Concurrent Use of Mirtazapine and Amitriptyline
Taking mirtazapine and amitriptyline together is not recommended due to the increased risk of serotonin syndrome, QT prolongation, anticholinergic effects, and excessive sedation. 1
Risks of Combined Use
Serotonin Syndrome Risk
- The FDA drug label for mirtazapine specifically warns against combining it with tricyclic antidepressants (TCAs) like amitriptyline due to the risk of serotonin syndrome 1
- Serotonin syndrome is potentially life-threatening and can cause:
- Mental status changes (agitation, confusion, hallucinations)
- Autonomic instability (tachycardia, fluctuating blood pressure, hyperthermia)
- Neuromuscular symptoms (tremor, rigidity, myoclonus)
- Gastrointestinal symptoms (nausea, vomiting, diarrhea)
Cardiac Risks
- Both medications can prolong QT interval 1
- Combining them increases the risk of dangerous cardiac arrhythmias including Torsades de Pointes
Additive Side Effects
- Both medications cause sedation, which would be compounded when taken together 2
- Both have anticholinergic effects (dry mouth, constipation, blurred vision) that would be additive 2
- Increased risk of cognitive impairment, especially in elderly patients
Alternative Approaches
If you're seeking treatment for:
Depression
- Use either mirtazapine OR amitriptyline as monotherapy, not both
- Mirtazapine (15-45mg daily) has been shown to be as effective as amitriptyline for depression with fewer anticholinergic and cardiac side effects 3, 4, 5
Insomnia
- If insomnia is the primary concern, low-dose mirtazapine (7.5-15mg) alone can be effective 6
- Alternatively, low-dose amitriptyline (10-25mg) alone can be used 7
Pain Management
- For neuropathic pain, amitriptyline (25-100mg/day) is a first-line option 2
- For pain associated with digestive disorders, TCAs like amitriptyline have shown efficacy 2
Special Populations Considerations
Elderly Patients
- Lower doses of either medication should be used
- Increased risk of falls, cognitive impairment, and anticholinergic effects
- Mirtazapine may be better tolerated than amitriptyline in this population 3
Patients with Cardiac Issues
- Both medications can affect cardiac conduction
- ECG monitoring would be necessary if either medication is used in patients with pre-existing cardiac disease
Bottom Line
Choose either mirtazapine OR amitriptyline based on the specific symptoms being targeted, patient's comorbidities, and potential side effect profile. Using both medications concurrently significantly increases risks without providing additional therapeutic benefit.