Kautio, A.L., Haanpaa, M., Leminen, A., Kalso, E., Kautiainen, H., & Saarto, T. (2009). Amitriptyline in the prevention of chemotherapy-induced neuropathic symptoms. Anticancer Research, 29, 2601–2606.

The purpose of the study was to determine if amitriptyline would be effective in treating chemotherapy-induced peripheral neuropathy (CIPN) compared to placebo.

Patients were allocated to amitriptyline or placebo groups. Treatment was started at 25 mg per day, and doses were elevated 25 mg per week up to a maximum dose of 100 mg per day if tolerated. Treatment was continued until the end of the neurotoxic chemotherapy. Follow-up visits were performed every two months and patients were asked to maintain a diary in which they graded neutopathic symptoms by a visual analog scale twice a week. The primary end point was the appearance or progression of neuropathic symptoms based on diary data.

• A total of 99 participants were recruited for this study, with women outnumbering men 72% to 28%, respectively.
• The mean age of study participants was 56 years with a range of 25–75 years.
• The most common diagnoses amongst the participants were ovarian cancer, lymphoma, and colorectal cancers.
• Other key characteristics include receiving vinca alkaloids, platinum-based taxanes, or a combination of these agents.
• Forty-seven percent of the participants were in first-line chemotherapy; 44% were receiving adjuvant chemotherapy.

The study was conducted in an outpatient, single-site setting in Helsinki, Finland.

The study was designed as a double blind, randomized, placebo-controlled parallel group.

Measurements include the National Cancer Institute's Common Terminology Criteria for Adverse Events, the European Organisation for the Research and Treatment of Cancer C30 quality-of-life measure, and a visual analog scale for symptom grading.

The median follow-up was at 19–21 weeks. Seventy-four percent of patients were on the highest dose of amtriptyline, which was well tolerated. Tiredness was the most frequent reason for dose reduction. In addition, no differences were noted in intensity of neuropathy between groups. In the majority of cases, the intensity of neuropathy was mild at grade 1. Neuropathy was seen in 76% of patients after nine cycles of treatment. Because of a lack of effect, the study was discontinued earlier than planned.

The study did not demonstrate any effect by amitriptyline on the prevention or treatment of CIPN.

• Small sample size (less than 100 participants).
• The study was underpowered.
• The study ended early because of a lack of effectiveness in the study design.

The findings from this study do not support the use of amitriptyline for the prevention and management of CIPN.