|LETTER TO EDITOR
|Year : 2020 | Volume
| Issue : 2 | Page : 93-95
Efficacy and safety of a sustained-release preparation of pregabalin in chronic pruritus
Manju Meena, Kapil Vyas, Manisha Balai, Ashok Kumar Khare, Lalit Kumar Gupta, Asit Mittal
Department of Dermatology, Venereology and Leprology, R.N.T. Medical College, Udaipur, Rajasthan, India
|Date of Submission||25-Mar-2020|
|Date of Decision||23-Oct-2020|
|Date of Acceptance||27-Oct-2020|
|Date of Web Publication||28-Dec-2020|
Department of Dermatology, Venereology and Leprology, R.N.T. Medical College, Udaipur, Rajasthan
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Meena M, Vyas K, Balai M, Khare AK, Gupta LK, Mittal A. Efficacy and safety of a sustained-release preparation of pregabalin in chronic pruritus. Indian J Drugs Dermatol 2020;6:93-5
|How to cite this URL:|
Meena M, Vyas K, Balai M, Khare AK, Gupta LK, Mittal A. Efficacy and safety of a sustained-release preparation of pregabalin in chronic pruritus. Indian J Drugs Dermatol [serial online] 2020 [cited 2021 Jan 16];6:93-5. Available from: https://www.ijdd.in/text.asp?2020/6/2/93/305123
Chronic pruritus is a troublesome symptom with complex etiopathogenesis. It has a significant effect on the quality of life of patients. There is a large unmet need regarding its pharmacological treatment. Due to known similarities between neurochemistry of pain and pruritus, drugs found effective in neuropathic pain are being increasingly explored in chronic pruritus. Pregabalin is a neuromodulator used in various neuropathic pain syndromes. It is an analog of the gamma-aminobutyric acid (GABA) that binds to the voltage-gated calcium channels and interrupts the transmission of pruritus by reducing the effects of pruritogens at neuronal level Dorsal Root Ganglion (DRG). Previous studies have claimed its effectiveness in pruritus of systemic origin beyond neuropathic pruritus in standard doses of 150–600 mg daily. Pregabalin is associated with benign central nervous system and systemic adverse effects like dizziness, sedation, dry mouth, and weight gain. To avoid adverse effect, it should either be given in divided dosage or gradually titrated to the optimal doses. Despite some reports of its successful use in different chronic itches, still there is a lack of sufficient data favoring its efficacy in chronic pruritus of differing etiologies, therefore, we decided to undertake this 8-week open-labeled, single-center prospective interventional study for evaluation of safety and efficacy of a sustained-release preparation of pregabalin in chronic pruritus. Sustained-release preparations are used to achieve the goal of attaining steady-state level of drug that is therapeutically effective and nontoxic for an extended period of time. The study included 17 patients of chronic pruritus of different etiology and was approved by the institutional review board. Chronic pruritus was defined as pruritus of any etiology for more than 6-week duration. Patients with cardiac disorders; pregnancy and lactational state; on antiepileptics/antidepressants/sedatives; or on other topical/systemic/physical therapy for pruritus for a period of 15 days before enrolment were excluded from the study. At baseline, the diagnostic evaluation of chronic pruritus was ascertained by thorough history, clinical examination, and laboratory tests. Clinical and demographic data were recorded according to predesigned pro forma [Table 1]. All patients received 75 mg of sustained-release pregabalin tablet daily at bedtime for a period of 8 weeks. The intensity of pruritus was assessed using the Numerical Rating Scale (NRS) ranging from 0 (no pruritus) to 10 (the most intense pruritus patient can imagine). NRS is a validated instrument used in clinical trials also. The NRS score was evaluated at the baseline and subsequent weeks till the 8th-week duration. Additional evaluation was performed to check for adverse drug effects. Statistical analysis was carried out with quantitative variables, expressed using measures of central location (mean) and measures of dispersion (standard deviation). Pre- and posttreatment NRS were compared using nonparametric tests (Wilcoxon signed-rank test), with significance set at P < 0.05.
14 of 17 participants completed the study and were available for the final analysis. Three patients dropped out because of dizziness and sedation. The mean NRS score at baseline, 1st week, 2nd week, 4th week, and 8th week was (7.07 ± 1.38), (3.64 ± 1.69), (2.28 ± 2.05) (1.71 ± 1.89), and (1.78 ± 1.88), respectively. The improvement in mean NRS compared to baseline was significant at 1st week (3.42 ± 1.55) (P < 0.0001), 2nd week (4.78 ± 1.92) (P < 0.0001), 4th week (5.35 ± 1.73) (P < 0.0001) and 8th week (5.28 ± 1.81) (P = 0.0000). The improvement in NRS was noticed as early as 1-week posttreatment and continued throughout the study period, however, no statistically significant improvement was achieved beyond 4 weeks (i.e., between week 4–8) with a mean improvement of only (0.07 ± 0.26) (P = 0.33) [Figure 1] and [Table 2]. Apart from the 3 patients who dropped out because of side effects, all other patients accepted therapy well. The only adverse effects observed were mild sedation in 7 patients, dizziness in 2 patients, and tingling sensation in 1 patient [Table 1].
|Figure 1: Line diagram showing comparative analysis of intensity of pruritus (Numerical Rating Scale) across 8 weeks of pregabalin sustained release therapy|
Click here to view
The sustained-release preparation of pregabalin provides the advantage of slow release of the drug over an extended period of time, thus ensuring a better control of plasma drug level, less dosage frequency, less side effects, and increased efficacy. Using sustained-release preparation of Pregabalin we were able to use a lower dosage protocol (75 mg/day of pregabalin) which is far below the upper limit of dosage of pregabalin recommended by the Food and Drug Administration (600 mg/day). Our study reveals the utility of sustained-release pregabalin in chronic pruritus of both localized and generalized types and of different causes. Patients of chronic kidney disease pruritus had the largest reduction in NRS. Clinical improvement was noticed as early as one week following treatment and was sustained over the next 4 weeks. It has been suggested in the literature that pregabalin effect may reach a plateau within around 4 weeks. Limitations of our study include a small sample size and open-label design. Despite these limitations, sustained-release preparation of pregabalin was found to achieve statistically meaningful improvement in the intensity of itch as indicated by NRS. Large-scale randomized controlled trials are warranted to further evaluate the efficacy of sustained-release preparation of pregabalin in chronic pruritus of varied origin.
We would like to thank Dr. Vishal Vyas, Assistant Professor, ABV-Indian Institute of Information Technology and Management, Gwalior, Madhya Pradesh, 474015.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ständer S, Weisshaar E, Mettang T, Szepietowski JC, Carstens E, Ikoma A, et al
. Clinical classification of itch: A position paper of the International Forum for the Study of Itch. Acta Derm Venereol 2007;87:291-4.
Shneker BF, McAuley JW. Pregabalin: A new neuromodulator with broad therapeutic indications. Ann Pharmacother 2005;39:2029-37.
Darandale AS, Ghuleprashant J, Aherabhijit A, Narwate BM. Sustained release dosage form: A concise review. Int J Pharm Drug Anal 2017;5:153-60.
Weisshaar E, Dalgard F. Epidemiology of itch: Adding to the burden of skin morbidity. Acta Derm Venereol 2009;89:339-50.
Reich A, Halupczok J, Ramus M, Stander S, Szepietowski J. New data on the validation of VAS and NRS in pruritus assessment: Minimal clinically important difference and itch frequency measurement. Acta Derm Venereol 2011;91:636.
Park JM, Jwa SW, Song M, Kim HS, Ko HC, Kim MB, et al
. Efficacy and safety of pregabalin for the treatment of chronic pruritus in Korea. J Dermatol 2012;39:790-1.
[Table 1], [Table 2]