Abstract
Purpose
Gabapentinoids are mainly prescribed for neuropathic pain and certain seizure disorders, but their off-label use has increased significantly. This rise raises concerns about the insufficient evidence supporting some applications, as well as potential risks of misuse, dependence, and adverse effects. The study aims to examine the prescribing patterns and off-label use of gabapentinoids at Dhulikhel Hospital (DH), Nepal, focusing on understanding the extent of off-label practices and patient knowledge regarding their medications.
Patients and Methods
A cross-sectional survey of 385 adult patients prescribed gabapentinoids was conducted at the outpatient pharmacy of DH. Data were collected via patient interviews and prescriptions. Off-label use was assessed according to the licensed indications of the US Food and Drug Administration (FDA) and the UK British National Formulary (BNF). Statistical analysis was performed using Statistical Package for the Social Sciences version 26.
Results
Among patients prescribed gabapentinoids, 73.0% received gabapentin while 27.0% were prescribed pregabalin. Most patients were middle-aged females with comorbid conditions, primarily orthopedic outpatients. Off-label use was prevalent, with 96.1% of prescriptions being off-label by FDA indications and 28.1% by BNF indications. Pregabalin was prescribed at a sub-therapeutic dose (75 mg/day) for neuropathic pain. Patient knowledge about gabapentinoids was found to be poor, particularly regarding side effects and drug interactions.
Conclusion
This study highlights the extensive off-label and sub-therapeutic use of gabapentinoids at Dhulikhel Hospital and reveals significant gaps in patient knowledge. This emphasizes the need for stricter prescribing guidelines, improved healthcare provider education, and better patient information to optimize the use and minimize risks. The frequent prescription of low-dose pregabalin for neuropathic pain raises the possibility that it may be used for night-time sedation rather than for pain management, indicating the need for further investigation.
Keywords: off-label use, gabapentin, pregabalin, Nepal, prescribing patterns, patient education
Introduction
The urgent need for alternative pain management strategies during the opioid crisis led to increased prescribing of gabapentinoids for pain relief.1 Gabapentinoids are antiepileptic medications initially approved for the treatment of seizures because of their anticonvulsant properties. Their ability to reduce neuronal hyperexcitability has expanded their use and made them integral components of multimodal analgesia protocols.2 Gabapentinoids are now widely recognized and recommended as first-line therapy for neuropathic pain in many international guidelines.3 Their role as non-narcotic medications for managing both neuropathic and certain non-neuropathic pain conditions has garnered significant attention, offering prescribers valuable tools for addressing persistent challenges in this field.4
Currently, both gabapentin and pregabalin have United States Food and Drug Administration (FDA) indications for the treatment of post herpetic neuralgia in adults and as adjunctive therapies for the management of partial-onset seizures, however pregabalin is licensed for neuropathic pain associated with diabetic peripheral neuropathy, fibromyalgia and neuropathic pain associated with spinal cord injury.5,6 The British National Formulary (BNF) and the Nepalese National Formulary (NNF) both specify a notably broader range of uses for these agents. Gabapentin is indicated for the treatment of peripheral neuropathic pain, whereas pregabalin is approved for both central and peripheral neuropathic pain.7 However, gabapentinoids are not indicated for sedation or for treating non-neuropathic pain.
The off-label use of gabapentinoids is believed to constitute a significant portion of all prescriptions, although determining accurate prevalence rates at both the national and global levels can be difficult.8 Gabapentinoids are frequently prescribed for different therapeutic indications, including chronic back pain, perioperative pain, pruritus, anxiety, attention deficit disorder, bipolar disorder, migraines, sleep disorders, alcohol withdrawal seizures and more.9–11 In the United States, gabapentin is extensively used off-label, often alongside opioid analgesics, with 83% to 95% of its prescriptions being for off-label indications, primarily due to its perceived safety and efficacy in managing pain and other conditions.12,13 Although off-label drug use is legal and common, the increased use of gabapentinoids has sparked debate owing to insufficient or low-quality evidence supporting their effectiveness in these cases.14,15 There are growing concerns about the potential misuse of gabapentinoids because of their risk of adverse effects, dependency, and abuse. This risk is heightened when these drugs are prescribed alongside other central nervous system depressants such as opioids.16
The off-label use of gabapentinoids is a significant yet understudied issue, particularly in Nepal. This study aimed to address the research gaps by analyzing the prescribing patterns of gabapentin and pregabalin at a tertiary care hospital in Nepal. The objective was to understand both the approved and off-label uses of these medications and to evaluate the knowledge of users about their prescriptions.
Materials and Methods
Study Design, Study Site and Sample Size
This study was a cross-sectional survey conducted from April 7 to June 15, 2024, at the outpatient pharmacy department of Dhulikhel Hospital, Kathmandu University Hospital, Nepal. The sample size was calculated to be 385 patients based on 95% confidence interval and a 5% margin of error, assuming a 50% prevalence of off-label use of gabapentinoids. Purposive sampling was used in this study.
Eligibility Criteria
Adult patients (≥18 years) who were prescribed gabapentinoids as outpatients and who visited the outpatient pharmacy for these medications were included in the study. Proxy medication recipients and patients who did not consent to participate in the study were also excluded.
Ethical Approval and Informed Consent
Ethical approval for this study was granted by the Institutional Review Committee of the School of Medical Sciences at Kathmandu University (Approval No: KUSMS-IRC 108/24). Before joining the study, potential participants were given a complete explanation of the procedures. Participation was voluntary, and individuals could withdraw at any time without any repercussions. Informed consent was acquired from all participants prior to the study. The study adhered to the ethical standards outlined in the Helsinki Declaration, ensuring patient data privacy and confidentiality.
Data Collection
Data were collected from copies of prescriptions provided to patients upon receiving their medication. The information gathered included demographic characteristics, indications for gabapentinoid use, specific gabapentinoid prescribed, complete dosage regimen details, department from which the gabapentinoid was prescribed, and other relevant factors. In cases where patients had multiple prescriptions, only prescriptions containing gabapentinoids at the time of the survey were considered. All the participants provided written informed consent. Patients were interviewed face to face via a pretested, structured, and validated investigator-administered questionnaire (Supplementary Figure 1) as they exited the pharmacy. This questionnaire, adapted from a previous study, aimed to evaluate patients’ knowledge about their prescribed gabapentinoids.17
Categorization of off-Label Use
Gabapentinoid prescriptions were assessed based on the indications specified by the FDA and BNF as listed in Table 1.18–21 The use of these medications was classified into labeled and off-label categories. Additionally, instances of sub-therapeutic dosing and combination therapy were documented and analyzed.
Table 1.
List of Indications of Gabapentin and Pregabalin as Listed by Different Authorities
| Source | Gabapentin Indications | Pregabalin Indications |
|---|---|---|
| FDA | Post herpetic neuralgia | Post herpetic neuralgia |
| Adjunctive therapy for partial-onset seizures, with or without secondary generalization, in adults and children aged 3 years and older with epilepsy | Adjunctive therapy for partial-onset seizures in patients aged 4 years and older | |
| Neuropathic pain associated with diabetic peripheral neuropathy | ||
| Fibromyalgia | ||
| Neuropathic pain associated with spinal cord injury | ||
| BNF | Adjunctive therapy for focal seizures with or without secondary generalization | Adjunctive therapy for focal seizures with or without secondary generalization |
| Peripheral neuropathic pain | Peripheral and central neuropathic pain | |
| Monotherapy for focal seizures with or without secondary generalization | Generalized anxiety disorder | |
| Menopausal symptoms, particularly hot flushes, in women with breast cancer* | ||
| Oscillopsia in multiple sclerosis* | ||
| Spasticity in multiple sclerosis* | ||
| Muscular symptoms in motor neuron disease* | ||
| NNF | Adjunctive treatment of partial seizures, with and without secondary generalization | Adjunctive therapy for focal seizures with or without secondary generalization |
| Bipolar affective disorder | Generalized anxiety disorder | |
| Post herpetic neuralgia | Peripheral and central neuropathic pain | |
| Neuropathic pain |
Note: (*) denotes indications that are unlicensed in the United Kingdoms.
Abbreviations: BNF, British National Formulary; FDA, Food and Drug Administrations; NNF, Nepalese National Formulary.
Categorization of the Knowledge Level of Patients
The questionnaire assessed patients’ knowledge of their gabapentinoid medication. Patients were given two points each when they knew the medication’s name, dosage, form, and frequency and one point each when they understood its therapeutic use, treatment duration, side effects, interactions, and action taken after missed doses. Scoring was categorized as insufficient knowledge of safe use (≤7 points), average knowledge sufficient for normal use (8–10 points), and good knowledge, ensuring safe use under all circumstances (≥11 points).
Variables
The dependent variables included prescription patterns (frequency of gabapentinoid prescriptions, dosage and duration of prescriptions, and combination with other medications), off-label use (frequency of off-label prescriptions, specific off-label conditions being treated), and knowledge of patients regarding their prescription. Independent variables included patient demographics (age, sex, ethnicity, education status and education level), clinical characteristics (diagnoses, comorbidities), and healthcare system factors (department, insurance coverage).
Statistical Analysis
Data were analyzed using SPSS version 26. Descriptive statistics were used to characterize the dataset and the baseline characteristics were summarized as frequencies and percentages. Non-parametric tests were applied owing to skewed data. Categorical variables were assessed via chi-square tests (or Fisher’s exact tests when applicable), whereas continuous variables are reported as medians with interquartile ranges (IQRs) and were compared via the Mann‒Whitney U-test. Binary logistic regression was performed to identify factors associated with “off-label gabapentinoid use” and “good knowledge of prescribed gabapentinoids.” Univariate analysis was followed by multivariate analysis for significant factors, with the results presented as odds ratios (ORs), 95% confidence intervals, and p values. Significance was set at p < 0.05.
Results
Baseline Characteristics of the Sample
Table 2 presents the demographic and clinical characteristics of 385 patients, of whom 281 (73.0%) were prescribed gabapentin and 104 (27.0%) were prescribed pregabalin. The cohort was predominantly female (69.1%), with a median age of 49 years (IQR: 39.5–59.5). The majority of prescriptions were for follow-up visits (51.7%), with the orthopedic department accounting for 87.5% of all prescriptions. Additionally, 90.1% of patients had insurance coverage. There is a significant difference in the proportion of patients with diabetes mellitus (p=0.008), orthopedic co-morbidity (p=0.007) and department visited (p<0.001) between those taking gabapentin and pregabalin.
Table 2.
Baseline Characteristics of the Patients Prescribed with Gabapentinoids at Dhulikhel Hospital, Nepal
| Characters | Total (n=385) | Gabapentin (n=281) | Pregabalin (n=104) | p-value | |
|---|---|---|---|---|---|
| Gender | Male | 119 (30.9) | 90 (32.0) | 29 (27.9) | 0.435a |
| Female | 266 (69.1) | 191 (68.0) | 75 (72.1) | ||
| Age | Median (IQR) | 49 (39.5–59.5) | 49 (40.0–59.0) | 49.5 (37.25–61.5) | 0.839c |
| 18–25 | 11 (2.9) | 10 (3.6) | 1 (1.0) | 0.158a | |
| 26–35 | 57 (14.8) | 35 (12.5) | 22 (21.2) | ||
| 36–45 | 85 (22.1) | 66 (23.5) | 19 (18.3) | ||
| 46–55 | 106 (27.5) | 78 (27.8) | 28 (26.9) | ||
| 56–65 | 67 (17.4) | 53 (18.9) | 14 (13.5) | ||
| >65 (Elderly) | 59 (15.3) | 39 (13.9) | 20 (19.2) | ||
| Education Status | Illiterate | 154 (40.0) | 108 (38.4) | 46 (44.2) | 0.504a |
| Literate | 231 (60.0) | 173 (61.6) | 58 (55.8) | ||
| Education Level of Literate Population | Primary Education | 105 (27.3) | 78 (27.8) | 27 (26.0) | 0.533a |
| Secondary Education | 111 (28.8) | 82 (29.2) | 29 (27.9) | ||
| Higher Education | 15 (3.9) | 13 (4.6) | 2 (1.9) | ||
| Comorbidities Present | 164 (42.6) | 115 (40.9) | 49 (47.1) | 0.275a | |
| Comorbidities | Hypertension | 76 (19.7) | 50 (17.8) | 26 (27.2) | 0.115a |
| Cardiovascular Disorders | 7 (1.8) | 5 (1.8) | 2 (1.9) | 0.606b | |
| Dyslipidemia | 21 (5.5) | 14 (5.0) | 7 (6.7) | 0.502a | |
| Diabetes mellitus | 32 (8.3) | 17 (6) | 15 (14.4) | 0.008a* | |
| Thyroid diseases | 29 (7.5) | 25 (8.9) | 4 (3.8) | 0.437a | |
| Orthopedic co-morbidity | 31 (8.1) | 29 (10.3) | 2 (1.9) | 0.007a* | |
| Pulmonary co-morbidity | 18 (4.7) | 13 (4.6) | 5 (4.8) | 0.563b | |
| Others | 25 (6.5) | 17 (6.0) | 8 (7.7) | 0.502a | |
| Prescription type | Follow-up | 199 (51.7) | 151 (53.7) | 48 (46.2) | 0.071a |
| New | 175 (45.5) | 125 (44.5) | 50 (48.1) | ||
| Re-fill | 11 (2.9) | 5 (1.8) | 6 (5.8) | ||
| Department visited | Orthopedics | 337 (87.5) | 263 (93.6) | 74 (71.2) | 0.00b* |
| Medicine | 32 (8.3) | 11 (3.9) | 21 (20.2) | ||
| Dermatology | 9 (2.3) | 6 (2.1) | 3 (3.3) | ||
| Others | 7 (1.8) | 1 (0.4) | 6 (5.8) | ||
| Prescription Coverage | Insurance | 347 (90.1) | 255 (90.7) | 92 (88.5) | 0.504a |
| Cash | 38 (9.9) | 26 (9.3) | 12 (11.5) | ||
| Median score of knowledge regarding their Gabapentinoid | 8 (7–9) | 8 (7–9) | 8 (7–9) | 0.802c | |
| Knowledge Status | Inadequate | 168 (43.5) | 122 (43.4) | 46 (44.2) | 0.699a |
| Average | 196 (51.0) | 142 (50.5) | 54 (51.9) | ||
| Good | 21 (5.5) | 17 (6.0) | 4 (3.8) | ||
Notes: (*) Indicates significant differences in the values between the categories after the respective tests at p<0.05. aChi-square test of independence, bFischer exact test, cMann–Whitney U-test.
Prescribing Patterns of Gabapentinoids
The study revealed that the most common dosage regimen was 300 mg once daily for a month for gabapentin (56.23%) and 75 mg once daily for a month for pregabalin (62.5%). Table 3 shows that among the patients, 60.5% were first-time gabapentinoid users, with neuropathic pain being the primary indication (72.0%). NSAIDs were co-prescribed in 73.2% of the patients and controlled substances were co-prescribed in 9.1% of the patients. The most common supplements included methylcobalamin (62.6%), vitamin D3 (39.5%), and calcium (31.4%). Polypharmacy was observed in 50.6% of patients, with a median of five medications prescribed. Physiotherapy was recommended for 38.0% of patients, and 77.0% had a follow-up scheduled. Off-label prescribing was prevalent, with 96.1% based on FDA indications and 28.1% according to BNF indications.
Table 3.
Prescribing Pattern of Gabapentinoids at Dhulikhel Hospital, Nepal
| Categories | Total (n=385) | Gabapentin (n=281) | Pregabalin (n=104) | |
|---|---|---|---|---|
| First time users | 233 (60.5) | 164 (58.4) | 69 (66.3) | |
| Off-label use as per FDA indication | 370 (96.1) | 274 (97.5) | 96 (92.3) | |
| Off-label use as per BNF indication | 108 (28.1) | 81 (28.8) | 27 (26.0) | |
| Indication | Neuropathic Pain | 277 (71.9) | 200 (71.2) | 77 (74.0) |
| Non-neuropathic Pain | 108 (28.1) | 81 (28.8) | 27 (26.0) | |
|
Co-prescribed non-steroidal anti-inflammatory drugs |
Total | 282 (73.2) | 220 (78.3) | 62 (59.6) |
| Etoricoxib | 188 (48.8) | 146 (52.0) | 42 (40.4) | |
| Aceclofenac | 75 (19.5) | 60 (21.4) | 15 (14.4) | |
| Naproxen | 10 (2.6) | 8 (2.8) | 2 (1.9) | |
| Acetaminophen and Ibuprofen combination | 6 (1.5) | 4 (1.4) | 2 (1.9) | |
| Diclofenac | 3 (0.8) | 2 (0.7) | 1 (1.0) | |
| Co-prescribed controlled substances | Total | 35 (9.1) | 23 (8.2) | 12 (11.5) |
| Opioids | 5 (1.3) | 2 (0.7) | 3 (2.9) | |
| Amitriptyline | 11 (2.9) | 8 (2.8) | 3 (2.9) | |
| Duloxetine | 16 (4.2) | 12 (4.3) | 4 (3.8) | |
| Olanzapine | 3 (0.8) | 1 (0.4) | 2 (1.9) | |
| Co-prescribed Supplements | Vitamin B12 (Methylcobalamin) | 241 (62.6) | 188 (66.9) | 53 (51) |
| Calcium | 121 (31.4) | 101 (35.9) | 20 (19.2) | |
| Vitamin D3 (Cholecalciferol) | 152 (39.5) | 132 (47.0) | 20 (19.2) | |
|
Other co-prescribed medications |
Steroids | 50 (12.98) | 40 (14.23) | 10 (9.62) |
| Diclofenac gel | 47 (12.2) | 40 (14.2) | 7 (6.7) | |
| Muscle relaxants | 67 (17.4) | 57 (20.3) | 10 (9.6) | |
| Proton Pump Inhibitors | 140 (36.4) | 109 (38.8) | 31 (28.8) | |
| Acyclovir | 6 (1.5) | 4 (1.4) | 2 (1.9) | |
| Adjuvant orthopedics medications | 17 (4.4) | 13 (4.6) | 4 (3.8) | |
| Others | 86 (22.3) | 44 (15.6) | 42 (40.4) | |
| Number of medicines prescribed | Gabapentinoid only | 3 (0.8) | 0 | 3 (2.9) |
| 2 | 39 (10.1) | 25 (8.9) | 14 (13.5) | |
| 3 | 62 (16.1) | 36 (12.8) | 26 (25.0) | |
| 4 | 86 (22.3) | 64 (22.8) | 22 (21.2) | |
| 5 or more (Polypharmacy) | 195 (50.6) | 156 (55.5) | 39 (37.5) | |
| Median number of medicines | 5 (3–5) | 5 (4–5) | 4 (3–5) | |
| Non-pharmacological measure suggested | Physiotherapy | 146 (37.9) | 116 (41.3) | 30 (28.8) |
| Immobilizer/Support | 3 (0.8) | 2 (0.7) | 1 (1.0) | |
| Physiotherapy and Orthopedics Support | 12 (3.1) | 10 (3.6) | 2 (1.9) | |
| Follow-up scheduled | 296 (76.9) | 228 (81.1) | 68 (65.4) | |
Off-Label Use of Gabapentinoids
Figure 1 illustrates the dosing of gabapentinoids, highlighting that pregabalin was predominantly prescribed at a sub-therapeutic dose, accounting for 94.0% of the all pregabalin prescriptions. 12 out of 104 pregabalin prescriptions were found to be in fixed dose combinations with methylcobalamin.
Figure 1.
Stacked bar chart illustrating the dosing of gabapentin and pregabalin categorized as therapeutic and sub-therapeutic.
Table 4 presents the distribution of gabapentinoid prescriptions across FDA-approved indications, BNF indications for neuropathic pain, and off-label uses without documented neuropathic symptoms. The most common FDA-approved use was post-herpetic neuralgia (13.1%), with pregabalin additionally prescribed for fibromyalgia (3.0%) and diabetic peripheral neuropathy (0.4%). Among the BNF indications, most prescriptions (11.7%) targeted musculoskeletal and neurological conditions. Symptomatic treatment accounted for 19.5% of the cases, predominantly with pregabalin (28.8%). Off-label use was prevalent for musculoskeletal conditions without neuropathic symptoms (14.5%) and for perioperative scenarios (4.7%). Gabapentinoids were also used for psychiatric conditions (1.0%), with pregabalin being more common (3.0%).
Table 4.
Descriptive Statistics of Gabapentinoid Use as per Indication
| Indications | Total (n=385) | Gabapentin (n = 281) | Pregabalin (n =104) |
|---|---|---|---|
| FDA-approved indications for both pregabalin and gabapentin | |||
| Post-herpetic neuralgia | 12 (3.1) | 7 (2.5) | 5 (5.4) |
| FDA-approved indications for pregabalin only | |||
| Fibromyalgia | 4 (1) | 1 (0.4) | 3 (2.9) |
| Diabetic peripheral neuropathy | 1 (0.3) | 1 (0.4) | – |
| BNF Indications (Confirmed or probable neuropathic pain) | |||
| Degenerative orthopedic condition* | 27 (7.0) | 17 (6.0) | 10 (9.6) |
| Low back pain* | 5 (1.3) | 4 (1.4) | – |
| Mechanical back pain* | 3 (0.8) | 1 (0.4) | 2 (1.9) |
| Musculoskeletal condition* | 44 (11.4) | 40 (14.2) | 4 (3.8) |
| Musculoskeletal and neurological condition | 45 (11.7) | 36 (12.8) | 9 (8.7) |
| Nerve compression | 19 (4.9) | 14 (5.0) | 5 (4.8) |
| Neurological condition | 34 (8.8) | 27 (9.6) | 7 (6.7) |
| Peripheral neuropathy | 10 (2.6) | 6 (2.1) | 5 (4.8) |
| Skeletal disorder* | 2 (0.5) | 2 (0.7) | – |
| Symptomatic treatment | 75 (19.5 | 45 (16.0) | 30 (28.8) |
| Off-label Use (Diagnosis without labelled indication or documented symptoms of neuropathic pain) | |||
| Degenerative Orthopedic Condition | 14 (3.6) | 11 (3.9) | 3 (2.9) |
| Low Back Pain | 5 (1.3) | 5 (1.8) | – |
| Mechanical Back Pain | 7 (1.8) | 7 (2.5) | – |
| Musculoskeletal Condition | 56 (14.5) | 41 (14.6) | 15 (14.4) |
| Perioperative Use | 18 (4.7) | 15 (5.3) | 3 (2.9) |
| Psychiatric Condition | 4 (1.0) | 1 (0.4) | 3 (2.9) |
Note: (*) denotes indication that included a primary condition with concurrent documentation of neuropathic pain symptoms.
Table 5 highlights the factors linked to off-label gabapentinoid use according to FDA guidelines. Patients visiting the orthopedics department were notably more likely to receive off-label prescriptions (OR: 24.750; p < 0.001), an association that remained significant after adjustment (AOR: 16.163; p = 0.001). Although patient age, type of gabapentinoid prescribed, analgesic co-prescription, and non-pharmacological measures were significant in univariate analysis, these factors were no longer significant after multivariate adjustment.
Table 5.
Factors Associated with “Off-Label Use of Gabapentinoids as per FDA Indication”
| Variables | OR (95% CI) | p-value | AOR (95% CI) | p-value |
|---|---|---|---|---|
| Gender | ||||
| Male | 1.827 (0.506–6.597) | 0.358 | – | – |
| Female | Reference | |||
| Patient’s Age | 0.970 (0.937–1.005) | 0.090* | 0.983 (0.950–1.019) | 0.352 |
| Indication | ||||
| Non-neuropathic pain | 2.218 (0.615–8.002) | 0.223 | 0.966 (0.228–4.095) | 0.962 |
| Neuropathic pain | Reference | |||
| Gabapentinoid prescribed | ||||
| Pregabalin | 0.307 (0.108–0.868) | 0.026* | 0.857 (0.249–2.950) | 0.807 |
| Gabapentin | Reference | |||
| Department Visited | ||||
| Orthopedics | 24.750 (7.502–81.658) | 0.000* | 16.163 (3.061–85.351) | 0.001* |
| Other Departments | Reference | |||
| Polypharmacy | ||||
| Yes | 0.894 (0.318–2.516) | 0.832 | – | – |
| No | Reference | |||
|
Analgesics co-prescription |
||||
| Yes | 6.409 (2.134–19.251) | 0.001* | 0.890 (0.185–4.257) | 0.884 |
| No | Reference | |||
| Non-pharmacological measures | ||||
| Yes | 10.67 (1.388–81.964) | 0.023* | 3.06 (0.329–28.456) | 0.326 |
| No | Reference | |||
Note: (*) Indicates odds ratio and adjusted odds ratio with 95% confidence interval is significant at p<0.05.
Abbreviations: OR, Odds Ratio; AOR, Adjusted Odds Ratio.
Knowledge of Patients Regarding Their Prescribed Gabapentinoids
Figure 2 illustrates the patient’s knowledge status regarding their prescription. The majority (51.0%) of patients had average knowledge, 43.5% had inadequate knowledge and only 5.5% demonstrated good knowledge, suggesting limited in-depth understanding among the study population.
Figure 2.
Pie chart depicting the level of knowledge among patients regarding their gabapentinoid prescription.
Table 6 shows that 87.8% of patients did not know the name of their gabapentinoid, but most were aware of their dose (91.0%), usage (91.4%), and administration timing (92.5%). Indirect knowledge was limited as only 25.7% knew what to do if they missed a dose, 11.4% were aware of drug/food interactions, and 7.3% understood possible side effects. Table 7 indicates that 233 patients (60.5%) were first-time users of the medication, while 152 patients were repeat users. Among the repeat users of the prescribed gabapentinoid, 23.0% experienced minor side effects. 89.6% of the patients responded with need for more information regarding their prescribed gabapentinoid. According to Table 8, age negatively impacted knowledge (AOR = 0.938, p = 0.003), whereas higher education (AOR = 7.954, p = 0.001) and fewer medications (AOR = 0.684, p = 0.047) were linked to better knowledge. Gender and repeat use had no significant impact.
Table 6.
Survey Responses and Knowledge Scores (Median and IQR) Reflecting Patients’ Understanding of Their Prescribed Gabapentinoids
| Category | Questions regarding | Did not know | Incorrect response | Correct response | Median score obtained (IQR) |
|---|---|---|---|---|---|
| Information Directly related to drug administrationa | Name of the drug | 338 (87.8) | 2 (0.5) | 45 (11.7) | 6 (6–6) |
| Dose | 31 (8.1) | 4 (1.0) | 350 (90.9) | ||
| Form of use | 28 (7.3) | 5 (1.3) | 352 (91.4) | ||
| Time of administration | 26 (6.8) | 3 (0.8) | 356 (92.5) | ||
| Information Indirectly related to drug administrationb | Therapeutic indication | 129 (33.5) | 65 (16.9) | 191 (49.6) | 2 (1–2) |
| Duration of treatment | 87 (22.6) | 2 (0.5) | 296 (76.9) | ||
| Attitude when one or more dosages are missed | 273 (70.9) | 13 (3.4) | 99 (25.7) | ||
| Interactions with other drugs and/or foods | 319 (82.9) | 22 (5.7) | 44 (11.4) | ||
| Adverse effects | 336 (87.3) | 21 (5.5) | 28 (7.3) |
Notes: aeach question in this category scores 2 points, b each question in this category scores 1 point.
Table 7.
Additional Information from the Survey
| Additional Information | n (%) |
|---|---|
| Patients who experienced side effect of gabapentinoids on repeat use | 35 (23.03) |
| Patients who needed more drug information | 345 (89.6) |
Table 8.
Factors Associated with “Good Knowledge on Gabapentinoids”
| Variables | OR (95% CI) | P-value | AOR (95% CI) | P-value |
|---|---|---|---|---|
| Gender | ||||
| Male | 1.732 (0.709–4.229) | 0.228 | 1.785 (0.670–4.751) | 0.246 |
| Female | Reference | |||
| Patient’s Age | 0.926 (0.890–0.964) | 0.00* | 0.938 (0.899–0.978) | 0.003* |
| Education Level | ||||
| Higher Education | 15.778 (4.971–50.078) | 0.00* | 7.954 (2.390–26.472) | 0.001* |
| Below Graduate level | Reference | |||
| Gabapentinoid Use | ||||
| Repeat Use | 0.94 (0.38–2.325) | 0.894 | – | – |
| First time use | Reference | |||
| Total number of medicine | 0.6 (0.431–0.835) | 0.002* | 0.684 (0.471–0.995) | 0.047* |
Note: (*) Indicates odds ratio and adjusted odds ratio with 95% confidence interval is significant at p<0.05.
Abbreviations: OR, Odds Ratio; AOR, Adjusted Odds Ratio.
Discussion
There has been a substantial and consistent increase in multinational gabapentinoid consumption over the years where off-label prescriptions accounted for more than half of total prescriptions.22 Examining gabapentinoid usage patterns is crucial because of their increasing prevalence, particularly concerning off-label and non-medical use, which has been linked to various potential risks.23 In 2019, the United Kingdom (UK) government reclassified gabapentinoids as scheduled 3 (class C) controlled drugs in the UK because of the high risks and deaths associated with their misuse.24
The study revealed that gabapentin was prescribed more often than pregabalin. This preference likely stems from gabapentin’s longer history and established reliability in treating neuropathic pain. In contrast, pregabalin, despite being a newer drug, has faced issues with increased dependency and abuse in Nepal, which may have led to its less frequent prescription.25 Recent studies conducted in the USA have also identified gabapentin as the most commonly used gabapentinoid, possibly because of the classification of pregabalin as a controlled substance nationwide in the USA.26,27 However, studies from Oman and Australia reported greater usage of pregabalin, which was attributed to its more favorable pharmacokinetic and pharmacodynamics profile.28,29
Gabapentinoids were predominantly prescribed to middle-aged female patients, many of whom had comorbid conditions and insurance coverage. The majority of prescriptions were made in the orthopedics department for pain-related issues. Similar to previous studies, these prescriptions often addressed both neuropathic and non-neuropathic pain, including musculoskeletal conditions.30,31 This pattern underscores their broad application within clinical practice despite limited formal approval.
Our study found that gabapentin and pregabalin were frequently used off-label across various departments. This practice may be influenced by factors such as the failure or contraindication of first-line medications, their role as adjuvant therapy, their use alongside surgical interventions, the clinical experience of prescribers, patient feedback, and literature-based guidelines. Gabapentinoids are commonly used off-label for orthopedic, neurological, and psychiatric conditions in pediatric, adult, and geriatric populations, highlighting the need for careful consideration in these settings.32–35
The evidence on the safety and efficacy of gabapentinoids for off-label uses, such as perioperative care, musculoskeletal pain management, and neurological disorders, ranges from conflicting to significant.36–38 Gabapentinoids demonstrate only modest effectiveness in managing perioperative pain, and their role in treating spinal stenosis remains unclear.39,40 However, they are beneficial in multimodal pain management, as they improve pain relief and reduce opioid use in surgical settings.41 Given the lack of compelling evidence regarding the safety and efficacy of gabapentinoids for both neuropathic and non-neuropathic pain conditions, it is important to exercise caution when prescribing and utilizing these drugs.
The recommended doses for neuropathic pain are 1200–3600 mg/day for gabapentin, starting at 300 mg/day, and 300–600 mg/day for pregabalin, starting at 150 mg/day. These doses are gradually increased based on the patient’s response.42,43 International guidelines indicate that gabapentin and pregabalin are either minimally effective or ineffective at doses below the recommended levels for neuropathic pain.44 Pregabalin was predominantly found to be prescribed at an initiating dose generally considered to be sub-therapeutic (75 mg once daily) for neuropathic pain. This variability may be attributed to the symptomatic nature of the indications and the lower risk of abuse and potential side effects for the general Nepalese population at sub-standard dosing. The dosage requirements for gabapentinoids have been found to differ across populations and conditions.45 The frequent prescription of low-dose pregabalin for neuropathic pain raises the possibility that it may be used for night-time sedation rather than for pain management, indicating the need for further investigation.
Pregabalin was often prescribed with methylcobalamin to potentially enhance its analgesic effects for neuropathic pain. Studies in India have shown that pregabalin is frequently initiated at sub-therapeutic doses, which are gradually increased as needed to improve patient tolerance. Additionally, pregabalin is often used in combination with methylcobalamin to enhance its synergistic effects and improve patient adherence.46,47 However, this combined use lacks support from national and international guidelines. A study conducted in Germany showed a moderate prevalence of pregabalin dependency.48 In our study, two patients on a pregabalin regimen were diagnosed with dependency. For those patients, pregabalin discontinuation was planned with a gradual tapering strategy. This approach aimed to prevent withdrawal symptoms, including insomnia, nausea, headache, diarrhea, anxiety, and hyperhidrosis, which can arise from abrupt discontinuation, particularly after long-term use.49
The majority of the patients were first-time users and wanted more information about their prescribed gabapentinoids. Some patients reported having experienced minor side effects after drug use, such as somnolence, dizziness, and sedation, which are common with gabapentinoid use.50 Studies in Scotland and US Medicare beneficiaries revealed that more than half of gabapentinoid prescriptions were co-prescribed with opioids, benzodiazepines, or both, posing potential dangers.51,52 In contrast to studies in Western countries, our study found that gabapentinoid users were predominantly co-prescribed with non-opioid analgesics and vitamins, and had a very low rate of co-prescription with controlled substances. This suggests more responsible prescribing practices, potentially due to stricter regulations and the associated risks of prescribing or co-prescribing controlled drugs.
Younger patients, those with higher education levels, and those with fewer prescribed medications generally had a better understanding of their treatment. Patients were typically well-informed about drug administration details such as dose, form, and timing. However, there was a significant lack of knowledge about clinical aspects, including therapeutic indications, drug interactions, and adverse effects. This highlights the need for enhanced patient education on these broader aspects of their medication regimens. These findings are consistent with those of a 2020 study in Nepal, which also revealed poor patient knowledge about prescription drugs.53 Similar findings were reported in Sri Lanka and India, where half of the patients had poor knowledge about their prescribed medications.54,55 A study in Lebanon found that pharmacists were knowledgeable about the indications, side effects, and addiction risks of gabapentin and pregabalin, but they had misconceptions about drug interactions and off-label use.56 This underscores the need for further investigation into healthcare prescribers’ knowledge, attitudes, and perceptions regarding the use and off-label use of gabapentinoids.
This study has several important limitations while providing insights into gabapentinoid prescribing patterns in Nepal. The single-center data limits the study’s generalizability within Nepal, requiring multi-center research for broader applicability. The study also could not establish a direct causal relationship between gabapentinoid use and prescribing behaviors, particularly regarding off-label practices. Reliance on medical records may have led to an underestimation or overestimation of off-label prescriptions and the reasoning behind them. Despite its limitations, this study provides valuable insights into the widespread off-label and sub-therapeutic use of gabapentinoids in Nepal, indicating the need for further research on the specific use of gabapentinoids in the Nepalese population. It identifies the need for enhanced education and training for healthcare providers, stricter guidelines, and improved patient education. Further research is needed to assess long-term outcomes and the effectiveness of gabapentinoids use and off-label use to optimize prescribing practices. Policymakers should also consider reviewing the classification of gabapentinoids in Nepal to mitigate risks of dependency and misuse.
Conclusion
This study offers a comprehensive investigation into gabapentinoid prescribing patterns at Dhulikhel Hospital, revealing a notable prevalence of off-label use and significant gaps in patient knowledge about their prescribed medications. It is important to recognize that prescribing decisions often appear to be guided more by empirical experience than by robust clinical evidence. This reliance on empirical practice may introduce potential concerns regarding the efficacy, safety, and risk of misuse associated with gabapentinoids. Given these issues, there is a clear need for rigorous research to explore optimal dosing regimens and to assess safety and efficacy of gabapentinoid use in the outpatient setting. Continuous monitoring of prescribing practices is essential to ensure they align with established guidelines and to mitigate the risk of misuse. Enhanced patient education and provider training are also crucial in addressing gaps in knowledge and improving adherence to best practices. Policymakers and healthcare providers should consider these findings to refine prescribing practices and develop more precise guidelines, ultimately aiming to enhance the safe and effective use of gabapentinoids and minimize associated risks.
Acknowledgments
The authors sincerely appreciate the volunteers who took part in this study. We are also grateful to the healthcare professionals and staff of Dhulikhel Hospital for their contribution to the research.
Abbreviations
BNF, British National Formulary; FDA, Food and Drug Administration; IQR, Interquartile Range; KUSMS, Kathmandu University School of Medical Sciences; IRC, Institutional Review Committee; NNF, Nepalese National Formulary; NSAIDs, Non-Steroidal Anti-Inflammatory Drugs; OR, Odds Ratio; PPIs, Proton Pump Inhibitors; SPSS, Statistical Package for Social Science; UK, United Kingdom; US, United States.
Data Sharing Statement
The data supporting the findings of this study are presented within the article, and the raw data from the survey have been provided as a supplementary file. (Supplementary table 1)
Author Contributions
All authors made substantial contributions across all critical aspects of this work, including conception, study design, execution, data collection, analysis, and interpretation. Additionally, all authors participated in drafting, revising, or critically reviewing the manuscript, approved the final version for publication, agreed on the journal submission, and assumed responsibility for the work throughout.
Disclosure
The authors report no conflicts of interest in this work.
References
- 1.Goodman CW, Brett AS. Gabapentin and Pregabalin for Pain — is Increased Prescribing a Cause for Concern? N Engl J Med. 2017;377(5):411–414. doi: 10.1056/NEJMp1704633 [DOI] [PubMed] [Google Scholar]
- 2.Chincholkar M. Analgesic mechanisms of gabapentinoids and effects in experimental pain models: a narrative review. Br J Anaesth. 2018;120(6):1315–1334. doi: 10.1016/j.bja.2018.02.066 [DOI] [PubMed] [Google Scholar]
- 3.Bates D, Schultheis BC, Hanes MC, et al. A Comprehensive Algorithm for Management of Neuropathic Pain. Pain Med off J Am Acad Pain Med. 2019;20(Suppl 1):S2–S12. doi: 10.1093/pm/pnz075 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Dowell D. CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022. MMWR Recomm Rep. 2022;71. doi: 10.15585/mmwr.rr7103a1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Cross A, Viswanath O, Sherman AP. StatPearls. 2024. Available from: https://www.statpearls.com/point-of-care/27618. Accessed July 14, 2024.
- 6.Yasaei R, Katta S, Saadabadi A. Gabapentin. In: StatPearls. StatPearls Publishing; 2023. http://www.ncbi.nlm.nih.gov/books/NBK493228/. Accessed January 8, 2024. [PubMed] [Google Scholar]
- 7.DDA: Nepalese National Formulary (NNF). 2024. Available from: https://www.dda.gov.np/content/nepalese-national-formulary-nnf. Accessed January 23, 2024.
- 8.Johansen ME, Maust DT. Update to Gabapentinoid Use in the United States, 2002-2021. Ann Fam Med. 2024;22(1):45–49. doi: 10.1370/afm.3052 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Athavale A, Murnion B. Gabapentinoids: a therapeutic review. Aust Prescr. 46(4):80–85. doi: 10.18773/austprescr.2023.025 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Hong JSW, Atkinson LZ, Al-Juffali N, et al. Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: systematic review, meta-analysis, and rationale. Mol Psychiatry. 2022;27(3):1339–1349. doi: 10.1038/s41380-021-01386-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Sreekantaswamy SA, Mollanazar N, Butler DC. Gabapentinoids for Pruritus in Older Adults: a Narrative Review. Dermatol Ther. 2021;11(3):669–679. doi: 10.1007/s13555-021-00513-z [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Pauly NJ, Delcher C, Slavova S, Lindahl E, Talbert J, Freeman PR. Trends in Gabapentin Prescribing in a Commercially Insured U.S. Adult Population, 2009-2016. J Manag Care Spec Pharm. 2020;26(3):10.18553/jmcp.2020.26.3.246. doi: 10.18553/jmcp.2020.26.3.246 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Peet ED, Dana B, Sheng FY, Powell D, Shetty K, Stein BD. Trends in the Concurrent Prescription of Opioids and Gabapentin in the US, 2006 to 2018. JAMA Intern Med. 2022:e225268. doi: 10.1001/jamainternmed.2022.5268 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Agarwal V. Off-label Medication Use: a Double-edged Sword. Indian J Crit Care Med. 2021;25:845–846. doi: 10.5005/jp-journals-10071-23951 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Lam K, Rochon PA, Steinman MAOO-L. Questionable Gabapentinoid Use Noted at Hospital Admission Warrants Deprescribing. J Hosp Med. 2019;14(9):579–580. doi: 10.12788/jhm.3245 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Evoy KE, Sadrameli S, Contreras J, Covvey JR, Peckham AM, Morrison MD. Abuse and Misuse of Pregabalin and Gabapentin: a Systematic Review Update. Drugs. 2021;81(1):125–156. doi: 10.1007/s40265-020-01432-7 [DOI] [PubMed] [Google Scholar]
- 17.Fröhlich SE, Dal Pizzol TDS, Mengue SS. Instrument to evaluate the level of knowledge about prescription in primary care. Rev Saúde Pública. 2010;44:1046–1054. doi: 10.1590/S0034-89102010000600009 [DOI] [PubMed] [Google Scholar]
- 18.MedicinesComplete — CONTENT > BNF > Drug: pregabalin. Available from: https://www.medicinescomplete.com/#/content/bnf/_985503629?hspl=pregabalin. Accessed July 14, 2024.
- 19.MedicinesComplete — CONTENT > BNF > Drug: gabapentin. Available from: https://www.medicinescomplete.com/#/content/bnf/_626504433. Accessed July 14, 2024.
- 20.Drugs@FDA: FDA-Approved Drugs. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021446. Accessed September 1, 2024.
- 21.Drugs@FDA: FDA-Approved Drugs. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020235. Accessed September 1, 2024.
- 22.Chan AYL, Yuen ASC, Tsai DHT, et al. Gabapentinoid consumption in 65 countries and regions from 2008 to 2018: a longitudinal trend study. Nat Commun. 2023;14(1):5005. doi: 10.1038/s41467-023-40637-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Fonseca F, Lenahan W, Dart RC, et al. Non-medical Use of Prescription Gabapentinoids (Gabapentin and Pregabalin) in Five European Countries. Front Psychiatry. 2021;12:676224. doi: 10.3389/fpsyt.2021.676224 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Ashworth J, Bajpai R, Muller S, et al. Trends in gabapentinoid prescribing in UK primary care using the Clinical Practice Research Datalink: an observational study. Lancet Reg Health. 2023:27. doi: 10.1016/j.lanepe.2022.100579 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Sharma P. Pregabalin Abuse: an Area of Concern in Nepal. J Psychiatr Assoc Nepal. 2021;10(2):1–2. [Google Scholar]
- 26.Huang LL, Wright JA, Fischer KM, et al. Gabapentinoid Prescribing Practices at a Large Academic Medical Center. Mayo Clin Proc Innov Qual Outcom. 2023;7(1):58–68. doi: 10.1016/j.mayocpiqo.2022.12.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Banks C, Bowman A, Merrey J L, Waldfogel JM. Characterization of Outpatient Gabapentinoid Prescribing for Pain. J Pain Palliat Care Pharmacother. 2023;37(2):143–147. doi: 10.1080/15360288.2023.2174635 [DOI] [PubMed] [Google Scholar]
- 28.Badi ASA, Hashar AA, Riyami IA, Za’abi MA. A snapshot on the usage pattern of gabapentinoids in Oman. Pharm Pract. 2022;20(3):2693. doi: 10.18549/PharmPract.2022.3.2693 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Prior FH. A snapshot of the prescribing patterns and off‐label use of gabapentinoid agents in tertiary care: a retrospective, cross‐sectional, descriptive study. J Pharm Pract Res. 2021;51(2):121–128. doi: 10.1002/jppr.1693 [DOI] [Google Scholar]
- 30.Maloy GC, Halperin SJ, Ratnasamy PP, Grauer JN. Characterizing Gabapentinoid Use Among Patients With Isolated Low Back Pain. Glob Spine J. 2024;21925682231224390. doi: 10.1177/21925682231224390 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Rassi J, Khazaka S, Hlais S, Rassi S, Daher M, Samaha T. Gabapentinoid prescriptions for neuropathic and musculoskeletal pain in Lebanon. Future Sci OA. 2024;10(1):FSO960. doi: 10.2144/fsoa-2023-0219 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Gingras MA, Lieu A, Papillon-Ferland L, Lee TC, McDonald EG. Retrospective Cohort Study of the Prevalence of Off-label Gabapentinoid Prescriptions in Hospitalized Medical Patients. J Hosp Med. 2019;14(9):547–550. doi: 10.12788/jhm.3203 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Donado C, Nedeljkovic K, Wangnamthip S, Solodiuk JC, Bourgeois FT, Berde CB. Trends in Gabapentin and Pregabalin Prescribing in a Tertiary Pediatric Medical Center. Hosp Pediatr. 2021;11(8):909–914. doi: 10.1542/hpeds.2020-003582 [DOI] [PubMed] [Google Scholar]
- 34.Appleyard T, Ashworth J, Bedson J, Yu D, Peat G. Trends in gabapentinoid prescribing in patients with osteoarthritis: a United Kingdom national cohort study in primary care. Osteoarthritis Cartilage. 2019;27(10):1437–1444. doi: 10.1016/j.joca.2019.06.008 [DOI] [PubMed] [Google Scholar]
- 35.González-Bueno J, Calvo-Cidoncha E, Desongles-Corrales T, Santos Rubio M, Chamorro De Vega E, Bautista-Paloma F. DI-024 Off-label use of gabapentin and pregabalin in a tertiary hospital. Eur J Hosp Pharm. 2015;22(Suppl 1):A84.3–A85. doi: 10.1136/ejhpharm-2015-000639.202 [DOI] [Google Scholar]
- 36.Giménez-Campos MS, Pimenta-Fermisson-Ramos P, Díaz-Cambronero JI, Carbonell-Sanchís R, López-Briz E, Ruíz-García V. A systematic review and meta-analysis of the effectiveness and adverse events of gabapentin and pregabalin for sciatica pain. Aten Primaria. 2022;54(1):102144. doi: 10.1016/j.aprim.2021.102144 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Shanthanna H, Gilron I, Rajarathinam M, et al. Benefits and safety of gabapentinoids in chronic low back pain: a systematic review and meta-analysis of randomized controlled trials. PLoS Med. 2017;14(8):e1002369. doi: 10.1371/journal.pmed.1002369 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Davari M, Amani B, Amani B, Khanijahani A, Akbarzadeh A, Shabestan R. Pregabalin and gabapentin in neuropathic pain management after spinal cord injury: a systematic review and meta-analysis. Korean J Pain. 2020;33(1):3. doi: 10.3344/kjp.2020.33.1.3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Tsai SHL, Hu CW, El Sammak S, et al. Different Gabapentin and Pregabalin Dosages for Perioperative Pain Control in Patients Undergoing Spine Surgery: a Systematic Review and Network Meta-Analysis. JAMA Network Open. 2023;6(8):e2328121. doi: 10.1001/jamanetworkopen.2023.28121 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Martinez V, Carles M, Marret E, Beloeil H. Perioperative use of gabapentinoids in France. Mismatch between clinical practice and scientific evidence. Anaesth Crit Care Pain Med. 2018;37(1):43–47. doi: 10.1016/j.accpm.2017.01.010 [DOI] [PubMed] [Google Scholar]
- 41.Sherman M, Sethi S, Hindle AK, Chanza T. Multimodal Pain Management in the Perioperative Setting. Open J Anesthesiol. 2020;10(2):47–71. doi: 10.4236/ojanes.2020.102005 [DOI] [Google Scholar]
- 42.Wiffen PJ, Derry S, Bell RF, et al. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;2017(6):CD007938. doi: 10.1002/14651858.CD007938.pub4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Derry S, Bell RF, Straube S, Wiffen PJ, Aldington D, Moore RA. Pregabalin for neuropathic pain in adults. Cochrane Database Syst Rev. 2019;2019(1):CD007076. doi: 10.1002/14651858.CD007076.pub3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44.Serpell M, Latymer M, Almas M, Ortiz M, Parsons B, Prieto R. Neuropathic pain responds better to increased doses of pregabalin: an in-depth analysis of flexible-dose clinical trials. J Pain Res. 2017;10:1769–1776. doi: 10.2147/JPR.S129832 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Shaheen A, Alam SM, Ahmad A, Khan M. Clinical efficacy and tolerability of Gabapentinoids with current prescription patterns in patients with Neuropathic pain. Pak J Med Sci. 2019;35(6):1505–1510. doi: 10.12669/pjms.35.6.652 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.Anantharamu T, Sinha S. Consumption pattern of gabapentinoids in a tertiary health-care system: a five year study from 2012-2017. Int J Basic Clin Pharmacol. 2019;8. doi: 10.18203/2319-2003.ijbcp20192117 [DOI] [Google Scholar]
- 47.Gor KA, Shah KN, Joshi PB, Joshi HM, Rana DA, Malhotra SD. Off-label drugs use in neurology outpatient department: a prospective study at a tertiary care teaching hospital. Perspect Clin Res. 2020;11(1):31. doi: 10.4103/picr.PICR_117_18 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Snellgrove BJ, Steinert T, Jaeger S. Pregabalin Use Among Users of Illicit Drugs: a Cross-Sectional Survey in Southern Germany. CNS Drugs. 2017;31(10):891–898. doi: 10.1007/s40263-017-0467-3 [DOI] [PubMed] [Google Scholar]
- 49.Freynhagen R, Baron R, Kawaguchi Y, et al. Pregabalin for neuropathic pain in primary care settings: recommendations for dosing and titration. Postgrad Med. 2021;133(1):1–9. doi: 10.1080/00325481.2020.1857992 [DOI] [PubMed] [Google Scholar]
- 50.Chincholkar M. Gabapentinoids: pharmacokinetics, pharmacodynamics and considerations for clinical practice. Br J Pain. 2020;14(2):104–114. doi: 10.1177/2049463720912496 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.Torrance N, Veluchamy A, Zhou Y, et al. Trends in gabapentinoid prescribing, co-prescribing of opioids and benzodiazepines, and associated deaths in Scotland. Br J Anaesth. 2020;125(2):159–167. doi: 10.1016/j.bja.2020.05.017 [DOI] [PubMed] [Google Scholar]
- 52.Chen C, Winterstein AG, Lo-Ciganic WH, Tighe PJ, Wei YJJ. Concurrent use of prescription gabapentinoids with opioids and risk for fall-related injury among older US Medicare beneficiaries with chronic noncancer pain: a population-based cohort study. PLOS Med. 2022;19(3):e1003921. doi: 10.1371/journal.pmed.1003921 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53.Gyanwali P, Dhakal N, Humagain B, Karki K. Medicine Prescribing Pattern and Knowledge on Medicine Use at Different Level of Health Care Settings in Nepal. J Nepal Health Res Counc. 2020;18:520–524. doi: 10.33314/jnhrc.v18i3.2885 [DOI] [PubMed] [Google Scholar]
- 54.R T, H IU, M MY, G P. Patients’ knowledge about medicines improves when provided with written compared to verbal information in their native language. PLoS One. 2022;17(10):e0274901. doi: 10.1371/journal.pone.0274901 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.Roy V, Tayal V, Kansal A. Patients Knowledge of Prescribed Medications and Factors Affecting it in a Tertiary Care, Public, Teaching Hospital in New Delhi, India. MAMC J Med Sci. 2020;6(3):204. doi: 10.4103/mamcjms.mamcjms_45_20 [DOI] [Google Scholar]
- 56.Tarhin F, Taky R, Jaffal LH, et al. Awareness of Lebanese Pharmacists towards the Use and Misuse of Gabapentinoids and Tramadol: a Cross-sectional Survey. Dr Sulaiman Al Habib Med J. 2020;2(1):24–30. doi: 10.2991/dsahmj.k.200206.002 [DOI] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data supporting the findings of this study are presented within the article, and the raw data from the survey have been provided as a supplementary file. (Supplementary table 1)