From the Guidelines
For a 40-year-old male with generalized anxiety disorder who has not responded to an SSRI and is reluctant to take benzodiazepines, the next best option would be a serotonin-norepinephrine reuptake inhibitor (SNRI) such as venlafaxine or duloxetine, as supported by the most recent clinical practice guideline 1. The SNRI class of medications has been shown to be effective in the treatment of anxiety disorders, likely due to complex interactions with other neurotransmitters including serotonin, as noted in the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1. Some key points to consider when prescribing SNRIs include:
- The primary mechanism of action of SNRIs is deemed sufficiently similar across individual medications to warrant extension of the findings to the medication class 1.
- Duloxetine is the only SNRI to have an FDA indication for the treatment of generalized anxiety disorder, but other SNRIs like venlafaxine may also be effective 1.
- The choice of medication for anxiety within the SNRI class may also be governed by other considerations such as pharmacokinetics, pharmacodynamics, tolerability, cost, insurance formularies, and unique risks leading to warnings or precautions 1.
- Venlafaxine extended release, desvenlafaxine, and duloxetine have sufficiently long elimination half-lives to permit single daily dosing, which may improve adherence 1. Given these considerations, venlafaxine could be started at 37.5 mg daily and gradually increased to 75-225 mg daily as needed and tolerated, or duloxetine could be initiated at 30 mg daily and increased to 60-120 mg daily, as these medications have been found to be effective in managing anxiety disorders without the dependence concerns associated with benzodiazepines 1.
From the FDA Drug Label
Buspirone hydrochloride tablets are indicated for the management of anxiety disorder or the short-term relief of the symptoms of anxiety. The efficacy of buspirone hydrochloride tablets has been demonstrated in controlled clinical trials of outpatients whose diagnosis roughly corresponds to Generalized Anxiety Disorder (GAD).
The next best option for a 40-year-old male with generalized anxiety disorder who has had no response to SSRI and is reluctant to take benzodiazepine is buspirone.
- Key points:
- Buspirone is indicated for the management of anxiety disorder
- Efficacy has been demonstrated in controlled clinical trials for Generalized Anxiety Disorder (GAD) 2 The patient should be periodically reassessed for the usefulness of the drug.
From the Research
Next Best Option for Generalized Anxiety Disorder
The patient has had no response to SSRI, and is reluctant to take benzodiazepine. Considering this, the next best option can be:
- Serotonin-norepinephrine reuptake inhibitors (SNRIs) as they are useful first-line agents for most of the anxiety disorders, particularly given the frequent comorbidity with mood disorders 3
- Azapirones, such as buspirone, which have been used effectively for generalized anxiety disorder 3, 4
- Other antidepressants, such as tricyclic antidepressants or monoamine oxidase inhibitors, although they are generally reserved as second- and third-line strategies due to tolerability issues 3
- Anticonvulsants and atypical antipsychotics, which may have an adjunctive role to antidepressants in cases of treatment resistance 3, 5
- Pregabalin, which is a second-line pharmacotherapy for adults with GAD 4
Considerations for Treatment Selection
When selecting a treatment, clinicians should consider multiple factors, including:
- Age
- Co-morbidity
- Prior treatment
- Efficacy and tolerability of selected agents in different age groups 4