Impact of sex and complex PTSD comorbidity on pharmacological treatment response in bipolar disorder patients

Background: The prevalence of bipolar disorder (BD) is similar in men and women. However, factors such as sex and comorbid psychiatric conditions can influence its clinical presentation and treatment outcomes, including complex PTSD (cPTSD), a newly categorized trauma-related condition. Little is known about how sex and cPTSD comorbidity affect the response to mood stabilizers, a cornerstone treatment for BD. This observational, cross-sectional study examines the impact of sex and cPTSD comorbidity on clinical and behavioral BD features as well as their interplay in influencing pharmacological treatment response. Methods: A cohort of BD patients (females = 177, males = 166, age range: 19-76; BD-I = 253, BD-II = 90) was recruited over three years. Clinical assessments were conducted, and patients were administered the International Trauma Questionnaire to evaluate cPTSD comorbidity and the Alda Scale to assess response to mood stabilizers. Results: Our results show distinct clinical profiles based on sex and cPTSD. Female BD patients exhibit more hypomanic episodes, antidepressant-induced mania, and longer periods of untreated illness than males. Comorbid cPTSD was diagnosed in 154 patients (44.8 %), among which 69 were females. Patients with cPTSD display more severe BD symptoms, including earlier onset, more frequent episodes, and a higher prevalence of psychosis and suicidality. Importantly, comorbid cPTSD was associated with poorer mood stabilizer response, particularly in males, who otherwise responded better to treatment than females. Conclusions: These findings underscore the importance of addressing trauma symptoms in BD treatment and highlight the need for individualized approaches considering both sex and comorbid trauma, as standard mood stabilizers may be insufficient for certain subgroups.