Fixed dose combination of low dose pregabalin and duloxetine, or pregabalin monotherapy for neuropathic pain: A double-blind, randomized, parallel-group study [version 1; peer review: 2 approved]
Background: Treatment of neuropathic pain is challenging. Pregabalin and duloxetine are used as first-line therapy. Various international guidelines recommend a combination of first-line agents for the management of neuropathic pain. The objective of this study was to evaluate the efficacy and safet...
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F1000 Research Ltd
2023-03-01
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| Online Access: | https://f1000research.com/articles/12-353/v1 |
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| author | Sunil Dutt Pankaj Rattan Ankit Dadhania Pankaj Jha Krishnaprasad K. Ashutosh Kakkad Altaf Makwana Ram Gupta Deepa Joshi |
| author_facet | Sunil Dutt Pankaj Rattan Ankit Dadhania Pankaj Jha Krishnaprasad K. Ashutosh Kakkad Altaf Makwana Ram Gupta Deepa Joshi |
| author_sort | Sunil Dutt |
| collection | DOAJ |
| description | Background: Treatment of neuropathic pain is challenging. Pregabalin and duloxetine are used as first-line therapy. Various international guidelines recommend a combination of first-line agents for the management of neuropathic pain. The objective of this study was to evaluate the efficacy and safety of a fixed-dose combination (FDC) of low-dose pregabalin and duloxetine compared to pregabalin monotherapy at week 7 in patients with moderate to severe neuropathic pain. Methods: This was a phase 3, randomized, double-blind, double-dummy parallel-group non-inferiority study conducted at 17 sites across India. Three hundred and twenty-eight adult patients with moderate to severe neuropathic pain were randomized in a ratio of 1:1 to receive a FDC of pregabalin and duloxetine or pregabalin monotherapy for 7 weeks followed by a one-week follow-up. The pregabalin-duloxetine combination was initiated at 50 plus 20 mg per day and gradually titrated to a maximum of 75mg plus 30mg twice daily. Pregabalin was initiated at 75mg/day and gradually titrated to a maximum of 150mg twice daily. The main efficacy outcome was a mean change in pain intensity at the end of 7 weeks. Results: Two hundred and ninety-eight patients completed the study, 148 in the pregabalin-duloxetine group and 150 in the pregabalin group. The mean change in daily pain at 7 weeks was as follows: -4.49 with FDC and -4.66 with pregabalin (p<0.0001). The non-inferiority of a low-dose FDC compared to pregabalin monotherapy was demonstrated at the end of the study. The incidence of dizziness and somnolence was comparable between both treatments. A higher frequency of peripheral oedema was observed with pregabalin monotherapy than in the FDC group (p>0.05). Conclusions: A FDC of low doses of pregabalin and duloxetine and high dose of pregabalin monotherapy achieved similar analgesia with dizziness, and somnolence as the most frequent adverse event. Trial registration: CTRI/2020/09/027555 |
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| id | doaj.art-f4ec5f1e2e49490f88fa5f70c390669e |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-04-24T09:59:19Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-f4ec5f1e2e49490f88fa5f70c390669e2024-04-14T00:00:03ZengF1000 Research LtdF1000Research2046-14022023-03-0112143095Fixed dose combination of low dose pregabalin and duloxetine, or pregabalin monotherapy for neuropathic pain: A double-blind, randomized, parallel-group study [version 1; peer review: 2 approved]Sunil Dutt0Pankaj Rattan1Ankit Dadhania2Pankaj Jha3https://orcid.org/0000-0003-2447-4377Krishnaprasad K.4https://orcid.org/0000-0003-1409-0230Ashutosh Kakkad5https://orcid.org/0009-0008-5821-418XAltaf Makwana6https://orcid.org/0000-0002-8856-8738Ram Gupta7Deepa Joshi8Torrent Pharmaceuticals Limited, Torrent Research Center, Bhat, Gandhinagar, Gujarat, 382428, IndiaTorrent Pharmaceuticals Limited, Torrent Research Center, Bhat, Gandhinagar, Gujarat, 382428, IndiaTorrent Pharmaceuticals Limited, Torrent Research Center, Bhat, Gandhinagar, Gujarat, 382428, IndiaMedical Services, Torrent Pharmaceuticals Limited, Gandhinagar, Gujrat, 382428, IndiaMedical Services, Torrent Pharmaceuticals Limited, Gandhinagar, Gujrat, 382428, IndiaMedical Services, Torrent Pharmaceuticals Limited, Gandhinagar, Gujrat, 382428, IndiaMedical Services, Torrent Pharmaceuticals Limited, Gandhinagar, Gujrat, 382428, IndiaTorrent Pharmaceuticals Limited, Torrent Research Center, Bhat, Gandhinagar, Gujarat, 382428, IndiaTorrent Pharmaceuticals Limited, Torrent Research Center, Bhat, Gandhinagar, Gujarat, 382428, IndiaBackground: Treatment of neuropathic pain is challenging. Pregabalin and duloxetine are used as first-line therapy. Various international guidelines recommend a combination of first-line agents for the management of neuropathic pain. The objective of this study was to evaluate the efficacy and safety of a fixed-dose combination (FDC) of low-dose pregabalin and duloxetine compared to pregabalin monotherapy at week 7 in patients with moderate to severe neuropathic pain. Methods: This was a phase 3, randomized, double-blind, double-dummy parallel-group non-inferiority study conducted at 17 sites across India. Three hundred and twenty-eight adult patients with moderate to severe neuropathic pain were randomized in a ratio of 1:1 to receive a FDC of pregabalin and duloxetine or pregabalin monotherapy for 7 weeks followed by a one-week follow-up. The pregabalin-duloxetine combination was initiated at 50 plus 20 mg per day and gradually titrated to a maximum of 75mg plus 30mg twice daily. Pregabalin was initiated at 75mg/day and gradually titrated to a maximum of 150mg twice daily. The main efficacy outcome was a mean change in pain intensity at the end of 7 weeks. Results: Two hundred and ninety-eight patients completed the study, 148 in the pregabalin-duloxetine group and 150 in the pregabalin group. The mean change in daily pain at 7 weeks was as follows: -4.49 with FDC and -4.66 with pregabalin (p<0.0001). The non-inferiority of a low-dose FDC compared to pregabalin monotherapy was demonstrated at the end of the study. The incidence of dizziness and somnolence was comparable between both treatments. A higher frequency of peripheral oedema was observed with pregabalin monotherapy than in the FDC group (p>0.05). Conclusions: A FDC of low doses of pregabalin and duloxetine and high dose of pregabalin monotherapy achieved similar analgesia with dizziness, and somnolence as the most frequent adverse event. Trial registration: CTRI/2020/09/027555https://f1000research.com/articles/12-353/v1Pregabalin duloxetine fixed-dose combination neuropathic pain numeric pain rating scale (NPRS)eng |
| spellingShingle | Sunil Dutt Pankaj Rattan Ankit Dadhania Pankaj Jha Krishnaprasad K. Ashutosh Kakkad Altaf Makwana Ram Gupta Deepa Joshi Fixed dose combination of low dose pregabalin and duloxetine, or pregabalin monotherapy for neuropathic pain: A double-blind, randomized, parallel-group study [version 1; peer review: 2 approved] F1000Research Pregabalin duloxetine fixed-dose combination neuropathic pain numeric pain rating scale (NPRS) eng |
| title | Fixed dose combination of low dose pregabalin and duloxetine, or pregabalin monotherapy for neuropathic pain: A double-blind, randomized, parallel-group study [version 1; peer review: 2 approved] |
| title_full | Fixed dose combination of low dose pregabalin and duloxetine, or pregabalin monotherapy for neuropathic pain: A double-blind, randomized, parallel-group study [version 1; peer review: 2 approved] |
| title_fullStr | Fixed dose combination of low dose pregabalin and duloxetine, or pregabalin monotherapy for neuropathic pain: A double-blind, randomized, parallel-group study [version 1; peer review: 2 approved] |
| title_full_unstemmed | Fixed dose combination of low dose pregabalin and duloxetine, or pregabalin monotherapy for neuropathic pain: A double-blind, randomized, parallel-group study [version 1; peer review: 2 approved] |
| title_short | Fixed dose combination of low dose pregabalin and duloxetine, or pregabalin monotherapy for neuropathic pain: A double-blind, randomized, parallel-group study [version 1; peer review: 2 approved] |
| title_sort | fixed dose combination of low dose pregabalin and duloxetine or pregabalin monotherapy for neuropathic pain a double blind randomized parallel group study version 1 peer review 2 approved |
| topic | Pregabalin duloxetine fixed-dose combination neuropathic pain numeric pain rating scale (NPRS) eng |
| url | https://f1000research.com/articles/12-353/v1 |
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