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Mirtazapine + quetiapine is a combination therapy investigated by Dartmouth-Hitchcock Medical Center for the treatment of alcohol dependence, particularly in very heavy drinkers. Mirtazapine is a second-generation tetracyclic antidepressant that acts as a potent alpha-2 adrenergic receptor antagonist, while quetiapine is an atypical antipsychotic acting as a dopamine D2 and serotonin 5-HT2 receptor antagonist. The combination is hypothesized to reduce alcohol consumption by synergistically modulating dopaminergic and noradrenergic systems. This specific repurposing study, led by Dr. Alan Green, evaluated whether the addition of mirtazapine to quetiapine XR was more effective than quetiapine monotherapy in reducing heavy drinking days by targeting reward and stress pathways involved in alcohol use disorder.
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