To evaluate the role of interpersonal psychological therapy (IPT) in antidepressant therapy and explore its mechanism using 1 H-MRS. Methods: Seventeen patients with depression were included in the patient group, and 17 healthy volunteers who underwent physical examination were included as the control group. Patients with depression were treated with IPT for 4 weeks. The positive and negative symptoms scale (PANSS) and Hamilton Depression Scale (HAMD-24) were employed before treatment and after 28 days of treatment to evaluate efficacy. 1 H-MRS of the hypothalamus was performed to analyze and compare the N-acetyl aspartic acid (NAA)/[choline complex (Cho) + creatine (Cr)], NAA/Cr, NAA/Cho, and Cho/Cr ratios in the 2 groups before and after treatment. Results: In patients, PANSS negative symptoms, general condition, total score, and HAMD-24 score were significantly decreased after treatment (P<0.01), and PANSS positive symptoms were not statistically significant (P>0.05). The NAA/(Cho + Cr), NAA/Cr, and NAA/Cho in the patient group before treatment were significantly lower than those of the control group (P<0.01). After treatment, patient group NAA/(Cho+Cr), NAA/Cr, and NAA/Cho were significantly higher than those before treatment (P<0.01) though still lower than those of the control group (P<0.01). There was no statistically significant difference in Cho/Cr between the three groups (P>0.05). NAA/(Cho+CR) was significantly correlated with the PANSS total score and HAMD-24 score (P<0.05); NAA/Cho was significantly correlated with the PANSS total score; and NAA/Cr was significantly correlated with the HAMD-24 score (P<0.05). Conclusion: IPT can improve the severity of depression in patients, possibly by regulating the ratio of metabolites in the hippocampus.