A comparative study to analyze the effect of gabapentin with amitriptyline versus pregabalin with amitriptyline in neuropathic pain in cancer patients undergoing palliative care

Nipun Lamba; Anukriti Pareek; Shikha Dhal; Sumit Goyal; Ruchika Makkar; Sudha Sarna

doi:10.4103/amit.amit_64_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 9 | Issue : 2 | Page : 124-126

A comparative study to analyze the effect of gabapentin with amitriptyline versus pregabalin with amitriptyline in neuropathic pain in cancer patients undergoing palliative care

Nipun Lamba¹, Anukriti Pareek², Shikha Dhal³, Sumit Goyal³, Ruchika Makkar², Sudha Sarna²
¹ Department of Palliative Medicine, SRCC, Mahatma Gandhi Medical College & Hospital, Jaipur, Rajasthan, India
² Department of Palliative Medicine, SRCC, Mahatma Gandhi Medical College & Hospital, Jaipur, Rajasthan, India
³ Department of Radiation Oncology, SRCC, Mahatma Gandhi Medical College & Hospital, Jaipur, Rajasthan, India

Date of Submission	21-Jul-2022
Date of Decision	19-Sep-2022
Date of Acceptance	19-Sep-2022
Date of Web Publication	29-Dec-2022

Correspondence Address:
Dr. Sumit Goyal
SRCC MGH, Jaipur, Rajasthan
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/amit.amit_64_22

Abstract

Introduction: Antiepileptics and antidepressant medications are known for managing neuropathic pain. We aim to compare the effects of pregabalin with low-dose amitriptyline and gabapentin with low-dose amitriptyline in managing neuropathic pain in cancer patients undergoing palliative care. Materials and Methods: We conducted our study on 160 cancer patients who were having neuropathic pain and were undergoing palliative care treatment in our institute. It was a hospital-based, randomized, tertiary cancer center-based observational study. After taking approval from the institutional ethics committee and taking written informed consent from patients, the patients were divided into two groups and the effect of medicines on incidence of neuropathic pain was observed; the incidence of burning sensation and the incidence of adverse effects of medications were also analyzed. Statistical analysis was done using paired t-test and SPSS version 20 software. Results: The onset of relief in pain was earlier in the pregabalin group as compared to the gabapentin group. There was more reduction in a burning sensation in the pregabalin group as compared to the gabapentin group. The incidence of headaches was the same in both groups. Nausea and vomiting were more in the pregabalin group but the overall difference in adverse effects was not statistically significant (P > 0.05) Conclusions: In the management of neuropathic pain in cancer patients who are undergoing palliative care, a combination of pregabalin with amitriptyline was found to be more effective in pain relief than gabapentin with amitriptyline.

Keywords: Amitriptyline, gabapentin, pain medicine, palliative care, pregabalin

How to cite this article:
Lamba N, Pareek A, Dhal S, Goyal S, Makkar R, Sarna S. A comparative study to analyze the effect of gabapentin with amitriptyline versus pregabalin with amitriptyline in neuropathic pain in cancer patients undergoing palliative care. Acta Med Int 2022;9:124-6

How to cite this URL:
Lamba N, Pareek A, Dhal S, Goyal S, Makkar R, Sarna S. A comparative study to analyze the effect of gabapentin with amitriptyline versus pregabalin with amitriptyline in neuropathic pain in cancer patients undergoing palliative care. Acta Med Int [serial online] 2022 [cited 2023 May 29];9:124-6. Available from: https://www.actamedicainternational.com/text.asp?2022/9/2/124/365868

Introduction

Gabapentin and pregabalin are adjuvant antiepileptic medications which are used for the relief of neuropathic pain. Amitriptyline is a tricyclic antidepressant medication which apart from its mood-elevating properties also has an effect on neuropathic pain.

Cancer-related mortality has been on decreasing trend and survival is increased.^[1] Neural dysfunction due to cancer is the cause of neuropathic pain and this dysfunction may be spontaneous or may be due to a painful stimulus.^[2]

In cancer patients who are undergoing palliative care, the role of neuropathic medicines in providing relief is well known. Inadequate pain relief is the most common cause of treatment discontinuation and distress to the patient. Multimodal analgesia using the WHO step ladder is the most common mode of standardized treatment. Relief from pain is a basic human right. We, in our study, have tried to compare the effects of the medications and tried to provide better pain management guidelines for patients.

Materials and Methods

We conducted our study in a tertiary care cancer center in the pain and palliative medicine department. It was a prospective, observational, randomized, comparative study. SRCC was the place of study. This study was conducted in 160 patients undergoing supportive care. We conducted our study after taking due permission from the institutional ethics committee and taking written informed consent from our participants. IEC No./MGMC&H/IEC/JPR/2021/1154. One hundred and sixty patients were enrolled in the study, and for study purposes, we have divided participants into two groups. Patients in Group A received pregabalin 75 mg and 25 mg amitriptyline at bedtime, and patients in Group B received gabapentin 300 mg and 25 mg amitriptyline. We have used the Visual Analog Scale (VAS) for analyzing pain scores. Follow-up was done for 30 days. For statistical analysis, we have used paired t-test and IBM SPSS Statistics for Windows, version 20.0. Armonk, NY, USA: IBM Corp software.

Group A: Eighty cases were given pregabalin 75 mg and amitriptyline 25 mg
Group B: Eighty cases were given gabapentin 300 mg and amitriptyline 25 mg.

Inclusion criteria

Patients undergoing cancer treatment having neuropathic pain were included in the study.

Exclusion criteria

Patient refusal
Patients having organ dysfunction
Patients with clouded sensorium.

Results

The mean age in Group A was 39.24 ± 7.12 and Group B was 40.22 ± 7.32, having P > 0.05. These groups were comparable. Mean weight in Group A was 73.24 ± 6.18 and Group B was 72.21 ± 7.23 P > 0.05 [Table 1].

Table 1: Patients demographics

Click here to view

Incidence of burning sensation in Group A was 93.75%, 80%, 72.50%, and 65% at respective 1, 2, 3, and 4 weeks and in Group B was 96.25%, 90%, 94%, and 75% at respective weeks [Table 2].

Table 2: Incidence of burning sensation

Click here to view

In Group A incidence of spontaneous pain was in 76.25% patients, this reduced to 65.00% in 1^st week, 57.5% in 2^nd week, 37.50% in 3^rd week and 27.50% in 4^th week and in Group B baseline incidence of spontaneous pain was in 78.75% patient's and it reduced to 71.25% in 1^st week, 52.50% in 2^nd week, and 47.50% in 3^rd week and 33.75% in 4^th week. There was more reduction in the incidence of spontaneous pain in patients of Group A as compared to Group B [Table 3].

Table 3: Incidence of spontaneous pain

Click here to view

There was more reduction in pain in Group A from 8.23 ± 2.42 to 3.24 ± 4.41 as compared to Group B from 8.54 ± 2.27 to 3.92 ± 4.79 at 4 weeks. The mean improvement in pain on VAS was more in Group A as compared to Group B was 4.63 ± 4.24–4.24 ± 4.16 [Table 4].

Table 4: Visual Analog Score

Click here to view

There was an incidence of nausea, vomiting, dizziness, drowsiness, headache, and visual disturbances in both Group A and Group B. There was no incidence of urinary retention and respiratory depression [Table 5].

Table 5: Adverse effects

Click here to view

Discussion

Pregabalin and gabapentin both are adjuvant antiepileptic medications which are used in the management of neuropathic pain. The addition of an antidepressant as an adjuvant, in this case, amitriptyline was done. Their effects were evaluated in the management of neuropathic pain and a comparative analysis was done. Their effects were evaluated for 1 month. It is well known that pain is a symptom of the underlying disease and it may be caused by nerve damage.^[3] There are many causes of neuropathic pain. It may be central or peripheral neuropathic origin in nature.^[4] Amitriptyline has a role in relieving neuropathic pain and also has antitumor properties.^[5] Adjuvant medications are useful when neuropathic pain becomes opioid unresponsive.^[6] Yilmaz et al. found no difference between gabapentin and pregabalin statistically in managing neuropathic pain.^[7] Hong et al.'s results showed that gabapentinoids used in psychiatric states are not supported by evidence.^[8] Richter et al. reported that pregabalin provides >50% decrease in pain intensity in about 40% of patients.^[9] Rayani et al. reported that pregabalin is more effective in relieving pain and quality of life in chronic inflammatory demyelinating polyneuropathy, patients as compared to gabapentin.^[10] In pain due to spinal cord injury, pain relief was better with pregabalin and gabapentin has a better safety profile.^[11] Pregabalin has a better pain-relieving effect than gabapentin and amitriptyline but gabapentin was found to have less side effects.^[12] Pregabalin and gabapentin were both effective in pain relief but gabapentin provided better pain relief with lesser side effects than pregabalin.^[13]

Manjushree et al. state that for treatment of chemotherapy-induced peripheral neuropathy, gabapentin and pregabalin were equally effective but adverse effects were found to be more in the gabapentin group.^[14] Madhanagopal et al. state that pain relief was better in the pregabalin group than in gabapentin and placebo with an equal incidence of adverse effects except for nausea which was more in the pregabalin group.^[15] In our study, we concluded that there was a reduced incidence of spontaneous pain, and better improvement in VAS score in the pregabalin group than in the gabapentin group. There was an increased incidence of nausea and vomiting in the pregabalin group than gabapentin group. Dizziness was slightly more incident in the pregabalin group and headache and drowsiness were equal in both groups. The overall difference in the incidence of adverse effects was found to be insignificant while comparing both groups P > 0.05.

Conclusions

In the management of neuropathic pain in cancer patients who are undergoing palliative care, pregabalin with amitriptyline was found to be more effective in providing pain relief than gabapentin with amitriptyline.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin 2021;71:7-33.
2.	Gül ŞK, Tepetam H, Gül HL. Duloxetine and pregabalin in neuropathic pain of lung cancer patients. Brain Behav 2020;10:e01527.
3.	Shkodra M, Brunelli C, Zecca E, Formaglio F, Bracchi P, Lo Dico S, et al. Neuropathic pain: Clinical classification and assessment in patients with pain due to cancer. Pain 2021;162:866-74.
4.	Shkodra M, Caraceni A. Treatment of neuropathic pain directly due to cancer: An update. Cancers (Basel) 2022;14:1992.
5.	Asensi-Cantó A, López-Abellán MD, Castillo-Guardiola V, Hurtado AM, Martínez-Penella M, Luengo-Gil G, et al. Antitumoral effects of tricyclic antidepressants: Beyond neuropathic pain treatment. Cancers (Basel) 2022;14:3248.
6.	Matsuoka H, Clark K, Fazekas B, Oyamada S, Brown L, Ishiki H, et al. Phase III, international, multicentre, double-blind, dose increment, parallel-arm, randomised controlled trial of duloxetine versus pregabalin for opioid-unresponsive neuropathic cancer pain: A JORTC-PAL16 trial protocol. BMJ Open 2022;12:e050182.
7.	Yilmaz B, Yasar E, Omac OK, Goktepe AS, Tan AK. Gabapentin versus pregabalin for the treatment of neuropathic pain in patients with spinal cord injury: A crossover study. Turk J Phys Med Rehab 2015;61:1-5.
8.	Hong JS, Atkinson LZ, Al-Juffali N, Awad A, Geddes JR, Tunbridge EM, et al. Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale. Mol Psychiatry 2022;27:1339-49.
9.	Richter RW, Portenoy R, Sharma U, Lamoreaux L, Bockbrader H, Knapp LE. Relief of painful diabetic peripheral neuropathy with pregabalin: A randomized, placebo-controlled trial. J Pain 2005;6:253-60.
10.	Rayani M, Ansari B, Boroujeni SA, Veshnavei HA, Basiri K. Gabapentin versus pregabalin for management of chronic inflammatory demyelinating polyradiculoneuropathy. Am J Neurodegener Dis 2021;10:50-6.
11.	Tong C, Zhengyao Z, Mei L, Dongpo S, Qian H, Fengqun M. Pregabalin and gabapentin in patients with spinal cord injury-related neuropathic pain: A network meta-analysis. Pain Ther 2021;10:1497-509.
12.	Kancherla N, Babu GC, Singh H, Khandelwal M, Sharma N, Kuma MB. Comparative study of safety and efficacy of pregabalin, gabapentin and amitriptyline in management of neuropathic pain. Int J Basic Clin Pharmacol 2021;10:64-9.
13.	Robertson K, Marshman LA, Plummer D, Downs E. Effect of gabapentin versus pregabalin on pain intensity in adults with chronic sciatica: A randomized clinical trial. JAMA Neurol 2019;76:28-34.
14.	Manjushree N, Chakraborty A, Shashidhar V. Efficacy and safety of gabapentin and pregabalin in chemotherapy-induced peripheral neuropathy. Asian J Pharm Clin Res 2021;14:130-2.
15.	Madhanagopal R, Balasubramanian AK, Gowda PS, Rathnasabapathy B, Shankar R. Comparison of post-operative analgesic effect between pregabalin and gabapentin given as premedication drugs for patients undergoing laproscopic cholecystectomy. Indian J Clin Anaesth 2021;8:179-84.