Can a patient take Remeron (mirtazapine) and Luvox (fluvoxamine) and Zyprexa (olanzapine) together?

Can a Patient Take Remeron, Luvox, and Zyprexa Together?

This combination carries significant risk and should generally be avoided due to documented cases of serotonin syndrome when combining these medications, particularly the combination of mirtazapine (Remeron) with fluvoxamine (Luvox). 1

Primary Safety Concern: Serotonin Syndrome

The major risk with this three-drug combination is serotonin syndrome, a potentially life-threatening condition that can develop within 24-48 hours of combining serotonergic medications. 2

Specific Drug Interactions

Mirtazapine + Fluvoxamine:

• This specific combination has been directly documented to cause serotonin syndrome in published case reports. 1
• A 26-year-old patient developed tremors, restlessness, twitching, flushing, diaphoresis, and nausea when mirtazapine was added to fluvoxamine therapy. 1
• Both pharmacodynamic (additive serotonergic effects) and pharmacokinetic interactions (fluvoxamine inhibits mirtazapine metabolism) contribute to the risk. 1

Mirtazapine + Olanzapine:

• This combination has also been documented to cause severe serotonin syndrome complicated by rhabdomyolysis, acute renal failure, and acute pulmonary edema. 3
• A 34-year-old patient developed acute consciousness disturbance, extremely high fever, rigidity, and spontaneous clonus when mirtazapine was added to olanzapine. 3

Triple Combination Risk:

• Adding all three medications together compounds the serotonergic burden significantly beyond what has been studied in the literature.
• While the combination of fluvoxamine with olanzapine alone may be used clinically, adding mirtazapine creates an unacceptable risk profile based on documented adverse events. 3, 1

Clinical Manifestations of Serotonin Syndrome

Watch for these specific symptoms if this combination is being considered:

Early symptoms (within 24-48 hours): 2

• Mental status changes (agitation, confusion, restlessness)
• Neuromuscular hyperactivity (tremor, myoclonus, hyperreflexia, rigidity)
• Autonomic hyperactivity (diaphoresis, tachycardia, fever, mydriasis)

Advanced symptoms: 2, 3

• High fever (potentially extreme)
• Seizures
• Cardiac arrhythmias
• Unconsciousness
• Rhabdomyolysis
• Acute renal failure

Alternative Approaches

If treating depression with psychotic features or treatment-resistant depression:

• Consider fluvoxamine with olanzapine WITHOUT mirtazapine (this combination is used in clinical practice). 4
• Consider quetiapine monotherapy or with a mood stabilizer, which has become more commonly used for bipolar depression. 4
• If augmentation is needed, consider lamotrigine or lithium rather than adding a second antidepressant. 4

If the patient is already on two of these medications:

• Do NOT add the third medication without first consulting a psychiatrist.
• If serotonin syndrome develops, immediately discontinue ALL serotonergic agents and treat with intravenous benzodiazepines and oral cyproheptadine. 3

Critical Pitfalls to Avoid

• Never assume that commonly prescribed antidepressants are automatically safe in combination. 2
• Do not underestimate the risk in vulnerable populations (elderly, those with underlying medical conditions, or those with low body weight/anorexia). 1, 5
• Fluvoxamine is a potent CYP450 inhibitor that can dramatically increase mirtazapine levels through pharmacokinetic interactions, compounding the pharmacodynamic serotonergic effects. 1
• Individual vulnerability plays a significant role - some patients may tolerate combinations that cause severe reactions in others. 6

Bottom Line

This three-drug combination should be avoided. If all three medications are deemed absolutely necessary for a specific clinical situation, this should only be attempted under close inpatient psychiatric monitoring with full informed consent about the documented risks of severe serotonin syndrome, and with immediate access to emergency medical intervention. 3, 1