Attention-Deficit/Hyperactivity Disorder (ADHD), Bipolar Disorder (BD) and Alcohol Use Disorder (AUD) are common medical conditions often coexisting and exerting mutual influence on disease course and pharmacological treatment response. Each disorder, when considered separately, relies on different therapeutic approaches, making it crucial to detect the plausible association between them. Treating solely the emerging condition (e.g., alcoholism) and disregarding the patient’s whole psychopathological ground often lead to treatment failure and relapse. Clinical experience and scientific evidence rather show that tailoring treatments for these three conditions considering their co-occurrence as a sole complex disorder yields more fulfilling and durable clinical outcomes. In light of the above considerations, the purpose of the present review is to critically discuss the pharmacological strategies in the personalized treatment of complex conditions defined by ADHD-bipolarity-alcoholism coexistence.

Bipolar disorders (BDs) are a heterogeneous group of severe affective disorders generally described by the alternation of (hypo)manic, depressive, and mixed phases, with euthymic intervals of variable duration. BDs are burdened with high psychiatric and physical comorbidity, increased suicide risk and reduced life expectancy. In addition, BDs can progress into complicated forms (e.g., mixed states, rapid/irregular cycling), which are more difficult to treat and often require personalized pharmacological combinations. Mood stabilizers, particularly Lithium and Valproic acid (VPA), still represent the cornerstones of both acute and chronic pharmacotherapies of BDs. Lithium is the gold standard in BD-I and BDII with typical features, while VPA seems more effective for atypical forms (e.g., mixed-prevalence and rapid-cycling). However, despite appropriate mood stabilization, many patients show residual symptoms, and more than a half recur within 1-2 years, highlighting the need of additional strategies. Among these, the association of atypical antipsychotics (AAPs) with mood stabilizers is recurrent in the treatment of acute phases, but it is also being growingly explored in the maintenance pharmacotherapy. These combinations are clinically more aggressive and often needed in the acute phases, whereas simplifying pharmacotherapies to mood stabilizers only is preferable in the long-term, whenever possible. When mood stabilizers are not enough for maintenance treatment, Quetiapine and, less consistently, Aripiprazole have been proposed as the most advisable adjunctive strategies, for their safety and tolerability profiles. However, in view of the increased risk of serious adverse effects, a careful patient-centered balance between costs and benefits is mandatory.