Introduction: Major depressive disorder (MDD) represents a significant global health concern, characterized bya pervasive low mood, loss of interest or pleasure and a range of cognitive and somatic symptoms. Statinsbiological effects have spurred interest in the potential utility of statins in various conditions beyondcardiovascular disease, including neurological and psychiatric disorders. Given their established safety profileand the growing understanding of their pleiotropic actions, statins represent a promising class of medications forpotential repurposing as adjunctive therapies in the management of depression.Methods: This study employed a prospective observational design to evaluate the effects of adjunctive statintherapy on clinical outcomes and the TyG index in individuals with depression over a 12-month period. Thestudy included two groups of participants: the Adjunctive Statin Group with Antidepressant and theAntidepressant-Only Group. The Adjunctive Statin Group consist of patients with a diagnosis of MDD whowere receiving a stable dose of antidepressant medication and whose treating physician had initiated statintherapy as part of their clinical management within one month prior to or at the time of study enrollment. TheAntidepressant-Only Group served as the control group and comprised patients with MDD who were alsoreceiving a stable dose of antidepressant medication but will was not prescribed a statin during the study period.Results: The mean age was similar between groups (45.2 vs. 44.6 years, p=0.74), with a comparable proportionof females (53.3% vs. 56.7%, p=0.71). Both groups were having overweight with BMI values (27.1 vs. 26.8kg/m², p=0.66) and a comparable mean duration of depression (~6.5–6.8 years, p=0.72). Baseline HAM-D,MADRS, and PHQ-9 scores did not differ significantly (all p>0.7), confirming that the groups started withsimilar severity of depressive symptoms. Medication classes were comparable, with SSRIs being the mostcommonly prescribed (~55%). As expected, only the adjunctive group received statins (45% atorvastatin, 35%rosuvastatin, 20% simvastatin). Baseline triglycerides, glucose, and TyG index values were nearly identicalacross groups (p-values 0.74–0.87).Conclusion: The results have the potential to contribute to our understanding of novel treatment strategies formajor depressive disorder, considering the intricate interplay between mental health and metabolic factors. Bycarefully observing and analyzing the outcomes in a naturalistic clinical setting, this research seeks to informfuture clinical practice and guide further investigations into the therapeutic potential of statins in themanagement of depression.

Introduction: Major depressive disorder (MDD) represents a significant global health concern, characterized bya pervasive low mood, loss of interest or pleasure and a range of cognitive and somatic symptoms. Statinsbiological effects have spurred interest in the potential utility of statins in various conditions beyondcardiovascular disease, including neurological and psychiatric disorders. Given their established safety profileand the growing understanding of their pleiotropic actions, statins represent a promising class of medications forpotential repurposing as adjunctive therapies in the management of depression.Methods: This study employed a prospective observational design to evaluate the effects of adjunctive statintherapy on clinical outcomes and the TyG index in individuals with depression over a 12-month period. Thestudy included two groups of participants: the Adjunctive Statin Group with Antidepressant and theAntidepressant-Only Group. The Adjunctive Statin Group consist of patients with a diagnosis of MDD whowere receiving a stable dose of antidepressant medication and whose treating physician had initiated statintherapy as part of their clinical management within one month prior to or at the time of study enrollment. TheAntidepressant-Only Group served as the control group and comprised patients with MDD who were alsoreceiving a stable dose of antidepressant medication but will was not prescribed a statin during the study period.Results: The mean age was similar between groups (45.2 vs. 44.6 years, p=0.74), with a comparable proportionof females (53.3% vs. 56.7%, p=0.71). Both groups were having overweight with BMI values (27.1 vs. 26.8kg/m², p=0.66) and a comparable mean duration of depression (~6.5–6.8 years, p=0.72). Baseline HAM-D,MADRS, and PHQ-9 scores did not differ significantly (all p>0.7), confirming that the groups started withsimilar severity of depressive symptoms. Medication classes were comparable, with SSRIs being the mostcommonly prescribed (~55%). As expected, only the adjunctive group received statins (45% atorvastatin, 35%rosuvastatin, 20% simvastatin). Baseline triglycerides, glucose, and TyG index values were nearly identicalacross groups (p-values 0.74–0.87).Conclusion: The results have the potential to contribute to our understanding of novel treatment strategies formajor depressive disorder, considering the intricate interplay between mental health and metabolic factors. Bycarefully observing and analyzing the outcomes in a naturalistic clinical setting, this research seeks to informfuture clinical practice and guide further investigations into the therapeutic potential of statins in themanagement of depression.