41 The Pharmacotherapy of Anxiety Disorders Eric Bui, MD, PhD, Mark H. Pollack, MD, Gustavo Kinrys, MD, Hannah Delong, BA, Débora Vasconcelos e Sá, BA, MSc, and Naomi M. Simon, MD, MSc

KEY POINTS (Prozac) and extended-release venlafaxine Effexor-XR) are Food and Administration (FDA)-approved for the treat- ment of , though other SSRIs including citalo- • A variety of pharmacological agents are effective for 1 the treatment of anxiety disorders. pram (Celexa), and escitalopram (Lexapro), and fluvoxamine (Luvox)2 have also demonstrated anti-panic efficacy in both • The SSRIs and SNRIs are first-line pharmacological open and double-blind trials. A recently introduced SNRI, agents for the treatment of anxiety disorders. duloxetine (Cymbalta), has also been reported effective for • are effective, rapidly acting and panic disorder in case reports,3 and in an open-label trial4 well-tolerated, but are associated with the risk of though no randomized controlled trials (RCTs) are currently abuse and dependence, and lack efficacy for reported. co-morbid . A recent meta-analysis on 50 clinical trials (yielding over • , atypical antipsychotics, adrenergic 5,000 participants) confirmed that citalopram, paroxetine, fluoxetine, and venlafaxine were superior to placebo in the antagonists, and other agents also play role in the 5 treatment of anxiety disorders. treatment of panic disorder. , Finally while the majority of data supporting the efficacy of pharmacological agents for • Many patients remain symptomatic despite standard panic disorder derive from short-term trials, several long-term treatments; this necessitates the creative use of studies have also demonstrated sustained efficacy over time.6 available interventions (alone and in combination), Because the SSRI/SNRIs have the potential to cause and spurs the development of novel therapeutics. initial restlessness, , and increased anxiety, and because panic patients are commonly sensitive to somatic sen- sations, the starting doses should be low, typically half (or less) of the usual starting dose (e.g., fluoxetine 5 to 10 mg/d, sertra- OVERVIEW line 25 mg/d, paroxetine 10 mg/d [or 12.5 mg/d of the controlled-release formulation], controlled-release venlafaxine As described elsewhere in this volume (Chapter 32), anxiety 37.5 mg/d), to minimize the early anxiogenic effect. Doses can disorders are associated with both significant distress and dys- usually begin to be raised, after about a week of acclimation, function. In this chapter we will review the pharmacotherapy toe achiev typical therapeutic levels, with further gradual titra- of panic disorder with or without co-morbid agoraphobia, tion based on clinical response and side effects, although even generalized (GAD), and social anxiety disor- more gradual upward titration is sometimes necessary in par- der (SAD); the treatment of posttraumatic stress disorder ticularly sensitive or somatically-focused individuals. Although (PTSD) is discussed in Chapter 34, and obsessive-compulsive the nature of the dose–response relationship for the SSRIs in disorder (OCD) is discussed in Chapter 33. Table 41-1 includes panic is still being assessed, available data support doses for dosing information and common side effects associated with this indication in the typical antidepressant range, and some- the pharmacological agents commonly used for the treatment times higher, i.e., fluoxetine 20 to 40 mg/d, paroxetine 20 to of, anxiety referred to in the following sections. 60 mg/d (25 to 72.5 mg/d of the controlled-release formula- tion), sertraline 100 to 200 mg/d, citalopram 20 to 60 mg/d, PANIC DISORDER AND AGORAPHOBIA escitalopra