Can you take mirtazapine and Lexapro together? Safety, Risks, and Medical Oversight

October 10, 2025 •

2 min read

For some patients with treatment-resistant depression, monotherapy with a single antidepressant is insufficient. This leads to questions like, "Can you take mirtazapine and Lexapro together?", which represents a dual-action strategy sometimes used under careful medical oversight to manage complex cases.

Quick Summary

Combining mirtazapine (Remeron) and Lexapro (escitalopram) is a potential treatment for resistant depression but requires strict medical supervision due to serious risks, including serotonin syndrome. The decision hinges on a patient's specific needs and tolerance for side effects.

Key Points

Requires Medical Supervision: Combining mirtazapine and Lexapro is not a decision to be made independently and must be managed by a qualified healthcare provider due to significant risks.
Risk of Serotonin Syndrome: The combination significantly increases the risk of serotonin syndrome, a potentially life-threatening condition caused by excess serotonin.
Enhanced Efficacy: This combination is primarily used for treatment-resistant depression, with the rationale that the dual action on different neurochemical pathways may provide complementary effects.
Offsetting Side Effects: Mirtazapine can help counter some common SSRI side effects, such as insomnia and sexual dysfunction.
Mixed Clinical Evidence: Large-scale studies have shown conflicting results regarding the superior efficacy of this combination over monotherapy, while also noting a higher side-effect burden.
Side Effects and Monitoring: Common side effects include sedation and weight gain, and regular monitoring for vital signs and mood changes is essential.
Don't Adjust Doses: Patients should never change dosages or stop either medication without a doctor's explicit instruction.

The Rationale Behind Combining Mirtazapine and Lexapro

Combining antidepressants, known as augmentation therapy, is considered when an initial medication is ineffective. Lexapro (escitalopram), an SSRI that increases serotonin levels, is sometimes combined with Mirtazapine (Remeron), a tetracyclic antidepressant that affects norepinephrine and serotonin. This combination aims for a synergistic effect by acting on different neurological pathways and is primarily used for patients who haven't responded to a single antidepressant. This combination is sometimes called "California Rocket Fuel". Potential benefits include enhanced efficacy and offsetting side effects, as mirtazapine's sedative properties may counter SSRI-induced insomnia, and it has a lower risk of sexual side effects.

Significant Risks and Side Effects

Combining mirtazapine and Lexapro carries significant risks and must be decided by a doctor. The most serious risk is serotonin syndrome, caused by excessive serotonin activity.

Symptoms of Serotonin Syndrome

Be aware of serotonin syndrome symptoms and seek immediate medical attention if they occur. These include changes in mental status (agitation, confusion), autonomic instability (rapid heart rate, fever), neuromuscular effects (shivering, rigidity), and gastrointestinal issues. Other side effects can include increased appetite, weight gain, sedation, dry mouth, and headaches. Elderly patients have an increased risk of QT interval prolongation and hyponatremia.

The Crucial Role of Medical Supervision

Due to the risks, a healthcare provider must manage this combination. Key aspects of medical oversight include cautious, gradual dosing; regular monitoring for side effects and effectiveness; patient education on serotonin syndrome symptoms; and strict instruction against self-adjusting dosages.

Comparison: Mirtazapine vs. Lexapro vs. The Combination


Feature	Mirtazapine (Remeron)	Lexapro (Escitalopram)	Mirtazapine + Lexapro (Combo)
Mechanism of Action	Increases norepinephrine and serotonin	Increases serotonin levels	Combined dual-action
Primary Use	Depression, anxiety, sleep issues	Depression, generalized anxiety disorder	Treatment-resistant depression
Common Side Effects	Sedation, weight gain, dry mouth	Insomnia, nausea, sexual dysfunction	Increased risk of serotonin syndrome, sedation, weight gain
Sexual Side Effects	Low risk	Common	Mirtazapine may help offset SSRI sexual side effects
Serotonin Syndrome Risk	Low (alone)	Low (alone)	Higher, especially with dose increases
Medical Supervision	Standard supervision	Standard supervision	Strict, constant monitoring is essential

Conflicting Evidence in Clinical Studies

Studies on combining antidepressants, including mirtazapine and SSRIs, have shown mixed results. While some early studies suggested benefits, larger trials like the 2018 MIR trial found no significant benefit over placebo for treatment-resistant depression and noted more side effects in the combination group. The 2011 CO-MED trial also didn't find a superior remission rate for initial combination therapy. This highlights the need for an individualized approach decided by a healthcare professional.

Conclusion: A Cautious Path to Combination Therapy

While combining mirtazapine and Lexapro is possible, it's typically reserved for treatment-resistant depression under strict medical supervision. The potential benefits are balanced against the heightened risk of serious side effects, particularly serotonin syndrome. Patients should have a thorough discussion with their doctor about the risks, benefits, and monitoring required for this combination. Additional information on antidepressant combinations is available from resources like the National Center for Biotechnology Information (NCBI).

Frequently Asked Questions

The primary risk is a rare but serious condition called serotonin syndrome. It occurs when there is excessive serotonin activity in the central nervous system, leading to symptoms like agitation, rapid heart rate, confusion, and muscle stiffness.

A doctor may prescribe this combination for treatment-resistant depression when a single antidepressant has not been effective. The rationale is that the two medications have complementary mechanisms of action, which could lead to a more robust therapeutic effect.

Potential benefits include enhanced antidepressant efficacy through dual action on serotonergic and noradrenergic systems. Mirtazapine can also help counteract some common SSRI side effects, such as insomnia and sexual dysfunction.

Besides the risk of serotonin syndrome, other potential side effects include increased appetite, weight gain, increased sedation or drowsiness, and dry mouth. Elderly patients also face an increased risk of QT prolongation and hyponatremia.

'California Rocket Fuel' is a nickname for the combination of a selective serotonin reuptake inhibitor (SSRI), like Lexapro, and mirtazapine. It is a dual-action strategy sometimes used for difficult-to-treat depression.

Yes, some clinical studies, including the large-scale MIR trial, have found no significant benefit of adding mirtazapine to an SSRI/SNRI for treatment-resistant depression compared to a placebo, and noted a higher burden of side effects.

If you experience symptoms such as confusion, agitation, hallucinations, a rapid or irregular heartbeat, or extreme changes in blood pressure, you should seek immediate medical attention.