Buspirone Augmentation for SSRI-Induced Sexual Dysfunction
Buspirone augmentation is not recommended as a first-line strategy for managing sertraline-induced sexual dysfunction, as the evidence shows it has similar efficacy to other augmentation approaches but with significantly higher discontinuation rates due to adverse events compared to alternatives like bupropion. However, since bupropion is not tolerated in your patient, buspirone represents a reasonable second-line pharmacologic option with established safety data from major trials. 1
Evidence Quality and Limitations
The primary evidence comes from the STAR*D trial, which found that buspirone augmentation of citalopram (an SSRI similar to sertraline) showed no superiority over other augmentation strategies for depression treatment. 1 Critically, buspirone had significantly higher discontinuation rates due to adverse events (20.6%) compared to bupropion SR (12.5%; P < 0.001). 1
The American College of Physicians rates this evidence as low quality, meaning there is substantial uncertainty about the magnitude of benefit. 2 The STAR*D trial was not specifically designed to assess sexual dysfunction as an outcome—it evaluated overall depression response and remission rates. 1
Specific Evidence for Sexual Dysfunction
There is minimal high-quality evidence specifically supporting buspirone for SSRI-induced sexual dysfunction. One 2024 case report describes resolution of sertraline-induced delayed ejaculation with buspirone augmentation, but this represents the lowest level of evidence (single case report). 3
The mechanism by which buspirone might help is theoretically sound: it acts as a partial agonist at serotonin 5-HT1A receptors, potentially counteracting some serotonergic effects that contribute to sexual dysfunction. 2 However, this theoretical rationale has not been validated in controlled trials specifically examining sexual side effects.
Practical Implementation Strategy
If you proceed with buspirone augmentation despite the limited evidence:
Start with 5 mg twice daily and titrate gradually up to a maximum of 20 mg three times daily as needed. 2
Set realistic expectations: Buspirone requires 2-4 weeks to reach full therapeutic effect, unlike benzodiazepines which work immediately. 2 Patients expecting rapid improvement will be disappointed.
Monitor for serotonin syndrome during the initial combination period and with any dose adjustments, particularly in the first 24-48 hours after changes. 2 Watch for mental status changes, neuromuscular hyperactivity (tremor, hyperreflexia, clonus), and autonomic hyperactivity (tachycardia, diaphoresis, hyperthermia). 2
Safety Advantages of Buspirone
Unlike benzodiazepines, buspirone does not cause tolerance, addiction, cognitive impairment, or paradoxical agitation, making it safer for long-term use. 2 This is particularly relevant if your patient requires extended treatment.
The combination of sertraline and buspirone can be safely taken together according to the American Academy of Family Physicians, though the theoretical risk of serotonin syndrome requires vigilance. 2
Alternative Strategies to Consider
Given the weak evidence for buspirone specifically treating sexual dysfunction:
Cognitive behavioral therapy showed similar efficacy to medication augmentation in STAR*D with numerically fewer discontinuations due to adverse events (9.2% vs. 18.8% for medication groups; P = 0.086). 1 This should be discussed as an alternative or adjunctive option. 2
Switching strategies: Consider switching from sertraline to a different antidepressant with lower sexual dysfunction rates. The American College of Physicians found no differences in efficacy between various switch strategies (to escitalopram, duloxetine, venlafaxine, or vortioxetine). 1 However, bupropion would typically be the preferred switch option given its significantly lower rates of sexual dysfunction compared to sertraline. 1, 4, 5
Dose reduction of sertraline: While not specifically addressed in the guidelines, this is a commonly employed clinical strategy that may reduce sexual side effects while maintaining antidepressant efficacy.
Common Pitfalls to Avoid
Expecting immediate results: Patients may discontinue buspirone prematurely before the 2-4 week window needed for efficacy. 2
Inadequate dosing: Starting at 5 mg twice daily is appropriate, but some patients may require titration to higher doses (up to 60 mg/day total) for therapeutic effect. 2
Missing early serotonin syndrome: Symptoms can be mistaken for worsening anxiety or other conditions. 2
Abrupt discontinuation: Sertraline has been associated with discontinuation syndrome and should be tapered if switching is ultimately chosen. 2