Critical
Fluoxetine × Methylthioninium chloride (methylene blue)
Selective serotonin reuptake inhibitors×Antidotes (V03AB17). The drug has one FDA-approved indication – methaemoglobinaemia. Biohacker use is off-label.
Mechanism
IV methylene blue inhibits MAO-A. Fluoxetine and its active metabolite norfluoxetine raise synaptic serotonin. Norfluoxetine persists for up to 5 weeks – serotonin syndrome risk outlasts the dose by weeks.
Symptoms
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.
Management
Avoid the combination. Stop fluoxetine 5 weeks before planned methylene blue. In emergencies (methaemoglobinaemia), administer for life-threatening indications under ICU monitoring with cyproheptadine available.