Is it appropriate to increase mirtazapine (Remeron) in a patient with Generalized Anxiety Disorder (GAD), Major Depressive Disorder (MDD), and Autism Spectrum Disorder (ASD), currently taking mirtazapine 15mg (milligrams) at bedtime, quetiapine (Seroquel) 25mg (milligrams) daily, and hydroxyzine (Vistaril) 25mg (milligrams) as needed, who reports suicidal ideation, anxiety, and low mood symptoms?

Increasing Mirtazapine in a Patient with GAD, MDD, ASD, and Suicidal Ideation

Yes, increasing mirtazapine from 15mg to 30-45mg is appropriate and should be done promptly, as the current 15mg dose is subtherapeutic for treating major depression and generalized anxiety disorder, and the FDA-approved dosing allows increases up to 45mg daily with dose changes at 1-2 week intervals. 1

Rationale for Dose Increase

• The FDA label for mirtazapine specifies that the recommended starting dose is 15mg once daily, but if patients do not have an adequate response to the initial 15mg dose, the dose should be increased up to a maximum of 45mg per day 1
• Mirtazapine 15-45mg/day has demonstrated efficacy in treating major depression with rapid and sustained improvements in depressive symptoms 2
• In patients with major depression and comorbid GAD, mirtazapine showed significant reductions in both Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety scores, with improvement noted after the first week of therapy and continuing improvement over 8 weeks 3
• A fixed-dose study of mirtazapine 30mg for GAD achieved a 79.5% response rate and 36.4% remission rate at 12 weeks, supporting efficacy at higher doses 4

Recommended Dosing Strategy

• Increase mirtazapine to 30mg immediately, as this is the dose that has been specifically studied and shown effective for GAD 4
• Dose changes should not be made in intervals of less than 1 to 2 weeks to allow sufficient time for evaluation of response to a given dose 1
• If inadequate response persists after 2 weeks at 30mg, further increase to 45mg (the maximum FDA-approved dose) 1
• Administer preferably in the evening prior to sleep to leverage sedating effects 1

Critical Safety Monitoring for Suicidal Ideation

• This patient requires immediate close monitoring for suicidal thinking and behavior, especially during the first months of treatment and following dosage adjustments, as all antidepressants carry a boxed warning for suicidal thinking and behavior through age 24 years 5
• The pooled absolute rates for suicidal ideation across all antidepressant classes have been reported to be 1% for youths treated with an antidepressant versus 0.2% for placebo, with a number needed to harm of 143 5
• Assess for suicidal thoughts and behaviors at every visit, particularly during the first 1-2 months after dose increases 5
• Monitor for behavioral activation/agitation (motor or mental restlessness, insomnia, impulsiveness, aggression), which may occur early in treatment or with dose increases 5

Addressing the Current Medication Regimen

• The quetiapine 25mg daily dose is subtherapeutic for treating depression or anxiety and is likely only providing sedation without meaningful antidepressant or anxiolytic benefit 2
• Hydroxyzine 25mg PRN is appropriate for acute anxiety management, though evidence shows it is more effective than placebo for GAD but has a high risk of bias in supporting studies 6
• Consider whether the quetiapine 25mg is providing any benefit beyond sedation; if not, it may be discontinued as mirtazapine is increased, simplifying the regimen 2

Expected Timeline for Response

• Mirtazapine may have a more rapid onset of action than SSRIs, with improvement noted after the first week of therapy 2, 3
• Allow 8-12 weeks at the optimized dose (30-45mg) before declaring treatment failure 1, 4
• Continuing improvement should be expected over the full 8-12 week treatment period 3

Drug Interaction Considerations

• Mirtazapine dosage may need adjustment if the patient is taking strong CYP3A inducers (carbamazepine, phenytoin, rifampin) or strong CYP3A4 inhibitors (ketoconazole, clarithromycin) 1
• There is a theoretical risk of serotonin syndrome when combining serotonergic medications, though mirtazapine's mechanism (noradrenergic and specific serotonergic) differs from SSRIs 5
• Monitor for symptoms of serotonin syndrome including mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity, especially in the first 24-48 hours after dose increases 5

Common Pitfalls to Avoid

• Do not continue the current subtherapeutic 15mg dose for extended periods, as this delays recovery and worsens outcomes 1
• Do not make dose changes more frequently than every 1-2 weeks, as this prevents adequate assessment of therapeutic response 1
• Do not abruptly discontinue mirtazapine if switching medications; gradually reduce the dosage to avoid discontinuation syndrome 1
• Do not overlook the need for adjunctive psychotherapy (particularly cognitive-behavioral therapy), which demonstrates superior efficacy compared to medication alone for anxiety and depression 5

Continuation Treatment

• Once adequate response is achieved, continue treatment for 4-9 months after satisfactory response in patients with a first episode of major depressive disorder 5
• For patients who have had 2 or more episodes, longer duration of therapy (years to lifelong) may be beneficial 5