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Topical 5% lidocaine patches for treating postherpetic neuralgia: a survey among nurses and patients
1NEMA Research Inc., 868 106th Ave North, Naples, FL 34108, USA
2Mid-America Poly Clinic, 7100 College Boulevard, Overland Park, Overland Park, KS 66210, USA
3Department of MESVA, University of L’Aquila, 67100 L’Aquila, Italy
4Paolo Procacci Foundation, Via Tacito 7, 00193 Roma, Italy
*Corresponding Author(s):rtaylor@nemaresearch.com; robert.taylor.phd@gmail.com (Robert Taylor Jr.)
| History | Submitted: 18 January 2021 | Accepted: 18 May 2021 | Published: 08 January 2022 |
| Copyright: | ©2022 The Author(s). Published by MRE Press. |
Introduction: Postherpetic neuralgia (PHN) is associated with moderate to severe pain with peripheral and central mechanisms. While there is no clear-cut first-line therapeutic approach to PHN pain control, lidocaine patches are frequently used as monotherapy or part of a multimodal pain regimen.
Methods: An online survey, the first of its kind, was conducted among PHN patients (n = 153) and nurses (n = 151) in order to determine clinical and patient knowledge, attitudes and practices toward the lidocaine patch and current unmet needs.
Results: Results of the survey indicated that PHN patients are prescribed a mean of 2.6 medications to control their PHN pain, including the lidocaine patch. There were negative responses related to the patches’ ability to adhere to the skin. Patients reported the use of tape to hold the patches in place and/or patches that detached completely, truncating the therapeutic dose period. Most nurses (53%) found the biggest obstacle to PHN pain control was noncompliance and 98% stated that reliable patch adhesion for the intended 12-hour application was “somewhat important” or “very important” for PHN pain control. Forty-five percent of nurses said that poor patient adherence to PHN analgesic regimens was related to poor adhesion of the lidocaine patch.
Conclusion: A new bioequivalent lidocaine patch has been developed with better adhesive characteristics, nine-fold greater bioavailability, and improved form factor.
Cite this article
Joseph V. Pergolizzi Jr., Sri Nalamachu, Kailyn Mitchell, Antonella Paladini, Robert Taylor Jr., Giustino Varrassi. Topical 5% lidocaine patches for treating postherpetic neuralgia: a survey among nurses and patients. Signa Vitae. 2022; 18(1): 84-95. doi: 10.22514/sv.2021.114
1. Plain language summary
Post-herpetic neuralgia (PHN) occurs when pain persists following an episode of shingles. PHN can cause moderate to severe pain, which may be treated in several ways. One of the most frequent pain-control treatments is the use of a lidocaine patch. A survey was conducted to assess the knowledge, attitudes and practices of clinicians and patients about the lidocaine patch and uncover current unmet needs. Patients and nurses were surveyed about the use of the lidocaine patch and one of the drawbacks of an older version of the patch was the fact that it did not remain properly affixed for the 12 hours needed for treatment. Most patients and nurses found that the patch provided effective pain control. On average, patients refilled their lidocaine patch prescription three times and 26% of patients used more than three refills. Since the time of the survey, a new lidocaine transdermal system has been developed which has higher bioavailability, lighter in weight and designed for better, long-lasting adhesion. Since most patients (80%) and most nurses (88%) thought a lidocaine patch with longer-lasting ability to adhere to the body was needed, the introduction of this new product is timely.
2. Introduction
Postherpetic neuralgia (PHN) is the most frequently reported complication of varicella zoster (VZ) viral infection (shingles) with an estimated incidence of 9% to 19% [1, 2, 3]. PHN typically occurs among older people who have had chickenpox more than 20 years ago and is likely to become increasingly prevalent with the aging population [1]. Risk factors for PHN include advanced age, stress, suppressed immune system, the use of immunosuppressive drugs, autoimmune disorders, certain solid cancer, certain chronic diseases such as chronic obstructive pulmonary disease, depression, recent physical trauma, and recent exposure to the VZ virus [1].
PHN is associated with moderate to severe or very severe pain of varying characteristics (dull, throbbing, electric, shooting, stabbing) and an unpredictable manifestation. Thirty to 50% of those with PHN have pain that has persisted a year or more [4]. Pain typically follows the course of the nerve along the acute segmental rash of the VZ [5, 6]. Guidelines for the control of pain associated with PHN recommend lidocaine plasters as well as systemic agents such as anticonvulsants, tricyclic antidepressants, and opioids. Therapy may involve a single agent or combination. There is no clear optimal first-line course of treatment, but lidocaine plasters are among the first- or second-line medications recommended and are often an important part of multimodal pain therapy [7, 8, 9]. See Table 1 (Ref. [7, 8, 10, 11]).
| AAN 2004 (ret) | EFNS 2010 | CPS 2014 | NeuPSIG of IASP 2015 | |
| PHN | Neuropathic pain (PHN section) | Neuropathic pain | Neuropathic pain | |
| 1st Line | Gabapentin/pregabalin | Gabapentin/pregabalin | Gabapentin/pregabalin | Gabapentin/pregabalin |
| Lidocaine patch | Lidocaine patch (in elderly) | SNRI* | Lidocaine patch (especially frail, elderly) | |
| Opioid* | TCA* | TCA* | SNRI* | |
| TCA* | TCA* | |||
| 2nd Line | Aspirin in cream or ointment* | Opioid* | Lidocaine patch (for PHN) | For peripheral pain: |
| IT methyl-prednisonlone* | Topical capsaicin | Opioid* | Capsaicin patch | |
| Topical capsaicin | Tramadol* | Lidocaine patch | ||
| Tramadol* | ||||
| AAN, American Academy of Neurology; CPS, Canadian Pain Society; EFNS, European Federation of Neurological Societies; IASP, International Association for the Study of Pain; IT, intrathecal; NeuoPSIG, Neurological Pain Special Interest Group; PHN, post herpetic neuralgia; SNRI, selective norepinephrine reuptake inhibitor; TCA, tricyclic antidepressant. The asterisk (*) designates a therapy that is not approved by the U.S. Food and Drug Administration for post-herpetic neuralgia (PHN) pain. |
Despite numerous options for PHN pain control, there is no clear-cut first-line therapy and PHN analgesia remains suboptimal. In fact, less than half of all PHN patients report a >50% pain reduction with any type of therapy [12, 13]. This creates concern and frustration among both patients and healthcare professionals that is exacerbated by the fact that PHN pain is complex. Since PHN involves a reactivation of latent VZ virus that results in an inflammatory response, it is capable of destroying both peripheral and central neurons [14, 15]. Even when the rash of PHN resolves, neural damage and inflammation can lead to central sensitization and chronic pain, resulting in a complex pain syndrome with a neuropathic component [6, 13, 16, 17]. The lidocaine patch concept confers the apparent advantage over systemic pharmacological treatments in that there is low systemic absorption of the drug, associated with fewer and milder side effects [18, 19]. This can be of particular importance for patients on polypharmacy, which is more prevalent among geriatric than younger patients [20]. Furthermore, topical delivery systems are thought to be relatively easy to use and well accepted by patients.
The introduction of a 5% lidocaine plaster (Lidoderm®, Hind Health Care, Inc., San Jose, California) in 1999 provided topical delivery of lidocaine to PHN patients. Lidocaine patches were soon considered a first-line approach to PHN by many specialty societies and found resonance among patients and prescribers [7, 8, 10]. Early reports of inadequate patch adhesion occurred in the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) [21]. Anecdotal reports of patient dissatisfaction and suboptimal compliance followed. A new topical lidocaine patch (ZTLIDO®, SCILEX, San Diego, California) was designed to overcome the adhesion problem. This new patch uses 1.8% lidocaine but is bioequivalent to the 5% patch, meaning both products are similarly efficacious.
Compliance with the older patch system has been suboptimal, which has resulted in the pain of PHN not being effectively controlled. Furthermore, there may be other unmet medical needs associated with pain control of PHN. In order to better understand the needs of PHN patients with respect to lidocaine plaster therapy and the attitudes of the nurses caring for such patients, a survey was conducted to determine the unmet medical needs in PHN and the potential role of lidocaine plasters. The objective of this survey was to better describe PHN therapy using lidocaine patches and the perceptions and opinions of patients and their nurses about lidocaine patches used to help manage PHN pain. Note that this survey predated the market release of this new and improved lidocaine patch and the views about lidocaine patches expressed in the survey refer exclusively to the older patch models.
The purpose of this survey was to assess the attitudes of nurses and patients using the lidocaine patch in terms of its safety, efficacy, and practicality.
3. Methods
Two companion internet anonymized surveys were conducted in May 2016. The “patient survey” was conducted among American adults >18 years with a PHN diagnosis within the past two years and who used lidocaine patches in that time for pain control. The “nurse survey” was conducted at the same time by the same investigators among American registered nurses and nurse practitioners who were >18 years or older, employed full-time in a non-pediatric healthcare practice and who consulted with at least five PHN patients in the past six months and who have used lidocaine patches to treat PHN in the past two years. Survey participants consented into the survey prior to answering any questions. No identifying information was obtained or recorded during the course of the survey. No identifying information was recorded to link a person with the data such that it could reasonably harm the individual’s reputation, employability, financial standing, or place them at risk for criminal or civil liability. The surveys were not reviewed by an IRB.
Data from patients about their diagnoses, conditions, and prescription medications came from patients’ responses to the survey and were not cross-checked against medical records.
4. Results
A total of 153 patients and 151 nurses participated in these surveys. Demographic data appears in Table 2. Surveys covered PHN pain and its impact on daily living, PHN treatments and unmet medical needs, and the evaluation of lidocaine patches for PHN treatment.
| Nurses | Patients | ||
| Population | 151 | 153 | |
| Mean age | 43.3 years | 45.2 years | |
| Sex (percentage males) | 21% | 50% | |
| Educational background | |||
| High school or less | 3% | 20% | |
| Attended college and/or college degree | 54% | 51% | |
| Graduate school and/or graduate degree | 42% | 25% | |
| Race, ethnicity | |||
| White | 59% | 51% | |
| Hispanic | 9% | 38% | |
| African-American, black | 23% | 8% | |
| Asian | 5% | 2% | |
| Native American or Alaskan Native | 1% | 0 | |
| Declined to answer | 2% | 0 | |
| Marital status | |||
| Married or civil union | 65% | 55% | |
| Divorced, widowed, separated | 17% | 13% | |
| Living with partner | 5% | 10% | |
| Never married | 14% | 23% | |
| Nursing roles | |||
| Registered nurse | 71% | Not applicable | |
| Nurse practitioner | 29% | ||
| Hospital-based work setting | 48% | ||
| Physician office work setting | 23% | ||
| Mean number of PHN patients treated in past six months | 23.7 patients | ||
| Mean number of patients with shingles treated in past six months | 39.7 patients | ||
| Patient employment | |||
| Total employed in some capacity | Not applicable | 79% | |
| Full-time employment | 65% | ||
| Part-time employment | 4% | ||
| Self-employed, full-time | 7% | ||
| Self-employed, part-time | 3% | ||
| Not employed but seeking work | 4% | ||
| Retired | 9% | ||
| Not employed due to disability or illness | 5% | ||
| Stay-at-home spouse or partner | 3% | ||
| Student | 0 | ||
| Patient conditions | |||
| Shingles | Not applicable | 100% | |
| Hypertension | 63% | ||
| High cholesterol | 60% | ||
| Anxiety | 52% | ||
| Diabetes | 46% | ||
| Depression | 42% | ||
| Stomach ulcers or bleeding | 27% | ||
| Liver disease or cirrhosis | 26% | ||
| History of myocardial infarction | 24% | ||
| Medicines prescribed in past two years for PHN | |||
| Lidocaine patch (inclusion criterion) | 100% | 100% | |
| Opioids | 56% | 49% | |
| NSAIDs | 65% | 48% | |
| Gabapentin or pregabalin | 65% | 45% | |
| Tricyclic antidepressants | 43% | 37% | |
| Geographical region | |||
| South | 48% | 43% | |
| Midwest | 23% | 11% | |
| West | 16% | 28% | |
| East | 14% | 19% |
4.1 HN background and its impact on daily living
Patients (68%) stated that the after-shingles pain lasted 1 to 6 months, with a mean of 6.2 months. 5% of patients said their pain lasted ≥13 months. When asked to rate PHN pain intensity, 91% of patients and 74% of nurses said that PHN pain was moderate to severe. Nurses reported PHN pain in their patients as mild more frequently than patients did (26% vs. 9%, respectively). Key findings are summarized in Table 3.
| Finding | Key data | Comments |
| After-shingles pain persists for an average | 1–6 months (68% of respondents) | 32% of patients had pain for >6 |
| of 6.2 months in survey respondents | 7–12 months (22% of respondents) | months |
| 13+ months (5% of respondents) | ||
| Most patients and nurses describe PHN as moderate to severe | Patients: 91%, Nurses 74% | Only 9% of patients said pain was mild compared to 26% of nurses |
| The ability to engage in daily activities is negatively impacted by PHN pain | Moderate to severe adverse impact reported by 85% of patients and 88% of nurses | |
| PHN pain has negative impact on various aspects of patients’ lives | Most affected areas: sleep, exercise, social activities, chores, work |
When asked the extent to which PHN pain affected the patients’ ability to engage in the activities of daily living, 37% of patients said their PHN pain had adversely affected daily living “a great deal” and 32% of nurses said the same. PHN patients specifically reported that PHN pain negatively affected their ability to exercise (58%), sleep (57%), participate in social or recreational activities (56%), and perform household tasks (50%). Only 4% of patients and 3% of nurses reported that PHN pain had no effect at all on their ability to go about ordinary daily activities. Patients reported that their PHN pain “moderately” or “significantly” affected their ability to work (33% and 40%, respectively) and 74% said it “moderately” or “significantly” impacted their self-esteem. PHN pain interfered with the patient’s relationship with spouse/partner “moderately” or “significantly” for 69% of respondents. See Fig. 1.
Fig. 1.Patients and nurses were asked which areas of the patients’ live have been negatively impacted by after-shingles pain. Respondents could give more than one answer.
4.2 PHN treatments and unmet medical needs
There is no standard course of treatment for PHN pain control, and there remain many gaps in treatments despite the fact that there are numerous treatment options. See Table 4. Patients who consult prescribers for PHN pain relief are prescribed a mean of 2.6 medications; only 11% said they got only one prescription, and 13% got four or five medications. In clinical practice, lidocaine is typically a first-line treatment [22] with about two-thirds of patient respondents (66%) in our survey saying they were prescribed a patch alone or as part of combination therapy as their initial treatment. The most commonly prescribed combination therapy reported was the lidocaine patch plus an NSAID (15%).
| Finding | Key data | Comments |
| The average number of pain medications prescribed as front-line treatment is 2.6 | 78% of patients were prescribed 2 or more medications during first pain experience | Most patients report multimodal therapy is more effective than monotherapy |
| First-line treatment typically includes lidocaine patches | 66% of patients were prescribed the lidocaine patch alone or with other medicines as first treatment | When combined, lidocaine patches were most often used with an NSAID |
| When second-line therapy was prescribed, lidocaine patches were also the most frequent choice | ||
| Moderate satisfaction with first-line pain relief | 54% of patients and 87% of nurses were very or somewhat satisfied with pain control | Almost half of patients (46%) were very or somewhat dissatisfied while most nurses were very or somewhat satisfied |
| Nearly all who were dissatisfied spoke to the doctor | Only 1% did not speak to anyone; 97% talked to the physician | Patients seemed most comfortable speaking to a physician |
| Lidocaine patches used to augment opioid-only therapy in many | When PHN pain is not controlled by opioid monotherapy, 67% of the time a lidocaine patch is added | Lidocaine patches are frequently used as part of multimodal therapy |
| Patches are also prescribed most often second-line | When any therapy must be augmented with another pain reliever, 38% of the time, lidocaine patches are used | 47% of PHN patients who are not prescribed patches as first-line treatment require two analgesics to control pain |
| Nurses believe that patient satisfaction is higher with multimodal therapy | Nearly all nurses (95%) report that patients are very or somewhat satisfied when 2 or more analgesics are used | Fewer patients (66%) than nurses say they are satisfied or very satisfied with two or more analgesics |
| Most patients say that healthcare providers are not always able to provide the answers they need | According to patients, nurses have the answers 40% of the time compared to pharmacists at 47% and physicians at 70% | 61% of patients say they are very comfortable asking questions of their physician compared to 44% who are very comfortable asking nurses and 32% are very comfortable asking pharmacists |
| Complete understanding of pain is low | Only 22% of patients report that they have complete understanding of pain and their medications | 23% of patients said they “don’t fully understand” or have no understanding of pain and their medications |
| Complete confidence in treatment plan is low | 26% of patients report being “very confident” about their treatment plan for PHN pain | Most patients were less than fully confident in their treatment strategy |
| Few patients say medicine offered complete pain relief | 16% reported complete pain relief and 51% said PHN pain was more bearable after taking medications | 54% of patients overall said they needed more than one medication to control their PHN pain |
| Patient noncompliance seen as challenge to treatment efficiency | 53% of nurses saw patient noncompliance as a challenge with PHN treatment and 12% said it was the single “biggest challenge” | Other challenges were patients not understanding how to take their medicine, comorbidities, lack of PHN guidelines, drug-drug interactions, adverse events, and poor efficacy |
| Nurses report patch-related factors as contributing to noncompliance | 45% of nurses say that poor adhesion led to poor compliance | Poor adhesion can cause the patch to move off the pain site, detach, or require tape to hold in place; patients and nurses view this as an inconvenience |
| One in five not aware the American Academy of Neurology recommends patches for PHN treatment | 18% of nurses did not know that the American Academy of Neurology recommended lidocaine patches | There are few guidelines specific to PHN pain control |
While 87% of nurses stated they believed their patients were satisfied with pain relief offered by their first-line approaches to PHN pain (including but not limited to lidocaine patches), fewer patients (54%) reported satisfaction with first-line approaches. Patients dissatisfied with their PHN treatment almost always chose to speak with their physician (97%) with 33% addressing their concerns to a nurse and 28% to a pharmacist. Only 1% of patient respondents said they did not express therapeutic dissatisfaction to anyone. When patients on opioid monotherapy complained of inadequate analgesia, 67% of nurses reported the physician would add the lidocaine patch, 53% added an anticonvulsant, 44% added NSAIDs, and 36% added tricyclic antidepressants. Nurses stated that about half of their patients required a second analgesic to get effective pain relief and 38% of them said in such cases a lidocaine patch was added compared to 17% getting an add-on anticonvulsant and 15% an opioid. Multimodal therapy is common in PHN patients and 95% of nurses stated that patients were “very” or “somewhat” satisfied with such combination regimens.
When patients had questions about PHN pain or wanted to know about ways to treat it, 42% of patients said they were “always” satisfied with what they learned from the physician, 20% were “always” satisfied with answers from their pharmacists, and 18% were “always” satisfied with the answers provided by nurses. Patients reported they were most comfortable speaking to physicians (61%) compared to nurses (44%) and pharmacists (32%).
Only 22% of patients reported they had “complete understanding” of their PHN pain and 26% said they had “full confidence” in their treatment plans to manage this pain. About half of patients (54%) said that they needed more than one medication to control PHN pain and 51% reported that their PHN pain was more bearable after taking their prescribed medication(s).
The barriers to better analgesia for PHN were described by nurses, with the most-reported obstacle being noncompliance (named by 53% of nurses). In fact, 12% of nurses rated noncompliance as the single “biggest challenge” in PHN patient care. Other barriers to optimal care were lack of patient understanding about when and how to take their medications, difficulties with comorbidity management, lack of specific PHN pain control guidelines, drug-drug interactions, and adverse events. Patient compliance must be considered one of the main barriers to optimal PHN pain control for all types of treatments. Nurses reported that poor compliance for all PHN treatment regimens had to do with managing multiple medications (57%) and a lack of patient understanding how and when to take or use their medications (51%). For lidocaine patches specifically, poor adhesion of the patch (45%), inconvenience (34%), and messiness of using a patch (34%) were reported. With respect to systemic agents, noncompliance was thought by nurses to be associated with adverse events (29%) or poor efficacy (23%). When the nurses were asked to name the major factors contributing to patient noncompliance in general, they named lack of understanding of how and when to take or use the medications (23%), the difficulties in managing multiple medications (22%), poor adhesion offered by lidocaine patches (15%), inconveniences associated with both patches and gels (11%), and inadequate efficacy (11%).
Despite the wealth of pain medications in the PHN armamentarium, 18% of nurses were not aware that the American Academy of Neurology (AAN) recommends lidocaine patches for treating PHN pain.
4.3 Evaluation of PHN treatment using lidocaine patches
Most patients and nurses (79% and 84%, respectively) reported that the lidocaine patch was prescribed as first- or second-line treatment for PHN pain and 16% of both patients and nurses said it was first prescribed as third-line treatment. Patients and nurses expressed strong opinions about current patches; see Table 5. On average, patients refilled their prescription for the lidocaine patch 3.0 times and 26% refilled it ≥4 times. When nurses were asked the key factors of importance to them in selecting a lidocaine patch, they said it was “very” or “somewhat” important that the patch maintain skin contact over 12 hours (98%), maintain skin contact even during heat or during exercise (94%), and that data on patch adhesion be available (87%). About a third of nurses (36%) reported they found the lidocaine patch “very effective” in treating PHN pain while 91% found the patch “very” or “somewhat” effective. A variety of factors were reported by nurses as to why they found patches less than efficacious. See Fig. 2.
| Finding | Key data | Comments |
| Most patients and nurses say lidocaine patches are prescribed first- or second-line | 80% of patients reported the patch was first- or second-line therapy, similar to nurses where 84% said the patch was first or second line | Only 16% of both patients and nurses reported the patch was used as a third-line treatment |
| The patch prescription is typically refilled three times | Mean refill is 3.0 and 26% of patients refill their prescription >3 times | 10% of patients filled their lidocaine patch prescription only once |
| Patch adhesion considered very important in treatment choice for nurses | Nearly all nurses (98%) said it was very or somewhat important that the patch adhere to skin during normal activities for 12 hours, 94% said it was important or very important that adhesion was maintained during heat or exercise | 87% of nurses said that the availability of data on patch adhesion was very or somewhat important |
| Not all nurses think patches are “very effective” | 91% of nurses said patches were “effective” but only 36% rated them as “very effective” | Most nurses did not find the lidocaine patch “very effective” |
| Nurses say patch efficacy is limited by lack of adhesion | 60% said the main factor limiting efficacy of the patch was that the patch could not maintain contact with the skin over the prescribed 12 hours | About half of nurses (51%) said the patch irritated patients with sensitive skin |
| Few patients are “very satisfied” with their patch | 30% of patients are “very satisfied” with the lidocaine patch and another 50% are “somewhat satisfied” | Most nurses (58%) report they think patients are “satisfied” with the patch |
| Nurses say patient dissatisfaction with the patch is due to adhesion and efficacy | 57% of nurses thought that if patients were not satisfied with the patch, it was because of adhesion problems, 55% said it provided inadequate pain control, and 46% said the patch had to be taped in place | 23% of nurses said they thought patients found the patches difficult to apply |
| Many patients frustrated with patch adhesion | 62% of patients say they are “frustrated” with the patch staying appropriately adhered; 14% were “very frustrated” | Lack of adhesion limits therapeutic efficacy and is inconvenient |
| Very few patients say the patch always stays attached for the full treatment time | 13% said the patch rarely stayed attached for the full treatment time and 51% of patients said the patch became detached or moved off the application site ≥3 times in the 12-hour treatment period | 11% of patients said the patch did not move or become detached in 12 hours |
| Patients say adhesion issues hinder exercise | 80% said they “agreed” or “strongly agreed” that the patch impeded their ability to exercise | |
| Nurses say more than one in three patients report problems with patch adhesion | Nurses say about a third of patients (35%) report the patch becomes detached and 35% of patients require patch re-attachment after the initial application | |
| Patients unable to wear patch because of need for tape, adhesion issues | 41% of patients said they had to tape the patch in place, 39% said the patch moved off the application site, and 37% said the patch fell off | 21% of lidocaine patch patients reported they were not able to wear the patch for 12 hours |
| Few patients are very satisfied with patch adhesion | 26% of patients are “very satisfied” with patch adhesion and 50% more were “somewhat satisfied” compared to 54% of nurses who thought patients were “satisfied” | |
| Some patients speak with their nurse about patch adhesion | 73% of patients said they told a healthcare professional (58% physician, 38% nurses, 31% other) about adhesion problems | On average, about a third (37%) of patients complain to their healthcare team that the patch does not adhere properly |
| Patch adhesion is critical to pain relief | 86% of patients and 94% of nurses thought that adequate patch adhesion for the full 12 hours was critical to pain relief | Nearly all nurses and most patients understand the importance of adhesion to therapeutic efficacy |
| Pain relief top concerns regarding patch adhesion | The concerns reported by patients were: inadequate patch adhesion: running out of patches (41%), inadequate duration of therapy (39%), having to tape the patch (39%), not getting adequate analgesia (37%), costs (24%) | The biggest concern was that with poor adhesion, pain control would not last all day (29% said this was their “biggest concern”) |
| Half of patients use tape to assist with patch adhesion | 46% said they used tape to hold the patch in place and of those patients 65% found this inconvenient and 41% said it was uncomfortable on their skin | 24% of patients who had trouble with patch adhesion said they requested a different patch |
| Additional adherence measures lessen the likelihood of receiving full treatment | 72% of patients said that if the patch adhered better and they did not have to use tape, they would have been more likely to get the full 12 hours of pain relief | Patients recognize that adhesion problems decrease the therapeutic efficacy of the patch |
| Half of patients switch patches because of adhesion issues | 37% of patients have asked for a different brand of patch because of adhesion issues but only 49% actually switched. The mean number of times patients switched patches was 1.2 times | 26% of patients switched patch brands ≥2 times |
| Patient likelihood to try patch is higher if no tape is needed | 80% of patch patients said they would be “very” or “somewhat” likely to try the patch again if PHN pain recurred. If they could be sure tape was not needed, 90% said they were “very” or “somewhat” likely to try the patch again | Overall, 20% of patients said they were “not very” or “not at all” likely to use the patch again but if they could be assured tape would not be necessary, only 10% were “not very” or “not at all” likely to use the patch again |
| Nurses say available patches don’t provide adequate adhesion | 69% of nurses agree or strongly agree that patches do not provide adequate adhesion | This was a source of concern for nurses and a common complaint of patients |
| Patients and nurses agree that better patch options are needed | 80% of patients and 88% of nurses wish there were better patch options | This represents an unmet medical need |
Fig. 2.Asked of nurses (n = 151): “Which of the following factors, if any, do you believe limit the efficacy of the lidocaine patches that are currently available?” Respondents were permitted to select more than one answer.
Only a subset of patients (30%) report being “very” satisfied with the lidocaine patch with 50% more reporting being “somewhat” satisfied. In contrast, 58% of nurses thought patients were “somewhat satisfied” with the lidocaine patch. Nurses felt that patients were dissatisfied with the patch because of poor adhesion (57%), lack of efficacy (55%), the need to use tape or other means to keep the patch in place (46%), and difficulty applying the patch (23%). About two-thirds of patients (62%) agreed that they were frustrated with patch adhesion or that it did not stay in place over the affected site. In fact, 14% stated they were “very” frustrated about patch adherence. The patch is to remain in place for 12 hours for the recommended treatment, but 85% of patients said the patch did not always remain properly affixed for the duration of treatment. More than half of patients (51%) said the patch moved or became detached ≥3 times. Most patients (80%) agreed that the patch would lift or detach when they exercised. About a third of patients (35%) reported the patch did not stay attached during the 12-hour treatment regimen and 35% said the patch required reattachment after the initial application. Of those who could not keep the patch properly adhered over the 12-hour treatment, 41% said they had to use tape to hold the patch in place. While 54% of nurses reported being “somewhat” satisfied with patch adhesion, 50% of patients said the same. Only 26% of patients agreed that they were “very satisfied” with the patch’s ability to adhere properly in place over the 12-hour treatment. Patients reported that they discussed poor patch adhesion with the physician (58%), nurses (38%), or another healthcare provider (31%). Both patients (86%) and nurses (94%) agreed that the ability of the patch to stay in place over the 12-hour course of therapy was crucial to analgesic efficacy. Patients were concerned about lack of therapeutic benefit, costs, and inconvenience due to adhesion problems. See Fig. 3.
Fig. 3.Asked of all patients (n = 153), “Which of the following, if any, are you biggest concerns about the lidocaine patch not staying attached to your skin and/or not staying in place over the area of after-shingles pain?” Respondents were permitted to give more than one answer.
Almost half of patients (46%) reported that when they had problems with patch adhesion thus used tape to hold the patch in place, something they reported inconvenient (65%), uncomfortable (41%), caused them to lose faith in the quality of the patch (35%), cost (32%), extra trips to the pharmacy (30%), and difficult (29%). Adhesion issues caused 24% of respondents to request a different brand of patch and 16% discontinued patch therapy for this reason. Most patients (72%) “strongly” or “somewhat” agreed that if they did not have to take extra measures like using tape to affix the patch, they would have been more likely to get the benefits from 12 hours of pain relief. A third of patients (37%) asked to switch patches and the mean number of times a patient changed patch brands was 1.2 times. About a quarter of patients (26%) switched brands ≥2 times.
When asked if they would use the lidocaine patch again if PHN pain recurred, 42% of patients said they would be “very likely” to use a patch again. If that patch did not require tape to affix it in place, 54% said they would be “very likely” to use a patch again. More than two-thirds of nurses (69%) agreed “strongly” or “somewhat” that the currently available lidocaine patches do not offer patients the adhesion they need to get the full treatment. Nearly all nurses (88%) and most patients (80%) agreed with the statement that better lidocaine patch options would better meet treatment needs.
5. Discussion
This is the only survey of patients and nurses about their direct experiences with PHN of which the authors are aware. Our results are congruent with other findings about PHN. The literature has reported that PHN is associated with moderate to severe pain in many patients [23, 24] and functional deficits [25, 26]. As many as 40% of PHN patients may suffer long-term pain [27]. The lidocaine patch has been recognized as an important treatment modality [26, 27]. In a clinical study of 77 PHN patients, the 5% lidocaine patch was found in two weeks to significantly reduce pain [28].
This is not a trivial problem; PHN has a prevalence of 2.7% in patients referred to general practitioner, in a population of over 1000 patients [29]. Their quality of life is generally poor [30, 31]. No guidelines offer advice specific to PHN treatment (See Table 1), but there are suggestions on pharmacological [9] or non-pharmacological managements [32]. Experimental data suggest that the antagonism of the complement may become an efficacious therapy, in the future [33]. At the moment, as shown in this study, it is frequently considered a pain that may benefit of the use of anti-inflammatories, especially the ones suggested as more safe [34, 35]. Multimodal analgesia has resulted very frequently used in this study, and it represents always a better choice than a monotherapy [36, 37].
Our survey provided patients the opportunity to self-report pain symptoms and these results align with previous studies. Our study did find that although the American Academy of Neurology recommends lidocaine patches for treating PHN pain, one out of five nurses surveyed were not aware of this. First-line treatments typically include one or more of the following: the lidocaine patch, gabapentin, pregabalin, systemic NSAIDs, or tricyclic antidepressants. Opioids and the capsaicin patch are recognized treatment modalities, but they are not usually used as first line therapy [7, 8, 9]. While there are many therapeutic options, there is no clear-cut first therapy choice. Patients may be treated first with monotherapy or a multimodal approach, but it is estimated that fewer than half of all PHN patients achieve a 50% or greater reduction in their pain [12, 13].
The 5% lidocaine patch, first cleared for market release in 1999, offered some apparent advantages over systemic pharmacological therapy: as a topical system, it provided low systemic absorption, which theoretically may translate into fewer and milder adverse effects. The most commonly reported adverse event for the lidocaine patch is a mild application-site skin reaction [18, 19]. Since many patients with PHN are elderly and may be on polypharmacy, the benefits of a topical formulation seem particularly relevant. However, the FAERS database and anecdotal evidence from healthcare professionals revealed that patients were experiencing difficulties with patch adhesion.
The introduction of a new lidocaine topical system was intended to offer equivalent analgesic efficacy but better adhesion; the 1.8% lidocaine patch (ZTlido®, SCILEX, San Diego, California) was developed to be bioequivalent to the 5% lidocaine patch (Lidoderm®, Hind Health Care, Inc., San Jose, California.) meaning that these two products are similarly efficacious. The 1.8% topical system was specifically designed to solve the sticky problem of patch adherence by using a lower amount of lidocaine (reducing patch weight and bulkiness) but maintaining the same surface area for treatment with a superior adhesive and an easy-peel backing. This new patch system can offer nine times the lidocaine bioavailability as earlier patches because of its proprietary zero-water adhesive system and it was redesigned to offer an improved form factor, being much lighter in weight and 50% thinner. By comparison, the older 5% lidocaine patch contained more lidocaine (700 mg vs. 35 mg), is correspondingly heavier and thicker, and has a backing that must be peeled off from an edge. It must be noted that the survey preceded the introduction of this new patch and reflects viewpoints on the older patch systems. The new 1.8% plaster more efficiently utilizes residual drug in the system, allowing for a lighter, more flexible design. In studies by the manufacturer, these 1.8% topical systems achieved >90% patch adhesion at the end of a 12-hour treatment in >90% of subjects, and patches were able to adhere effectively to patients even during moderate levels of exercise.
Proper and reliable adhesion is crucial to transdermal drug delivery, therapeutic efficacy, and patient compliance [22, 23]. Therapeutic efficacy requires the entire delivery area of the patch must maintain reliable skin contact throughout the prescribed therapeutic time [22]. If the patch does not have or maintain this full therapeutic contact or if the patch becomes displaced or detaches, an inadequate dose of medication may be delivered, providing subtherapeutic benefits [22].
To better measure patch adhesion characteristics, the FDA developed a five-point adhesion scale to evaluate patches where a score of 0 means ≥90% of the patch adhered to the skin and a score of 4 means the patch completely detached. In two open-label, single-dose studies conducted by SCILEX comparing the 1.8% patch to the 5% plaster, the 1.8% transdermal system demonstrated superior adhesion properties [38].
Thus, the new 1.8% lidocaine plaster meets a previously unmet medical need for safe, effective, and reliable PHN analgesia by responding to reports from patients and healthcare professionals about the need for a safe, effective, but more reliably adhesive lidocaine patch. This may improve compliance and, in that way, offer more effective pain control.
Our survey has several limitations. It was an anonymous survey using a convenience sample from the internet. Patients self-reported their pain, functional limitations, and other aspects of their condition. Nurses also self-reported their impressions. The nurse sample was derived independently from the patient sample meaning that the nurses in our study were not the same nurses who cared for the patients in our study. We surveyed only nurses, not physicians, as nurses have more direct experience with patch application and use than physician-prescribers. Any survey is subject to survey bias in that the type of person who responds to a survey may be inherently different from the sample population, particularly from those who do not respond to surveys. The survey offered multiple-choice answers meaning that respondents selected answers rather than provided original narrative comments. The survey was anonymous and therefore no medical records were used and diagnostic criteria and other aspects of care could not be independently confirmed.
6. Conclusions
PHN is associated with moderate to severe peripheral and central pain with no clear-cut first-line treatment. Lidocaine patches are a frequently used first-line therapy but were not as effective or frequently used as they might have been because of poor patch adhesion. Patients and nurses generally found lidocaine patches to be effective but greatly limited by their lack of reliable adherence to the skin. The bioequivalent 1.8% lidocaine transdermal delivery system overcomes this problem with a better-adhering patch.
Author contributions
JP, SN, KM, AP, RT, GV provided substantial contribution to the design of the work and interpretation of data; revised it critically; provided final approval and agreed to be accountable for all aspects of the written work. JP, SN, KM, AP, RT, GV did not design or conduct the survey.
Ethics approval and consent to participate
This article is based on an anonymized online survey and does not contain any studies with human participants or animal performed by the authors without a previous Ethics Committee approval.
Acknowledgment
The authors are grateful to patients and nurses that voluntarily participated in the survey. They also acknowledge medical writing services from Jo Ann LeQuang of Angleton, TX, USA. Moreover, they thank NEMA Research Inc., Naples, FL, USA, and Paolo Procacci Foundation, Roma, Italy, for the support on editing and publishing the results of the research.
Funding
NEMA Research received funding for the editorial and medical writing services from Scilex Pharmaceuticals. NEMA Research did not receive funding to conduct the survey.
Conflict of interest
JP and GV are members of the editorial board of this journal. JP is also a Consultant/ Speaker, Owner, and Researcher for Spirify, US World Meds, Salix, Enalare, Scilex, Pfizer, Lilly, Teva, Taketa, Regeneron, Grunenthal, Neumentum, NEMA Research, BDSI and Bridge Therapeutics. The other authors have no potential conflict of interests.
Authorship
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
