What are first-line pharmacologic treatments for GAD?

• A. SSRIs and SNRIs (e.g., escitalopram, sertraline, fluoxetine; venlafaxine, duloxetine); buspirone may be used; benzodiazepines are not first-line long-term.
• B. Antipsychotics.
• C. Monoamine oxidase inhibitors.
• D. Tricyclic antidepressants.

Answer: (C)

The main concept here is identifying medications that are best suited for long-term management of generalized anxiety disorder. The preferred first-line options are selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. These classes have robust evidence showing they reduce pervasive worry and physical symptoms over weeks to months, and they are generally well tolerated for long-term use. Examples include SSRIs such as escitalopram, sertraline, and fluoxetine, and SNRIs such as venlafaxine and duloxetine.

Buspirone is also used in some patients as a non-benzodiazepine option; it can be helpful for anxiety without causing sedation or dependence, but it may take several weeks to work and isn’t as consistently effective for all individuals as SSRIs/SNRIs.

Benzodiazepines, while effective for rapid relief of acute anxiety, are not considered first-line for long-term treatment because of risks of dependence, tolerance, and withdrawal, so they’re typically reserved for short-term use or bridging until an SSRI/SNRI takes effect.

Monoamine oxidase inhibitors and tricyclic antidepressants are not first-line choices due to safety concerns, tolerability issues, and monitoring requirements: MAOIs require dietary restrictions and have significant drug interactions, and TCAs tend to have more anticholinergic and cardiovascular side effects with poorer tolerability.

In practice, treating GAD focuses on initiating an SSRI or SNRI for long-term control, considering buspirone as an alternative in certain cases, and avoiding benzodiazepines as a long-term solution.