Can a patient safely add buspirone (Buspar) 7.5 mg to their morning and afternoon regimen while taking sertraline (Zoloft) 150 mg every night at bedtime, with the goal of eventually discontinuing sertraline once buspirone's efficacy for anxiety is established?

Can Buspirone Be Added to Sertraline with Plan to Discontinue Sertraline?

Yes, buspirone 7.5 mg twice daily can be safely added to sertraline 150 mg nightly, but this combination carries a risk of serotonin syndrome that requires close monitoring, particularly in the first 24-48 hours after initiation and with any dose changes. 1, 2, 3

Safety Considerations for Combination Therapy

Serotonin Syndrome Risk

• Both sertraline (an SSRI) and buspirone are serotonergic agents, and combining two non-MAOI serotonergic drugs requires caution due to potential serotonin syndrome. 1, 2, 3

• The FDA label for buspirone explicitly warns that serotonin syndrome can develop with concomitant use of SSRIs and buspirone, though it occurs "particularly with concomitant use of other serotonergic drugs." 3

• Monitor closely for serotonin syndrome symptoms: mental status changes (confusion, agitation, anxiety), neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis, hyperthermia). 1, 2, 3

• Critical monitoring period: Symptoms can arise within 24-48 hours after combining medications, so the first 48 hours after adding buspirone are highest risk. 1

Evidence for Combined Use

• A small study (n=14) demonstrated that patients taking sertraline did not experience significant side effects when buspirone was added, with 103 total episodes monitored. 4

• However, a case report documented possible serotonin syndrome in a patient taking fluoxetine when buspirone was added, presenting with confusion, diaphoresis, incoordination, diarrhea, and myoclonus. 5

• Both medications are recognized as effective for generalized anxiety disorder, and combining them may be appropriate when monotherapy is inadequate. 6, 7

Dosing Strategy

Starting Buspirone

• The proposed dose of 7.5 mg twice daily (morning and afternoon) is reasonable as a starting approach, though guidelines emphasize starting low when combining serotonergic agents. 1

• When combining serotonergic drugs, caution entails "starting the second non-MAOI serotonergic drug at a low dose, increasing the dose slowly, and monitoring for symptoms, especially in the first 24 to 48 hours after dosage changes." 1

• Standard buspirone dosing begins at 5 mg twice daily, with gradual titration to therapeutic doses of 20-30 mg daily in divided doses. 1, 7

Maintaining Sertraline

• Continue sertraline 150 mg nightly unchanged while initiating buspirone to avoid introducing multiple variables simultaneously. 1

• Sertraline is associated with discontinuation syndrome, so any future taper must be gradual. 1

Discontinuing Sertraline After Buspirone Efficacy

Timeline Considerations

• Buspirone may take 2-4 weeks to become effective, so premature discontinuation of sertraline could leave the patient without adequate anxiety control. 1

• Allow adequate time (minimum 4-6 weeks) to assess buspirone efficacy before considering sertraline discontinuation. 1, 6

Sertraline Discontinuation Protocol

• Sertraline must be tapered gradually due to risk of discontinuation syndrome characterized by dizziness, fatigue, nausea, insomnia, anxiety, irritability, and sensory disturbances. 1

• Discontinue over 10-14 days minimum to limit withdrawal symptoms, though longer tapers may be needed given the 150 mg dose. 1

• Monitor closely during taper for return of anxiety symptoms or emergence of discontinuation syndrome. 1

Critical Pitfalls to Avoid

• Do not abruptly discontinue sertraline once buspirone appears effective—this risks both discontinuation syndrome and anxiety relapse. 1

• Do not increase buspirone dose rapidly while on sertraline—this increases serotonin syndrome risk. 1

• Immediately discontinue both medications if serotonin syndrome symptoms develop (fever, seizures, severe rigidity, altered consciousness) and seek emergency care. 1, 2

• Educate the patient about serotonin syndrome symptoms before starting combination therapy so they can recognize early warning signs. 1, 3

Alternative Consideration

• If avoiding serotonin syndrome risk is a priority, consider tapering sertraline first, then initiating buspirone monotherapy after a washout period, though this leaves a treatment gap. 7

• For older adults specifically, sertraline or escitalopram are preferred first-line agents, with buspirone as an alternative if avoiding sexual side effects is priority. 7