Antidepressant unable to prevent chemotherapy-associated nerve damage, suggests study

A randomized trial conducted by the Alliance for Clinical Trials in Oncology with support from the National Cancer Institute has found that duloxetine, a medication commonly used to treat chronic pain and psychiatric conditions, does not prevent nerve damage caused by chemotherapy in patients with colorectal cancer. The primary analysis of Alliance A221805 was published in JCO Oncology Advances.

Oxaliplatin is a standard chemotherapy drug used to treat colorectal cancer, but it can often lead to peripheral neuropathy, a sometimes permanent side effect that causes numbness, tingling, and pain in the hands and feet. Duloxetine, often prescribed for chronically painful conditions such as osteoarthritis and diabetic neuropathy, and numerous psychological conditions (e.g., anxiety, depression), is already recommended for the treatment of established painful chemotherapy-induced peripheral neuropathy.

“Since we know duloxetine is effective at treating painful neuropathy caused by neurotoxic chemotherapy drugs, we wanted to see if the medication could also prevent the side effect from developing in the first place,” said Ellen M. Lavoie Smith, PhD, MSN, Interim Associate Dean of Research and Scholarship at the University of Alabama at Birmingham School of Nursing and study chair for Alliance A221805. “The results show that duloxetine is not more effective than a placebo at preventing neuropathy caused by chemotherapy in patients with colorectal cancer.”

Led by Dr. Smith, this is the largest randomized trial to date specifically designed to evaluate whether duloxetine can prevent oxaliplatin‑induced peripheral neuropathy.

In the double‑blind, placebo‑controlled trial, 199 adults with stage II or III colorectal cancer were enrolled at 73 cancer centers throughout the United States. Participants had no pre‑existing neuropathy and were randomly assigned to receive:

• Duloxetine 30 mg daily
• Duloxetine 60 mg daily
• Placebo

Treatment began on the first day of oxaliplatin‑based chemotherapy and continued for 17 weeks. The primary endpoint was a patient‑reported composite measure of neuropathy severity and onset, assessed several weeks after completion of chemotherapy. Results showed no statistically or clinically meaningful difference between either duloxetine dose or placebo.

“While duloxetine remains an important option for managing painful chemotherapy‑induced neuropathy once it develops, this trial confirms that it should not be used for prevention,” Dr. Smith said.

The findings highlight the ongoing unmet need for effective strategies to prevent chemotherapy‑induced nerve damage, which can significantly affect long‑term quality-of-life for cancer survivors.

Reference:

Ellen M. Lavoie Smith et al. Alliance A221805: Duloxetine to Prevent Oxaliplatin-Induced Chemotherapy-Induced Peripheral Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase II Study. JCO Oncol Adv 3, e2500107(2026). mDOI:10.1200/OA-25-00107