What is the next course of treatment for a patient with anxiety and rumination on Zyprexa (olanzapine), Remeron (mirtazapine), and Propranolol (propranolol)?

Next Course of Treatment for Anxiety and Rumination

Add cognitive behavioral therapy (CBT) focused on anxiety management and consider augmenting with an SSRI (sertraline or escitalopram) while reassessing the current medication regimen, as the patient is on atypical antipsychotic and antidepressant combinations that lack strong evidence for primary anxiety treatment.

Current Medication Assessment

The patient's current regimen requires critical evaluation:

• Olanzapine (Zyprexa) has limited evidence as a primary anxiety treatment and is associated with significant metabolic side effects including weight gain 1, 2. While olanzapine showed some benefit as augmentation therapy in refractory GAD, it resulted in average weight gain of 11 pounds over 6 weeks and should be reserved for treatment-resistant cases 2.

• Mirtazapine (Remeron) is noted in guidelines as "potent and well tolerated" and "promotes sleep, appetite, and weight gain" 3. While it has neuromodulatory properties for chronic pain conditions 3, it is not a first-line agent for primary anxiety disorders.

• Propranolol is specifically deprecated by the Canadian Clinical Practice Guideline for social anxiety disorder based on negative evidence 3, though it may have utility for performance anxiety in specific contexts.

Recommended Treatment Algorithm

First Priority: Add Evidence-Based Psychotherapy

Implement CBT specifically designed for anxiety disorders 3:

• Structure treatment as 10-20 individual sessions over approximately 4 months, with each session lasting 60-90 minutes 3
• Include exposure and response prevention (ERP) components 3
• CBT combined with SSRI medication shows superior outcomes compared to either treatment alone, with moderate strength of evidence 3

Second Priority: Optimize Pharmacotherapy

Add an SSRI as first-line pharmacologic treatment 3:

• Sertraline or escitalopram are preferred first-line agents 3

  • Sertraline is "well tolerated" and "has less effect on metabolism of other medications" compared to other SSRIs 3
  • Escitalopram is listed as a first-line agent with favorable tolerability 3

• Dosing approach 3:

  • Start with subtherapeutic "test" dose due to potential initial anxiety/agitation side effect
  • Increase dose in smallest available increments at 1-2 week intervals for shorter half-life SSRIs
  • Continue titration until benefit-to-harm ratio is optimized
  • Full therapeutic trial requires at least 4-8 weeks at maximum tolerated dose 3

Third Priority: Address Rumination Component

For rumination specifically, consider adding a tricyclic antidepressant (TCA) with behavioral techniques 4:

• Combining a TCA with diaphragmatic breathing/relaxation techniques showed 90.9% of patients reporting improvement, with mean subjective improvement of 68.9% 4
• This addresses the gastric visceral hypersensitivity and anxiety components underlying rumination 4
• Low-dose TCAs (such as desipramine 10-25 mg or nortriptyline 10 mg) have proven efficacy for neuromodulation 3

Fourth Priority: Reassess Current Medications

Consider tapering olanzapine unless there are specific treatment-refractory features or comorbid psychotic symptoms 1:

• Olanzapine is not a first-line anxiety treatment and carries significant metabolic burden 1, 2
• If maintained, use lowest effective dose (5 mg showed efficacy in one study) 5, 2

Evaluate mirtazapine continuation:

• May be maintained if providing benefit for sleep and appetite, as it has neuromodulatory properties 3
• However, it is not a first-line anxiety agent

Discontinue or reassess propranolol unless used for specific performance anxiety situations 3

Common Pitfalls to Avoid

• Polypharmacy without evidence-based foundation: The current regimen combines medications without strong evidence for primary anxiety treatment 3, 1
• Neglecting psychotherapy: CBT should not be deferred, as combination treatment shows superior outcomes 3
• Inadequate SSRI trials: Ensure at least 8 weeks at maximum tolerated dose before declaring treatment failure 3
• Abrupt discontinuation: When adjusting medications, taper over 10-14 days to limit withdrawal symptoms, particularly with shorter-acting agents 3
• Ignoring the rumination component: This requires specific behavioral interventions (diaphragmatic breathing) in addition to pharmacotherapy 4

Monitoring Parameters

• Assess treatment response using standardized anxiety rating scales at regular intervals 3
• Monitor for SSRI side effects including initial anxiety/agitation, gastrointestinal symptoms, and sexual dysfunction 3
• Track weight and metabolic parameters if continuing olanzapine 1, 2
• Evaluate for serotonin syndrome risk given multiple serotonergic agents 3
• Reassess medication need after 9-12 months of stability with consideration for dose reduction 3