Patient on sertraline and bupropion 300 mg (Wellbutrin) is crying constantly while tapering bedtime lorazepam; what medication adjustments and adjunctive therapies are recommended?

Medication Adjustment for Patient on Sertraline, Bupropion 300mg, and Tapering Lorazepam with Persistent Crying

Increase bupropion to 400mg daily (200mg twice daily) or augment with a low-dose atypical antipsychotic such as aripiprazole 2-5mg, while continuing the lorazepam taper at a slower rate to prevent benzodiazepine withdrawal from masquerading as treatment-resistant depression. 1

Critical Assessment: Benzodiazepine Withdrawal vs. Treatment-Resistant Depression

The constant crying during lorazepam taper strongly suggests benzodiazepine withdrawal syndrome rather than inadequate antidepressant therapy. This is a common and dangerous pitfall in clinical practice.

Benzodiazepine Withdrawal Considerations

• Abrupt discontinuation or rapid dosage reduction of lorazepam after continued use may precipitate acute withdrawal reactions, including severe emotional lability, crying spells, anxiety, and depression-like symptoms. 2
• Patients at increased risk of withdrawal adverse reactions include those who take higher dosages and those who have had longer durations of use. 2
• To reduce the risk of withdrawal reactions, use a gradual taper with a patient-specific plan; if moderate-to-severe withdrawal symptoms develop, maintain the current dose for 1-2 weeks before resuming the taper. 1

Immediate Management Strategy

Slow or pause the lorazepam taper immediately. The crying may resolve within 1-2 weeks once the taper is slowed, without any antidepressant adjustment. 1, 2

Antidepressant Optimization (If Symptoms Persist After Stabilizing Lorazepam Taper)

Bupropion Dose Escalation

If depressive symptoms persist after stabilizing the benzodiazepine taper:

• The maximum dose for bupropion SR is 400 mg per day (200mg twice daily), which can be considered if the patient tolerates 300mg without seizure risk factors. 1
• The second dose must be administered before 3 PM to minimize insomnia risk. 1
• Allow 6-8 weeks at the increased dose before determining treatment response. 1

Contraindications to Dose Increase

Do not increase bupropion above 300mg daily if the patient has:

• Any history of seizures or conditions predisposing to seizures 1
• Uncontrolled hypertension 1
• Eating disorders 1
• Recent alcohol or benzodiazepine discontinuation (which applies here) 1

Augmentation Strategy (Preferred Over Dose Increase During Benzodiazepine Taper)

Adding aripiprazole 2-5mg daily to the existing bupropion 300mg regimen is particularly effective for patients whose energy, motivation, and emotional regulation remain insufficient. 1

• Aripiprazole augmentation addresses persistent apathy and emotional dysregulation without increasing seizure risk during the vulnerable benzodiazepine withdrawal period. 1
• Monitor for increased agitation, as bupropion's activating properties combined with aripiprazole may initially worsen agitation in some patients. 1
• Assess for suicidal ideation, agitation, or unusual behavioral changes during the first 1-2 weeks after adding aripiprazole, as the risk of suicide attempts is highest in the first 1-2 months of treatment modification. 1

Alternative: Augment with SSRI Dose Increase

If the patient has been on sertraline at a subtherapeutic dose, increase sertraline to 200mg daily before considering bupropion adjustment. 1

• Augmenting SSRIs with bupropion decreases depression severity more effectively than other augmentation strategies, with significantly lower discontinuation rates (12.5%) compared to buspirone (20.6%, P < 0.001). 1
• The combination of sertraline and bupropion addresses depression through complementary mechanisms: sertraline affects serotonin while bupropion works via noradrenergic/dopaminergic pathways. 1, 3
• This combination has been effective in treatment-refractory patients with chronic depression and multiple failed medication trials. 3

Critical Safety Monitoring

Serotonin Syndrome Risk

Although rare, the combination of bupropion and sertraline can precipitate serotonin syndrome, particularly when doses are increased or during metabolic stress such as benzodiazepine withdrawal. 4

Monitor for:

• Myoclonic jerks, clumsiness, gait difficulties 4
• Confusion, forgetfulness, alternating agitation and lethargy 4
• Autonomic instability (fever, sweating, tachycardia) 4

The earliest manifestations of serotonin syndrome are often misinterpreted as aggravation of depression—do not add additional serotonergic agents if these symptoms appear. 4

Benzodiazepine-Opioid Interaction

If the patient is on any opioid medications (including buprenorphine/naloxone for substance use), the combination with lorazepam increases the risk of respiratory depression and death. 2

• Prescribe the lowest effective dosages and minimum durations of concomitant use. 2
• Follow patients closely for signs and symptoms of respiratory depression and sedation. 2

Recommended Treatment Algorithm

1. Immediately slow or pause the lorazepam taper and maintain the current dose for 1-2 weeks 1, 2
2. Reassess crying symptoms after stabilizing lorazepam—if symptoms resolve, continue slow taper 1
3. If crying persists after 2 weeks of stable lorazepam:
   • Option A: Add aripiprazole 2-5mg daily (preferred during benzodiazepine taper) 1
   • Option B: Increase sertraline to 200mg daily if currently subtherapeutic 1
   • Option C: Increase bupropion to 400mg daily ONLY if no seizure risk factors and lorazepam taper is complete 1
4. Monitor for serotonin syndrome symptoms weekly for the first month 4
5. Assess treatment response at 6-8 weeks after any medication adjustment 1

Common Pitfalls to Avoid

• Do not misinterpret benzodiazepine withdrawal symptoms as worsening depression requiring antidepressant escalation 2, 4
• Do not increase bupropion above 300mg during active benzodiazepine withdrawal due to compounded seizure risk 1, 2
• Do not add multiple serotonergic agents simultaneously without monitoring for serotonin syndrome 4
• Do not continue rapid lorazepam taper if withdrawal symptoms emerge—pause and stabilize first 1, 2