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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2007  |  Volume : 18  |  Issue : 3  |  Page : 378-381
Gabapentin: A Promising Drug for the Treatment of Uremic Pruritus


Department of Nephrology, Noor Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

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   Abstract 

Despite advances made in treatment, uremic pruritus remains a common and distressing symptom in patients on hemodialysis (HD). Gabapentin is an effective drug in the management of neuropathic pain. Considering that neuropathic pain and pruritus share similar pathogenic mechanisms, we conducted this study to evaluate the efficacy of gabapentin in controlling uremic itch. In a double blind, placebo-controlled trial, 34 adult patients on maintenance HD were enrolled. The patients were assigned to receive four weeks of treatment with either gabapentin (400 mg) or placebo administered twice weekly after HD sessions. Pruritus scores were measured using a visual analogue scale and compared between the two groups.After four weeks of treatment, the mean decrease in pruritus score in gabapentin and placebo groups was 6.7 ▒ 2.6 and 1.5 ▒ 1.8, respectively (p<0.001). None of the patients was forced to drop out of the study due to side effects of the treatment. Our study suggests that gabapentin is a safe and effective treatment for uremic itch.

Keywords: Gabapentin, uremic pruritus, hemodialysis

How to cite this article:
Naini AE, Harandi AA, Khanbabapour S, Shahidi S, Seirafiyan S, Mohseni M. Gabapentin: A Promising Drug for the Treatment of Uremic Pruritus. Saudi J Kidney Dis Transpl 2007;18:378-81

How to cite this URL:
Naini AE, Harandi AA, Khanbabapour S, Shahidi S, Seirafiyan S, Mohseni M. Gabapentin: A Promising Drug for the Treatment of Uremic Pruritus. Saudi J Kidney Dis Transpl [serial online] 2007 [cited 2019 Nov 18];18:378-81. Available from: http://www.sjkdt.org/text.asp?2007/18/3/378/33755

   Introduction Top


It is estimated that approximately 22% of the patients with chronic renal failure suffer from pruritus. [1] The pathophysiology of uremic itch is unclear; thus, various forms of treatment with different mechanisms of actions have been proposed. They include antihistamines, [2] opioid antagonists, [3] the serotonin receptor blocker, [4] thalidomide, [5] and ultraviolets, [6] but none have succeeded in alleviating the patients' symptoms. Gabapentin is a novel antiepileptic agent which modulates various receptor sites and alters dopamin, serotonin, and norepinephrine release. It has shown promising effects in the treatment of chronic neuropathic pain syndromes such as HIV-associated neuropathy, post herpetic neuralgia, and pain in diabetic neuropathy. [7],[8],[9] Also, the utility of gabapentin in the management of uremic itch has been proposed in one trial. [10] We conducted this study to evaluate the efficacy of gabapentin, given in a dose of 400 mg twice weekly, in the treatment of uremic pruritus in patients on maintenance hemodialysis (HD).


   Patients and Methods Top


Patients

A total of 34 patients with end-stage renal disease (ESRD) (16 males and 18 females; mean age: 62 ▒ 10, range: 43-81 years) that were complaining of itching for more than eight weeks and were unresponsive to antişhistamines were enrolled. The included subjects were on maintenance HD twice a week for at least three months. The exclusion criteria included anemia (hemoglobin < 7 g/dl), hyperparathyroidism (serum parathormone >300 pg/ml, normal range: 9-55 pg/ml) and/or serum phosphorus > 7mg/dl. None of the patients had concomitant elevation of liver enzymes, alkaline phosphatase, or bilirubin in the blood. In addition, patients with any evidence of skin disease other than uremic pruritus, as opined by an experienced dermatologist, were excluded from the study. Written, informed consent was obtained from all patients before inclusion.

Study protocol

Any medication with presumed antişpruritic effects was discontinued one week before the study. The patients were randomly allocated to receive either gabapentin 400 mg (PharmaScience, Montreal, Canada) or placebo. In order to prepare the placebo, we emptied gabapentin capsules and refilled them with flour, thus making them indistinguishşable from the original capsules. The prescribed medications were administered twice weekly, after each HD session for four weeks. Approval for the study was obtained from the ethics committee of The Isfahan University of Medical Sciences. The severity of the pruritus was measured at the commencement of the study and after each HD session using a visual analogue scale. The scale consisted of a 10 cm horizontal line marked from zero (no itch) to 10 (worst possible itch). The method of marking the pruritus scale was explained to each patient by the corresponding physician, but completion of the scale was performed in the absence of the nephrologist. The mean decrease in pruritus scores after the study period was compared between two groups with two-sample independent t tests. A P value less than 0.05 was considered significant. A statistical analysis was performed using SPSS version 11.0 software (SPSS Inc, Chicago, IL).


   Results Top


The mean pruritus score at baseline was 7.2 ▒ 2.3 (range: 3-10). After four weeks of treatment, the mean decreases in pruritus score in the gabapentin and placebo groups were 6.7 ▒ 2.6 and 1.5 ▒ 1.8, respectively (p < 0.001). The trend of decrease is shown in [Figure - 1].

Somnolence, dizziness, and nausea were the most commonly reported side effects of gabapentin. The severity of adverse effects was mild to moderate, and usually subsided within 5-10 days from the first dose of gabapentin. Also, one patient in the gabapentin group complained of attacks of dizziness in the first week of treatment, which gradually subsided. None of the patients were forced to drop out of the study due to side effects of treatment.


   Discussion Top


This study demonstrates that gabapentin can effectively alleviate pruritus in uremic patients. In 2003, a review of over 150 original papers approved the use of gabapentin for neuropathic pain, neuritis or neuralgia of various sorts, and suggested the assessment of its role in the management of pruritus. [11] The efficacy of gabapentin in the treatment of brachoradial pruritus, which has a neuroşgenic source, has been approved in previous studies. [12],[13] Finally, a study in Turkey on 25 adult patients concerning the maintenance of HD showed that 300 mg of gabapentin taken thrice weekly, given at the end of HD sessions, significantly reduces uremic itch. As was similar to our study, the compliance of the patients was good and none of the patients were forced to drop out of the study due to adverse effects of gabapentin. [10]

The effectiveness of gabapentin is best explained with the combination of neuropathic and altered divalent ion metabolism hypotheses for uremic itch. It has been suggested that gabapentin affects voltageşdependent calcium-ion channels. By blocking neuronal calcium influx, it may inhibit ectopic discharge activity from injured nerves thus interrupting the series of events that perhaps lead to the pruritus sensation in uremic patients. [9],[14] Neuropathy occurs in more than 65% of patients with chronic renal failure. [15] Involvement of the peripheral nervous system in uremic patients may manifest itself as burning feet, paresthesia, and restless leg syndrome in the early stages. 16 Nerve fiber damage finally leads to a diminished threshold of perception; subsequently, pruritus develops against a wide range of environmental stimuli.

Gabapentin is now widely used to treat chronic neuropathic pain syndromes such as post herpetic neuralgia, HIV-associated neuropathy, and chronic pain syndromes in diabetics. [7],[8] Like pain, itch originating in the skin is induced by the stimulation of the free nerve endings and conducted to the sensory cortex by C-fibers. A similar mechanism of pain and itch may elucidate the observed clinical benefit of gabapentin in our uremic patients.

In conclusion, our study shows that gabapentin is an effective therapy for uremic itch in patients on HD. In order to reduce the adverse effects of treatment, further investigations should be performed to find the optimal dose and frequency of drug administration.

 
   References Top

1.Mettang T, Pauli-Magnus C, Alscher DM. Uraemic pruritus: new perspectives and insights from recent trials. Nephrol Dial Transplant 2002;17:558-63.  Back to cited text no. 1    
2.Schwartz IF, Iaina A. Uraemic pruritus. Nephrol Dial Transplant 1999;14:834-9.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Pauli-Magnus C, Mikus G, Alscher DM, et al. Naltrexone does not relieve uremic pruritus: results of a randomized, doubleşblind, placebo-controlled crossover study. J Am Soc Nephrol 2000;11:514-9.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Weisshaar E, Dunker N, Rohl FW, Gollnick H. Antipruritic effects of two different 5şHT3 receptor antagonists and an antihistamine in haemodialysis patients. Exp Dermatol 2004;13:298-304.  Back to cited text no. 4    
5.Silva SR, Viana PC, Lugon NV, Hoette M, Ruzany F, Lugon JR. Thalidomide for the treatment of uremic pruritus: a crossover randomized double-blind trial. Nephron 1994;67(3):270-3.  Back to cited text no. 5    
6.Gilchrest BA, Rowe JW, Brown RS, Steinman TI, Arndt KA. Ultraviolet phototherapy of uremic pruritus. Long-term results and possible mechanism of action. Ann Intern Med 1979;91:17-21.  Back to cited text no. 6    
7.Nicholson B. Gabapentin use in neuropathic pain syndromes. Acta Neurol Scand 2000; 101:359-71.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Tremont-Lukats IW, Megeff C, Backonja MM. Anticonvulsants for neuropathic pain syndromes: mechanisms of action and place in therapy. Drugs 2000;60:1029-52.  Back to cited text no. 8  [PUBMED]  
9.Rose MA, Kam PC. Gabapentin: pharmacology and its use in pain management. Anaesthesia 2002;57:451-62.  Back to cited text no. 9    
10.Gunal AI, Ozalp G, Yoldas TK, Gunal SY, Kirciman E, Celiker H. Gabapentin therapy for pruritus in haemodialysis patients: a randomized, placebo-controlled, doubleşblind trial. Nephrol Dial Transplant 2004; 19:3137-9.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Scheinfeld N. The role of gabapentin in treating diseases with cutaneous manifestations and pain. Int J Dermatol 2003;42:491-5.Bueller HA, Bernhard JD, Dubroff LM. Gabapentin treatment for brachioradial pruritus. J Eur Acad Dermatol Venereol 1999;13:227-8.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Winhoven SM, Coulson IH, Bottomley WW. Brachioradial pruritus: response to treatment with gabapentin. Br J Dermatol 2004;150:786-7.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Taylor CP, Gee NS, Su TZ, et al. A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res 1998;29:233-49.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Murphy M, Carmichael AJ. Renal itch. Clin Exp Dermatol 2000;25:103-6.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.Zakrzewska-pniewska B, Jedras M. Is pruritus in chronic uremic patients related to peripheral somatic and autonomic neuropathy? Study by R-R interval variation test (RRIV) and by sympathetic skin response (SSR). Neurophysiol Clin 2001;31:181-93.  Back to cited text no. 15    

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Correspondence Address:
Afsoon Emami Naini
Department of Nephrology, Noor Hospital, Isfahan University of Medical Sciences, Isfahan
Iran
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PMID: 17679749

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    Figures

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