
accompanied by a low tyramine diet. Their use is also contraindicated with other
antidepressants, and over-the-counter or prescribed medications containing
sympathomimetic stimulants or dextromethorphan.
Other adverse effects common at therapeutic doses include postural hypotension,

insomnia, paradoxical daytime sedation, sexual dysfunction, and weight gain. In many
instances, these side effects can be dose limiting.
Benzodiazepines — Two, small randomized trials found the high-potency

benzodiazepines, alprazolam [12] and clonazepam [13], to be efficacious as monotherapy
in the reduction of SAD symptoms. Clonazepam, a longer-acting agent with a slower rate
of onset, seems to be more commonly used for SAD than other benzodiazepines.
Sedation, the principal dose-limiting adverse effect, can be minimized by starting with low
doses and titrating upwards slowly until a satisfactory response is achieved. As either
monotherapy or in augmenting a serotonin reuptake inhibitor, clonazepam can be started
at 0.25 to 0.50 mg twice daily, and increased to a maximum of 2 mg twice daily.
Benzodiazepines and SUD history — Sedation and the potential for misuse and
physiologic dependence limit the usefulness of these agents, which are generally avoided
in patients with a history of a substance use disorder (SUD). If other agents are not
effective, however, patients with history of an SUD could be judiciously prescribed a
benzodiazepine, provided that the SUD was not active and the patient’s use of the
medication were carefully monitored.
Gabapentin — Gabapentin (an anticonvulsant) has demonstrated modest effectiveness

(response rates <45 percent) for SAD [14] in a randomized clinical trial. Sixty-nine patients
were randomly assigned to receive double-blind treatment with either gabapentin (dosed
flexibly between 900 and 3600 mg daily in three divided doses) or placebo for 14 weeks.
Patients receiving gabapentin experienced reduced SAD symptoms compared with
patients receiving placebo. Adverse events were consistent with the known side effect
profile of gabapentin (eg, dizziness, dry mouth, somnolence).
Based upon case reports and human studies, the United States Food and Drug
Administration issued a safety alert in 2019, warning that gabapentin may be associated
with respiratory depression when administered to patients receiving central nervous
system depressants or patients with underlying respiratory impairment [15]. In
prescribing gabapentin to patients with these risk factors, it is prudent to start the drug at
a relatively low dose (eg, 100 mg three times daily) and monitor patients for symptoms of
respiratory depression (eg, unusual dizziness, dyspnea, or extreme sedation).
Pregabalin — Pregabalin, a compound related to gabapentin, has demonstrated modest

effectiveness (response rates <45 percent) for DSM-IV generalized SAD [16]. Pregabalin
was approved in 2006 for the treatment of anxiety in Europe [17,18]. The medication
inhibits calcium currents via high-voltage-activated channels containing the a2d-1 subunit,
though the relationship of this mechanism to its efficacy for anxiety is not known. Side
effects include sedation and dizziness. Tolerance, withdrawal, and dependence are
possible, but pregabalin is generally better tolerated than benzodiazepines. Doses of
pregabalin for SAD typically range from 150 to 600 mg per day.
The United States Food and Drug Administration issued a safety alert in 2019, warning
that gabapentinoids may be associated with respiratory depression. (See 'Gabapentin'
above.)
Other agents — Other medications have yielded mixed or negative results in clinical
trials, or have not been sufficiently tested:
● Moclobemide – Moclobemide, a reversible MAOI selective for inhibition of MAO-A,

has shown, at best, mixed results in randomized controlled trials of SAD [19-21].
Moclobemide is not marketed in the United States, but is available in many other
countries. In contrast to non-reversible MAOIs (such as phenelzine or
tranylcypromine), moclobemide does not require a low tyramine diet, and generally
has fewer adverse effects overall.
● Mirtazapine – Mirtazapine has shown mixed results in patients with SAD. In a

randomized trial of 66 women with SAD, mirtazapine (30 mg a day) was found to be
efficacious for SAD compared with placebo [22]. In a more recent randomized
controlled trial of 60 males and females with generalized SAD randomized to either
30 to 45 mg/day of the medication or placebo for 12 weeks, mirtazapine was no
more effective than placebo (13 versus 13 percent response rate).
● Beta-blockers – Beta-blockers are not an effective treatment for SAD [23,24], but are
effective for the performance-only SAD subtype. (See 'Social anxiety disorder,
performance only' below.)
● Tricyclic antidepressants (TCAs) – The TCAs have not been well studied in clinical
trials of patients with SAD. A small open-label trial of imipramine suggested that it
was not effective. It is possible that TCAs with more potent serotonergic reuptake
blockade (eg, clomipramine) might be useful, but this is unknown.
● Second-generation antipsychotics – Very small randomized controlled trials of

olanzapine and quetiapine suggested that these atypical (or “second-generation”)
antipsychotics might be effective for SAD [25,26]. Considerable further study is
needed as well as consideration of metabolic side effects of these agents [27].
● Buspirone – The limited available data suggest that buspirone is ineffective as

monotherapy for SAD [28].
● Atomoxetine – Atomoxetine, an SNRI (marketed for the treatment of attention

deficit disorder/hyperactivity [ADHD]), was not shown to be effective for DSM-IV
generalized SAD in a small randomized controlled trial [29]. However, there is some
evidence from a trial in adults with comorbid ADHD and SAD [30] that atomoxetine
may be helpful for both ADHD and SAD symptoms in patients who have both.
● Oxytocin – Intranasal oxytocin (24 international units) versus placebo has been
shown to improve some social behaviors and anxious appearance in 40 patients with
SAD [31], but an effect on symptoms or overall functioning was not observed in that
study [31] or in an earlier placebo-controlled trial [32].
AUGMENTATION
A substantial number of patients with social anxiety disorder (SAD) respond only partially
to monotherapy [4], leading to clinical trials in DSM-IV generalized SAD of medications
augmenting selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine
reuptake inhibitors (SNRIs) with other agents:
● Buspirone – A small uncontrolled trial found that 7 of 10 patients partially

responsive to SSRIs appeared to benefit from augmentation with buspirone [33].
● Clonazepam – Randomized trials have found some evidence in support of

augmentation of an SSRI with clonazepam [34,35]. As an example, in the larger trial,
181 patients with social anxiety disorder who had no more than a partial response to
10 weeks of sertraline were randomly assigned to 12 weeks of continuation on
sertraline augmented by either clonazepam or placebo [35]. (A third arm, in which
patients were switched from sertraline to venlafaxine, is described separately.) (See
"Approach to treating social anxiety disorder in adults", section on 'No substance use
disorder history'.)
The proportion of patients responding to treatment (defined as a Liebowitz Social

Anxiety Scale [LSAS] score <50) was greater in patients receiving sertraline plus
clonazepam compared to the other two groups. Patients receiving sertraline plus
clonazepam had a clinically significant decrease in LSAS severity compared to
patients receiving sertraline plus placebo. A numerical advantage favoring a higher
rate of remission (an LSAS score ≤30) in patients receiving sertraline plus
clonazepam compared with patients continuing on sertraline plus placebo and to
patients switched to venlafaxine (27 versus 17 and 19 percent); the results did not
reach statistical significance.
The use of benzodiazepines in patients with a history of a substance use disorder is

described above. (See 'Benzodiazepines and SUD history' above.)
● Other
• Pindolol – A small randomized trial did not show a benefit of augmenting

paroxetine with the beta-blocker pindolol compared to placebo augmentation
[36].
• Monoamine oxidase inhibitors – Monoamine oxidase inhibitors should not be

combined with other antidepressants due to the risk of serotonin syndrome. (See
"Serotonin syndrome (serotonin toxicity)".)
• Ketamine – A small randomized clinical trial of a single dose of intravenous

ketamine (0.5 mg/kg over 40 minutes) versus placebo in 18 adults with SAD found
that patients were more likely to exhibit a treatment response (defined as >35
percent reduction on the LSAS) after ketamine relative to placebo in the first two
weeks following infusion (33.3 versus 0 percent) [37]. The response rate to both
treatments is low. More work is needed to determine the efficacy and safety of
ketamine infusions for SAD.
SOCIAL ANXIETY DISORDER, PERFORMANCE ONLY
In the transition from DSM-IV to DSM-5, the subtypes of generalized and nongeneralized
social anxiety disorder (SAD) were replaced by SAD and SAD, performance only (specifier)
[38].
Medication treatment is often prescribed on an "as needed" basis for performance-only

SAD. We suggest benzodiazepines or beta-blockers as first-line medication treatment.
Administering a test dose prior to treatment, at the same dose intended to be used prior
to the performance situations(s), can be useful to assess the drug's effects.
Benzodiazepines — Benzodiazepines can also be used on an "as needed" basis to treat

performance-only SAD [39]. Clonazepam 0.25 to 1 mg or lorazepam 0.5 to 2 mg can be
given 30 to 60 minutes before the performance. Tolerance and physical dependence are
not a concern with occasional use. But the potential for misuse, highest in persons with a
history of alcohol or other substance use, should also limit their use in this context.
Sedation can be a side effect of benzodiazepines, particularly at higher doses. For this
reason, the patient should be encouraged to try out the medication in advance of a
potentially precipitating event to determine how well it is tolerated and to see if it is
efficacious. The prescribing physician may need to fine-tune the dose for the individual.
Patients may have used alcohol in the past to cope with similar situations and should be
explicitly cautioned not to mix alcohol with benzodiazepines.
Beta-adrenergic blockers — There is no evidence from clinical trials on the effectiveness

of beta-blockers (such as propranolol) in the treatment of performance-only SAD [40].
Beta-blockers are nonetheless used at times for the management of performance anxiety;
clinical experience suggests that only half (or fewer) people find as-needed beta-blockers
useful for performance anxiety.
Beta-adrenergic blockers may be most useful for patients who have prominent awareness
of physiological symptoms such as tachycardia or tremor.
Propranolol can be taken orally 30 to 60 minutes prior to the anxiety-inducing situation, at

an initial dose of 10 or 20 mg. The patient should be encouraged to try out the medication
in advance of a potentially precipitating event to determine how well it is tolerated and to
see if it is efficacious. If tolerated but not sufficiently effective, increase the dose next time
by 10 or 20 mg. Some patients may eventually require a dose of 60 mg. Contraindications
to the prescription of beta-blockers include: a history of beta-blocker intolerance or
allergy, diabetes, and certain cardiac conditions (eg, conduction problems). (See "Major
side effects of beta blockers".)
Cannabinoids — A small, randomized, double-blind study of 600 mg cannabidiol (n = 12)

versus placebo (n = 12) never-treated patients with SAD found that cannabidiol reduced
anxiety during a public speaking task [41]. More recently, cannabidiol 300 mg oral (n = 39)
versus placebo (n = 41) did not enhance the effects of exposure therapy on outcomes in a
study that included patients with SAD and panic disorder with agoraphobia [42].
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links: Anxiety
and anxiety disorders in adults".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, “The Basics” and “Beyond the
Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
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about a given condition. These articles are best for patients who want a general overview
and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces
are longer, more sophisticated, and more detailed. These articles are written at the 10th to
12th grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
● Basics topic (see "Patient education: Social anxiety disorder (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Monotherapy – Several classes of drugs are effective in the treatment of social

anxiety disorder (SAD), including selective serotonin reuptake inhibitors (SSRIs),
serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors
(MAOIs), and benzodiazepines. (See 'Monotherapy' above.)
• SSRIs – Although some SSRIs have been more extensively studied than others in
the treatment of SAD, there is no evidence of superiority of one SSRI over
another. (See 'Selective serotonin reuptake inhibitors' above.)
• SNRIs – Although less well studied than the SSRIs, the SNRI venlafaxine extended
release appears to be equally effective for SAD on the basis of a comparable
effect size compared with various SSRIs. (See 'Serotonin-norepinephrine reuptake
inhibitors' above.)
• MAOIs – The MAOIs have the longest track record of use for SAD; however, side
effects and dietary restrictions limit their use. MAOIs are generally reserved for
SAD refractory to other treatments. (See 'Monoamine oxidase inhibitors' above.)
• Benzodiazepines – The high-potency benzodiazepines, alprazolam and

clonazepam, have been found to be efficacious as monotherapy in the treatment
of symptoms of SAD. For individuals with a history of benzodiazepine use or
substance use disorder (SUD) we avoid treatment with benzodiazepines and use
gabapentin or pregabalin as alternative treatment. (See 'Benzodiazepines' above
and 'Benzodiazepines and SUD history' above.)
• Other agents with limited or mixed supporting data – Moclobemide,

mirtazapine, beta blockers, tricyclic antidepressants, buspirone, second-
generation antipsychotics, atomoxetine, and oxytocin have mixed or limited data
supporting their use in the treatment of SAD. (See 'Other agents' above.)
SSRIs, SNRIs, and MAOIs may take four to six weeks for an initial response and 12 to
16 weeks to achieve their full effect. We typically continue these and other
medications for SAD for at least 6 to 12 months to decrease the likelihood of relapse.
Some patients may need continuing treatment to maintain the gains achieved. (See
'Monotherapy' above.)
● Augmentation – A substantial number of patients with SAD respond only partially to

monotherapy. Clinical trials have found limited evidence supporting clonazepam,
buspirone, and ketamine as augmenting agents. (See 'Augmentation' above.)
● SAD, performance only – In the transition from American Psychiatric Association’s

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) to
DSM-5, the subtypes of generalized and nongeneralized SAD were replaced by SAD
and SAD, performance only (specifier). (See 'Social anxiety disorder, performance
only' above.)
• We suggest not treating performance-only SAD with medication. However,

medication is a reasonable alternative if preferred by the patient or if a therapist
trained to provide cognitive-behavioral therapy were not available.
• When medication is used to treat SAD, performance-only specifier, we suggest

treatment with a benzodiazepine in patients who lack a history of an SUD (Grade
2C).
• For patients with an SUD history or who experience sedation with a

benzodiazepine, a beta-blocker is a reasonable alternative unless the patient has
a contraindication to their use.
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27. Depping AM, Komossa K, Kissling W, Leucht S. Second-generation antipsychotics for

anxiety disorders. Cochrane Database Syst Rev 2010; :CD008120.
28. van Vliet IM, den Boer JA, Westenberg HG, Pian KL. Clinical effects of buspirone in
social phobia: a double-blind placebo-controlled study. J Clin Psychiatry 1997; 58:164.
29. Ravindran LN, Kim DS, Letamendi AM, Stein MB. A randomized controlled trial of
atomoxetine in generalized social anxiety disorder. J Clin Psychopharmacol 2009;
29:561.
30. Adler LA, Liebowitz M, Kronenberger W, et al. Atomoxetine treatment in adults with
attention-deficit/hyperactivity disorder and comorbid social anxiety disorder. Depress
Anxiety 2009; 26:212.
31. Voncken MJ, Dijk C, Stöhr F, et al. The effect of intranasally administered oxytocin on
observed social behavior in social anxiety disorder. Eur Neuropsychopharmacol 2021;
53:25.
32. Guastella AJ, Howard AL, Dadds MR, et al. A randomized controlled trial of intranasal
oxytocin as an adjunct to exposure therapy for social anxiety disorder.
Psychoneuroendocrinology 2009; 34:917.
33. Van Ameringen M, Mancini C, Wilson C. Buspirone augmentation of selective
serotonin reuptake inhibitors (SSRIs) in social phobia. J Affect Disord 1996; 39:115.
34. Seedat S, Stein MB. Double-blind, placebo-controlled assessment of combined
clonazepam with paroxetine compared with paroxetine monotherapy for generalized
social anxiety disorder. J Clin Psychiatry 2004; 65:244.
35. Pollack MH, Van Ameringen M, Simon NM, et al. A double-blind randomized
controlled trial of augmentation and switch strategies for refractory social anxiety
disorder. Am J Psychiatry 2014; 171:44.
36. Stein MB, Sareen J, Hami S, Chao J. Pindolol potentiation of paroxetine for generalized
social phobia: a double-blind, placebo-controlled, crossover study. Am J Psychiatry
2001; 158:1725.
37. Taylor JH, Landeros-Weisenberger A, Coughlin C, et al. Ketamine for Social Anxiety
Disorder: A Randomized, Placebo-Controlled Crossover Trial.
Neuropsychopharmacology 2018; 43:325.
38. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorde
rs, Fifth Edition (DSM-5), American Psychiatric Association, 2013.
39. Ravindran LN, Stein MB. Anxiety Disorders: Somatic Treatment. In: Kaplan and Sadock
Comprehensive Textbook of Psychiatry, 9th ed, Sadock BJ, Sadock VA, Ruiz P (Eds), Lip
pincott Williams & Wilkins, Philadelphia, PA 2009. p.1906.
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anxiety disorders: Systematic review and meta-analysis. J Psychopharmacol 2016;
30:128.
41. Bergamaschi MM, Queiroz RH, Chagas MH, et al. Cannabidiol reduces the anxiety
induced by simulated public speaking in treatment-naïve social phobia patients.
Neuropsychopharmacology 2011; 36:1219.
42. Kwee CM, Baas JM, van der Flier FE, et al. Cannabidiol enhancement of exposure
therapy in treatment refractory patients with social anxiety disorder and panic
disorder with agoraphobia: A randomised controlled trial. Eur
Neuropsychopharmacol 2022; 59:58.
Topic 505 Version 36.0
GRAPHICS
Antidepressant medications: Usual dosing in adults and half-life

information
Usual Low Usual Available Mean half-

Trade
Generic drug starting starting daily oral life, hours
name
name dose dose dose doses (active
(US)
(mg)* (mg)* (mg) (mg) metabolites) ¶
Selective serotonin reuptake inhibitors (SSRIs)
Citalopram Celexa 20 10 20 to 10, 20, 40, 35; prolonged in

Δ◊
40 L hepatic
impairment and
older adults
Escitalopram Lexapro 10 5 to 10 10 to 5, 10, 20, L 27 to 32;

20 prolonged in
hepatic
impairment and
older adults
Fluoxetine Prozac 20 5 to 10 20 to 10, 20, 40, 120 (223);

60 Δ 60, L prolonged in
severe hepatic
Fluoxetine Prozac 90 NA 90
impairment
weekly Weekly
Fluvoxamine Luvox 50 25 50 to 25, 50, 100 15; prolonged in

300 Δ older adults
100, 150
(controlled
release)
Paroxetine Paxil 20 5 to 10 20 to 10, 20, 30, 21

60 Δ 40, L
Paroxetine CR Paxil CR 25 25 to 12.5, 25, 15 to 20

62.5 37.5
Sertraline Zoloft 50 12.5 to 25 50 to 25, 50, 100, 26 (66)

200 Δ L
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Desvenlafaxine Khedezla, 50 25 50 to 25, 50, 100 11; prolonged in
Pristiq 100 severe renal and

hepatic
impairment
Duloxetine Cymbalta, 30 20 60 to 20, 30, 40, 12; prolonged in

Irenka 120 60 older female
patients
Venlafaxine Effexor 37.5 25 75 to 25, 37.5, 5 (11); prolonged

375 50, 75, 100 in severe renal
and hepatic
Venlafaxine XR Effexor 37.5 75 to 37.5, 75,
impairment
XR 225 150, 225
L: liquid; NA: not applicable; CR: controlled release; XR: extended release.
* Lower starting doses are recommended for elderly patients and patients with panic disorder,
significant anxiety, or hepatic disease.
¶ Mean half-lives of active metabolites are given in parentheses.
Δ Dose varies with diagnosis. Refer to text for specific guidelines.
◊ Maximum recommended dose of citalopram is 20 mg for patients >60 years of age, with
significant hepatic insufficiency, or taking interacting medications that can increase citalopram
levels. Refer to topic review of pharmacology of SSRI antidepressants for more information.
Specific interactions of citalopram and other medications may be determined using the drug
interactions tool (Lexi-Interact) included in UpToDate.
Data from: Martinez M, Marangell LB, Martinez JM. Psychopharmacology. In: American Psychiatric Publishing
Textbook of Psychiatry, 5th ed, Hales RE, Yudofsky SC, Gabbard, GO (Eds), American Psychiatric Publishing, Inc, 2008
and Lexicomp Online. Copyright © 1978-2023 Lexicomp, Inc. All Rights Reserved.
Graphic 81315 Version 16.0
Contributor Disclosures
Murray B Stein, MD, MPH Equity Ownership/Stock Options: EpiVario [Substance use disorders and
PTSD]; Oxeia Biopharmaceuticals [Traumatic brain injury]. Consultant/Advisory Boards: Acadia
Pharmaceuticals [Anxiety and traumatic stress-related disorders]; Aptinyx [Anxiety and traumatic
stress-related disorders]; atai Life Sciences [Anxiety and traumatic stress-related disorders];
BigHealth [Anxiety and traumatic stress-related disorders]; Biogen [Anxiety and traumatic stress-
related disorders]; Bionomics [Anxiety and traumatic stress-related disorders]; BioXcel Therapeutics
[Anxiety and traumatic stress-related disorders]; Boehringer-Ingelheim [Anxiety and traumatic
stress-related disorders]; EmpowerPharm [Anxiety and traumatic stress-related disorders]; Engrail
Therapeutics [Anxiety and traumatic stress-related disorders]; Janssen [Anxiety and traumatic stress-
related disorders]; Jazz Pharmaceuticals [Anxiety and traumatic stress-related disorders];
NeuroTrauma Sciences [Traumatic brain injury]; Oxeia Biopharmaceuticals [Traumatic brain injury];
Roche/Genentech [Anxiety and traumatic stress-related disorders]; Sage Therapeutics [Anxiety and
traumatic stress-related disorders]. Other Financial Interest: Biological Psychiatry [Deputy Editor];
Depression and Anxiety [Editor-in-chief]. All of the relevant financial relationships listed have been
mitigated. Peter P Roy-Byrne, MD Employment: Mass Medical Society [Psychiatry]. All of the
relevant financial relationships listed have been mitigated. Michael Friedman, MD No relevant
financial relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found,
these are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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Literature review current through: Sep 2023.

TYPES OF SOCIAL ANXIETY DISORDER

Whenever pharmacotherapy is prescribed for SAD, it is good clinical practice to

Selective serotonin reuptake inhibitors — A meta-analysis of seven trials that compared

● Paroxetine can be started at 10 mg/day taken orally and increased to a therapeutic

Serotonin-norepinephrine reuptake inhibitors — Although less well studied than the

Other adverse effects common at therapeutic doses include postural hypotension,

Benzodiazepines — Two, small randomized trials found the high-potency

Gabapentin — Gabapentin (an anticonvulsant) has demonstrated modest effectiveness

Pregabalin — Pregabalin, a compound related to gabapentin, has demonstrated modest

● Moclobemide – Moclobemide, a reversible MAOI selective for inhibition of MAO-A,

has fewer adverse effects overall.

● Mirtazapine – Mirtazapine has shown mixed results in patients with SAD. In a

● Second-generation antipsychotics – Very small randomized controlled trials of

● Buspirone – The limited available data suggest that buspirone is ineffective as

● Atomoxetine – Atomoxetine, an SNRI (marketed for the treatment of attention

● Buspirone – A small uncontrolled trial found that 7 of 10 patients partially

● Clonazepam – Randomized trials have found some evidence in support of

The proportion of patients responding to treatment (defined as a Liebowitz Social

The use of benzodiazepines in patients with a history of a substance use disorder is

• Pindolol – A small randomized trial did not show a benefit of augmenting

• Monoamine oxidase inhibitors – Monoamine oxidase inhibitors should not be

• Ketamine – A small randomized clinical trial of a single dose of intravenous

SOCIAL ANXIETY DISORDER, PERFORMANCE ONLY

Medication treatment is often prescribed on an "as needed" basis for performance-only

Benzodiazepines — Benzodiazepines can also be used on an "as needed" basis to treat

Beta-adrenergic blockers — There is no evidence from clinical trials on the effectiveness

Propranolol can be taken orally 30 to 60 minutes prior to the anxiety-inducing situation, at

Cannabinoids — A small, randomized, double-blind study of 600 mg cannabidiol (n = 12)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

● Monotherapy – Several classes of drugs are effective in the treatment of social

• Benzodiazepines – The high-potency benzodiazepines, alprazolam and

and 'Benzodiazepines and SUD history' above.)

• Other agents with limited or mixed supporting data – Moclobemide,

● Augmentation – A substantial number of patients with SAD respond only partially to

● SAD, performance only – In the transition from American Psychiatric Association’s

• We suggest not treating performance-only SAD with medication. However,

• When medication is used to treat SAD, performance-only specifier, we suggest

• For patients with an SUD history or who experience sedation with a

Use of UpToDate is subject to the Terms of Use.

9. Liebowitz MR, Mangano RM, Bradwejn J, et al. A randomized controlled trial of

gabapentin: a placebo-controlled study. J Clin Psychopharmacol 1999; 19:341.

27. Depping AM, Komossa K, Kissling W, Leucht S. Second-generation antipsychotics for

Antidepressant medications: Usual dosing in adults and half-life

Usual Low Usual Available Mean half-

Selective serotonin reuptake inhibitors (SSRIs)

Citalopram Celexa 20 10 20 to 10, 20, 40, 35; prolonged in

Escitalopram Lexapro 10 5 to 10 10 to 5, 10, 20, L 27 to 32;

Fluoxetine Prozac 20 5 to 10 20 to 10, 20, 40, 120 (223);

Fluvoxamine Luvox 50 25 50 to 25, 50, 100 15; prolonged in

Paroxetine Paxil 20 5 to 10 20 to 10, 20, 30, 21

Paroxetine CR Paxil CR 25 25 to 12.5, 25, 15 to 20

Sertraline Zoloft 50 12.5 to 25 50 to 25, 50, 100, 26 (66)

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Desvenlafaxine Khedezla, 50 25 50 to 25, 50, 100 11; prolonged in

Pristiq 100 severe renal and

Duloxetine Cymbalta, 30 20 60 to 20, 30, 40, 12; prolonged in