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Evidence summaries

Venlafaxine in the Treatment of Neuropathic Pain

Venlafaxine is effective in the treatment of different kinds of neuropathic pain, with a significantly better side-effects profile than tricyclic antidepressants. Level of evidence: "A"

Venlafaxine is an antidepressive agent acting as a serotonin and a weak noradrenaline reuptake inhibitor. Venlafaxine has no anticholinergic effects.

A double-blind, randomized, placebo-controlled study1 on the efficacy and safety of 6 weeks of venlafaxine ER (extended-release; 75 mg and 150-225 mg) treatment included 244 adult outpatients with metabolically stable type 1 or 2 diabetes with painful diabetic neuropathy. Baseline pain intensity was 68.7 mm (moderately severe) on the daily 100 mm Visual Analog Pain Intensity (VAS-PI). At week 6, the percentage reduction from baseline in VAS-PI was 27% (placebo), 32% (75 mg), and 50% (150-225 mg; p<0.001 vs placebo). Mean VAS-PR (Pain Relief) scores in the 150-225 mg group were significantly greater than placebo at week 6 (44 vs 60 mm; p<0.001). The number needed to treat (NNT) for 50% pain intensity reduction with venlafaxine ER 150-225 mg was 4.5 at week 6. These NNT values for higher dose venlafaxine ER are comparable to those of tricyclic antidepressants and the anticonvulsant gabapentin. Nausea and somnolence were the most common treatment-emergent adverse events. Seven patients on venlafaxine had clinically important ECG changes during treatment.

In a randomized, double blind, and placebo-controlled study 2 with a three-way crossover, venlafaxine was compared with imipramine in the treatment of painful polyneuropathy. Forty patients were assigned to one of the treatment sequences, and 29 completed all three study periods, each of 4 weeks' duration. The daily doses were venlafaxine 225 mg and imipramine 150 mg. The sum of the individual pain scores during treatment week 4 was lower on venlafaxine (80% of baseline score; p=0.006) and imipramine (77%; p=0.001) than on placebo (100%) and did not show any statistical difference between venlafaxine and imipramine (p=0.44). The individual pain scores for pain paroxysms, constant pain, and pressure-evoked pain showed a similar pattern, whereas touch-evoked pain was uncommon and was not altered by any of the drugs. Numbers needed to treat to obtain one patient with moderate or better pain relief were 5.2 for venlafaxine and 2.7 for imipramine.

Postmastectomy pain syndrome (PMPS) is a neuropathic pain syndrome that may develop following breast surgery. In a placebo-controlled study on the efficacy of venlafaxine in the prevention of PMPS 3, 100 patients scheduled for either partial or radical mastectomy with axillary dissection were administered either venlafaxine or placebo for two weeks starting the night before surgery. Patients were administered PCA morphine for the first 24 hours following surgery and then acetaminophen/oxycodone tablets. Pain scores were recorded at rest and movement on day 1, at 1 month, and at 6 months after surgery. At 6 months postoperatively, pain scores with movement were lower in the venlafaxine group. Pain scores at all other time intervals were similar. There was a significant decrease in the incidence of chest wall pain (55% vs. 19%, p=0.0002), arm pain (45% vs. 17%, p=0.003), and axilla pain (51% vs. 19%, p=0.0009) between the control group and the venlafaxine group, respectively. No significant differences were noted between the two groups with regard to edema, phantom pain, or sensory changes.

A randomized, double-blind, crossover comparison of venlafaxine and inactive placebo in the treatment of neuropathic pain following treatment of breast cancer 4 included thirteen patients. The study lasted 10 weeks. The number of tablets (18.75 mg) taken daily was increased by one at a 1 week interval. The average daily pain intensity as reported in the diary (primary outcome) was not significantly reduced by venlafaxine compared with placebo. However, the average pain relief (diary) and the maximum pain intensity (retrospective assessment by the Painscreen-computer program) were significantly lower with venlafaxine compared with placebo. Anxiety and depression were not affected. Adverse effects did not show significant differences between treatments. High blood concentrations of venlafaxine were associated with excellent pain relief.

A randomized, double-blind, crossover comparison of venlafaxine and placebo in the treatment of atypical facial pain (AFP) 5 consisted of 2 treatment periods, each of 4 weeks' duration, separated by a 2-week washout period. Thirty patients diagnosed with AFP were recruited; twenty patients completed the trial (two were uneligible, eight discontinued because of adverse effects and two were excluded because of non-compliance). There was no significant difference in pain intensity reduction between the maximum tolerated dose of venlafaxine (75 mg in most cases) and the placebo. Pain relief was significantly greater with venlafaxine than with the placebo treatment. Significantly more escape medication was consumed during the placebo period compared with the venlafaxine period. No significant correlation was found between the serum concentration of the drug and the response to treatment. Anxiety and depression scores did not differ between venlafaxine and placebo treatment. Adverse effects were equally common during both treatments.

In patients with migraine with or without aura the prophylactic effect of amitriptyline and venlafaxine was compared in a randomized double-blind crossover study 6. The patients (n=52) were randomly treated with one of the study medications for 12 weeks. After a wash-out period lasting 4 weeks the patients were treated with the other drug for further 12 weeks. Intolerable side effects resulted in drop out of five patients on amitriptyline (hypersomnia, difficulty in concentration, orthostatic hypotension) and one on venlafaxine (nausea and vomiting). Total number of side effects of venlafaxine was low when compared with the side effect profile of amitriptyline. Both drugs had significant beneficial effect on pain parameters.It is suggested that venlafaxine may be considered for the prophylaxis of migraine because of its low and/or tolerable side effect properties.

    References

    • Rowbotham MC, Goli V, Kunz NR, Lei D. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain 2004 Aug;110(3):697-706. [PubMed]
    • Sindrup SH, Bach FW, Madsen C, Gram LF, Jensen TS. Venlafaxine versus imipramine in painful polyneuropathy: a randomized, controlled trial. Neurology 2003 Apr 22;60(8):1284-9. [PubMed]
    • Reuben SS, Makari-Judson G, Lurie SD. Evaluation of efficacy of the perioperative administration of venlafaxine XR in the prevention of postmastectomy pain syndrome. J Pain Symptom Manage. 2004 Feb;27(2):133–9.
    • Tasmuth T, Härtel B, Kalso E. Venlafaxine in neuropathic pain following treatment of breast cancer. Eur J Pain 2002;6(1):17-24. [PubMed]
    • Forssell H, Tasmuth T, Tenovuo O, Hampf G, Kalso E. Venlafaxine in the treatment of atypical facial pain: a randomized controlled trial. J Orofac Pain 2004 Spring;18(2):131-7. [PubMed]
    • Bulut S, Berilgen MS, Baran A, Tekatas A, Atmaca M, Mungen B. Venlafaxine versus amitriptyline in the prophylactic treatment of migraine: randomized, double-blind, crossover study. Clin Neurol Neurosurg 2004 Dec;107(1):44-8. [PubMed]
    • Mattia C, Paoletti F, Coluzzi F, Boanelli A. New antidepressants in the treatment of neuropathic pain. A review. Minerva Anestesiol 2002 Mar;68(3):105-14. [PubMed]

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