Duloxetine, an antidepressant, was shown to reduce painful peripheral neuropathy caused by neurotoxic chemotherapy in a study published in JAMA. Researchers from the University of Michigan School of Nursing added that duloxetine benefited the majority of patients in their study.
Many patients who undergo chemotherapy develop neuropathy – an unpleasant sensation of tingling and numbness in their hands and feet. This discomfort can sometimes work its way up to the shins, calf muscles, and the forearm.
In about 2 to 4 in every 10 patients who undergo neurotoxic chemotherapy (e.g. bortezomib, vinca, taxanes, alkaloids and platinums) neuropathy can linger for years after treatment. The pain and discomfort can seriously undermine the quality of life of cancer survivors.
The authors explained that chemo-induced peripheral neuropathy is very hard to manage. The majority of randomized controlled trials that have tested a range of drugs with diverse mechanisms of action have not revealed any compellingly effective treatment.
Assistant Professor Ellen M. Lavoie Smith, Ph.D., APRN, AOCN, and team set out to determine whether duloxetine might help relieve the symptoms of peripheral neuropathy in patients who received chemotherapy. The drug has been shown to help diabetic patients with peripheral neuropathy.
Duloxetine, sold under brand names Cymbalta, Duzela, Yentreve, and Ariclaim is an SNRI (serotonin-norepinephrine reuptake inhibitor), a type of antidepressant that is manufactured and marketed by Eli Lilly. It has been approved for the treatment of major depressive disorder and generalized anxiety disorder. Duloxetine is also approved in Europe for stress urinary incontinence. It is also used to relieve the symptoms of peripheral neuropathy among diabetic patients, as well as controlling the symptoms of fibromyalgia.
The team carried out a randomized Phase III trial involving 231 patients aged at least 25 years. The study spanned from April 2008 to March 2011. They were all followed up regularly until July 2012. To be eligible, patients needed to have a pain score of 4 or more on a scale of 0 to 10.
The patients were randomly selected into two groups:
- The duloxetine followed by placebo group
- The placebo followed by duloxetine group
Initially, treatment consisted of taking one 30mg capsule each day of either duloxetine or placebo during week 1, and then 2 capsules of either 30mg of placebo or duloxetine each day for four weeks.
At the end of the initial treatment period:
- Those in the duloxetine followed by placebo group experienced an improvement in pain score of 1.06
- The patients in the placebo followed by duloxetine group experienced an improvement in pain score of 0.34
The observed average difference in the average pain score between the duloxetine followed by placebo group and placebo followed by duloxetine group was 0.73.
Fifty-nine percent of those in the duloxetine first group reported a reduction in pain, compared to 38% in the placebo first group. Ten percent reported greater pain and 30% reported no change in pain among the duloxetine-treated patients.
Patients who had been on platinums (oxaliplatin) appeared to benefit more from duloxetine therapy compared to those who had received taxanes.
The study found that pain-related quality-of-life improved significantly more among participants on duloxetine during the initial treatment compared to patients who were on placebo. The researchers wrote:
“In conclusion, 5 weeks of duloxetine treatment was associated with a statisti¬cally and clinically significant improve¬ment in pain compared with placebo. Exploratory analyses raise the possibility that duloxetine may work better for oxaliplatin-induced rather than taxane-induced painful chemotherapy-induced peripheral neuropathy.”
Dr. Smith reported at the American Society of Clinical Oncology Annual Meeting in June 2012 that duloxetine helped relieve painful tingling feelings caused by chemotherapy in 59 percent of patients in a study. Participants had been randomly selected to receive duloxetine or placebo for five weeks. Dr. Smith said “These drugs don’t work in everyone. The good news is it worked in the majority of patients. We need to figure out who are the responders. If we can predict who they are, we can target the treatment to the people it’s going to work for.”