What to do if a patient taking Wellbutrin (bupropion) 300 mg for Post-Traumatic Stress Disorder (PTSD) is no longer effective?

Management of Ineffective Bupropion for PTSD

When bupropion 300 mg is no longer effective for PTSD, switching to an SSRI (such as sertraline or paroxetine) is recommended as these medications have FDA approval and stronger evidence for PTSD treatment.

Assessment of Treatment Failure

When a patient reports that bupropion is no longer effective for PTSD symptoms, evaluate:

• Duration of treatment and adherence
• Specific PTSD symptoms that have worsened (re-experiencing, avoidance, hyperarousal)
• Presence of comorbid conditions (depression, anxiety, substance use)
• Side effects experienced with bupropion
• Previous medication trials and responses

Evidence-Based Treatment Options

First-Line Recommendation: Switch to an SSRI

• SSRIs have the strongest evidence for PTSD treatment, with sertraline and paroxetine having FDA approval 1
• Studies show 53-85% of patients respond to SSRI treatment for PTSD, significantly higher than placebo 1
• Begin with:
  • Sertraline: Start 25-50mg daily, titrate to 100-200mg daily
  • Paroxetine: Start 10-20mg daily, titrate to 20-60mg daily

Alternative Pharmacological Options

If SSRIs are contraindicated or previously ineffective:

1. SNRIs (e.g., venlafaxine, duloxetine)

   • Start duloxetine at 30mg daily, increase to 60mg after 1 week 2

2. Mirtazapine

   • Start at 7.5mg at bedtime, maximum 30mg at bedtime 2
   • Particularly useful if insomnia is a prominent symptom

3. Augmentation strategies if partial response:

   • Consider adding low-dose atypical antipsychotics
   • Prazosin specifically for nightmares (1-15mg at bedtime)

Discontinuation of Bupropion

• Taper bupropion gradually to minimize withdrawal symptoms
• Reduce to 150mg once daily for at least one week before complete discontinuation 2
• Schedule follow-up 1-2 weeks after complete discontinuation to monitor for:
  • Return of depressive symptoms
  • Withdrawal symptoms
  • Need for alternative treatment 2

Psychotherapy Integration

• Combine medication with evidence-based psychotherapy
• Cognitive-Behavioral Therapy (CBT) with exposure components shows 60-95% of patients losing PTSD diagnosis after treatment 1
• Exposure therapy is particularly effective for PTSD and should be recommended alongside medication changes 1
• Stress Inoculation Training (SIT) has shown 42-50% of participants no longer meeting PTSD criteria 1

Monitoring and Follow-Up

• Assess response to new medication after 4-6 weeks at therapeutic dose
• Monitor for side effects, particularly during transition between medications
• If no response after 8 weeks on adequate dose, consider another switch or augmentation
• Evaluate need for longer-term maintenance treatment

Important Considerations

• Bupropion has limited evidence for PTSD compared to SSRIs, which are considered first-line treatments
• Studies of bupropion for PTSD show mixed results, with some showing improvement in depressive symptoms but limited effect on core PTSD symptoms 3, 4
• Relapse rates are higher with medication discontinuation (26-52%) compared to completion of CBT 1
• Patient preference should be considered, but evidence strongly favors SSRIs and trauma-focused psychotherapy for PTSD

Remember that PTSD is a chronic condition that may require long-term treatment and periodic reassessment of medication effectiveness.