By Thomas G. Ciccone
Serotonin-norepinephrine reuptake inhibitors (SNRIs) typically are considered first-line treatments for neuropathic pain.1 Duloxetine and venlafaxine are 2 selective SNRIs considered appropriate for neuropathic pain patients, although new data suggest duloxetine may be a superior option to venlafaxine.
A new study conducted by researchers based out of the VA Tennessee Valley Healthcare System in Murfreesboro, Tennessee, completed a head-to-head analysis between the 2 drugs, examining the percentage of patients able to achieve a therapeutic dose, time taken to reach therapeutic dose, and any adverse effects associated with the treatments.2
They found significantly more patients were able to achieve a therapeutic dose taking duloxetine. Titrating to a therapeutic dose was also much faster compared to venlafaxine. Duloxetine also appeared to be an effective alternative for patients who had been nonresponders to previous venlafaxine therapy.2
“When looking at efficacy in neuropathic pain, these medications are thought to be comparable,” because up to this point, there simply has been a lack of research into which medication could be more preferable, lead investigator Kelsie Flynn, PharmD, told PPM.
Given that health care systems base such formulary decisions on cost, generic venlafaxine has been considered the more cost-effective treatment. It wasn’t until 2013 that duloxetine became available in generic form. “Before that, it was only available through the brand Cymbalta [Eli Lilly and Company],” Dr. Flynn explained. Maintaining the status quo, health care systems may have stuck to venlafaxine as the SNRI of choice for neuropathic pain. However, given these new data, duloxetine may offer superior benefit to patients with neuropathic pain.2
SNRIs for Neuropathic Pain
Proper drug selection of neuropathic pain is a chief concern for practitioners. Previous research into duloxetine has found this drug a preferable option for patients with diabetic peripheral neuropathy (DPN), with strong indications for sustained efficacy over 1 year.3 Indeed, a 2012 study found that veterans benefitted the most from duloxetine treatments for their diabetic peripheral neuropathic pain (DPNP).4
In this new VA study, researchers similarly looked at retrospective chart data of veterans who started initial prescriptions of either venlafaxine or duloxetine over a 3-year period (January 1, 2011 to January 1, 2014).
Researchers examined numerous patient characteristics, including:
Concomitant Antidepressants and Anticonvulsants On Date of Initiation
Out of the 302 patients featured in the study, researchers split the study population into 2 groups (n-1510: patients initiating duloxetine and patients initiating venlafaxine (Table 1).2
Duloxetine appeared to offer a superior rate of success in titrating patients to a successful, therapeutic dose, considering 37.6% more patients who were taking duloxetine were able to achieve a therapeutic dose compared to those taking venlafaxine, at 120 vs. 82, respectively (P<0.0001).2 Unfortunately, researchers were not able to assess types of neuropathic pain or pain severity scores and correlate the data to titration success with either drug.
“Pain severity is very difficult to accurately assess in a retrospective study and is highly subjective and dependent on quality of documentation between providers,” Dr. Flynn explained. But titration schedules did show a high success rate with duloxetine, regardless of patient indications. Duloxetine also appeared to work faster, in general, for neuropathic pain patients, with a median time to therapeutic dose (TTD) of 7 days (0-44.25, IQR).2 This was significantly different from venlafaxine titrations, which had a median TTD of 31.5 days (10-115, IQR).
“As venlafaxine and duloxetine have very different titration schedules, [the data] highlights the difference in tolerability between medications, depending on how quickly each is titrated to their therapeutic dose,” Dr. Flynn said. “We also assessed reasons for discontinuation, including side effects and these results may prove beneficial when selecting an SRNI on a patient-to-patient basis.”
Importance of Titration With SNRI’s
Titration schedule with venlafaxine appeared to have a serious impact on the rate of discontinuation seen in patients, accounting for approximately 80% of discontinuation cases that occurred in the first 60 days of titration. On the other hand, duloxetine’s titration schedule appeared more forgiving, only accounting for approximately 60% of discontinuation cases in the first 14 days of titration, decreasing up to the 90-day point.
“As duloxetine’s therapeutic dose is 60 mg daily and venlafaxine’s therapeutic dose is 150 mg to 225 mg daily, the titration schedule for venlafaxine is more complex and has more steps compared to duloxetine, where most patients are initiated on 30 mg daily and then increased to 60 mg daily,” Dr. Flynn said. Rate of titration also can play a significant factor in whether a patient is likely to stick to a medication. If titration schedules are too fast, adverse events could force patients to discontinue.
“Conversely, if the titration schedule is too slow, patients may not achieve adequate pain relief with the medication,” Dr. Flynn said. Side effects appeared to be less common for patients taking duloxetine, where 22% of patients taking duloxetine reported side effects compared to the 37% of those taking venlafaxine (P=0.0053). Duloxetine may also be a useful alternative for patients unresponsive to venlafaxine, considering 117 (77%) of patients who were in the duloxetine group had had a previous unsuccessful trial with venlafaxine.
“This could be seen as a major limitation to the research,” Dr. Flynn noted. Because the vast majority of patients in the duloxetine group already had an unsuccessful trial with venlafaxine, they could have been considered at higher risk for medication failure. The duloxetine patients were also older than the patients taking venlafaxine.
“Older patients with previous failure of venlafaxine would not be expected to succeed at a higher rate with an alternative medication in the same class,” just another factor that makes the results all the more surprising, said Dr. Flynn. “The best treatment outcome is remaining on the prescribed medication at a therapeutic dose, long-term, which was significantly higher in the duloxetine group,” added Dr. Flynn, who believes these data could offer some practical insight for practitioners making the first choice of SNRI for a neuropathic pain patient.
“Both medications are thought to provide similar pain relief at their individual therapeutic doses. However, as duloxetine’s therapeutic dose can be achieved with only a one-step titration, this may be more attractive to providers. More impressive, however, is that more patients will succeed and tolerate the titration and ultimately stay on it longterm as compared to venlafaxine,” Dr. Flynn concluded.
The authors of the study reported no relevant conflicts of interest.
- Dworkin RH, O’Connor AB, Audette J, et al. Recommendations for the pharmacological management of neuropathic pain: An overview and literature update.Mayo Clin Proc. 2010;85(3Suppl):S3-S14.
- Flynn K, Atkinson T, Baker J. Comparison of venlafaxine and duloxetine: Measuring clinical impact of time to therapeutic dose (TTD) among patients achieving therapeutic dosing for pain. Presented at: PAINWeek 2016; September 6-10, 2016; Las Vegas, Nevada.
- Raskin J, Smith TR, Wong K, et al. Duloxetine versus routine care in the long-term management of diabetic peripheral neuropathic pain.J Palliat Med. 2006;9(1):29-40.
- Zhao Y, Liu J, Thethi T, et al. Predictors of duloxetine versus other treatments among veterans with diabetic peripheral neuropathic pain: A retrospective study.Pain Pract. 2012;12(5):366-373.