In the second study, 295 patients with generalized SAD were randomized to receive fluoxetine, comprehensive group CBT, fluoxetine plus comprehensive group CBT plus placebo, or placebo for 14 weeks. All active treatments outperformed placebo and were comparable to each other. No advantage was seen with combination therapy.18
Pharmacological interventions
Before choosing a pharmacological intervention, it is important first to determine whether the patient has generalized or circumscribed SAD. Those with circumscribed SAD, which is limited to such settings as public speaking or artistic performance, usually respond well to medications on an as-needed basis. Patients with generalized SAD usually require standing-dose schedules of medications.
Selective serotonin reuptake inhibitors
SSRIs are currently considered appropriate first-line treatment for SAD. Their efficacy in this setting is supported by several randomized controlled trials and by systematic reviews and meta-analyses.19-31 The number of head-to-head comparisons of various SSRIs is limited. Currently available comparisons fail to show superiority of one SSRI over another, and the selection of an individual SSRI is typically based on matching specific patient parameters with the SSRI (eg, adverse-effect profile, previous history, comorbid general medical conditions, drug interactions).32,33
It may take as long as 8 to 12 weeks of treatment with an SSRI before a favorable response is manifested. Treatment for 12 months or longer is generally advised, once a favorable response is achieved, to prevent relapse. Some patients may require maintenance therapy to sustain benefits.33,34 Relapse rates are relatively high once medication is discontinued—up to 60% at 3- to 6-month follow-up after a 5- to 12-month course and even higher after shorter courses of treatment.33
SSRIs are generally well tolerated. Common adverse effects include sleep problems, fatigue, sexual dysfunction (eg, decreased sex drive, delayed or absent orgasm, erectile dysfunction), restlessness, agitation, and GI symptoms. It is advisable to start with a dosage that is lower than the conventional starting dose for depression and gradually to titrate upward.
In 2004, the FDA released an advisory concerning SSRIs and risk of suicidal ideation. Although rare, it is possible for symptoms to worsen initially. Hence, it is important to monitor symptoms during this time.
When it is time to discontinue, it is advisable to taper an SSRI gradually because abrupt discontinuation can result in a relapse of anxiety symptoms. In some cases, abrupt withdrawal can trigger serotonin discontinuation syndrome, which presents with flu-like symptoms, anxiety, difficulty with coordination, tingly sensations, vivid dreams, and depressed mood.
Serotonin norepinephrine reuptake inhibitors
The serotonin norepinephrine reuptake inhibitors (SNRIs) include venlafaxine and duloxetine. Several controlled studies have reported efficacy of venlafaxine in the treatment of SAD.32,35-38 In a controlled study of 440 patients who were randomized to venlafaxine extended release (ER), paroxetine, or placebo for 12 weeks, a similar response rate was reported for venlafaxine and paroxetine; both were superior to placebo.32
In a second trial that compared venlafaxine with paroxetine, no significant differences in primary or secondary efficacy variables were observed between the 2 active treatments.35 The primary efficacy variable was the Liebowitz Social Anxiety Scale total score. Secondary efficacy variables included the patient-rated social phobia inventory and the proportion of responders in each group (a responder was defined as having a clinical global impression improvement score of 1 or 2). At week 12 the response rates were 69%, 66%, and 36% for the venlafaxine ER, paroxetine, and placebo groups, respectively. Both active treatments were generally well tolerated and were associated with a similar incidence of adverse events.
Monoamine oxidase inhibitors
Phenelzine has been considered the best studied and perhaps the most efficacious pharmacological treatment for SAD until quite recently.15,39-41 Evidence that supports the efficacy of monoamine oxidase inhibitors (MAOIs) is well summarized by Blanco and colleagues.42
MAOIs require dietary restrictions (a low tyramine diet), and they can be associated with substantial adverse events. A potentially fatal hypertensive reaction can occur if users of MAOIs do not comply with the diet. The MAOIs cannot be used in conjunction with some common over-the-counter medications; these include cold and cough formulas.
Reversible MAOIs, such as moclobemide, which do not require dietary restrictions and have fewer adverse effects than traditional MAOIs, showed promise in early trials but provided mixed results in more recent ones.13,43-45
Given the availability of safer medications with similar efficacy, the use of MAOIs should probably be limited to those patients who have not responded to other first-line treatments.
Beta-adrenergic blockers
b-Blockers are currently used on an as-needed basis for circumscribed social anxiety, mostly based on anecdotal evidence of utility for performance anxiety (eg, propranolol in low doses [10 to 40 mg] taken an hour before a performance that is the focus of anxiety).
