What adjunct medication can be added for a 50‑year‑old woman with anxiety that is not adequately controlled on sertraline?

Adjunct Medication for Anxiety Not Controlled with Sertraline

Add cognitive-behavioral therapy (CBT) as the first-line adjunct to sertraline before considering any additional medication, as combination therapy demonstrates superior efficacy compared to medication alone for anxiety disorders. 1

Initial Optimization Before Adding Adjunct Medication

Before adding any adjunct medication, ensure the following steps have been completed:

• Verify adequate sertraline dosing and duration: The patient must be on sertraline 100–200 mg daily for a minimum of 8–12 weeks before declaring treatment failure. 1 Many patients are prescribed subtherapeutic doses; simply optimizing to the therapeutic range often resolves persistent anxiety symptoms. 1

• Assess medication adherence and rule out comorbid conditions (substance use, thyroid dysfunction, bipolar disorder) that may interfere with treatment response. 1

• Monitor treatment response every 2–4 weeks using standardized anxiety rating scales to objectively track symptom change. 1

Primary Recommendation: Add Cognitive-Behavioral Therapy

Individual CBT following the Clark-and-Wells or Heimberg models, delivered by a trained therapist over approximately 14 sessions (60–90 minutes each) across 4 months, should be initiated immediately while maintaining optimized sertraline. 2, 1

• The combination of SSRI with CBT has demonstrated greater efficacy than monotherapy in controlled studies. 1

• CBT can be started without waiting for medication optimization, providing synergistic benefit. 1

• If face-to-face CBT is not acceptable to the patient, structured self-help CBT with therapist support is an evidence-based alternative. 2, 1

Pharmacological Augmentation Options (If CBT Is Insufficient or Unavailable)

Option 1: Buspirone Augmentation (Preferred Pharmacological Adjunct)

Initiate buspirone at 5 mg twice daily and titrate to 20 mg three times daily (total 60 mg/day) over 2–4 weeks. 1

• Buspirone augmentation should only be considered after confirming adequate sertraline trial duration (8–12 weeks) and dose optimization (100–200 mg daily). 1

• Anticipate a therapeutic onset of 2–4 weeks for buspirone's anxiolytic effect. 1

• Important caveat: Discontinuation rates due to adverse events are significantly higher with buspirone (20.6%) compared to other augmentation strategies. 1

Option 2: Bupropion SR Augmentation (Alternative)

Start bupropion SR at 150 mg once daily and increase by 150 mg every 3–7 days, targeting a total daily dose of 300–400 mg. 1

• Bupropion SR augmentation has significantly lower discontinuation rates due to adverse events (12.5%) compared to buspirone (20.6%, p<0.001). 1

• The STAR*D trial demonstrated similar efficacy between bupropion and buspirone augmentation. 1

• Contraindication: Avoid bupropion in patients who are highly agitated or have a history of seizure disorders or eating disorders. 1

• Administer the second dose before 3 p.m. to reduce insomnia risk. 1

Switching Strategy (If Augmentation Fails)

If the patient does not respond after 8 weeks of optimized combination therapy:

Switch to an SNRI—either venlafaxine (150–225 mg daily) or duloxetine (40–120 mg daily). 1

• SNRIs have demonstrated statistically significant superior response and remission rates compared to SSRIs in treatment-resistant anxiety. 1

• The American College of Physicians found no significant difference between switching versus augmenting strategies overall, with approximately 25% of patients achieving remission after a switch. 1

• Venlafaxine is listed as a second-line pharmacotherapy option in international guidelines for anxiety disorders. 2

Critical Safety Monitoring

• Assess for suicidal ideation at every patient contact during the first 1–2 months after any medication change, as suicide risk peaks during this period. 1

• Monitor closely for serotonin syndrome when adding any adjunct medication: mental status changes (confusion, agitation), neuromuscular hyperactivity (tremor, hyperreflexia), and autonomic hyperactivity (tachycardia, diaphoresis). 1

• Do not combine sertraline with other serotonergic agents (MAO inhibitors, other SSRIs, triptans) due to serotonin syndrome risk. 1

Common Pitfalls to Avoid

• Do not add adjunct medication before completing an adequate sertraline trial (minimum 8–12 weeks at 100–200 mg daily), as premature changes delay recovery and miss therapeutic response opportunities. 1

• Do not switch medications before allowing adequate trial duration (8 weeks at therapeutic dose), as this represents premature transition. 1

• Do not continue ineffective treatment beyond 8 weeks; guideline-recommended reassessment occurs at 6–8 weeks. 1

Duration of Continuation Therapy

• After achieving satisfactory response, continue treatment for 6+ months after remission for first episode of anxiety disorder. 1

• For recurrent anxiety (≥2 episodes), consider maintenance therapy for years to prevent relapse. 1