What is the best medication to add for a patient with generalized anxiety disorder and obsessive‑compulsive disorder who is currently taking clonazepam and fluvoxamine (Luvox) and has worsening anxiety?

Augmentation Strategy for Treatment-Resistant Anxiety in GAD with OCD

Add bupropion SR 150 mg daily (titrating to 300–400 mg) to the current regimen of clonazepam and fluvoxamine, as this provides the strongest evidence for augmentation in treatment-resistant anxiety with comorbid OCD. 1

Primary Recommendation: Bupropion SR Augmentation

• Bupropion SR augmentation achieves remission rates of approximately 50% compared to 30% with SSRI monotherapy alone, with significantly lower discontinuation rates due to adverse events (12.5%) compared to buspirone (20.6%, p<0.001). 1

• Start bupropion SR at 150 mg once daily and increase by 150 mg every 3–7 days as tolerated, targeting a total daily dose of 300–400 mg given in divided doses, with the second dose administered before 3 p.m. to reduce insomnia risk. 1

• Bupropion's norepinephrine-dopamine reuptake inhibition complements fluvoxamine's serotonergic activity, providing synergistic relief for anxiety symptoms that persist despite adequate SSRI therapy. 1

Critical Safety Contraindications for Bupropion

• Do not prescribe bupropion if the patient has a history of seizure disorders or eating disorders, as it significantly increases seizure risk in these populations. 1

• Avoid bupropion in patients who are currently highly agitated, as its activating properties may exacerbate agitation. 1

Alternative Augmentation: Buspirone (If Bupropion Is Contraindicated)

• Initiate buspirone at 5 mg twice daily and titrate to 20 mg three times daily over 2–4 weeks, with therapeutic onset expected in 2–4 weeks for mild-to-moderate anxiety. 1

• Buspirone augmentation demonstrates similar efficacy to bupropion in the STAR*D trial but carries a 67% higher discontinuation rate due to adverse effects. 1

Optimize Current Fluvoxamine Dosing First

• Before adding any augmentation agent, confirm the patient is receiving an adequate fluvoxamine dose (200–300 mg daily for OCD) for at least 8–12 weeks, as OCD requires substantially higher SSRI doses than GAD alone. 2, 3

• Fluvoxamine demonstrates response rates of 38–52% in OCD at doses of 100–300 mg daily, compared to 0–18% with placebo, and is recommended as first-line treatment for both OCD and anxiety disorders. 2, 3

• The controlled-release formulation of fluvoxamine offers less daily fluctuation in drug levels and more rapid titration, potentially improving efficacy in treatment-resistant cases. 4

Addressing the Clonazepam Component

• Benzodiazepines like clonazepam should be used with caution and time-limited duration due to abuse potential, dependence risk, and cognitive impairment. 1

• Consider a gradual taper of clonazepam once augmentation therapy achieves therapeutic effect, as long-term benzodiazepine use is associated with tolerance and withdrawal complications. 1

Psychotherapy Augmentation (Highest Priority)

• Adding cognitive-behavioral therapy (CBT) to the current medication regimen provides superior efficacy for both GAD and OCD compared to medication alone, and should be initiated immediately. 1, 5

• Individual CBT following evidence-based protocols (Clark-and-Wells or Heimberg models for anxiety; exposure and response prevention for OCD) delivered by a trained therapist is the recommended first-line psychotherapy addition. 1

Monitoring Protocol After Augmentation

• Assess treatment response every 2–4 weeks using standardized anxiety and OCD rating scales (GAD-7, Y-BOCS) to objectively track symptom improvement. 1

• Monitor closely for suicidal ideation during the first 1–2 months after adding bupropion, as this period carries the highest risk for treatment-emergent suicidality. 1

• Watch for behavioral activation (restlessness, insomnia, agitation) during the first 2–4 weeks of bupropion therapy, particularly in anxiety-prone patients. 1

Expected Timeline for Response

• Allow 6–8 weeks at the optimized augmentation dose before declaring treatment failure, as full therapeutic effects may take this long to manifest. 1, 5

• Approximately 38% of patients do not achieve response within 6–12 weeks of initial treatment, supporting the need for augmentation strategies in this population. 5

Alternative Strategy If Augmentation Fails

• Switch from fluvoxamine to venlafaxine extended-release 150–225 mg daily, as SNRIs demonstrate statistically significantly better response and remission rates than SSRIs in treatment-resistant anxiety with prominent symptoms. 1

• Ensure venlafaxine is maintained at therapeutic doses (150–225 mg daily) for at least 6–8 weeks before declaring treatment failure. 1

Common Pitfalls to Avoid

• Do not add another SSRI to fluvoxamine, as combining two serotonergic agents markedly raises the risk of serotonin syndrome without demonstrated efficacy benefit. 1

• Do not make medication changes before allowing adequate trial duration (8–12 weeks at therapeutic fluvoxamine doses of 200–300 mg for OCD). 1, 2

• Do not exceed fluvoxamine 300 mg daily without careful monitoring, as higher doses increase adverse event burden without additional benefit in most patients. 2, 3

Treatment Duration After Response

• Continue combination therapy for a minimum of 4–9 months after achieving satisfactory response for first-episode anxiety, and consider longer duration (≥1 year) for recurrent or chronic symptoms. 1, 5

• For patients with multiple anxiety episodes, maintenance therapy for years to lifelong may be beneficial to prevent relapse. 1