How do I manage a 47-year-old female patient with a history of depression, anxiety, post-traumatic stress disorder (PTSD), and smoking, who is currently on Wellbutrin (bupropion), Xanax (alprazolam), and Buspar (buspirone), and reports ongoing anxiety, feelings of being overwhelmed, and depressive symptoms?

Management of Treatment-Resistant Depression, Anxiety, and PTSD

Switch from Wellbutrin to an SSRI (sertraline or fluoxetine) as your primary antidepressant, taper and discontinue the Xanax while maintaining Buspar, and add evidence-based smoking cessation treatment with behavioral therapy. This patient requires medication optimization given persistent symptoms despite triple therapy.

Immediate Medication Changes

Antidepressant Optimization

• Discontinue bupropion (Wellbutrin) and initiate an SSRI 1, 2
  • Sertraline 50-200 mg daily or fluoxetine 20-40 mg daily are first-line for comorbid depression, anxiety, and PTSD 2
  • SSRIs demonstrate superior efficacy for PTSD avoidance/numbing symptoms compared to other antidepressants, with sertraline FDA-approved for PTSD 2
  • Bupropion is ineffective for PTSD and may worsen anxiety symptoms due to its activating properties 1, 2, 3
  • The combination of bupropion with SSRIs (which she may need) carries risk of serotonin syndrome 4

Benzodiazepine Management

• Taper alprazolam (Xanax) gradually over 2-4 weeks 1, 3
  • Benzodiazepines are ineffective for core PTSD symptoms and may worsen depression long-term 2, 3
  • Abrupt discontinuation increases seizure risk, particularly concerning given her smoking and potential future bupropion use for cessation 5
  • Continue buspirone 15-60 mg daily as it provides anxiolytic effects without benzodiazepine risks 2, 3

Smoking Cessation Strategy

Pharmacotherapy for Smoking

• Delay smoking cessation pharmacotherapy until psychiatric symptoms stabilize on new regimen 1
  • Once stable on SSRI (4-8 weeks), consider combination nicotine replacement therapy (NRT) - patch plus short-acting form 1
  • Avoid reintroducing bupropion for smoking cessation given its inefficacy for her PTSD and anxiety 1, 5, 2
  • Varenicline is contraindicated due to FDA warnings about neuropsychiatric events including depression, anxiety, and suicidal ideation in patients with psychiatric conditions 1

Behavioral Intervention

• Initiate smoking cessation counseling immediately (4+ sessions over 12 weeks, 10-30 minutes each) 1
  • Behavioral therapy combined with medication yields highest cessation rates (OR 3.25) 1
  • Address smoking as coping mechanism for PTSD/anxiety symptoms 6
  • Refer to state quitline for additional telephone counseling support 1

Monitoring and Follow-up

Safety Monitoring

• Weekly visits for first month during medication transition 5
  • Monitor for suicidal ideation, worsening depression, anxiety, agitation, or behavioral changes during SSRI initiation 5
  • Assess benzodiazepine withdrawal symptoms (anxiety, insomnia, tremor, seizures) 5
  • Screen for serotonin syndrome if any serotonergic agents overlap 4

Efficacy Assessment

• Expect 5-8 weeks at therapeutic SSRI dose for PTSD/depression response 2, 3
  • Target SSRI dose: sertraline 150-200 mg or fluoxetine 40 mg for PTSD 2
  • Plan for 9-12 months of antidepressant continuation after symptom remission 1
  • If inadequate response at 8 weeks, consider augmentation with mirtazapine 7.5-30 mg at bedtime (addresses insomnia, anxiety, and has favorable profile) 1, 2

Common Pitfalls to Avoid

• Do not combine bupropion with SSRIs - increases serotonin syndrome risk and bupropion is ineffective for her PTSD 2, 4
• Do not abruptly stop alprazolam - taper over 2-4 weeks to prevent withdrawal seizures, especially critical given smoking status 5
• Do not start varenicline - FDA black box warning for neuropsychiatric events in patients with psychiatric disorders 1
• Do not use bupropion for smoking cessation - contraindicated with her anxiety/PTSD and increases seizure risk with benzodiazepine withdrawal 1, 5, 2