What is the best course of treatment for a patient with MDD, panic attacks, and GAD, currently taking hydroxyzine 25mg (as needed), trazodone 150mg at bedtime, Ativan (lorazepam) 0.5mg daily (as needed), and olanzapine 5mg (as needed)?

Treatment Optimization for MDD, Panic Disorder, and GAD

Critical Medication Regimen Concerns

This patient's current regimen requires immediate restructuring: the PRN use of benzodiazepines (Ativan) and atypical antipsychotics (olanzapine) is inappropriate for chronic anxiety and mood disorders, and the absence of a first-line antidepressant represents a fundamental treatment gap. 1

Primary Issues with Current Regimen

Benzodiazepine Dependence Risk:

• Lorazepam 0.5mg daily PRN for panic attacks creates significant problems: regular benzodiazepine use leads to tolerance, addiction, depression, and cognitive impairment 2
• The FDA labeling emphasizes gradual taper requirements to avoid withdrawal reactions, indicating these medications should not be used long-term 1
• Benzodiazepines are particularly problematic as they can worsen depression and do not address the underlying pathophysiology of MDD or GAD 2

Inappropriate PRN Antipsychotic Use:

• Olanzapine 5mg PRN is not evidence-based for anxiety or mood disorders in non-psychotic patients 3
• Olanzapine carries substantial risks including significant weight gain (adolescent data shows 42.4% gained 11-22 lbs within 6 weeks, 26.7% gained this amount by 6 months), metabolic syndrome, orthostatic hypotension, and tardive dyskinesia with chronic use 3
• The FDA warns that olanzapine should be "prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia" and reserved for chronic illnesses that respond to antipsychotics 3

Missing First-Line Treatment:

• Trazodone 150mg at bedtime is being used off-label for sleep, not as primary antidepressant therapy 4, 5
• While trazodone has antidepressant properties, it is typically dosed 200-400mg/day for depression treatment 2, 5
• No SSRI or SNRI is present in this regimen, which are first-line treatments for MDD, panic disorder, and GAD 2

Recommended Treatment Algorithm

Step 1: Initiate First-Line Antidepressant Therapy

Start an SSRI immediately:

• Sertraline 25-50mg daily, titrating to 200mg daily as needed - this is the preferred choice as it is well-tolerated, has less effect on metabolism of other medications compared to other SSRIs, and is effective for MDD, panic disorder, and GAD 2
• Alternative options include paroxetine 10mg daily (maximum 40mg) or citalopram 10mg daily (maximum 40mg), though these have more drug interactions 2
• Allow 4-8 weeks for full therapeutic trial before adjusting 2

Step 2: Taper and Discontinue Lorazepam

Begin gradual benzodiazepine withdrawal with hydroxyzine support:

• Use hydroxyzine 50mg three times daily during lorazepam taper to reduce withdrawal symptoms and anxiety 6
• Progressive withdrawal is preferable to abrupt discontinuation - reduce lorazepam by 25% every 1-2 weeks 1, 6
• Hydroxyzine 50mg showed significant improvement in anxiety levels and reduction of withdrawal symptomatology compared to placebo 6
• The patient is already on hydroxyzine 25mg PRN, so increase to scheduled 50mg TID during taper 6

Step 3: Optimize Trazodone Dosing

Continue trazodone for sleep but clarify its role:

• Maintain trazodone 150mg at bedtime for insomnia management 4, 5
• Trazodone is effective for sleep disorders in MDD patients and may help counteract SSRI-induced insomnia 4, 5
• Monitor for orthostatic hypotension, especially when combined with other medications 2

Step 4: Discontinue Olanzapine

Eliminate PRN olanzapine immediately:

• No indication for antipsychotic use in non-psychotic anxiety and mood disorders 3
• Risk of metabolic complications, weight gain, and tardive dyskinesia outweighs any potential benefit 3
• If acute agitation occurs, use scheduled hydroxyzine or increase SSRI dose rather than antipsychotic 6

Monitoring and Follow-Up Strategy

Week 1-2:

• Begin SSRI (sertraline 25-50mg daily) 2
• Increase hydroxyzine to 50mg TID scheduled 6
• Begin lorazepam taper (reduce to 0.25mg daily) 1
• Discontinue olanzapine 3

Week 3-4:

• Continue lorazepam taper (reduce to 0.25mg every other day) 1
• Assess SSRI tolerability and increase sertraline to 100mg if tolerated 2
• Monitor for SSRI side effects: sweating, tremors, nervousness, insomnia, dizziness, GI disturbances 2

Week 5-8:

• Complete lorazepam discontinuation 1, 6
• Titrate sertraline to therapeutic dose (typically 150-200mg for anxiety disorders) 2
• Begin tapering hydroxyzine to 25mg PRN once benzodiazepine withdrawal complete 6

Week 8-12:

• Assess full therapeutic response to SSRI 2
• If inadequate response, consider increasing to maximum dose or augmentation strategies 2
• Maintain trazodone 150mg at bedtime for sleep 4

Critical Pitfalls to Avoid

Do not continue benzodiazepines long-term:

• The evidence clearly shows regular benzodiazepine use worsens outcomes in depression and anxiety disorders 2
• Paradoxical agitation occurs in 10% of patients treated with benzodiazepines 2

Do not use antipsychotics without psychotic features:

• Olanzapine carries serious metabolic and neurological risks that are not justified in non-psychotic patients 3
• The FDA specifically warns about using the smallest dose for the shortest duration 3

Do not expect immediate SSRI response:

• Full therapeutic trial requires 4-8 weeks, with dose increases every 5-7 days as tolerated 2
• Early side effects (first 1-2 weeks) often resolve with continued treatment 2