Treating GAD: Is Buspirone a Good Option?

Darrell Hulisz, PharmD

Disclosures

July 17, 2014

Question

What is the role of buspirone for treatment of generalized anxiety disorder (GAD)?

Response from Darrell Hulisz, PharmD
Associate Professor, Case Western Reserve University School of Medicine; Clinical Specialist in Family Medicine, University Hospitals, Case Medical Center, Cleveland, Ohio; Associate Clinical Professor of Pharmacy Practice, Ohio Northern University, Raabe College of Pharmacy, Ada, Ohio

Although the anxiolytic drug buspirone has been available for nearly 30 years, its role in treating anxiety disorders, generalized anxiety disorder (GAD) in particular, is not well defined and is sometimes questioned. The drug first became available at a time when benzodiazepines were used routinely for GAD. Buspirone is approved for GAD and lacks the abuse and dependence potential of benzodiazepines, and thus was marketed as a safer alternative for long-term treatment of GAD. With persistent treatment, the efficacy of buspirone is similar to that of benzodiazepines in patients with GAD.[1]

However, at the present time, the selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are first-line agents for many anxiety disorders, including GAD. Unfortunately, in clinical practice, not all patients tolerate these drugs well. Sexual dysfunction, adverse gastrointestinal effects, insomnia, and potential drug interactions can sometimes complicate their use. As with SSRIs and SNRIs, buspirone does not depress respiratory drive, or cause psychomotor or memory impairment -- which is clearly a problem with benzodiazepines. Thus, it seems prudent to reexamine the role of buspirone for GAD.

Buspirone works through multiple mechanisms and is classified as a selective serotonin subtype 1A (5-HT1A) partial agonist, with activity at both presynaptic and postsynaptic 5-HT1A receptors.[2] The drug also uniquely interacts with dopamine receptors as an agonist and/or an antagonist. Buspirone appears to block presynaptic dopamine receptors selectively and produces an increased firing of midbrain dopamine neurons.[3] Thus, buspirone produces anxiolytic effects via postsynaptic receptor activity, while its activity at autoreceptors initially suppresses neuronal firing but gradually restores serotonergic neurotransmission.[4]

Buspirone was found to be as effective as the benzodiazepine oxazepam in treating GAD in a small, double-blind, multicenter, controlled trial. Patients were treated with either buspirone 5-10 mg 3 times/day or oxazepam 10-20 mg 3 times/day for 6 weeks. The mean decrease in the Hamilton Rating Scale for Anxiety (HAM-A) scores from baseline to end of study were similar between the groups and did not differ statistically. Adverse effects were similar in both groups.[5]

Another small clinical trial compared buspirone with sertraline (an SSRI) in elderly patients with GAD; both drugs demonstrated clinically significant anxiolytic effects by decreasing mean HAM-A scores. Although buspirone was superior at weeks 2 and 4 of the trial, no significant difference in efficacy was found at week 8 (P = .16).[6] In Davidson and colleagues' study,[7] however, extended-release venlafaxine (an SNRI) demonstrated significantly superior efficacy on an anxiety subscale compared with buspirone for treatment of GAD.

The approved initial dose of buspirone for GAD is 7.5 mg twice daily. The dose may be increased every 2-3 days in increments of 2.5 mg twice daily to a maximum of 30 mg twice daily. There is a significant delay in the onset of clinical activity, which can vary from 2 weeks to much longer. If patients are tolerating the drug well, a dose of 10-15 mg twice daily can be used. Both 2- and 3-times-daily dosing have been recommended.[1,6]

A drawback to using buspirone is that it may have little effect in patients with GAD previously treated with benzodiazepines.[8] The onset of anxiolysis is much more pronounced and rapid with benzodiazepines. Patients previously on long-term benzodiazepines may find the anxiolytic effect from buspirone to be attenuated or too delayed. Multiple daily dosing is also a potential drawback relative to benzodiazepines, SSRIs, and SNRIs. Although serotonin syndrome has been reported when used in combination with an SSRI, buspirone seems less likely to be associated with the interaction.[9]

To conclude, buspirone appears to have a role in treating GAD in patients who cannot tolerate, or fail to respond to, an SSRI or SNRI. It may have limited efficacy in patients with chronic GAD who have successfully been managed on a benzodiazepine. Buspirone is better suited for benzodiazepine-naive patients, especially if "on-demand" relief of anxiety is not a major therapeutic goal.

Acknowledgement: The author wishes to thank Jonathan Michelson for providing technical assistance.

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