Methylthioninium chloride (methylene blue) × Mirtazapine

IV methylene blue inhibits MAO-A. Mirtazapine raises synaptic serotonin via presynaptic α2-adrenergic blockade. Combined action sharply amplifies serotonergic transmission.

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: profuse sweating, tachycardia, hypertension, fever above 38.5 °C. Severe cases progress to seizures, rhabdomyolysis, disseminated intravascular coagulation, and death. First signs appear within hours of concurrent dosing.

Avoid the combination. Methylene blue is reserved for emergencies with mirtazapine withdrawn 5 days in advance. If unavoidable, monitor in ICU with cyproheptadine available.