Elevated salivary cortisol predicts response to adjunctive immune modulation in treatment-resistant bipolar depression

Abstract

• Adjunctive CBX treatment significantly improved response and remission rates in TRBDD. • Baseline high salivary cortisol independently predicted HAMD17 and MADRS scores at posttreatment. • Use of multivariate linear regression models can be of predictive value of end of treatment response. • A high HPA-axis setpoint at baseline may predict treatment response. Adjunctive inflammatory treatments improve response and remission rates in treatment-resistant bipolar depression (TRBDD), but underlying mechanisms remain unclear. Given the association between hypothalamic-pituitary-adrenal (HPA) axis dysregulation and treatment-resistant depression, we investigated the pre-treatment HPA-axis profile in relation to treatment response. This is a secondary analysis of 31 TRBDD patients with moderately severe depression scores as assessed with the Hamilton Depression Rating Scale 17 (HAMD17), who were randomized to receive either escitalopram (ESC) (10–40 mg daily) + celecoxib (CBX) (200 mg twice daily), or ESC (10–40 mg daily) + placebo (PBO) (twice daily). Salivary cortisol was measured at baseline. A multivariate linear regression model was applied to evaluate whether depression scores at Week 8 were related to CBX and baseline salivary cortisol, adjusting for sex, age, BMI, and baseline depression scores. We utilized the HAMD17 and Montgomery-Asberg Depression Rating Scale (MADRS). Coefficient of determination (R 2 ) for week 8 MADRS and HAMD17 scores were 0.907 and 0.624 (both p -value <0.001), respectively. Baseline salivary cortisol at 30 min after awakening (β=-0.374, p- value=0.004), before lunch (β=-1.764, p- value=0.002), and cortisol-awakening response (β=0.692, p- value=0.003) were significantly anticorrelated with MADRS at posttreatment. Similarly, baseline salivary cortisol before lunch (β=-0.665, p- value=0.041), and 3:00PM (β=-0.434, p- value=0.061) was significantly anticorrelated with HAMD17 at posttreatment. Both analyses were adjusted for sex, age, and BMI. / * Increased salivary cortisol levels at baseline diurnal timepoints independently predicted posttreatment depression scores in TRBDD patients treated with either with antidepressant monotherapy or combined CBX therapy.