A 20‑year‑old male with panic disorder on cariprazine (Vraylar) 3 mg daily, diazepam (Valium) 5 mg as needed, lamotrigine (Lamictal) 25 mg twice daily, and atenolol 25 mg twice daily still experiences panic attacks; what medication change should be made next to control his panic disorder?

Optimize Panic Disorder Treatment by Transitioning to Evidence-Based First-Line Therapy

The most critical medication change is to discontinue cariprazine (Vraylar) and initiate an SSRI or SNRI as first-line pharmacotherapy for panic disorder, while simultaneously beginning a gradual taper of diazepam (Valium) with the goal of complete discontinuation. 1, 2

Rationale for Discontinuing Cariprazine

• Cariprazine has no established role in panic disorder treatment and may actually worsen negative symptoms or contribute to akathisia that mimics or exacerbates anxiety 1
• Antipsychotics are only considered in treatment-resistant panic disorder after multiple failed trials of standard treatments, and even then, evidence is limited to specific agents (aripiprazole, olanzapam, risperidone) used as augmentation—not monotherapy 3
• The current regimen lacks any first-line evidence-based medication for panic disorder 1, 2

Recommended Medication Algorithm

Step 1: Initiate First-Line Antidepressant Therapy

Start an SSRI or SNRI immediately:

• SSRIs (escitalopram, paroxetine, or sertraline) are standard first-line treatments with the strongest evidence base 1, 2
• SNRIs (duloxetine or venlafaxine extended-release) are equally effective alternatives, particularly if comorbid generalized anxiety is present 1
• These medications typically require 2-4 weeks for initial response and 8-12 weeks for full therapeutic effect 1, 2

Step 2: Address the Benzodiazepine Problem

Diazepam 5 mg as needed is problematic for multiple reasons:

• Benzodiazepines provide only short-term symptomatic relief and do not address the underlying panic disorder 1, 4, 2
• Approximately 50% of patients prescribed benzodiazepines continuously for 12 months develop dependence 5
• Begin a gradual taper immediately: Reduce by 10-25% of the current dose every 1-2 weeks, with the goal of complete discontinuation over 6-12 months minimum 5
• The taper rate must be determined by the patient's tolerance, with pauses acceptable when withdrawal symptoms emerge 5

Critical safety consideration: Never stop benzodiazepines abruptly—this can cause seizures and death 5, 6

Step 3: Optimize Adjunctive Medications

Lamotrigine 25 mg BID:

• Current dose (50 mg/day total) is subtherapeutic for any psychiatric indication 1
• Lamotrigine has limited evidence in panic disorder, primarily studied as augmentation in treatment-resistant cases 3
• Consider discontinuing unless there is a specific indication (e.g., bipolar disorder, which is not mentioned in this case)

Atenolol 25 mg BID:

• Beta-blockers address only peripheral somatic symptoms (palpitations, tremor) but do not treat core panic disorder 1
• May be continued short-term for symptomatic relief during SSRI/SNRI titration, then reassess need after 8-12 weeks 1

Integrating Psychological Treatment

Cognitive Behavioral Therapy (CBT) is essential and should be initiated immediately:

• CBT combined with medication is the most successful treatment strategy for panic disorder 2
• Psychological treatment based on CBT principles is specifically recommended for people concerned about prior panic attacks 1, 4
• CBT during benzodiazepine tapering significantly increases success rates 5

Expected Timeline and Monitoring

Weeks 1-4:

• Start SSRI/SNRI at standard starting dose
• Begin benzodiazepine taper (reduce diazepam by 25% to approximately 3.75 mg)
• Initiate CBT referral
• Monitor for SSRI/SNRI side effects (nausea, activation, insomnia) and benzodiazepine withdrawal symptoms 1, 5

Weeks 4-12:

• Titrate SSRI/SNRI to therapeutic dose based on response
• Continue gradual benzodiazepine taper
• Expect initial improvement in panic frequency and severity by week 4-8 2

Months 3-6:

• Complete benzodiazepine taper
• Reassess need for atenolol—discontinue if panic symptoms controlled
• Continue SSRI/SNRI for minimum 9-12 months after recovery 1

Critical Pitfalls to Avoid

• Do not continue cariprazine without a clear indication beyond panic disorder 1, 3
• Do not rely on benzodiazepines as primary treatment—they mask symptoms without treating the underlying disorder 4, 2
• Do not taper benzodiazepines too rapidly—this increases risk of seizures and treatment failure 5
• Do not prescribe benzodiazepines beyond 2-4 weeks for new anxiety symptoms 6
• Do not expect immediate results from antidepressants—counsel patient about 2-4 week onset of action 1, 2

Monitoring for Serious Adverse Effects

SSRI/SNRI monitoring:

• Suicidal thinking and behavior (through age 24 years) 1
• Behavioral activation, hypomania, or mania 1
• Serotonin syndrome (especially if combining multiple serotonergic agents) 1
• Blood pressure monitoring with SNRIs (risk of sustained hypertension) 1

Benzodiazepine withdrawal monitoring:

• Anxiety, tremor, insomnia, sweating, tachycardia, seizures 5
• Follow up at least monthly during taper, more frequently during difficult phases 5