A 50-year-old woman with Generalized Anxiety Disorder (GAD) has failed two SSRIs over 2 years. She is now started on a drug that acts as a 5-HT1A partial agonist and D2 partial agonist, with no sedation or dependence. Which drug is this?
- A Pregabalin
- B Buspirone ✓
- C Duloxetine
- D Hydroxyzine
Explanation
Buspirone is a unique anxiolytic that acts as a 5-HT1A partial agonist (reducing serotonergic activity in the raphe nucleus) and a D2 partial agonist. It has no GABAergic activity, therefore no sedation, no dependence, no withdrawal, and no cross-tolerance with benzodiazepines. Its clinical onset is slow (2–4 weeks), so it is not useful for acute anxiety. It is particularly useful in GAD for patients where benzodiazepine dependence is a concern. Pregabalin also has evidence in GAD (alpha-2-delta calcium channel ligand) but can cause dependence. Duloxetine is an SNRI and is evidence-based for GAD but was not the failed trial mentioned.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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