What are the next steps for treating a patient with refractory anxiety and severe insomnia who has had adverse reactions to Selective Serotonin Reuptake Inhibitors (SSRIs) such as Prozac (fluoxetine), Effexor (venlafaxine), and Wellbutrin (bupropion), and is currently trying Mirtazapine (mirtazapine) 30mg?

Treatment for Refractory Anxiety and Severe Insomnia After Multiple Medication Failures

For a patient with refractory anxiety and severe insomnia who has failed multiple antidepressant trials including SSRIs, SNRIs, and bupropion, the most appropriate next step is to consider pregabalin or a benzodiazepine for short-term use while optimizing the current mirtazapine dose, followed by cognitive behavioral therapy (CBT) and potentially augmentation strategies. 1, 2

Current Medication Assessment

• Mirtazapine 30mg is a reasonable choice for this patient given their dual anxiety and severe insomnia symptoms, as it promotes sleep, appetite, and weight gain while treating anxiety 1
• Consider increasing mirtazapine to 45mg if 30mg is not providing adequate relief, as higher doses may be more effective for anxiety while maintaining the sedative properties 1, 3
• Mirtazapine has a more favorable side effect profile compared to SSRIs for patients with severe nausea (like this patient experienced with Prozac) 1, 4

Next Medication Options

First-line considerations:

• Pregabalin can be effective for anxiety disorders that have not responded to SSRIs/SNRIs and may help with sleep disturbances 2, 5
• Short-term benzodiazepine use (2-4 weeks) may be considered for immediate relief of severe anxiety and insomnia while other treatments take effect 1, 6
  • Must be used cautiously due to dependence potential and not recommended for long-term use 1

Second-line considerations:

• Low-dose tricyclic antidepressants like nortriptyline (10mg at bedtime, maximum 40mg) may be helpful for both anxiety and insomnia 1
  • Nortriptyline has sedating properties and may be useful for patients with agitated anxiety and insomnia 1
• Trazodone (a SARI) at low doses (25-100mg) specifically for insomnia while continuing mirtazapine for anxiety 1, 3

Non-Pharmacological Approaches

• Cognitive Behavioral Therapy (CBT) should be strongly considered as it has the highest level of evidence for anxiety disorders and can be particularly effective for those who have failed multiple medication trials 1, 2
• Sleep hygiene education including structured activities, environmental safety, and support for the patient 1
• For severe insomnia specifically, Cognitive Behavioral Therapy for Insomnia (CBT-I) is recommended before increasing sedating medications 1

Treatment Algorithm

1. Optimize current mirtazapine dose (consider increasing to 45mg if tolerated) 1, 3
2. Add short-term intervention for immediate symptom relief:
   • Pregabalin OR
   • Short-term benzodiazepine (2-4 weeks maximum) 1, 2, 6
3. Initiate CBT for anxiety while continuing pharmacotherapy 1, 2
4. If inadequate response after 4-6 weeks, consider:
   • Adding low-dose tricyclic antidepressant (e.g., nortriptyline) 1
   • Adding trazodone specifically for insomnia 1, 3
5. For persistent non-response, consider referral to a psychiatrist for specialized treatment approaches such as:
   • Combination therapy with multiple agents
   • Novel medication approaches
   • Intensive outpatient treatment 1, 7, 5

Important Considerations and Cautions

• Rule out medical causes of anxiety and insomnia, including thyroid disorders, caffeine overuse, or sleep apnea 5
• Assess for bipolar disorder, as antidepressant-induced mania/hypomania can present as anxiety or panic attacks (as experienced with Effexor) 1, 4
• Monitor for serotonin syndrome if combining mirtazapine with other serotonergic medications 4
• Avoid medications that have already caused adverse effects (fluoxetine, venlafaxine) 7
• Long-term treatment is necessary as anxiety disorders are chronic conditions requiring 6-12 months of medication after remission 2, 6

Monitoring

• Evaluate response to treatment every 2-4 weeks initially 2
• Monitor for side effects, particularly sedation, dizziness, and weight gain with mirtazapine 4
• Assess for suicidal ideation, especially when initiating or changing treatments 4
• Track sleep patterns using a sleep diary to objectively measure improvement in insomnia 1