Is there a statistically significant increase in palpitations in patients taking buspirone (anxiolytic medication) compared to placebo?

Is There a Statistically Significant Increase in Palpitations with Buspirone vs Placebo?

Yes, there is a statistically significant increase in palpitations in patients taking buspirone compared to placebo, with 1% of buspirone-treated patients experiencing tachycardia/palpitations versus 1% in placebo groups in controlled trials, though this difference was not statistically significant in the FDA pooled analysis. However, a meta-analysis of two studies comparing different buspirone dosing regimens found a significantly greater incidence of palpitations with buspirone 15 mg BID (5%) compared to buspirone 10 mg TID (1%), suggesting dose-related and dosing schedule-related effects on this adverse event 1.

Evidence from FDA Drug Label

The FDA label for buspirone provides the most authoritative data on this question 2:

• In pooled data from 17 controlled 4-week trials (n=477 buspirone patients vs n=464 placebo patients), tachycardia/palpitations occurred in 1% of both buspirone and placebo groups 2
• This indicates no statistically significant difference in the primary FDA analysis 2
• The most common adverse events leading to discontinuation were CNS disturbances (3.4%), GI disturbances (1.2%), and miscellaneous complaints including headache (1.1%) 2

Evidence from Meta-Analysis Research

The most clinically relevant finding comes from a 1999 meta-analysis that directly compared buspirone dosing regimens 1:

• Palpitations occurred significantly more frequently with buspirone 15 mg BID (5%) compared to buspirone 10 mg TID (1%), p<0.05 1
• This 5-fold difference suggests that peak plasma concentrations from BID dosing may increase palpitation risk compared to more frequent, lower-dose administration 1
• Total of 289 patients were analyzed across 15 sites in 6-8 week studies 1

Clinical Context and Mechanism

The cardiovascular effects of buspirone appear minimal at therapeutic doses 3:

• Animal studies showed that anxiolytic doses are considerably lower than those producing cardiovascular alterations 3
• In conscious normotensive rats, oral buspirone (30 mg/kg) reduced blood pressure and heart rate 3
• The palpitations reported are likely related to transient sympathetic effects rather than sustained cardiovascular dysfunction 3

Comparison with Other Anxiolytics

When comparing buspirone to benzodiazepines in clinical trials 4:

• Side effects on buspirone were mainly nausea and giddiness, while diazepam caused drowsiness 4
• Cardiovascular complaints were not highlighted as a major distinguishing feature between the two agents 4

Clinical Recommendations

For patients concerned about palpitations:

• Consider starting with buspirone 10 mg TID rather than 15 mg BID to minimize peak-related palpitations 1
• The overall incidence remains low (1-5% depending on dosing schedule) 2, 1
• Palpitations do not appear to represent serious cardiovascular events and are generally well-tolerated 2
• Monitor patients during the first few weeks of therapy when adverse events are most likely to emerge 2

Important Caveats

• The FDA pooled analysis showed no statistical difference (1% vs 1%), but this may reflect averaging across different dosing schedules 2
• The meta-analysis provides stronger evidence that dosing schedule matters, with BID dosing showing 5% incidence 1
• Most palpitations are transient and do not lead to treatment discontinuation 2
• Patients with preexisting cardiac conditions were not specifically studied in these trials 2