Imipramine Delays Local Recurrence, Distant Metastasis in Prostate Cancer

The tricyclic antidepressant imipramine may suppress the progression of prostate cancer by delaying local recurrence and distant metastasis following radical prostatectomy, according to a study presented at the 2022 American Urological Association Annual Meeting.

According to Seung-Hwan Jeong, MD, who presented the research findings, treatment with imipramine has previously been shown to result in improvements of stress incontinence following radical prostatectomy. These improvements are reportedly attributable to increased levels of norepinephrine and serotonin with promotion of anticholinergic signaling and relaxation of urinary bladder muscles.

Despite preclinical findings which have demonstrated the potential of imipramine in preventing prostate cancer progression via inhibition of migration and invasion, Dr. Jeong and colleagues noted that these findings have not been validated on clinical trials.

In their study, Dr. Jeong and colleagues evaluated data of patients with prostate cancer who were enrolled in the prospective cohort clinical database Seoul National University Prospective Enrolled Registry for Prostate Cancer (SUPER-PC) between March 2016 and December 2019.

The study cohort included 239 imipramine-naïve cases matched with 1256 imipramine-exposed cases. Those exposed to imipramine received the therapy for more than 3 months. A Cox proportional hazards regression model was used to assess biochemical recurrence (BCR), clinically proven local recurrence, and distant metastasis.

Propensity score matching resulted in a final cohort of 211 imipramine-naïve patients matched with 783 imipramine-exposed patients. Clinical characteristics such as ASA score, diabetes, and hypertension were similar between groups; however, mean age was significantly higher in patients who received imipramine (66.0 vs. 67.9 years, p<0.001).

The groups also had comparable unfavorable pathologic T (over T3: 33.2% vs. 35.6%, p=0.507) and N (N1: 5.2% vs. 3.6%, p=0.277) stages. Imipramine-exposed cases had more prevalent Gleason scores of 7 compared with imipramine-naïve cases (GS 6/7/8-10: 18.5/73.5/8.1% vs 11.4/83.3/5.4%, respectively; p=0.005).

Those who received imipramine did not experience a significant benefit in recovery of continence at 12 months after radical prostatectomy (98.6% vs. 96.9%, p=0.192). Additionally, there was no difference between the 2 groups in terms of BCR at 12 months (hazard ratio [HR]=0.96; 95% CI 0.66-1.38) in the multivariate analysis.

The imipramine-exposed cases, however, experienced significant delays in local recurrence (HR=0.21; 95% CI 0.05-0.78) and distant metastasis (HR=0.26; 95% CI 0.76-0.92) compared with cases not exposed to imipramine.