It is essential for societies projecting guidelines to constantly assess the consistency of physicians’ prescriptions with the set recommendations. Several studies conducted worldwide have focused on the epidemiology and treatment of neuropathic pain. However, none was performed in the Lebanese community. Our study was conducted across all Lebanese governorates to review the pattern of drug dispensing in patients with neuropathic pain in a community setting.
Most patients were suffering from neuropathic back pain or diabetic neuropathy. Those same predominating NeP types are also observed in the middle east region [9]. Furthermore, it was noted that the majority of enrolled patients were taking guideline-recommended first-line agents. Contrarily, a recent French study assessing general physicians’ extent of adherence to guidelines detected their obliviousness of first-line options [14].
Post-herpetic neuralgia was the most common etiology treated without any prescription. This can be attributed to the fact that many people seek advice and treatment from the community pharmacy to diagnose and manage skin conditions, including herpes zoster and its complications [15].
Gabapentinoids, mainly pregabalin, were the most commonly used drugs to treat neuropathic pain from different etiologies. While having a comparable mechanism of action, pregabalin has a higher analgesic potency than gabapentin, due to its higher binding affinity for the alpha-2/delta-1 subunit and higher bioavailability [16]. Pregabalin's specific pharmacokinetic benefits over gabapentin may have been the basis for its popularity among prescribing doctors.
In contrast, only a minority of patients used SNRIs and TCAs in the present study. The transition from TCAs to gabapentinoids can be attributed mainly to their low safety profile, especially in the elderly population as they can cause a broad range of adverse effects as orthostatic hypotension, xerostomia, and constipation. Secondary amines (nortriptyline or desipramine) has been associated with more minor anticholinergic effects and sedation and thus are better tolerated than other nonselective TCAs (amitriptyline and imipramine) [17]. TCAs also have a multitude of contraindications, including glaucoma, prostate hypertrophy, and cardiac conduction irregularities [9]. However, TCAs may be a preferred option for patients with severe renal insufficiency, given their hepatic elimination [9].
Surprisingly, although SNRIs have a relatively safer adverse-effects profile than TCAs (anticholinergic and cardiac side effects), their dispense rate was limited in this study. This may be attributed to the increased costs of SNRI compared to other first-line options in addition to the CYP2D6 inhibition and worsened glycemic control precipitated by duloxetine [9]. In general, these considerations may drive the Lebanese community’s preference for pregabalin over TCAs and SNRIs. In addition, gabapentinoids monotherapy is as effective as amitriptyline with better tolerable adverse effects [18]. Many studies supported the use of pregabalin as a first-line treatment in neuropathy and its efficacy in reducing pain, according to several types of pain assessment scores and improving sleep quality [19]. Sleep hygiene should be regarded as an important therapeutic target as insomnia significantly impacts pain severity.
Our findings point to significant concerns about particular combinations and the use of NSAIDs for treating neuropathic pain. Although the majority of patients were taking a combination of drugs, which is consistent with previous research showing that at least 45% of patients with neuropathic pain are treated with two or more drugs, the most common combinations encountered were gabapentinoid plus NSAID, gabapentinoid plus tramadol, and gabapentinoid plus NSAID plus tramadol [6]. It is noteworthy that we did not find any combination of the two first-line drugs recommended by NeuPSIG (for example, gabapentinoid plus TCA or SNRI) in case of inadequate relief with a single agent [5]. There is no clear agreement on the best next step in case of therapy failure; whether to alternate between same class or different class medications or even to add a particular new drug. However, the US Food and Drug Administration has expressed concern over the increasing use of gabapentinoids, especially when administered concurrently with opioid analgesics or benzodiazepines, due to increased risk of potential harm predisposed by drug interactions and accented adverse events [20]. An additional problem arises in the Lebanese community, where current governmental regulations are insufficient to control the dispensation of gabapentinoids, as confirmed by 43% of Lebanese pharmacists [13].
Thus, no surprise that the elderly received less prescriptions of first-line medications given the vulnerable safety profile of these drugs. Moreover, the decreased dispense of opioids amongst PDN and cervical or lumbar radiculopathy patients may be attributed to the lack of evidence regarding the role of opioids as a first line option for patients with DPN and their limited use in neuropathic back pain for a duration up to 2 months [4,5,6,7, 21]. However, the direct association between positive alcohol intake and smoking history is unsound as the use of opioid predisposes a grave issue due to the increased risk of overdose.
The second concern is the overuse of NSAIDs (diclofenac, naproxen, and ibuprofen) to provide additional pain relief in NeP disorders in the Lebanese community, despite the lack of solid evidence that proves their use. The continued widespread use of NSAIDs for neuropathic pain was also reported by Moore and colleagues, where an estimated 18 to 47% of NeP patients declared the use of NSAIDs specifically for their neuropathic pain [8]. Notably, in our current analysis, physicians visit was not directly associated with NSAIDs use. This directs the blame away from prescribing doctors and condemns patients and dispensing pharmacists given the over-the-counter dispensary of NSAIDs. In fact, self-medication has been widely detected in the Lebanese community, as reported by Awada and colleagues, where acetaminophen-based analgesics (48.7%) and NSAIDS (24.6%) were the most commonly consumed medications [22]. Thus, a strategy must be developed to implement influential community pharmacy-based interventions to raise patient and pharmacist awareness about the rational use of drugs for neuropathy.
To our knowledge, this is the first study that describes the patterns of pain medication dispensing in neuropathic diseases in Lebanon. Nevertheless, it was subject to some limitations. First, it is an observational study in which outcomes were not evaluated. Second, not all Lebanese pharmacies were included in the sample studied. Third, data were reported by the patient and may be subject to recall bias.
