Effectiveness of Mirtazapine in Panic Disorder
Mirtazapine appears to be effective for treating panic disorder with potentially faster onset of action compared to SSRIs, making it a reasonable alternative treatment option for panic disorder patients who cannot tolerate or do not respond to first-line agents.
Efficacy Evidence
Mirtazapine has demonstrated promising results in the treatment of panic disorder based on several studies:
In a double-blind, randomized trial comparing mirtazapine with fluoxetine, both medications showed significant improvement in panic symptoms, with mirtazapine showing superior results in patient global evaluation of phobic anxiety 1.
An open-label pilot study with a single-blind placebo run-in period found that 74% of patients were considered responders (defined as ≥50% decrease in panic attack frequency), with significant improvement in efficacy measures from the second week of treatment 2.
In an open study comparing mirtazapine with paroxetine, both treatments showed significant reductions in panic attacks, anxiety, and depression scores, with mirtazapine potentially showing a faster response at weeks 3 and 8 3.
Mechanism of Action
Mirtazapine's effectiveness in panic disorder may be attributed to its unique pharmacological profile:
It functions as a noradrenergic and specific serotonergic antidepressant (NaSSA) with dual enhancement of central noradrenergic and serotonin 5-HT1 receptor-mediated serotonergic neurotransmission 4.
Both serotonergic and noradrenergic neurotransmitter systems are implicated in the pathophysiology of panic disorder, making mirtazapine's dual action particularly relevant 5.
Speed of Response
A notable advantage of mirtazapine in panic disorder treatment appears to be its relatively rapid onset of action:
Evidence from 7 fair-quality studies showed that mirtazapine had a statistically significantly faster onset of action than citalopram, fluoxetine, paroxetine, or sertraline in depression treatment, although after 4 weeks most response rates were similar 6.
In panic disorder specifically, one study found that 4 of 10 patients met response criteria by weeks 2-3 5.
When compared to paroxetine, mirtazapine showed statistically significant differences in reducing the number of panic attacks at weeks 3 and 8, suggesting a faster response 3.
Side Effect Profile
Mirtazapine has a distinct side effect profile compared to SSRIs:
Most common side effects include increased appetite, weight gain, and sedation 5, 1, 4.
The sedative effects can be beneficial in the initial phase of treatment for patients with anxiety and sleep disturbances 5, 4.
Mirtazapine has a relative absence of serotonin-related adverse effects common with SSRIs, particularly gastrointestinal side effects and sexual dysfunction 4.
Dosing Considerations
In studies of panic disorder, the mean daily dose ranged from approximately 15-30 mg 1, 2.
The recommended starting dose is typically 7.5-15 mg at bedtime, with gradual increases as needed up to 30-45 mg 7.
Sedation appears to be more prominent at lower doses and may decrease at therapeutic doses (≥15 mg) 4.
Clinical Application
For patients with panic disorder:
Consider mirtazapine particularly when:
- SSRIs have failed or are not tolerated
- Rapid symptom relief is desired
- Comorbid insomnia or appetite/weight loss is present
- Sexual dysfunction from SSRIs is a concern
Monitor for:
- Weight gain and increased appetite
- Initial sedation (which may be beneficial for sleep disturbances)
- Potential for reduced sedation at higher therapeutic doses
Limitations and Caveats
Most studies on mirtazapine for panic disorder are small and open-label rather than large randomized controlled trials.
Long-term efficacy data beyond 6 months is limited.
Weight gain may be problematic for some patients and requires monitoring.
While mirtazapine appears effective, SSRIs and SNRIs remain first-line treatments for panic disorder based on more extensive evidence.