Is buspirone (an anxiolytic medication) a useful augmentation to sertraline (selective serotonin reuptake inhibitor) in treating social anxiety disorder in patients with autism spectrum disorder?

Buspirone Augmentation to Sertraline for Social Anxiety Disorder in Autism

Buspirone augmentation to sertraline is not recommended for social anxiety disorder, particularly in autistic patients, as the evidence shows no superiority over other strategies for social anxiety, and autism spectrum disorder is explicitly excluded from social anxiety disorder treatment guidelines. 1

Critical Guideline Exclusions

The Japanese Society of Anxiety and Related Disorders/Japanese Society of Neuropsychopharmacology explicitly states that social anxiety disorder symptoms cannot be explained by autism spectrum disorder, and patients with developmental disorders (including autism) are specifically excluded from their social anxiety disorder treatment guidelines. 1 This is a fundamental diagnostic distinction that must be recognized—if the social anxiety symptoms are better explained by autism, they should not be treated as primary social anxiety disorder.

Evidence for Buspirone Augmentation in Non-Autistic Populations

For patients without autism who have inadequate response to SSRIs like sertraline:

• The STAR*D trial found no difference in efficacy when augmenting citalopram (an SSRI similar to sertraline) with buspirone compared to bupropion or cognitive therapy for depression/anxiety. 1, 2

• Buspirone had significantly fewer discontinuations due to adverse events (12.5%) compared to other augmentation strategies (20.6%; P < 0.001), making it safer but not more effective. 1, 2, 3

• The American College of Physicians rates this evidence as low quality, meaning substantial uncertainty exists about the magnitude of benefit. 2, 3

• Cognitive therapy augmentation showed similar efficacy with potentially fewer adverse events and should be discussed as an alternative. 2

Evidence Specific to Autism Spectrum Disorder

For autistic patients specifically, the evidence picture is different and addresses anxiety in autism rather than social anxiety disorder:

• A 2023 systematic review concluded there is insufficient evidence to make recommendations on buspirone for co-occurring anxiety in autism, though it may be used as a safe off-label option due to lack of behavioral activation. 4

• A 2019 retrospective chart review (N=31, ages 8-17) of high-functioning autistic youth with anxiety disorders showed 58% had significant improvement and 29% had mild improvement on buspirone monotherapy (mean dose 41.6 mg/day), with excellent tolerability. 5

• However, this study used buspirone as monotherapy for anxiety in autism, not as augmentation to an SSRI for social anxiety disorder—a critical distinction. 5

Practical Clinical Algorithm

If the patient has autism:

1. Reassess the diagnosis: Determine whether social anxiety symptoms are better explained by autism spectrum disorder itself (difficulty with social communication, preference for routine, sensory sensitivities) rather than true social anxiety disorder. 1

2. If symptoms are autism-related social difficulties: Consider buspirone monotherapy (starting 5 mg twice daily, titrating to 10-30 mg twice daily) as it has shown promise for anxiety in autism with excellent tolerability. 2, 5

3. If true comorbid social anxiety disorder exists: Recognize you are treating an off-guideline population; buspirone augmentation offers no efficacy advantage but has better tolerability than alternatives. 1, 2

If the patient does not have autism:

1. Consider switching rather than augmenting: Moderate-quality evidence shows switching from one SSRI to another has similar efficacy to augmentation strategies. 6

2. If augmentation is preferred: Buspirone offers no efficacy advantage over bupropion or cognitive therapy augmentation, but has significantly fewer adverse events. 1, 2

3. Strongly consider cognitive therapy: Adding cognitive behavioral therapy has similar efficacy to medication augmentation with potentially fewer adverse events. 2, 6

Dosing and Monitoring Considerations

If proceeding with buspirone augmentation despite limited evidence:

• Start at 5 mg twice daily and titrate gradually to 10-30 mg twice daily (maximum 20 mg three times daily). 2, 3

• Allow 2-4 weeks for full therapeutic effect—unlike benzodiazepines, buspirone is not immediately effective. 2, 3

• Monitor for serotonin syndrome in the first 24-48 hours after initiation or dose changes (mental status changes, neuromuscular hyperactivity, autonomic hyperactivity), though risk is theoretical. 2

• In autistic children, pharmacokinetics show rapid absorption and elimination with extensive metabolism; plasma concentrations with 2.5-5 mg doses in young children are similar to 7.5-15 mg doses in older children. 7

Key Advantages of Buspirone

• No addiction potential, tolerance, or cognitive impairment unlike benzodiazepines, making it safer for long-term use. 2, 3

• Significantly lower discontinuation rate due to adverse events (12.5% vs 20.6%) compared to other augmentation strategies. 1, 2, 3

• Different mechanism of action (5-HT1A partial agonist) compared to SSRIs (serotonin reuptake inhibition), providing theoretical complementary effects. 2

Critical Pitfalls to Avoid

• Expecting immediate results: Buspirone requires 2-4 weeks to reach full therapeutic effect; patients expecting benzodiazepine-like rapid relief will be disappointed. 2, 3

• Misdiagnosing autism-related social difficulties as social anxiety disorder: This leads to inappropriate treatment selection and poor outcomes. 1

• Failing to consider cognitive therapy: This has equal efficacy with potentially fewer adverse events and should be offered as an alternative or adjunct. 2, 6

• Abrupt discontinuation of sertraline: This can cause discontinuation syndrome; any medication changes should be gradual. 2