Antidepressant Augmentation With Mirtazapine
Mirtazapine can be added to an existing SSRI regimen in selected patients who prefer combination treatment and are willing to accept increased side-effect burden. [1]
The concomitant use of mirtazapine with serotonergic drugs such as sertraline increases the risk of serotonin syndrome, so monitoring is recommended during initiation and dose increases. [2]
Because monotherapy with first-line antidepressants is generally preferable to combination of two antidepressants due to increased potential for drug-drug interactions and adverse effects, the risk-benefit of adding mirtazapine should be assessed. [3]
Medication Selection Algorithm
- Consider switching to another antidepressant (within-class or out-of-class) when partial or nonresponse occurs with the current antidepressant therapy. [3]
- Consider augmentation with a second-generation antipsychotic (SGA) such as quetiapine when pharmacologic augmentation is pursued. [3]
- Consider adding mirtazapine to an SSRI as a combination treatment option in patients willing to accept increased side-effect burden. [1]
Key Evidence Supporting This Recommendation
- NICE highlights that combination regimens can increase side-effect burden and recommends considering specialist input for combination approaches in depression when the patient is willing to accept increased adverse effects. [1]
- VA/DoD states that monotherapy with first-line antidepressants is preferable to combination of two antidepressants because of increased potential for drug-drug interactions, adverse effects, and lack of clinical benefit. [3]
Monotherapy Versus Combination Therapy
- Monotherapy with first-line antidepressants is generally preferable to combining two antidepressants because combination increases the potential for adverse effects and drug-drug interactions. [3]
- When combination pharmacotherapy is used, review for increased side-effect burden is recommended. [1]
Safety Considerations When Adding Mirtazapine to Sertraline
- Serotonin syndrome risk increases with concomitant use of mirtazapine and serotonergic drugs including SSRIs such as sertraline. [2]
- Monitoring for signs and symptoms of serotonin syndrome is recommended particularly during treatment initiation and dosage increases. [2]
- If serotonin syndrome occurs, discontinuation of mirtazapine and/or the concomitant serotonergic drug should be considered. [2]
Safety Considerations With Concomitant Quetiapine
- Quetiapine is listed as an example of an SGA option used in combination treatment strategies for depression. [1]
- Quetiapine was discussed by VA/DoD as a SGA with evidence supporting augmentation for major depressive disorder. [3]
Initiation Thresholds and Practical Monitoring
- Monitoring should be intensified at the time of mirtazapine initiation and during any mirtazapine dose increases because serotonin syndrome risk increases during initiation and titration. [2]
Common Pitfalls to Avoid
- Avoid using combination of two antidepressants without assessing increased adverse-effect burden and interaction risk, since monotherapy is generally preferable. [3]
- Avoid delayed recognition of serotonin syndrome by ensuring monitoring during initiation and dose increases. [2]
Target Outcomes for Therapy
- The clinical goal is adequate depressive symptom response and remission while minimizing adverse effects from increased pharmacotherapy complexity. [1] [3]