Pharmacotherapy for generalized anxiety disorder (GAD) in individuals who have not fully responded to first-line treatment with serotonin reuptake inhibitors (SRI)^*

GAD: generalized anxiety disorder; QTc: heart rate-corrected QT interval; SNRI: serotonin-norepinephrine reuptake inhibitor; SRI: serotonin reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor.

* SRIs include both SSRIs and SNRIs.

¶ An adequate trial is considered to be 6 weeks at a therapeutic dose range for medication.

Δ SRI choice is based on side effect profile, drug interactions, treatment history, and patient preference. Our preferred method of switching medications is to taper a medication while simultaneously titrating the second medication. In most cases, this can be done over 2 to 3 weeks.

◊ In most cases, gabapentin is our next choice in augmentation. Pregabalin is another option; however, due to the greater potential for misuse and dependence, we typically try gabapentin first.

§ We typically try augmentation with 2 different agents for a minimum of 4 to 6 weeks prior to considering the individual to be unresponsive to augmentation.

¥ Buspirone is used as monotherapy or as an augmentation agent in the treatment of GAD. It is typically our first choice as an augmenting agent. When used as monotherapy, it is typically used after failure to respond to 2 trials of SRIs or in those unable to tolerate SRIs. In either case, we titrate buspirone to the highest tolerated dose up to a maximum of 60 mg per day in divided doses. We treat for a full 6 weeks at this dose prior to assessing efficacy.

‡ For individuals with significant mood fluctuations (eg, irritability, lability, hypomania), augmentations with valproic acid or lamotrigine are acceptable alternatives.

† For individuals who respond adequately to medication management, we continue the effective agent for a minimum of 12 months prior to considering an attempt to lower the medication. For individuals who have experienced relapse after medication taper in the past, we treat for 2 years or longer.

** The choice of antidepressants is based on the symptoms present and the potential side effects of medications. In individuals with decreased appetite or insomnia, we would use mirtazapine. In individuals sensitive to weight gain, we would use vilazodone. Refer to UpToDate content for further discussion of the choice of antidepressant medication.

¶¶ For individuals with current unhealthy alcohol or substance use, we address these concerns prior to treating generalized anxiety. In some cases, such as low-risk use of alcohol, we address them concurrently.

ΔΔ Refer to UpToDate content for further discussion of choosing antipsychotic agents. When treating with an antipsychotic agent, we monitor for extrapyramidal symptoms, prolonged QTc, and metabolic dysregulation. Refer to UpToDate content for further discussion of choosing an antipsychotic agent, monitoring metabolic profile and side effects of antipsychotics, and their management.

◊◊ Refer to UpToDate content for further discussion of the use of hydroxyzine in the treatment of GAD.

§§ Benzodiazepines can be used as monotherapy in individuals who have not responded to any prior agents or as an adjunctive agent based on response to the previous agent. Refer to UpToDate content for further discussion.