The frequent co-occurrence of major depressive disorder (MDD) and substance use disorders
(SUDs) entails significant clinical challenges. Compared to patients with MDD alone, patients
with MDD and SUD often show increased anhedonia, emotional blunting, and impaired cognitive
function. These symptoms lead to an inability to control cravings, more substance use, increased relapse
rates, and poor adherence to the treatment. This fosters a detrimental cycle leading to more severe
depressive symptoms, functional impairment, and chronicity, culminating in heightened morbidity,
mortality, and healthcare resource utilization. Data on antidepressant treatment of MDD-SUD patients
are inconclusive and often conflicting because of a number of confounding factors in clinical trials
or difficulty in dissecting the specific contributions of pharmacological versus psychological interventions
in real-world studies. The patient's unique clinical features and specific SUD and MDD subtypes
must be considered when choosing treatments. Ideally, drug treatment for MDD-SUD should act
on both conditions and address core symptoms such as anhedonia, craving, and cognitive dysfunction
while ensuring minimal emotional blunting, absence of drug interactions, and no addictive potential.
This approach aims to address unmet needs and optimize the outcomes in a clinical population often
underrepresented in treatment paradigms.