Can a patient with anxiety and depression be treated with Buspar (buspirone) and hydroxyzine if they are unwilling to take a selective serotonin reuptake inhibitor (SSRI)?

Can Buspar and Hydroxyzine Be Used Together for Anxiety and Depression When SSRIs Are Refused?

Yes, buspirone and hydroxyzine can be used together for a patient with anxiety and depression who refuses SSRIs, though this combination addresses anxiety symptoms more effectively than depression and represents a suboptimal approach compared to guideline-recommended first-line treatments.

Evidence Supporting This Combination

Buspirone for Anxiety and Depression

• Buspirone is FDA-approved for generalized anxiety disorder and has demonstrated efficacy in patients with coexisting depressive symptoms 1. The FDA label specifically states that "many of the patients enrolled in these studies also had coexisting depressive symptoms and buspirone hydrochloride tablets relieved anxiety in the presence of these coexisting depressive symptoms" 1.

• Buspirone monotherapy has shown antidepressant effects in controlled trials, with 70% of buspirone-treated patients rated as moderately or markedly improved compared to 35% of placebo patients (p<0.01) after 8 weeks at doses up to 90 mg/day 2.

• The STAR*D trial demonstrated that buspirone augmentation of citalopram achieved similar efficacy to bupropion augmentation or cognitive therapy for treatment-resistant depression, though discontinuation due to adverse events was significantly higher with buspirone (20.6%) compared to bupropion (12.5%, p<0.001) 3, 4.

Hydroxyzine as Adjunctive Therapy

• Hydroxyzine can provide rapid anxiolytic effects while buspirone's therapeutic benefits develop, as buspirone typically requires 1-2 weeks for onset of anxiolytic effect 5.

• Both medications can prolong QTc interval, requiring baseline ECG monitoring in patients with cardiac risk factors, electrolyte abnormalities, or concurrent use of other QTc-prolonging medications 4.

Critical Limitations of This Approach

Depression Management Concerns

• This combination does not adequately address the depression component of the patient's presentation. The American College of Physicians recommends SSRIs or SNRIs as first-line pharmacotherapy for depression, with treatment duration of 4-9 months minimum after satisfactory response 6.

• Higher doses of SSRIs or bupropion are indicated within FDA guidelines only if the patient shows significant psychiatric comorbidity in the form of anxiety and depression 3.

Comparative Efficacy Issues

• Buspirone lacks the robust evidence base for depression that SSRIs possess. While it showed benefit in one controlled trial 2, SSRIs remain the evidence-based standard with number needed to treat of 7-8 for severe depression 6.

• Remission rates with buspirone monotherapy for anxiety are approximately 40%, signifying the need for improved treatment interventions 7.

Practical Implementation Algorithm

Step 1: Motivational Interviewing and Education (Before Prescribing)

• Explore the specific reasons for SSRI refusal (concerns about side effects, sexual dysfunction, stigma, previous negative experiences, or misinformation) and address these concerns with evidence-based information 4, 6.

• Emphasize that SSRIs treat both anxiety and depression simultaneously, while buspirone primarily targets anxiety 6.

• Discuss that cognitive behavioral therapy combined with medication demonstrates superior efficacy compared to medication alone 3, 4.

Step 2: If Patient Remains Unwilling to Try SSRIs

• Start buspirone 5 mg twice daily, titrating to 20-30 mg/day in divided doses over 2-4 weeks 1, 7.

• Add hydroxyzine 25-50 mg as needed for acute anxiety symptoms, particularly during the first 2 weeks while buspirone reaches therapeutic effect 5.

• Obtain baseline ECG if cardiac risk factors present before combining these medications 4.

Step 3: Monitoring Protocol

• Assess treatment response every 2-4 weeks using standardized anxiety and depression rating scales (GAD-7, PHQ-9) 4.

• Monitor specifically for suicidal ideation, as depression remains inadequately treated with this regimen 6.

• Warn patient that buspirone requires 1-2 weeks for onset of effect, unlike benzodiazepines or hydroxyzine which provide immediate relief 5.

Step 4: Reassessment at 6-8 Weeks

• If depression symptoms persist or worsen after 6-8 weeks, strongly reconsider SSRI therapy or refer to psychiatry 3, 6. The American College of Physicians recommends modifying treatment if inadequate response occurs within 6-8 weeks 4.

• If anxiety improves but depression remains, consider switching to venlafaxine (SNRI) which demonstrated statistically significantly better response rates than SSRIs for depression with prominent anxiety symptoms 4, 6.

• If both anxiety and depression improve, continue buspirone for at least 3-4 months, though long-term efficacy beyond this period has not been demonstrated in controlled trials 1.

Alternative Non-SSRI Options to Discuss

Bupropion Monotherapy

• Bupropion SR 150-400 mg daily treats depression without sexual dysfunction and has lower discontinuation rates than buspirone (12.5% vs 20.6%) 3, 4. However, bupropion may worsen anxiety in some patients and is contraindicated in seizure disorders.

SNRI Therapy (Venlafaxine or Duloxetine)

• SNRIs treat both depression and anxiety through dual serotonin-norepinephrine action 4, 6. Venlafaxine 37.5-225 mg daily may have statistically better response rates than SSRIs specifically for depression with prominent anxiety symptoms 4.

• SNRIs have higher rates of adverse effects (nausea, vomiting) compared to SSRIs, with 40-67% higher discontinuation rates 6.

Common Pitfalls to Avoid

• Do not use this combination as long-term monotherapy for moderate-to-severe depression. The evidence base for buspirone in depression is limited to one controlled trial 2, while SSRIs have extensive evidence demonstrating efficacy 6.

• Do not exceed buspirone 60 mg/day without psychiatric consultation, as the FDA-approved dose range is 15-30 mg/day for anxiety 1.

• Do not combine buspirone with MAOIs due to serotonin syndrome risk 4.

• Do not discontinue buspirone abruptly if switching to another agent; taper gradually to minimize discontinuation symptoms 4.

• Do not rely solely on hydroxyzine for chronic anxiety management due to anticholinergic effects, sedation, and lack of antidepressant properties 3.

When to Refer to Psychiatry

• If depression worsens or suicidal ideation emerges during treatment with buspirone/hydroxyzine 4, 6.

• If patient requires doses of buspirone exceeding 60 mg/day 1.

• If patient fails two adequate trials of non-SSRI medications and continues to refuse SSRIs 3.

• If comorbid substance use disorder is present, as this requires specialized treatment 6.