Title: Effect of music therapy on cardiac autonomic nerve function in patients  with major depressive disorder. Background: Association of reduced HRV in major depressive disorder (MDD) is related to increased risk of  cardiovascular disease (CVD). Music therapy had been reported to be effective in depression. Objective: To assess the effect of music therapy on cardiac autonomic nerve function (CANF) by HRV analysis in patients with MDD. Methods: This prospective  interventional study was conducted in the  Department of Physiology, BSMMU, Dhaka on 60 newly diagnosed MDD patients aged 20-40 years of both sex from the OPD of  Psychiatry ,BSMMU. These patients were subdivided into two groups according to the study design. Thirty patients received only antidepressant medication (Mirtazapine) for 3 months (Group B1). Another group of 30 patients listened to selected Raga Kafi based Rabindra Sangeet in addition to antidepressant medication for 3 months (Group B2). For comparison,  30 apparently  healthy subjects (Group A) with similar age, BMI and sex were also studied. All subjects were studied at day 0 and after day 90 (3 months). CANF were assessed by Heart Rate Variability (HRV) analysis. HRV data were recorded by Powerlab. Serum cortisol level of all subjects were assayed by ELISA in a similar manner. For statistical analysis paired and unpaired sample t test, ANOVA were done as applicable. Results: At baseline i.e. before intervention period, resting pulse rate(p<0.001), systolic (SBP) and diastolic blood pressure (DBP) (p<0.001), serum cortisol (p<0.001), mean heart rate (p<0.001), Low frequency in normalized unit (LF norm) (p<0.001) and Low frequency/High frequency (LF/HF) (p<0.001) were significantly higher and mean RR interval(p<0.001), standard deviation of the RR intervals (SDRR)(p<0.001), the coefficient of variation of the RR interval (CVRR)(p<0.001), the standard deviation of the difference between successive RR intervals (SDSD)(p<0.001), square root of mean squared differences of successive RR intervals (RMSSD)(p<0.001), proportion of RR interval with duration >50 ms (pRR50%)(p<0.001), Total power (TP)(p<0.001), Low Frequency (LF) power(p<0.001), High Frequency (HF) power(p<0.001), HF normalized unit (HF n.u.) (p<0.001), the standard deviation of the short term RR interval variability (SD1) (p<0.001),  the standard deviation of the long term RR interval variability (SD2)(p<0.001), the ratio of short term and long term variability (SD1/SD2) (p<0.01)were significantly lower in all patients with MDD in comparison to those of healthy control. In the group with music, resting pulse rate (p<0.05), SBP(p<0.001), DBP(p<0.05), serum cortisol (p<0.001), LF n.u. and LF/HF ratio(p<0.001) decreased significantly and SDRR(p<0.001), SDSD (p<0.001), RMSSD(p<0.001), pRR50%(p<0.05), Total power(p<0.05), HF power(<0.01), HF n.u. (p<0.001), SD1 (p<0.001),SD2 (p<0.05) and SD1/SD2 ratio (p<0.01) increased significantly after 3 months of listening to music. In the group with only antidepressant medication, only HF power (p<0.05), HF n.u. (p<0.05), SD2 (p<0.05) significantly increased but others parameters  did not show any significant change after 3 months. Conclusion: Music therapy significantly improved CANF  by increasing  parasympathetic activity and decreasing sympathetic activity and changing sympathovagal balance towards vagal dominance in MDD and antidepressant medication had no role on CANF in MDD.

Key words: Heart rate variability, major depressive disorder, music therapy, antidepressant medication.