Venlafaxine is used to treat depression and also sometimes is 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. It works by increasing the amounts of serotonin and norepinephrine in the brain. Venlafaxine comes as a tablet or extended-release capsule to take by mouth. Venlafaxine has been studied as an intervention for hot flashes, sleep-wake disturbances, peripheral neuropathy, and fatigue in patients with cancer.
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.
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
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
TOTAL REFERENCES RETRIEVED = 1,252
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.
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.
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.
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.
The aim of the study was to evaluate the efficacy of venlafaxine for the prevention and treatment of oxaliplatin-induced peripheral neuropathy.
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.
The study was conducted at a single outpatient setting in France.
Phase of care
The study had a double blind, placebo-controlled, randomized trial design.
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)
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.
Kus, T., Aktas, G., Alpak, G., Kalender, M.E., Sevinc, A., Kul, S., . . . Camci, C. (2016). Efficacy of venlafaxine for the relief of taxane and oxaliplatin-induced acute neurotoxicity: A single-center retrospective case-control study. Supportive Care in Cancer, 24, 2085–2091.
To evaluate the effect of venlafaxine 75 mg daily oral administration on peripheral neuropathy (PN) pain severity reduction rates in patients on taxane- or oxaliplatin-based chemotherapy with moderate to severe painful chemotherapy-induced PN (CIPN) compared to participants who refused treatment
Retrospective, case-control, nonblinded design with a venlafaxine-treated group and a case-matched control group that had rejected CIPN treatment
Every three weeks, PN was measured using the 10-item NPSI mean composite score, which ranged from 0 (“no pain”) to 10 (“worst pain imaginable”). Each NPSI item used the same 0–10 NRS to measure patient-reported severity for the past 24 hours of various neuropathic pain symptoms (e.g., burning pain, pain provoked by cold, abnormal pin-and-needle sensations). The severity of venlafaxine-associated adverse effects was also measured using the CTCAE, version 4.03, ranging from 0 (normal) to 4 (life-threatening).
This study provided weak evidence supporting the superiority of venlafaxine compared to no venlafaxine in decreasing PN symptoms among participants with moderate to severe painful CIPN and mild depression while receiving taxane- and/or platinum-based chemotherapy. Participants who received venlafaxine 75 mg once daily experienced a reduction in painful and nonpainful PN symptoms after three weeks that continued through nine weeks, compared to no change in participants who did not receive venlafaxine. Participants with milder PN before treatment experienced the most benefit. However, these results may not be reliable or valid because of the retrospective design and potentially biased study procedures/methods/analysis.
Additional testing of venlafaxine in large prospective, randomized, controlled trials is needed before it can be used in clinical practice to treat CIPN. However, the positive results of this trial emphasize the importance of continual nursing assessment of PN signs and symptoms throughout chemotherapy because pain treatments may be most beneficial to patients with acute mild CIPN.
Zimmerman, C., Atherton, P.J., Pachman, D., Seisler, D., Wagner-Johnston, N., Dakhil, S., . . . Loprinzi, C.L. (2016). MC11C4: A pilot randomized, placebo-controlled, double-blind study of venlafaxine to prevent oxaliplatin-induced neuropathy. Supportive Care in Cancer, 24, 1071–1078.
To obtain data to support conducting a phase III trial of venlafaxine to prevent oxaliplatin-induced neurotoxicity
Patients were stratified according to planned calcium and magnesium administration, cancer stage, and treatment cycle, then randomized to receive venlafaxine extended release 37.5 mg versus placebo twice daily. The study treatment was begun on the evening of the first or second chemotherapy treatment and continued for one week following completion of the FOLFOX treatment. Assessments were taken at baseline, prior to each FOLFOX treatment, and at 1, 3, 6, and 12 months postcompletion.
PHASE OF CARE: Active antitumor treatment
Randomized, double-blind, placebo-controlled trial
No significant differences in any measures of neuropathy outcomes existed between groups.
Venlafaxine did not reduce neuropathic toxicities associated with oxaliplatin.
Small sample (< 100)
Data from this trial do not support the use of venlafaxine for the prevention of neuropathic symptoms associated with oxaliplatin. Ongoing research is needed to identify effective interventions for this treatment complication.