Table 24.

Recommendations for pharmacotherapy for GAD

First-line	Agomelatine, duloxetine, escitalopram, paroxetine, paroxetine CR, pregabalin, sertraline, venlafaxine XR
Second-line	Alprazolam*, bromazepam*, bupropion XL*, buspirone, diazepam*, hydroxyzine, imipramine, lorazepam*, quetiapine XR*, vortioxetine
Third-line	Citalopram, divalproex chrono, fluoxetine, mirtazapine, trazodone
Adjunctive therapy	Second-line: pregabalin Third-line: aripiprazole, olanzapine, quetiapine, quetiapine XR, risperidone Not recommended: ziprasidone
Not recommended	Beta blockers (propranolol), pexacerfont, tiagabine

CR = controlled release; XL = extended release; XR=extended release.

*Note: These have distinct mechanisms, efficacy and safety profiles. Within these second-line agents, benzodiazepines would be considered first in most cases, except where there is a risk of substance abuse, while bupropion XL would likely be reserved for later. Quetiapine XR remains a good choice in terms of efficacy, but given the metabolic concerns associated with atypical antipsychotic, it should be reserved for patients who cannot be provided antidepressants or benzodiazepines. Please refer to text for further rationale for the recommendations.