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Fluoxetine + moclobemide is a combination of two antidepressant drugs used experimentally in the management of treatment-resistant depression. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that increases synaptic serotonin by inhibiting its reuptake, while moclobemide is a reversible inhibitor of monoamine oxidase A (RIMA), which increases levels of serotonin, noradrenaline, and dopamine by preventing their breakdown. The rationale for combining these agents is to enhance serotonergic neurotransmission through dual mechanisms. However, this combination carries significant risk for pharmacodynamic interactions, notably life-threatening serotonin toxicity (serotonin syndrome), especially in overdose or high-risk patients. Clinical studies have reported frequent adverse effects such as insomnia, dizziness, headache, nausea, dry mouth, and myoclonic jerks; severe cases can result in coma or death due to serotonin toxicity[1][3][5][6]. The efficacy data are limited and unproven; thus this combination should only be considered with extreme caution and under specialist supervision.
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