Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review

Abstract

Generalized anxiety disorder (GAD) often begins during adolescence or early adulthood and persists throughout the lifespan. Randomized controlled trials support the efficacy of selective serotonin and selective serotonin norepinephrine reuptake inhibitors (SSRIs and SNRIs, respectively), as well as benzodiazepines, azapirones, anti-adrenergic medications, melatonin analogs, second-generation antipsychotics, kava, and lavender oil in GAD. However, psychopharmacologic treatment selection requires clinicians to consider multiple factors, including age, co-morbidity, and prior treatment. Areas covered: The authors review the literature concerning pharmacotherapy for pediatric and adult patients with GAD with specific commentary on the efficacy and tolerability of selected agents in these age groups. The authors describe an algorithmic approach to the pediatric and adult patient with GAD and highlight considerations for the use of selected medications in these patients. Expert opinion: In adults with GAD, SSRIs and SNRIs represent the first-line psychopharmacologic treatment while second-line pharmacotherapies include buspirone, benzodiazepines, SGAs, and pregabalin. In pediatric patients with GAD, SSRIs should be considered the first line pharmacotherapy and psychotherapy enhances antidepressant response.

Keywords: Selective Serotonin Norepinephrine Reuptake Inhibitor (SNRI); Selective Serotonin Reuptake Inhibitor (SSRI); adult; antidepressants; benzodiazepine; buspirone; pediatric.

Figure 1:. Structures of antidepressant medications that have been systematically evaluated in patients with generalized anxiety disorder (GAD).

Structurally, SSRIs and SNRIs share many similarities and contain halogen atoms at specific positions, which are key determinants of their specificity for the serotonin transporter. The position and type of the specific substitution on an aromatic component of the antidepressant molecule determines the specificity at the serotonin transporter. Halogen substitutions at this ring are associated with the most binding specificity at the serotonin transporter and are mediated through binding within the halogen binding pocket (HBP). Colors represent specific atoms: nitrogen (blue); oxygen (red); halogens (fluorine and chloride) (green); sulfur (yellow); carbon (gray).

Figure 2:. Psychopharmacologic Treatment algorithm for moderate to severe generalized, anxiety disorder in adults (A) and in children and adolescents (B).

Cooler colors represent higher levels of evidence and reflect greater evidence of tolerability and safety. Trials of SSRI and SNRIs should be ≥8 weeks, although if there is no response by week 8, there is a low likelihood of additional improvement. In the pediatric population, clinicians should note that for buspirone, guanfacine, antihistamines, and maintenance administration of benzodiazepines, the evidence base is very weak or conflicting. SSRI, selective serotonin reuptake inhibitor; SNRI, selective serotonin norepinephrine reuptake inhibitor; TCA, tricyclic antidepressant.