The expert meeting was recorded and transcribed, topics were organized in themes and the panel’s main points and recommendations were summarized.

Navigating the Complexities of Gabapentinoids Regulation and Clinical Practice

The regulation, prescribing, and oversight of gabapentinoids, including gabapentin and pregabalin, has become increasingly complex due to concerns over abuse and the need for optimized pain management. Gabapentinoids are pivotal in managing neuropathic pain and are widely recognized as first-line therapies. They are frequently used as opioid-sparing alternatives in palliative care, particularly for patients experiencing specific types of terminal cancer pain, such as those with neuropathic components. Despite their therapeutic importance, regulatory restrictions have introduced significant challenges to clinical practice. These medications remain essential for treating conditions, such as diabetic peripheral neuropathy, postherpetic neuralgia, and chronic back pain with neuropathic components, such as radicular pain. Achieving a balance between regulatory control and optimizing clinical application is essential; this involves safe, effective, and evidence-based prescribing of gabapentinoids, tailored to meet the specific needs and risk profiles of individual patients. Moreover, it is critical to assess the impact of regulatory policies to ensure that they do not compromise patient access or treatment efficacy.

Before the SFDA’s restrictions on pregabalin, gabapentin addiction was rarely reported. A notable preference for pregabalin over gabapentin in cases of abuse has been consistently documented. Due to its rapid onset and euphoric effects, pregabalin carries a higher risk of misuse than gabapentin, particularly among younger individuals. This distinction is supported by data from a representative sample of the French population, where notably higher rate of misuse was observed in pregabalin compared to gabapentin users (12.8% vs. 6.6%; p < 0.001) [21]. Additionally, a higher proportion of pregabalin users experienced a first episode of misuse compared to gabapentin users (11.3% vs. 5.9%). Moreover, personality disorders were frequently associated with pregabalin misuse, which was not observed in gabapentin users [21].

Moreover, the prevalence of lifetime abuse is reported to be consistently lower with gabapentin [22]. Gabapentin received its first market authorization in the USA in 1993, nearly 17 years before the European Medicines Agency issued a warning regarding its potential for abuse [23, 24]. During this period, there were no significant issues of abuse linked to gabapentin. In contrast to pregabalin, the Saudi summary of product characteristics does not list euphoria as an adverse event associated with gabapentin [25, 26]. Furthermore, in the USA, there is no federal-level control of gabapentin utilization by the Drug Enforcement Administration [27]. However, since 2016, more than 26 states have reclassified gabapentin as a Schedule V medication at the state level or introduced mandatory reporting to prescription drug monitoring programs, such as the Ohio Automated Rx Reporting System [28,29,30]. Similarly, the risk of misuse, abuse, or dependence with gabapentin is not mentioned in the French SmPC, highlighting its lower misuse potential relative to pregabalin [21]. However, it should be noted that in October 2022, the EMA’s CMDh mandated the inclusion of specific warnings regarding the abuse potential of gabapentin in all EU Summary Product Characteristics (SmPC) [31]. Moreover, SmPCs often lag scientific developments and may not always reflect the most current understanding of the safety profile of medications.

Gabapentinoids are integral to the standard care of a wide range of neuropathic conditions. These include peripheral neuropathies such as diabetic polyneuropathy, central conditions like fibromyalgia, and mixed pain types such as specific types of cancer-related pain with neuropathic components. They are particularly valuable when opioids are ineffective or undesirable. When used in combination with opioids, gabapentinoids contribute to a decrease in the overall opioid doses needed, which minimizes the risks associated with opioid therapy, such as the development of tolerance and potential for addiction. However, this opioid-sparing effect has also led to gabapentin being misused as an “opioid-enhancer” by those struggling with opioid addiction, which varies across patients. Those at a higher risk of pregabalin abuse often have a history of substance abuse, particularly with benzodiazepines and marijuana [32]. Age also influences misuse patterns. Younger individuals are more likely to misuse pregabalin, while elderly patients are less prone due to intolerance to its side effects [21, 33]. Therefore, restricting gabapentinoid use among the elderly population may not be necessary, given their lower risk of developing addiction. Addressing these differences is essential in shaping regulations and clinical practices that minimize misuse while ensuring continued access to these vital medications for patients who genuinely benefit from them.

Gaps in Pain Management Education and Their Implications

A significant factor contributing to the inappropriate use of gabapentin is the lack of emphasis on pain management in medical education. As per a systematic literature review on pain medicine education in 383 medical schools in Australia, New Zealand, USA, Canada, UK, and Europe, the median number of hours dedicated to pain medicine in the entire curriculum ranged between 11 and 20 h [34]. Furthermore, it was noted that pain medicine is mainly taught within anesthesia or pharmacology courses, rather than as a separate module. In the UK and USA, 96% of medical schools and about 80% in Europe do not have compulsory pain medicine education [34]. Several studies from Saudi Arabia have also highlighted the lack of adequate training in pain management for both medicine and nursing students, suggesting the need for improved educational programs and formal curriculum on pain medicine [35,36,37,38]. Medical students, on average, receive only 13 h of pain management training (ranging from 6 to 50 h) compared to their veterinary counterparts, who receive around 27.4 h (ranging from 8.8 to 43 h) [39]. This inadequacy in training highlights a critical gap in the preparedness of physicians to manage pain effectively and differentiate the types of pain, which may lead to poor prescribing practices and improper titration of medications like gabapentin and pregabalin, thus increasing the risk of misuse and side effects. For example, there may be instances of prescribing higher doses when lower-dose options, such as gabapentin 100 mg are not available. In addition, the lack of targeted, evidence-based training contributes to both under-treatment and inappropriate prescribing patterns. Many healthcare providers, especially general practitioners and non-specialists, may not feel adequately equipped to assess neuropathic pain or balance the risk–benefit profile of gabapentinoids. This contributes to variability in clinical decisions, hesitancy in prescribing even when clinically indicated, and potential over-reliance on less appropriate alternatives. Enhancing pain education is essential not only to improve patient outcomes but also to assist prescribers in navigating regulatory frameworks and reducing misuse risks. Therefore, it is imperative to improve education and training in pain management to ensure the effective use of gabapentinoids in clinical practice.

Physicians’ Perspectives on Current Regulatory Framework in Saudi Arabia and Its Impact on Gabapentinoid UsePhysician Hesitancy and Impact on Clinical Practice

The trending focus that was aligned with the introduction of the Raqeeb platform in Saudi Arabia has raised concerns among healthcare providers. While its goal is to monitor and prevent over-prescription of controlled substances, physicians often face the risk of being flagged for prescribing gabapentinoids. This has resulted in increased caution and hesitancy, even when these medications are clinically indicated. In some cases, physicians have opted to prescribe alternative medications like duloxetine, amitriptyline, carbamazepine, or sometimes tramadol to avoid potential scrutiny, particularly for patients who are stable and receiving treatment with gabapentinoids. A cross-sectional study from Saudi Arabia found that after the implementation of a restricted pregabalin prescription policy, there was a significant reduction in pregabalin use, which was accompanied by an increased use of opioids such as tramadol and acetaminophen/codeine [40]. This shift towards alternative pain management options may not be as effective for certain patients and may carry their own risks, for instance, the risk of falls in elderly patients, which is 48% less with gabapentin than duloxetine [41, 42]. Further, the hesitancy among the prescribers not only delays the treatment of patients with chronic pain but also disrupts the continuity of care for those who have long relied on gabapentinoids for pain management. These regulatory challenges place an additional administrative burden on physicians, potentially leading to suboptimal pain management strategies.

Stigma and Patient Reluctance

The reclassification of gabapentinoids as controlled substances in Saudi Arabia has considerably impacted patients who rely on these medications for managing chronic pain. Many individuals, particularly those on long-term gabapentinoid therapy, are now reluctant to continue treatment due to concerns about being perceived as drug abusers. This stigma associated with controlled substances can lead to patients discontinuing treatment or avoiding necessary adjustments, resulting in inadequate pain management and a deterioration in QoL. The stigma is exacerbated by public perceptions that these drugs are mainly associated with addiction, overshadowing the legitimate medical needs.

Challenges with Low-Dose Gabapentinoids

Furthermore, the unavailability of lower-dose formulations, such as gabapentin 100 mg, exacerbates the problem. This specific dose is often unavailable in the Saudi market or in hospital formularies, forcing physicians to initiate therapy at higher doses. In response, some prescribers suggest a workable solution, advising patients to open a gabapentin 300-mg capsule, dissolve the contents in a liquid, consume half, and discard the rest. Although this approach helps reduce excessive initial higher doses and facilitates more gradual titration, it is not an ideal or sustainable long-term approach. This lack of lower-dose options remains a critical concern, emphasizing the need for better access to appropriate formulations to ensure safe, effective, and tailored pain management.

Complexity of Substance Abuse and Regulatory MeasuresSubjectivity of Pain and Drug-Seeking Behavior

Pain is inherently subjective, which complicates efforts to assess the abuse potential. Patients with substance use disorder may exhibit drug-seeking behavior, making it difficult for prescribers to distinguish between legitimate medical needs and abuse. In Jeddah, multiple autopsy reports have not directly implicated pregabalin abuse as a cause of death. However, pregabalin has been identified in conjunction with other toxic substances such as heroin and methamphetamine, highlighting its abuse in these instances [43]. Tough measures restricting access to gabapentinoids may push individuals at risk towards alternative sources.

A Comprehensive Approach to Substance Use Disorder

Addressing substance use disorders requires a holistic approach, targeting both the symptoms of dependance and the underlying causes, such as mental health issues, previous instances of substance abuse, and social factors. A comprehensive policy review is necessary to ensure that restrictions on gabapentinoids alone are not enacted to solve the problem but also address the underlying behavioral aspects. This approach will help prevent unintended consequences, such as a rise in the use of more harmful substances or restricted access to legitimate patients with neuropathic pain to effective treatments.

Expert Opinion and Practical Recommendations for Optimizing Gabapentinoid Management in Saudi ArabiaComprehensive Prescribing Guidelines

To address the challenges posed by the reclassification of gabapentinoids, it is crucial to implement comprehensive updated prescribing guidelines. The variations in the risk of abuse among specific patient populations, such as the elderly or those with epilepsy or terminal illnesses, need to be addressed to ensure that these patients continue to receive the necessary treatment without facing barriers to pain management. Additionally, these guidelines should offer detailed guidance for specific cases, such as transitioning patients from gabapentin and pregabalin, or from opioids to gabapentinoids, which could enhance patient care while minimizing misuse and medication errors. Restrictions should be tailored to the specific characteristics of each molecule, ensuring gabapentin is managed according to its lower risk for abuse and broader therapeutic dose range. Precautionary measures should focus on patients receiving high doses or those at higher risk of misuse, balancing safety with therapeutic efficacy.

Improving the Raqeeb Platform and Reducing Administrative Burden

While the Raqeeb platform is essential for monitoring controlled substances, its current implementation imposes a significant administrative burden on healthcare providers. Physicians report that navigating the system is time-consuming, which hinders their focus on patient care. Optimizing the platform’s functionality will aid in streamlining workflows, reducing administrative strain, and encouraging increased compliance with regulatory requirements. To improve efficiency and usability, the platform should integrate simplified data entry, automated prescription tracking, and clearer reporting mechanisms. Also, integrating a diagnosis verification tool for high-risk patients would support clinical decision making, ensuring that prescriptions are appropriate, justified, and aligned with best practices while minimizing the risk of misuse.

Risk-Based Patient Stratification and Multicriteria Assessment Tools

Implementing risk stratification tools can effectively identify patients at higher risk of misusing/abusing gabapentinoids. Key risk factors include a history of substance abuse, mental health disorders, chronic illness, familial instability, a feeling of loneliness and disconnection, and living in unhealthy environments. This approach aligns seamlessly with Saudi Arabia’s Vision 2030, which emphasizes protecting families as the cornerstone of a stable society across generations. Furthermore, men are generally at a higher risk of substance misuse/abuse compared to women, which is influenced by a range of cultural and environmental factors.

By employing tools like the DN4 questionnaire, physicians can ensure accurate diagnosis and create tailored treatment plans [44]. High-risk patients, including those with the aforementioned risk factors, should be monitored more closely, such as tracking for high dose prescriptions, dispensing for less duration, or asking for diagnosis reassurance. In contrast, low-risk patients, such as the elderly, should not face unnecessary barriers to access pain management therapies. This approach ensures that prescribing practices are tailored to individual needs, allowing safe and appropriate access to gabapentinoids for those who need them while maintaining vigilant oversight on those at higher risk.

Patient Questionnaires and Consent

Introducing patient questionnaires and obtaining consent for potential random drug testing (urine or blood samples for high-risk users) could help physicians assess a patient’s risk for misuse/abuse during treatment. This measure would not only help identify potential risks early but also support the ongoing need for monitoring throughout the course of treatment. It could alleviate concerns about misuse/abuse while maintaining access to gabapentinoids for patients with legitimate needs, ensuring that both patient safety and appropriate access to treatment are prioritized.

Increased Access to Low-Dose Formulations

Ensuring the availability of low-dose gabapentinoid formulations, such as gabapentin 100 mg, is crucial for safe and individualized treatment initiation. Restoring access to these lower doses would help minimize unnecessary side effects and reduce the risk of dependence, allowing for more precise dose adjustments in clinical practice.

Improving Physician Education

A significant factor contributing to gabapentinoid misuse is the lack of comprehensive education among physicians regarding appropriate dosing and pain management strategies. Many physicians, particularly those outside of specialized pain clinics, are not well-versed in the nuances of gabapentinoid pharmacology. As a result, inappropriate prescribing, such as inaccurate diagnosis, abrupt discontinuation or sudden withdrawal of high doses without proper titration can increase the risk of abuse and dependence. Addressing this educational gap through targeted training programs focused on pain management and appropriate dosing strategies can significantly improve prescribing practice, reduce the risk of misuse, and enhance patient outcomes.

Patient Education and Awareness Campaigns

Patient education initiatives are essential for reducing stigma surrounding gabapentinoids and enhancing patient understanding of their proper use. These campaigns should emphasize that, when used correctly, gabapentinoids can significantly improve QoL, while also educating patients on the risks of abuse. Importantly, patients must understand the differences between gabapentin and pregabalin, particularly regarding dosing and potency, as many are unaware of the distinctions. Contrary to common assumptions about substance addiction, gabapentinoid abuse is often associated with individuals who have higher levels of education and greater knowledge. These individuals may also have better access to pharmaceutical alternatives than street drugs, necessitating a more targeted approach to public education.

Campaigns should also emphasize the importance of gradual tapering to prevent withdrawal symptoms and reduce the likelihood of patients self-medicating or adjusting their dosage without medical supervision. Proper education on dose titration and the risk of abrupt discontinuation is critical for both preventing misuse and ensuring effective, long-term pain management.

Risk Stratification and Tracking

Implementing a system for defining high-risk patients would enable physicians to prescribe with confidence, knowing that these individuals are being closely monitored. This could also reduce the regulatory pressure on low-risk patients and allow for more effective pain management.

Need for Research

It is vital to conduct studies focused on gabapentinoids abuse in Saudi Arabia to get a deeper understanding of the associated risk factors, which will facilitate the development of more targeted interventions. More research in this area would enhance our knowledge of misuse/abuse patterns and inform future policy frameworks.

Clear Protocols for Managing Abuse

Physicians need well-defined protocols to manage suspected cases of gabapentinoid abuse. Standardized guidelines for tapering therapy or transitioning patients to alternative treatments must be standardized to ensure consistent, safe, and effective care.