158. RISK FACTORS AND PSYCHOTROPIC MEDICATION INFLUENCE IN THE PROGRESSION FROM MAJOR DEPRESSION TO BIPOLAR DISORDER: FINDINGS FROM A 16-YEAR STUDY

Abstract Background Major depressive disorder (MDD) and bipolar disorder (BD) are chronic psychiatric conditions with overlapping symptoms, but BD is distinguished by the presence of manic or hypomanic episodes. A proportion of patients initially diagnosed with MDD later transition to a BD diagnosis, and it is hypothesized that antidepressant use may partially contribute to this diagnostic shift. Aims & Objectives This study aimed to broadly examine the association between psychotropic medication uses and risk factors influencing the conversion rate from MDD to BD. Method We conducted a retrospective study using 16 years of electronic health records from the National Taiwan University Hospital-integrative Medical Data Center. The cohort included patients diagnosed with MDD from January 1, 2006, to June 30, 2022. We collected baseline characteristics, including age, sex, body-mass-index (BMI), occupation, marital status, and follow-up duration, along with clinical features, comorbidities, healthcare utilization, and psychiatric medication history. Comparisons were performed using Student’s t-tests and chi-square or Fisher’s exact tests. Logistic regression was employed to assess conversion risks associated with comorbidities, while Cox proportional hazards models were used to compare conversion risks based on psychotropic medication usage. Results A total of 7,682 MDD patients were included in the final analysis, of whom 595 (7.75%) later converted to BD[p1]. The median age at conversion was 45.8 years, with a median time to conversion of 2.25 years. Factors associated with higher conversion risk included younger age, female sex, unemployment, higher BMI, severe MDD, and increased healthcare utilization. Multivariate analysis revealed significant comorbidities associated with increased conversion risk, including ischemic heart disease (OR=2.01) and rheumatoid arthritis (OR=2.26), obesity (OR=2.23) and diabetes (OR=1.79). Antidepressant use was consistently associated with a higher risk of converting to BP across multiple time periods, with an overall hazard ratio (HR) of 1.27 (95% CI=1.13-1.42). Specifically, conversion risk was significantly elevated six months after the initial MDD diagnosis (HR=2.27, 95% CI=2.01-2.56). Specific antidepressants showed varied risk levels, with selective serotonin reuptake inhibitors (SSRIs) consistently showed a higher conversion risk, while other antidepressants also indicated elevated risks within the first six months post-diagnosis, notably norepinephrine–dopamine reuptake inhibitors (NDRIs)[p2] (HR=11.06) and serotonin antagonist and reuptake inhibitors (SARI[p3] s) (HR=8.03). Augmentation strategies involving antipsychotics and mood stabilizers revealed a significantly higher risk during the initial six-month period (HR=1.56). Benzodiazepine use also presented an elevated conversion risk across all timeframes (HR=1.17). Moreover, patients who later converted to BP had higher mean antidepressant and mood stabilizer usage compared to those who remained in the MDD group. Discussion & Conclusions This study demonstrates a significant link between increased psychotropic medication use, particular antidepressants, and the risk of progression from MDD to BP. Our findings highlight the importance of careful monitoring and tailored treatment for MDD patients, especially those with heightened risk factors. Future research is needed to uncover the mechanisms driving this progression and to explore preventive strategies.