PEP Topic 
Peripheral Neuropathy

Venlafaxine is used to treat depression and has also been used to treat hot flashes in women who have experienced menopause or who are taking medication to treat breast cancer. Venlafaxine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SNRIs) which increase the amounts of serotonin and norepinephrine in the brain. Venlafaxine comes as a tablet or extended-release capsule to take by mouth. In addition, venlafaxine has been studied as an intervention for sleep-wake disturbances, peripheral neuropathy, and fatigue in patients with cancer.

Effectiveness Not Established

Research Evidence Summaries

Durand, J.P., Deplanque, G., Montheil, V., Gornet, J.M., Scotte, F., Mir, O., . . . Goldwasser, F. (2012). Efficacy of venlafaxine for the prevention and relief of oxaliplatin-induced acute neurotoxicity: Results of EFFOX, a randomized, double-blind, placebo-controlled phase III trial. Annals of Oncology, 23, 200–205.

doi: 10.1093/annonc/mdr045

Study Purpose:

The aim of the study was to evaluate the efficacy of venlafaxine for the prevention and treatment of oxaliplatin-induced peripheral neuropathy.

Intervention Characteristics/Basic Study Process:

Patients who reported distressing acute neurotoxicity after oxaliplatin-based chemotherapy were randomly assigned to receive either placebo or venlafaxine hydrochloride 50 mg one hour prior to chemotherapy infusion and venlafaxine extended release 37.5 mg twice daily from day 2 to day 11. Placebo was given with the same timing. From day 12 on, no venlafaxine extended release was given. Study treatment continued as long as the oxaliplatin treatment lasted. Study evaluation and data collection was conducted pretreatment, daily on day 1 through 5 of chemotherapy treatment, and at three months after study completion.

Sample Characteristics:

  • A total of 42 patients were studied (21 women, 21 men)
  • The median age was 67.4 years with a range of 32–84.4 years.
  • Patients had multiple tumor types,
  • Most patients were receiving FOLFOX. The median number of cycles at study inclusion was 4.5.


The study was conducted at a single outpatient setting in France.

Phase of Care and Clinical Applications:

Phase of care

  • Active antitumor treatment

Study Design:

The study had a double blind, placebo-controlled, randomized trial design.

Measurement Instruments/Methods:

  • Neuropathic pain symptom inventory
  • Numeric rating scale for functional impairment


The proportion of patients reporting full relief of acute neurotoxic symptoms was 31.3% compared to 5.3% in the placebo group (p = 0.03).  In the venlafaxine group, 68.8% reported more than 50% symptom relief compared to 26.3% on placebo (p = 0.02). There were no grade 3 or 4 adverse events related to venlafaxine. Among those receiving venlafaxine, the most common adverse events were nausea and vomiting, asthenia, orthostatic hypotension, and somnolence. These side effects occurred more frequently in the venlafaxine group (p < 0.03).


The findings suggest that venlafaxine as studied here is effective in reducing acute neurotoxic symptoms associated with oxiplatin chemotherapy.


A small sample size (less than 100 participants)

Nursing Implications:

The findings provide support for the efficacy of venlafaxine to prevent acute oxiplatin-related neurotoxicity. The study is limited by sample size, so the results are inconclusive. Additional research in this area is warranted.

Systematic Review/Meta-Analysis

Hershman, D.L., Lacchetti, C., Dworkin, R.H., Lavoie Smith, E.M., Bleeker, J., Cavaletti, G., . . . American Society of Clinical Oncology. (2014). Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. Journal of Clinical Oncology, 32, 1941–1967.

doi: 10.1200/JCO.2013.54.0914


STUDY PURPOSE: To provide evidence-based guidance on optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy in adult cancer survivors

TYPE OF STUDY: Systematic review

Search Strategy:

DATABASES USED: Ovid Medline (1946–April, week 2, 2013); EMBASE (1980–2013, week 16); AMED Allied and Complementary Medicine (1985–April 2013)

KEYWORDS: chemotherapy-induced peripheral neuropathy; adult cancer survivors; randomized clinical trials

INCLUSION CRITERIA: Adult cancer survivors with chemotherapy-induced peripheral neuropathy; randomized trials

EXCLUSION CRITERIA: Phase 1 trials; published in a language other than English; less than 10 patients; focused on radiation or stem cell transplant neuropathy; animal studies

Literature Evaluated:


EVALUATION METHOD AND COMMENTS ON LITERATURE USED: An expert panel representing neurology, nursing, medical oncology, community oncology, pain research, and genetics met through teleconference and emails to review and develop the American Society of Clinical Oncology guidelines.

Sample Characteristics:

  • TOTAL PATIENTS INCLUDED IN REVIEW: Treatment studies: 780; prevention studies: 3,741

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Active antitumor treatment


Forty-two randomized clinical trials involved 19 various interventions for prevention of chemotherapy-induced peripheral neuropathy. These agents included anticonvulsants, antidepressants, vitamins, minerals, and other chemoprotectant drugs. Only six randomized clinical trials discovered six different drugs, such as antidepressants, anticonvulsants, and a topical gel, for the prevention of chemotherapy-induced peripheral neuropathy. The following are not recommended for use: acetyl-l-carnitine, amifostine, amitriptyline, calcium and magnesium, glutathione, nimodipine, ORG 2766, trans retinoic acid, rhuLIF, and vitamin E. Venlafaxine is not recommended for routine use in clinical practice. Although data support potential utility, evidence is not strong enough to suggest use. For treatment of chemotherapy-induced peripheral neuropathy, clinicians can offer duloxetine. No recommendation is made regarding ALC. Tricyclic antidepressants or gabapentin through trial use may be reasonable.  The panel felt that trying topical gel containing baclofen, amitriptyline, and ketamine would be reasonable. 


No agents were recommended for the prevention of chemotherapy-induced peripheral neuropathy, but duloxetine is moderately recommended for the treatment of chemotherapy-induce peripheral neuropathy. Even though conclusive evidence is lacking to recommend tricyclic antidepressants such as nortriptyline, gabapentin, and a topical gel containing baclofen,amitriptyline, and ketamine for treatment of chemotherapy-induced peripheral neuropathy, the expert panel agreed that offering these agents based on treatment for neuropathic pain is reasonable. The panel also recommended that patients be counseled regarding the lack of evidence in treating chemotherapy-induced peripheral neuropathy with these agents.


  • Small, insufficient sample
  • Inability to compare studies because of different outcomes
  • Measurements and instruments used at different points in treatment

Nursing Implications:

Nurses are at the frontline in assessing patients who are receiving agents with the potential for chemotherapy-induced peripheral neuropathy. Nurses should be aware of the standard of care in treating this population. Many drugs prescribed have no evidence in preventing or treating these patients. However, with these American Society of Clinical Oncology guidelines, a role for duloxetine is clear and a role for tricyclic antidepressants is possible. Nurses need to be knowledgeable about this information to better inform patients.