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Compulsive buying disorder (CBD) is a condition characterized by excessive preoccupations, impulses, and behaviors regarding buying, resulting in serious psychological, social, and financial problems. Even though it has not been included in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, “behavioral addictions” section, CBD is a hot topic in current clinical psychiatry, because of its relevant prevalence (at least 5% in adult populations) and severe effect on quality of life.The CBD shares some clinical features with substance-related and behavioral addictions, impulse control disorders, and obsessive compulsive disorder, and it is often comorbid with other psychiatric illnesses (especially depressive and anxiety disorders). The treatment of CBD is therefore difficult, and clear therapeutic guidelines are not yet available. Treating the comorbid disorders as the first-line approach, or combining drugs with different pharmacodynamic profiles, has been suggested to address this challenging condition.A 60-year-old woman affected by a severe form of CBD with comorbid major depressive disorder, resistant/intolerant to previous selective serotonin reuptake inhibitor treatments and only partially responder to mirtazapine, achieved a good clinical improvement adding bupropion.Combining 2 agents with different pharmacological profiles and mechanisms of action, such as bupropion and mirtazapine, could be a useful strategy in the management of complex CBD cases.