Effects of Venlafaxine and Carbamazepine for Painful Peripheral Diabetic Neuropathy: A Randomized, Double-blind and Double-dummy, Controlled Multi-center Trial_Chinese Journal of Evidence-Based Medicine

Authors：

JIA Haiyan ¹ , LI Qifu ² , SONG Dianping ³ , AN Zhenmei ¹ , LIU Yuping ¹ , RAN Xingwu ¹ , WU Renhua ¹ , TIAN Haoming ¹

1. Department of Endocrinology, West China Hospital of Sichuan University, Chengdu 610041, China 2. Department of Endocrinology, the First Affiliated Hospital of Chongqing University of Medical Science, Chongqing 400016, China 3. Department of Diabetes Mellitus, Kunming Medical College, Kunming 650031, China;

Corresponding author：

Keywords：

Painful peripheral diabetic neuropathy; Venlafaxine; Carbamazepine; Pain; Quality of life

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Objective 　To evaluate the safety and efficacy of venlafaxine and carbamazepine on painful peripheral diabetic neuropathy.
Methods 　This was a randomized, parallel-group, double-blind, double-dummy clinical trial. 132 patients a venlafaxine group (n=66) and a carbamazepine group (n=66) with painful peripheral diabetic neuropathy were recruited from 3 clinical centers. The venlafaxine group took venlafaxine 25 mg plus one dummy carbamazepine tablet twice a day and the carbamazepine group took carbamazepine 0.1 g plus one dummy venlafaxine tablet twice a day both for 2 weeks. The primary efficacy measurement consisted of a numeric pain intensity scale and the secondary measurement assessed quality of life.
Results 　One hundred and nineteen patients completed the trial. Venlafaxine was superior to carbamazepine in improving mean pain intensity scores at 5,7,10 and 14 days by per-protocol analysis (P=0.02, P=0.03, P=0.003 and P=0.001 respectively). The effects of venlafaxine on the improvement in the total quality of life scores were better than those of carbamazepine at 10 and 14 days (P=0.02 and P=0.01 respectively). Sleep interference and mood were improved by both venlafaxine and carbamazepine, but the efficacy of venlafaxine was superior to that of carbamazepine. The common adverse events of venlafaxine included mild gastrointestinal discomfort, dizziness and somnolence. The frequency of adverse events in the venlafaxine group was about 43.9% (4 patients withdrew because of adverse events) and in the carbamazepine group about 25.76% (2 patients withdrew because of adverse events) (P =0.06).
Conclusions　 Venlafaxine and carbamazepine are effective in the treatment of painful diabetic neuropathy, venlafaxine is superior to carbamazepine in improving pain and quality of life. Both drugs may be safe and well tolerated.

Citation： JIA Haiyan,LI Qifu,SONG Dianping,AN Zhenmei,LIU Yuping,RAN Xingwu,WU Renhua,TIAN Haoming. Effects of Venlafaxine and Carbamazepine for Painful Peripheral Diabetic Neuropathy: A Randomized, Double-blind and Double-dummy, Controlled Multi-center Trial. Chinese Journal of Evidence-Based Medicine, 2006, 06(5): 321-328. doi: Copy

1.	Diabetes Control and Complication Trial Research Group: The effect of intensive treatment of diabetes on development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl Med, 1993; 329 (14): 977-986.
2.	Holliday SM, Venlafax BP. A review of its pharmacology and therapeutic potential in depression. Drugs, 1995; 49(7): 280-294.
3.	Khawaja IS, Feinstein RE. Cardiovascular effects of selective serotonin reuptake inhibitors and other novel antidepressants. Heart Dis, 2003; 5(2): 153-160.
4.	Marchand F, Alloui A, Chapuy E, et al. The antihyperalgesic effect of venlafaxine in diabetic rats does not involve the opioid system. Neuroscience letters, 2003; 342(1-2): 105-108.
5.	Lang E, Hord AH, Denson D. Venlafaxine HCL (Effexor) relieves thermal hyperalgesia in rats with an experimental mononeuropathy. Pain, 1996; 68: 151-155.
6.	Kiayias JA, Vlachou ED, Lakka-Papadodima E. Venlafaxine HCL in the treatment of painful peripheral diabetic neuropathy. Diabetes Care, 2000; 23(5): 699.
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8.	Davis JL, Smith RL. Painful peripheral diabetic neuropathy treated with venlafaxine HCl extended release capsules. Diabetes Care, 1999; 22 (11): 1909.
9.	Sindrup, SH, Bach FW, Gram MC, et al. Venlafaxine versus imipramine in painful polyneuropathy: A randomized, controlled trialv. Neurology, 2003; 60(128): 1284-1289.
10.	Rowbotham MC, Goli V, Kunz NR, et al. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain, 2004; 110(3): 697-706.
11.	Backonja MM. Use of anticonvulsants for treatment of neuropathic pain. Nerurology, 2002; 59 (suppl 2): S14-S17.
12.	Chakrabarti AK, Samantaray SK. Diabetic peripheral neuropathy: nerve conduction studies before, during and after carbamazepine therapy. Aust N Z J Med, 1976; 6(6): 565-568.
13.	Gomez-Perez FJ, Choza R, Rios JM, et al. Nortriptyline-fluphenazine vs. carbamazepine in the symptomatic treatment of diabetic neuropathy. Arch Med Res, 1996; 27(4): 525–529.
14.	Eisenberg E, Lurie Y, Braker C, et al. Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study. Neurology, 2001; 57(3): 505-509.
15.	Simpson DA. Gabapentin and venlafaxine for the treatment of painful diabetic neuropathy. Journal of Clinical Neutomuscular Disease, 2001; 3(2): 53-62.
16.	Kapwz S, MannJJ MT. Antidepressant medication and the relative risk of suicide attempt and suicide. J Am Med Assoe, 1992; 268: 344-345.
17.	Grothe DR, Scheckner B, Albano D. Treatment of pain syndromes with venlafaxine. Pharmacotherapy, 2004; 24(5): 621-629.
18.	Muth EA, Haskins JT, Moyer JA, et al. Antidepressant biochemical profile of the novel bicyclic compound Wy-45030, an ethyl cyclohexanol derivative. Biochem Pharmacol, 1986; 35(24): 4493-4497.
19.	Shen ZZ, Wu SH, Shao FY, Guohui Chen. Chronic et al. Chief editor.Complications of diabetes mellitus. Shanghai:Publishing Company of Shanghai Medical University; 1999. 261.
20.	Ereshefsky L.Drug-drug interactions involving antidepressants: focus on venlafaxine.J Clin Psychopharmacol,1996;16(3Suppl2 ):37-50.
21.	Rudolph RL, Derivan AT. The safety and tolerability of venlafaxine HCL: analysis of the clinical trials database. J Clin Psychopharmacol, 1996; 16(suppl 12): 54-59.

1. Diabetes Control and Complication Trial Research Group: The effect of intensive treatment of diabetes on development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl Med, 1993; 329 (14): 977-986.
2. Holliday SM, Venlafax BP. A review of its pharmacology and therapeutic potential in depression. Drugs, 1995; 49(7): 280-294.
3. Khawaja IS, Feinstein RE. Cardiovascular effects of selective serotonin reuptake inhibitors and other novel antidepressants. Heart Dis, 2003; 5(2): 153-160.
4. Marchand F, Alloui A, Chapuy E, et al. The antihyperalgesic effect of venlafaxine in diabetic rats does not involve the opioid system. Neuroscience letters, 2003; 342(1-2): 105-108.
5. Lang E, Hord AH, Denson D. Venlafaxine HCL (Effexor) relieves thermal hyperalgesia in rats with an experimental mononeuropathy. Pain, 1996; 68: 151-155.
6. Kiayias JA, Vlachou ED, Lakka-Papadodima E. Venlafaxine HCL in the treatment of painful peripheral diabetic neuropathy. Diabetes Care, 2000; 23(5): 699.
7. Lithner F. Venlafaxine in treatment of severe painful peripheral diabetic neuropathy. Diabetes Care, 2000; 23(11): 1710-1711.
8. Davis JL, Smith RL. Painful peripheral diabetic neuropathy treated with venlafaxine HCl extended release capsules. Diabetes Care, 1999; 22 (11): 1909.
9. Sindrup, SH, Bach FW, Gram MC, et al. Venlafaxine versus imipramine in painful polyneuropathy: A randomized, controlled trialv. Neurology, 2003; 60(128): 1284-1289.
10. Rowbotham MC, Goli V, Kunz NR, et al. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain, 2004; 110(3): 697-706.
11. Backonja MM. Use of anticonvulsants for treatment of neuropathic pain. Nerurology, 2002; 59 (suppl 2): S14-S17.
12. Chakrabarti AK, Samantaray SK. Diabetic peripheral neuropathy: nerve conduction studies before, during and after carbamazepine therapy. Aust N Z J Med, 1976; 6(6): 565-568.
13. Gomez-Perez FJ, Choza R, Rios JM, et al. Nortriptyline-fluphenazine vs. carbamazepine in the symptomatic treatment of diabetic neuropathy. Arch Med Res, 1996; 27(4): 525–529.
14. Eisenberg E, Lurie Y, Braker C, et al. Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study. Neurology, 2001; 57(3): 505-509.
15. Simpson DA. Gabapentin and venlafaxine for the treatment of painful diabetic neuropathy. Journal of Clinical Neutomuscular Disease, 2001; 3(2): 53-62.
16. Kapwz S, MannJJ MT. Antidepressant medication and the relative risk of suicide attempt and suicide. J Am Med Assoe, 1992; 268: 344-345.
17. Grothe DR, Scheckner B, Albano D. Treatment of pain syndromes with venlafaxine. Pharmacotherapy, 2004; 24(5): 621-629.
18. Muth EA, Haskins JT, Moyer JA, et al. Antidepressant biochemical profile of the novel bicyclic compound Wy-45030, an ethyl cyclohexanol derivative. Biochem Pharmacol, 1986; 35(24): 4493-4497.
19. Shen ZZ, Wu SH, Shao FY, Guohui Chen. Chronic et al. Chief editor.Complications of diabetes mellitus. Shanghai:Publishing Company of Shanghai Medical University; 1999. 261.
20. Ereshefsky L.Drug-drug interactions involving antidepressants: focus on venlafaxine.J Clin Psychopharmacol,1996;16(3Suppl2 ):37-50.
21. Rudolph RL, Derivan AT. The safety and tolerability of venlafaxine HCL: analysis of the clinical trials database. J Clin Psychopharmacol, 1996; 16(suppl 12): 54-59.

Chinese Journal of Evidence-Based Medicine

Effects of Venlafaxine and Carbamazepine for Painful Peripheral Diabetic Neuropathy: A Randomized, Double-blind and Double-dummy, Controlled Multi-center Trial

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